CURRICULUM VITAE

N A M A ProfDrTAMSIL SYAFIUDDIN SpP (K)ALAMAT JlnKARSA No F 1 KOMPLEKS EKS KOWILHAN I

SEIAGUL MEDAN 20117PEKERJAAN Guru Besar FK- UISU FK- USU Ketua Perhimpunan Dokter Paru Indonesia Sumut

Penasihat Perhimpunan Dokter Paru Indonesia Pusat Anggota Kolegium Pulmonologi Indonesia Anggota Pokja Asma dan PPOK PDPI pusat Assesor Program Pendidikan Dokter Spesialis Paru Indonesia

RIWAYAT PENDIDIKAN -Dokter Umum FK-USU Medan1979 -Dokter Spesialis I Paru FK-UI Jakarta 1990 -Dokter Spesialis II Paru Konsultan AsmaPPOK 1995

Pendidikan tambahan

- Pelatihan Kanker Paru TSUKAGUCHI Hospital Kobe- Japan 1989 - Pelatihan PPOK AMAGASAKI Hospital Kobe- Japan 1990 - Pelatihan Respiratory Physiologi rdquoJAPAN RESPIRATORY PHYSIOLOGIST

CLUBrdquo Kyoto- Japan 1990 - Spirometry Training Course Department of Respiratory Medicine National University Hospital Singapore Singapore 1997

-ldquoWorkshop of Bronchoscopy and Autofluorecent Bronchoscopy RS Persahabatan Jakarta Jakarta September 2005

-ldquoTraining of the new interventional technique of bronchosfiberscopyrdquo (Optical Coherence Tommograhy) Department of Thoracic Surgery Tokyo Medical University HospitalTokyo - Japan 2007

- Workshop on Medical Thoracoscopy The American College of Chest Physicians-The Indonesian Association of Pulmonologist RS Persahabatan Jakarta Jakarta November 1997

- Workshop on Reformation of Higer Education SystemHEDS-JICAJakarta 1998

-Pulmonary Infections Course Postgraduate Medical Institute Singapore General Hospital Singapore 2001

- Bronchoscopy ampThoracoscopy Workshop Postgraduate Medical Institute Singapore General Hospital Singapore 2005

- Workshop on Transbronchial Lung Biopsy and Trasbronchial Needle Aspiration PDPI Cabang Jakarta RS Persahabatan Jakarta Jakarta Maret

1997

- Workshop on Respiratory Physiology and Its Clinical Application RS Pusat

Angkatan Darat Gatot Subroto Jakarta Jakarta Juni 1997

Departemen Pulmonologi dan Ilmu Kedokteran Respirasi

Fakultas Kedokteran

Universitas Islam Sumatera Utara

2012

ProfdrTamsil SyafiuddinSpP(K)

Asthma

Levels of competence

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Level of competence 4

bull Mampu membuat diagnosis klinik berdasarkan

lsquopemeriksaan fisikrsquo dan lsquopemeriksaan tambahanrsquo

yang diminta oleh dokter (misalnya pemeriksaan

laboratorum sederhana atau X-ray)

bull Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas

Recent issuesRecent issuesin asthma managementin asthma management

bullldquoldquoThe Unmet Needs of asthma ldquoThe Unmet Needs of asthma ldquo Theme of World Asthma Day 20052006Theme of World Asthma Day 20052006

ldquo ldquoYou can control your asthma ldquoYou can control your asthma ldquo Theme of World Asthma Day 200720Theme of World Asthma Day 2007201212

bullldquoldquoAdherence ldquoAdherence ldquo Self ManagementSelf Management

bullldquoldquoUUD No 29 2004rdquo Praktik KedokteranUUD No 29 2004rdquo Praktik Kedokteran CompetencyCompetency

bullldquoldquoPharmacoeconomic considerationrdquoPharmacoeconomic considerationrdquo Quality of LifeQuality of Life

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

-ldquoWorkshop of Bronchoscopy and Autofluorecent Bronchoscopy RS Persahabatan Jakarta Jakarta September 2005

-ldquoTraining of the new interventional technique of bronchosfiberscopyrdquo (Optical Coherence Tommograhy) Department of Thoracic Surgery Tokyo Medical University HospitalTokyo - Japan 2007

- Workshop on Medical Thoracoscopy The American College of Chest Physicians-The Indonesian Association of Pulmonologist RS Persahabatan Jakarta Jakarta November 1997

- Workshop on Reformation of Higer Education SystemHEDS-JICAJakarta 1998

-Pulmonary Infections Course Postgraduate Medical Institute Singapore General Hospital Singapore 2001

- Bronchoscopy ampThoracoscopy Workshop Postgraduate Medical Institute Singapore General Hospital Singapore 2005

- Workshop on Transbronchial Lung Biopsy and Trasbronchial Needle Aspiration PDPI Cabang Jakarta RS Persahabatan Jakarta Jakarta Maret

1997

- Workshop on Respiratory Physiology and Its Clinical Application RS Pusat

Angkatan Darat Gatot Subroto Jakarta Jakarta Juni 1997

Departemen Pulmonologi dan Ilmu Kedokteran Respirasi

Fakultas Kedokteran

Universitas Islam Sumatera Utara

2012

ProfdrTamsil SyafiuddinSpP(K)

Asthma

Levels of competence

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Level of competence 4

bull Mampu membuat diagnosis klinik berdasarkan

lsquopemeriksaan fisikrsquo dan lsquopemeriksaan tambahanrsquo

yang diminta oleh dokter (misalnya pemeriksaan

laboratorum sederhana atau X-ray)

bull Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas

Recent issuesRecent issuesin asthma managementin asthma management

bullldquoldquoThe Unmet Needs of asthma ldquoThe Unmet Needs of asthma ldquo Theme of World Asthma Day 20052006Theme of World Asthma Day 20052006

ldquo ldquoYou can control your asthma ldquoYou can control your asthma ldquo Theme of World Asthma Day 200720Theme of World Asthma Day 2007201212

bullldquoldquoAdherence ldquoAdherence ldquo Self ManagementSelf Management

bullldquoldquoUUD No 29 2004rdquo Praktik KedokteranUUD No 29 2004rdquo Praktik Kedokteran CompetencyCompetency

bullldquoldquoPharmacoeconomic considerationrdquoPharmacoeconomic considerationrdquo Quality of LifeQuality of Life

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Departemen Pulmonologi dan Ilmu Kedokteran Respirasi

Fakultas Kedokteran

Universitas Islam Sumatera Utara

2012

ProfdrTamsil SyafiuddinSpP(K)

Asthma

Levels of competence

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Level of competence 4

bull Mampu membuat diagnosis klinik berdasarkan

lsquopemeriksaan fisikrsquo dan lsquopemeriksaan tambahanrsquo

yang diminta oleh dokter (misalnya pemeriksaan

laboratorum sederhana atau X-ray)

bull Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas

Recent issuesRecent issuesin asthma managementin asthma management

bullldquoldquoThe Unmet Needs of asthma ldquoThe Unmet Needs of asthma ldquo Theme of World Asthma Day 20052006Theme of World Asthma Day 20052006

ldquo ldquoYou can control your asthma ldquoYou can control your asthma ldquo Theme of World Asthma Day 200720Theme of World Asthma Day 2007201212

bullldquoldquoAdherence ldquoAdherence ldquo Self ManagementSelf Management

bullldquoldquoUUD No 29 2004rdquo Praktik KedokteranUUD No 29 2004rdquo Praktik Kedokteran CompetencyCompetency

bullldquoldquoPharmacoeconomic considerationrdquoPharmacoeconomic considerationrdquo Quality of LifeQuality of Life

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Levels of competence

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Level of competence 4

bull Mampu membuat diagnosis klinik berdasarkan

lsquopemeriksaan fisikrsquo dan lsquopemeriksaan tambahanrsquo

yang diminta oleh dokter (misalnya pemeriksaan

laboratorum sederhana atau X-ray)

bull Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas

Recent issuesRecent issuesin asthma managementin asthma management

bullldquoldquoThe Unmet Needs of asthma ldquoThe Unmet Needs of asthma ldquo Theme of World Asthma Day 20052006Theme of World Asthma Day 20052006

ldquo ldquoYou can control your asthma ldquoYou can control your asthma ldquo Theme of World Asthma Day 200720Theme of World Asthma Day 2007201212

bullldquoldquoAdherence ldquoAdherence ldquo Self ManagementSelf Management

bullldquoldquoUUD No 29 2004rdquo Praktik KedokteranUUD No 29 2004rdquo Praktik Kedokteran CompetencyCompetency

bullldquoldquoPharmacoeconomic considerationrdquoPharmacoeconomic considerationrdquo Quality of LifeQuality of Life

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Standar Kompetensi Dokter Konsil Kedokteran Indonesia 2012

Level of competence 4

bull Mampu membuat diagnosis klinik berdasarkan

lsquopemeriksaan fisikrsquo dan lsquopemeriksaan tambahanrsquo

yang diminta oleh dokter (misalnya pemeriksaan

laboratorum sederhana atau X-ray)

bull Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas

Recent issuesRecent issuesin asthma managementin asthma management

bullldquoldquoThe Unmet Needs of asthma ldquoThe Unmet Needs of asthma ldquo Theme of World Asthma Day 20052006Theme of World Asthma Day 20052006

ldquo ldquoYou can control your asthma ldquoYou can control your asthma ldquo Theme of World Asthma Day 200720Theme of World Asthma Day 2007201212

bullldquoldquoAdherence ldquoAdherence ldquo Self ManagementSelf Management

bullldquoldquoUUD No 29 2004rdquo Praktik KedokteranUUD No 29 2004rdquo Praktik Kedokteran CompetencyCompetency

bullldquoldquoPharmacoeconomic considerationrdquoPharmacoeconomic considerationrdquo Quality of LifeQuality of Life

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Recent issuesRecent issuesin asthma managementin asthma management

bullldquoldquoThe Unmet Needs of asthma ldquoThe Unmet Needs of asthma ldquo Theme of World Asthma Day 20052006Theme of World Asthma Day 20052006

ldquo ldquoYou can control your asthma ldquoYou can control your asthma ldquo Theme of World Asthma Day 200720Theme of World Asthma Day 2007201212

bullldquoldquoAdherence ldquoAdherence ldquo Self ManagementSelf Management

bullldquoldquoUUD No 29 2004rdquo Praktik KedokteranUUD No 29 2004rdquo Praktik Kedokteran CompetencyCompetency

bullldquoldquoPharmacoeconomic considerationrdquoPharmacoeconomic considerationrdquo Quality of LifeQuality of Life

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Definition of asthma1048714 Chronic inflammatory disease of airways (AW)

1048714 uarr responsiveness of tracheobronchial tree1048714 Physiologic manifestation

AW narrowing relieved spontaneously or with BD plusmn Cster

1048714 Clinical manifestations a triad of paroxysms of cough dyspnea and

wheezing

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

NormalNormal AsthmaAsthma

InflammationInflammation(+)(ndash)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

Symptoms (+)Symptoms (+)Symptoms (-)Symptoms (-)

Tri

gg

ers

Bronchoconstriction ( - ) Bronchoconstriction ( + )

Tri

gg

ers

The pathogenesis of asthma

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

IDENTIFIKASI MASALAHANALISIS

MASALAHDATAKELUHAN

PEMECAHAN MASALAHRENCANA(Planning)

KURIKULUM BERBASIS KOMPETENSI (Problem Based Learning)

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

IDENTIFIKASI MASALAHANALISIS

bull Batukbull Sesak napas bull Batuk darahbull Nyeri dada

bull OBSTRUKTIFbull INFEKSI bull KEGANASANbull PENYAKIT ORGAN LAIN

MASALAHDATA

PEMECAHAN MASALAHRENCANA(Planning)

Daftar keluhan Standar Kompetensi Dokter Indonesia

bullDATA LAIN

bullRENCANA

BERIKUTPF

RoPFR

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Sesak napas

1Air way sistem Kelainan obstruktifAsma

2helliphelliphellip

Problem Based Learning

1 Wheezing

2 Riwayat keluarga

3 Riwayat obat terdahulu

4Riwayat kebiasaan

1 Pemeriksaan fisik

Wheezing

2 SpirometriPFR

3 Radiologi

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Anti Inflammations is Anti Inflammations is the mainstay therapythe mainstay therapy

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

ldquoLarge userdquo of short-acting

szlig2-agonists

ldquoFearrdquo of short-acting szlig2-agonists

Singleinhaler therapy

ICS+LABA

ICS treatment introduced

1972

Adding LAszligA to ICS therapy

Kips et al AJRCCM 2000 Pauwels et al NEJM 1997

Greening et al Lancet 1992

Bronchospasm Inflammation Remodelling

ICS Inhaled Corticosteroids LABA a Long-Acting Beta2 Agonist

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

ASTHMA MANAGEMENT ldquoCLINICALrdquo

bull QUICK RELIEVE MEDICATION

bull LONG TERM TREATMENT

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Guidelines on Asthma ManagementPast and Current Trends

LABA and ICS

ICS

LABA+ICS

GINA 1998 (adapted)

GINA 2011

Severe persisten

t

Moderate persisten

t

Mild persisten

tIntermittent

SABA Rapid onset of action LABA

ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classification

New classification

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Inhalation therapy is Inhalation therapy is the mainstay therapythe mainstay therapy

Because minimally side effect

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

ControllerControllerAnti inflammationAnti inflammation

bull budesonide (Pulmicortregreg) (Inflamidregreg)

bull beclomethasone dipropionate (Becotideregreg)

bull triamcinolone acetonide

bull fluticasone(Flexotideregreg)

bull sodium chromoglicate (Intalregreg)

bull ketotifen

bull sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

BronchodilatorBronchodilator

2 2 - - agonistagonist

bull XanthinXanthin

bullAnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

BRONCHODILATORBRONCHODILATORShort Acting Short Acting 22 AGONIST (SABA) AGONIST (SABA)bullsalbutamolalbuterol (Ventolin salbutamolalbuterol (Ventolin regreg))bullterbutaline (Bricasmaterbutaline (Bricasmaregreg))bullprocaterolprocaterolbullfenoterolfenoterolbullorciprenaline etcorciprenaline etc

ANTICHOLINERGICANTICHOLINERGIC

bullatropine sulfate atropine sulfate bullipratropium bromideipratropium bromidebulltiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC OTHER SYMPHATOMIMETIC bullephedrineephedrinebulladrenaline etcadrenaline etc

XANTHINEXANTHINEbulltheophyllinetheophyllinebullaminophyllineaminophylline

Long Acting Long Acting 22 AGONIST AGONIST

(LABA)(LABA)

bullsalmoterolsalmoterol

bullformoterolformoterol

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Combination therapyCombination therapy

SymbicortSymbicortregreg

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretideregreg

Fluticasone + SalmoterolFluticasone + Salmoterol

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Ig EIg EAgAg

YYMethyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidylethanolamineethanolamine

Phosphatidyl Phosphatidyl cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF NCFECF NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

5-HETE5-HETE LeucotrienesLeucotrienesLTBLTB44

LTCLTC44

LTDLTD44

LTELTE44

ThromboxanesThromboxanesTXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22

Mediator release in asthma reactions

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Disease Pattern1048714 Episodic --- acute exacerbations interspersed

with symptom-free periods

1048714 Chronic --- daily AW obstruction which

may be mild moderate or severe plusmn

superimposed acute exacerbations

1048714 Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

InapropriateInapropriate TreatmentTreatment

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

MBP ECPMBP ECP

Eosinophil

Epithelium

AIRWAY REMODELLING IN AIRWAY REMODELLING IN ASTHMAASTHMA

Desquamations of epitheliumDesquamations of epithelium

Thickening of basement membraneThickening of basement membrane

Increase in airway smooth muscleIncrease in airway smooth muscle

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Epithelial DamageEpithelial Damage

P Jeffery in Asthma Academic Press 1998

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Basement Membrane Basement Membrane ThickeningThickening

P Jeffery in Asthma Academic Press 1998

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery in Asthma Academic Press 1998

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

The Beginning of The Beginning of TreatmentTreatment

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment

Stable condition Stable condition

x

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Asthma management

Stable condition

Long-term therapy

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Assessment of treatment

bullObjective value

bullAsthma Control Test

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Peak flow meterPeak flow meter

600-700

0

300

( normal )bullObjectivObjective valuee value

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Inflammation can also be present Inflammation can also be present during symptom-free periodsduring symptom-free periods

Adapted from Woolcock A Clin Exp Allergy Rev 2001 1 62ndash64

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEF

Impaired FEV1

Start of treatment

R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Months

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Peak Flow Meter PEFRAPE

Must be avilable

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

PEFR MonitoringPEFR MonitoringA Major Tool in Asthma Self-ManagementA Major Tool in Asthma Self-Management

Chronic DiseasesChronic Diseases MonitorMonitor

HypertensionHypertension

DiabetesDiabetes

AsthmaAsthma

Blood pressureBlood pressure

Serum glucoseSerum glucose

PEFRPEFR

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

bullAsthma Control Asthma Control Test Test

(ACT)(ACT)

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Target of treatment

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Old Classification of Asthma Severity GINA 2003

STEP 4

Severe Persistent

STEP 3

Moderate Persistent

STEP 2

Mild Persistent

STEP 1

Intermittent

Global Initiative for Asthma (GINA) WHONHLBI 2003

SymptomsNighttimeSymptoms

PEF

CLASSIFY SEVERITYClinical Features Before Treatment

ContinuousLimited physical activity

Daily 2-agonist dailyAttacks affect activity

gt1 time a week but lt1 time a day

lt 1 time a weekAsymptomatic and normal PEF between attacks

Frequent

gt1 time week

gt2 times a month

lt2 times a month

lt60 predictedVariability gt30

gt60-lt80 predictedVariability gt30

gt80 predictedVariability 20-30

gt80 predictedVariability lt20

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many Clear therapeutic targets exist for many chronic diseaseschronic diseases

Philosophy of lsquotreat to targetrsquoPhilosophy of lsquotreat to targetrsquo

Hypertension Hypertension BP 14090 mmHg or lessBP 14090 mmHg or less

Diabetes Diabetes HbAHbA1c1c 7 or less 7 or less

Dyslipidaemia Dyslipidaemia LDL-cholesterol lt100 LDL-cholesterol lt100 mgdlmgdl

Asthma tAsthma treatment is designed to meet reatment is designed to meet specific targets and achieve lsquoCONTROLrsquospecific targets and achieve lsquoCONTROLrsquo

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Control Level Based on GINAControl Level Based on GINA 2008 2008

None (2 or less week)

None

None

None (2 or less week)

Normal

None

Daytime symptoms

Limitations of activitiesNocturnal symptoms awakening

Need for rescue ldquorelieverrdquo treatment

Lung function (PEF or FEV1)

Exacerbation

CONTROLLEDCharacteristics

More than twice week

Any

Any

More than twice week

lt 80 predicted or personal best (if known) on any day

Oncemore per year

PARTLY CONTROLLED

3 or more features of partly controlled asthma present in any week

One in any week

UNCONTROLLEDNew Asthma Classification

GINA updated 2008

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

DIFFERENTIAL DIAGNOSIS

1 Upper airway obstruction ndash glottic dysfunction2 Acute LV failure ndash pulmonary oedema

3 Pulmonary embolism4 Endobronchial disease

5 Chronic bronchitis6 Eosinophilic pneumonia

7 Carsinoid syndrome8 Vasculitis

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Life is not problem to be solvedLife is not problem to be solved but a reality to be experienced but a reality to be experienced

( Soren Kierkegaard)( Soren Kierkegaard)

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

Syafiuddin San You are the Inspiring woman

Imah San You are the Wind beneath my wings

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

DIAGNOSIS EXACERBATION ldquoCLINICALrdquo

1048714 Episodic asthma Paroxysms of wheeze dyspnoea and

cough asymptomatic between attacks

1048714 Acute severe asthma bull upright position use accessory resp muscles

bull canrsquot complete sentences in one breath bull tachypnea gt 25min tachycardia gt 110min PEF 33-50 of pred or best pulsus paradoxus

chest hyperresonant prolonged expiration breath sounds decreased inspiratory and

expiratory rhonchi cough

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

1048714 Life-threatening features PEF lt 33 of pred or bestsilent chest cyanosis

bradycardia hypotension feeble respiratory effort

exhaustion confusion coma PaO2 lt 60PCO2 normal or increased

acidosis (low pH or high [H+])

1048714 Chronic asthma

Dyspnea on exertion wheeze chest tightness and cough on daily basis usually at night and early morning intercurrent acute severe asthma (exacerbations)

and productive cough (mucoid sputum) recurrent respiratory infection expiratory rhonchi throughout and accentuated on forced expiration

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

MANAGEMENT 2

1048714 No improvement after 15-30 min Nebulized β2 agonist every 15-30 min + Ipratropium

1048714 Still no improvement Aminophyllin infusion 750mg24H (small pt) 1 500mg24H

(large pt) or alternatively salbutamol infusion

1048714 Monitor Rx

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 gt 90) + repeat blood gasesafter 2 hrs if initial PaO2 lt 60 PaCO2 normal or raised and

patient deteriorates

1048714 Deterioration

ICU intubate ventilate + muscle relaxant

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2

1048714 Acute severe asthma

MANAGEMENT 1

1Immediate Rx

O2 40-60 mask or cannula + SABA (salbutamol 5mg)

nebulizer + ICS 200 mcg nebulizer or hydrocortisone

200mg IV With lifethreatening features add 05mg

ipratropium to nebulized β2 agonist + Aminophyllin 250mg

iv over 20 min or salbutamol 250ug over 10 min

2 Subsequent Rx Nebulized SABA 6 hourly + ICS 200mcg

or hydrocortisone 200mg 6 hourly IV + 40-60 O2