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Departemen Pulmonologi

Fakultas Kedokteran

Universitas Sumatera Utara

2008

Tamsil Syafiuddin-Bintang Sinaga

Asthma

Levels of competence

Standar Kompetensi Dokter , Konsil Kedokteran Indonesia, 2006

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Standar Kompetensi Dokter , Konsil Kedokteran Indonesia, 2006

Level of competence 4:

• Dokter mampu membuat diagnosis klinik

berdasarkan ‘pemeriksaan fisik’ dan

‘pemeriksaan tambahan’ yang diminta oleh

dokter (misalnya: pemeriksaan laboratorum

sederhana atau X-ray).

• Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas.

Recent issuesRecent issues

in asthma managementin asthma management

••“The Unmet Needs of asthma ““The Unmet Needs of asthma “

Theme of World Asthma Day 2005/2006Theme of World Asthma Day 2005/2006

“You can control your asthma ““You can control your asthma “

Theme of World Asthma Day 2007/2008Theme of World Asthma Day 2007/2008

••“Adherence ““Adherence “

Self ManagementSelf Management

••“UUD No 29 / 2004” : Praktik Kedokteran“UUD No 29 / 2004” : Praktik Kedokteran

CompetencyCompetency

••“Pharmacoeconomic consideration”“Pharmacoeconomic consideration”

Quality of LifeQuality of Life

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Asthma is an inflammatory diseasesAsthma is an inflammatory diseases

Definition of asthma�� Chronic inflammatory disease of airways

(AW)�� ↑ responsiveness of tracheobronchial tree

�� Physiologic manifestation: AW narrowing relieved spontaneously or with

BD ± Cster�� Clinical manifestations:

a triad of paroxysms of cough, dyspnea and wheezing.

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Disease Pattern�� Episodic --- acute exacerbations

interspersed

with symptom-free periods

�� Chronic --- daily AW obstruction which

may be mild, moderate or severe ±

superimposed acute exacerbations

�� Life-threatening--- slow-onset or fast-onset

(fatal within 2 hours)

Classification :

• Level of asthma severity(by Clinical Features Before Treatment)

• Level of asthma control

(by Clinical Features After Treatment)

( GINA 2006 )

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Classification of Asthma Severity by

Clinical Features Before Treatment:

Intermittent:Symptoms less than once a week

Brief exacerbations

Nocturnal symptoms not more than twice a month

• FEV1 or PEF ≥ 80% predicted

• PEF or FEV1 variability < 20%

Mild Persistent:Symptoms more than once a week but less than once a day

Exacerbations may affect activity and sleep

Nocturnal symptoms more than twice a month

• FEV1 or PEF ≥ 80% predicted

• PEF or FEV1 variability < 20 – 30%

Moderate Persistent:Symptoms daily

Exacerbations may affect activity and sleep

Nocturnal symptoms more than once a week

Daily use of inhaled short-acting 2-agonist

• FEV1 or PEF 60-80% predicted

• PEF or FEV1 variability > 30%

Severe Persistent:Symptoms daily

Frequent exacerbations

Frequent nocturnal asthma symptoms

Limitation of physical activities

• FEV1 or PEF ≤ 60% predicted

• PEF or FEV1 variability > 30%

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Characteristic Controlled(All of the following)(All of the following)

Partly Controlled(Any measure present

in any week)

Uncontrolled

Daytime symptoms None (twice or

less/week)

More than twice/week Three or more features of partly controlled asthma present in any week

Limitations of

activities

None Any

Nocturnal

symptoms/awakening

None Any

Need for reliever/

rescue treatment

None (twice or

less/week)

More than twice/week

Lung function (PEF or

FEV1)

NormalNormal < 80% predicted or

personal best

(if known)

ExacerbationsExacerbations NoneNone One or more/yearOne or more/year One in any weekOne in any week

Levels of Asthma Control

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NormalNormal AsthmaAsthma

InflammationInflammation(+)(–)

Bronchial hyperreactivity ( + )Bronchial hyperreactivity ( - )

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

• •

•

•

•••

•••

Bronchoconstriction ( - ) Bronchoconstriction ( + )

The pathogenesis of asthma

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Ig EIg E

AgAg

YY

Methyl Methyl

transferasetransferasePhospholipidPhospholipid

PhosphatidylPhosphatidyl

ethanolamineethanolamine

Phosphatidyl Phosphatidyl

cholinecholine

PhosphoPhospholipase Alipase A22

CaCa++++ HistaminHistamin

CaCa++++ HistaminHistamin

ECF, NCFECF, NCFArachidonic acidArachidonic acid

lypoxygenaselypoxygenase cyclooxygenasecyclooxygenase

55--HETEHETE LeucotrienesLeucotrienesLTBLTB44LTCLTC44LTDLTD44LTELTE44

ThromboxanesThromboxanes

TXATXA22

ProstaglandinsProstaglandinsPGDPGD

PGFPGF22αααααααα

Mediator release in asthma reactions

Inflammation

Bronchial hyperreactivity

Symptoms

ControllerController

RelieverReliever

Medicines and Pathogenesis of asthma

Bronchoconstriction

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Asthma Therapy EvolutionAsthma Therapy Evolution

1975

1980

1985

1990 19952000

“Large use” of

short-acting

ß2-agonists

“Fear” of

short-acting

ß2-agonists

Single

inhaler

therapy

ICS+LABA

ICS treatment

introduced

1972

Adding

LAßA to ICS therapyKips et al, AJRCCM 2000

Pauwels et al, NEJM 1997

Greening et al, Lancet 1992

Bronchospasm Inflammation Remodelling

DIAGNOSIS EXACERBATION : “CLINICAL”

�� Episodic asthma:Paroxysms of wheeze, dyspnoea and

cough, asymptomatic between attacks.

��Acute severe asthma:

• upright position, use accessory resp muscles, • can’t complete sentences in one breath,

• tachypnea > 25/min, tachycardia > 110/min, PEF 33-50% of pred or best, pulsus paradoxus,

chest hyperresonant, prolonged expiration, breath sounds decreased, inspiratory and

expiratory rhonchi, cough.

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�� Life-threatening features: PEF < 33% of pred or best,silent chest, cyanosis,

bradycardia, hypotension, feeble respiratory effort,

exhaustion, confusion, coma, PaO2 < 60,

PCO2 normal or increased,

acidosis (low pH or high [H+]).

��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.

�� Acute severe asthma:

MANAGEMENT 1

1.Immediate Rx:

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

nebulizer + ICS 200 mcg/ nebulizer or hydrocortisone

200mg IV. With lifethreatening features add 0.5mg

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.

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MANAGEMENT 2

�� No improvement after 15-30 min:Nebulized β2 agonist every 15-30 min + Ipratropium.

�� Still no improvement:Aminophyllin infusion 750mg/24H (small pt), 1 500mg/24H

(large pt), or alternatively salbutamol infusion.

�� Monitor Rx:

Aminophyllin blood levels + PEF after 15-30 min +

oxymetry (maintain SaO2 > 90) + repeat blood gases

after 2 hrs if initial PaO2 < 60, PaCO2 normal or raised andpatient deteriorates.

�� Deterioration:

ICU, intubate, ventilate + muscle relaxant.

ASTHMA MANAGEMENT: “CLINICAL”

• QUICK RELIEVE MEDICATION

• LONG TERM TREATMENT

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Guidelines on Asthma Management:

Past and Current Trends

LABA and ICSLABA and ICSLABA and ICSLABA and ICSICSICSICSICS

LABA+ICSLABA+ICSLABA+ICSLABA+ICS

GINA 1998 GINA 1998 GINA 1998 GINA 1998 (adapted)(adapted)(adapted)(adapted)GINA 2006GINA 2006GINA 2006GINA 2006Severe Severe Severe Severe persistentpersistentpersistentpersistentModerate Moderate Moderate Moderate persistentpersistentpersistentpersistentMild Mild Mild Mild persistentpersistentpersistentpersistentIntermittentIntermittentIntermittentIntermittent

SABA / Rapid onset of action LABA Rapid onset of action LABA Rapid onset of action LABA Rapid onset of action LABA ExacerbationExacerbation

Stable condition

Total control Partially control Uncontrol

Old classificationOld classificationOld classificationOld classificationNew classificationNew classificationNew classificationNew classification

Anti Inflammations is Anti Inflammations is

the mainstay therapythe mainstay therapy !

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Inhalation therapy is Inhalation therapy is

the mainstay therapythe mainstay therapy

Because minimally side effect

!

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

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Epithelial DamageEpithelial Damage

P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998Basement Membrane Basement Membrane

ThickeningThickening

P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998

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Smooth Muscle HyperplasiaSmooth Muscle Hyperplasia

P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998P Jeffery, in: Asthma, Academic Press 1998Controller:Controller:

Anti inflammationAnti inflammation

• budesonide (Pulmicort®®)(Inflamid®®)

• beclomethasone dipropionate (Becotide®®)

• triamcinolone acetonide

• fluticasone(Flexotide®®)

• sodium chromoglicate

(Intal®®)

• ketotifen

• sodium nedocromil

Inhaled Cortico SteroidInhaled Cortico SteroidNon steroidNon steroid

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BronchodilatorBronchodilator

••ββββββββ2 2 -- agonistagonist

•• XanthinXanthin

••AnticholinergicAnticholinergic

RelieverReliever

BRONCHODILATORBRONCHODILATOR

Short Acting Short Acting ββββββββ22 AGONIST (SABA):AGONIST (SABA):

••salbutamol/albuterol (Ventolin salbutamol/albuterol (Ventolin ®®))

••terbutaline (Bricasmaterbutaline (Bricasma®®))

••procaterolprocaterol

••fenoterolfenoterol

••orciprenaline, etcorciprenaline, etc

ANTICHOLINERGIC:ANTICHOLINERGIC:

••atropine sulfate atropine sulfate

••ipratropium bromideipratropium bromide••tiotropium bromidetiotropium bromide

OTHER SYMPHATOMIMETIC: OTHER SYMPHATOMIMETIC:

••ephedrineephedrine••adrenaline, etcadrenaline, etc

XANTHINE:XANTHINE:

••theophyllinetheophylline

••aminophyllineaminophylline

Long Acting Long Acting ββββββββ22 AGONIST:AGONIST:

(LABA)(LABA)

••salmoterolsalmoterol

••formoterolformoterol

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Combination therapyCombination therapy

SymbicortSymbicort®®

Budesonide + FormoterolBudesonide + Formoterol

SeretideSeretide®®

Fluticasone + SalmoterolFluticasone + Salmoterol

The Beginning of The Beginning of

TreatmentTreatment

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ExacerbationExacerbation

The beginning of treatmentThe beginning of treatment?

Stable condition Stable condition √√√√

x

Asthma management

* Stable condition

* Long-term therapy

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Evaluations

Peak flow meterPeak flow meter

600-700

0

300

( normal )Objective Objective valuesvalues

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Peak Flow Meter /PEFR/APE

Must be avilable

PEFR Monitoring:PEFR Monitoring:PEFR Monitoring:PEFR Monitoring:PEFR Monitoring:PEFR Monitoring:PEFR Monitoring:PEFR Monitoring:A Major Tool in Asthma SelfA Major Tool in Asthma SelfA Major Tool in Asthma SelfA Major Tool in Asthma SelfA Major Tool in Asthma SelfA Major Tool in Asthma SelfA Major Tool in Asthma SelfA Major Tool in Asthma Self--------ManagementManagementManagementManagementManagementManagementManagementManagement

Chronic DiseasesChronic DiseasesChronic DiseasesChronic DiseasesChronic DiseasesChronic DiseasesChronic DiseasesChronic Diseases MonitorMonitorMonitorMonitorMonitorMonitorMonitorMonitor

HypertensionHypertensionHypertensionHypertensionHypertensionHypertensionHypertensionHypertension

DiabetesDiabetesDiabetesDiabetesDiabetesDiabetesDiabetesDiabetes

AsthmaAsthmaAsthmaAsthmaAsthmaAsthmaAsthmaAsthma

Blood pressureBlood pressureBlood pressureBlood pressureBlood pressureBlood pressureBlood pressureBlood pressure

Serum glucoseSerum glucoseSerum glucoseSerum glucoseSerum glucoseSerum glucoseSerum glucoseSerum glucose

PEFRPEFRPEFRPEFRPEFRPEFRPEFRPEFR

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DIFFERENTIAL DIAGNOSIS

1. Upper airway obstruction – glottic dysfunction.

2. Acute LV failure – pulmonary oedema.3. Pulmonary embolism.

4. Endobronchial disease.5. Chronic bronchitis.

6. Eosinophilic pneumonia.7. Carsinoid syndrome.

8. Vasculitis.

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

( Soren Kierkegaard)( Soren Kierkegaard)

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