Hospital Universitario VirgenMacarena. Sevilla

Dr. Agustín Valido

[ERS] A home-centered disease management program in severe chronic obstructive

pulmonary disease (Results of the COPD patient Management European Trial-COMET)

Kessler R, Casan P, Koehler D, Tognella S, Viejo JL, dal Negro R, et al.

Mesa 3

Introduction.-

Severe COPD impacts deeply on daily activities an is asociated with high hospitalisation rate and prognosis.

Objetive.-To investigate the effectiveness of home-centered disease management program in reducing all-cause hospitalisations in severe COPD.

Methods.-

- GOLD III/IV COPD patiens with at least 1 exacerbation in the previous year were randomised to disease (DM) or usual (UM) management.

- DM intervention included self-management coaching (“Livin Well With COPD”) and decision support in case of clinical worsening over about 1 year.

Results.- (I)

- 319 patients (74.3% on HOT, 27.3% on HMV) entered follow-up (Intention-To-Treat, ITT).

- Difference in yearly number of unscheduled all-cause hospital days (primary outcome) was -5,32 days [95%CI -13,69; 3,05](DM 17.4±35.4, UM 22.6±41.8, p=0.161, Wilcoxon, ITT).

- It was -7.99 days [95%CI -16.62; 0.64], p=0.070) in Per Protocol (PP, eligibility criteria not fulfilled and/or having received <25% of planned coaching, n=288).

Results.- (II)

- When considering acute care hospital days (without nursing facility days), adjusted means difference was -6.90 days ([95%CI -14.49; 0.68], p=0.074) in ITT and -8.26 ([95%CI -16.39; -0.12], p=0.047) in PP.

- No between-group differences were found in health status (SGRQ total score).

- More patients died in UM (n=23) than in DM (n=3, p<0.001, Chi2), mainly from respiratory cause (16 patients).

Conclusions.-

- This 1-yr intervention in severe COPD showed a non-statistically significant reduction of all-cause hospital days (those including nursing facility).

- Significant reductions in acute care hospital days (PP) and a lower number of deaths were shown with DM.

[ERS] Pharmacological characterization of the mechanism of action leading to synergism

between glycopyrronium bromide and indacaterol fumarate

Calzetta L, Rogliani P, Puxeddu E, Ora J, Facciolo F, Matera MG, et al.

Mesa 3

Introduction.-Nowadays there is a considerable gap in knowledge concerning the mechanism(s) by which long-acting β2 agonists (LABAs) and long-acting

muscarinic antagonists (LAMAs) interact to induce bronchodilation.

Objetive.-This study aimed to identify the mechanism(s) causing the synergistic interaction between the LAMA glycopyrronium bromide (GLY) and the LABA indacaterol fumarate (IND) in human bronchial tissue.

Methods.-

- The influence of GLY plus IND was assessed on the release of acetylcholine (ACh) and concentrations of cAMP in human isolated airways.

- Iberiotoxin (IbTX, 100 nM) was used to block the KCa++ channels, tetanus toxin (TeTX, 10 nM) to inhibit the synaptic vesicle exocytosis of ACh, and quinine (100 μM) to reduce the release of non-neurogenic ACh.

Results.- (I)

- The co-administration of GLY and IND reduced the release of ACh from epithelial cells (-36.6±4.7%, P<0.01 vs. control) but not from bronchi, and enhanced cAMP levels in both bronchi (+479.4±62.4%, P<0.01 vs. control) and epithelial cells (+29.1±7.1, P<0.05 vs. control), an effect that was inhibited by IbTX.

Results.- (II)- TeTX inhibited the release of parasympathetic ACh (−60.0%

±1.2%, P<0.001 vs. control), and both GLY and IND further enhanced this effect (−68.4%±1.8%, P<0.001 vs. control).

- Quinine did not influence (P>0.05) the effectiveness of GLY/IND combination in reducing the non-neurogenic release of ACh.

Conclusions.-

- GLY/IND co-administration leads to a synergistic improvement of bronchodilation by increasing cAMP concentrations in both airway smooth muscle and bronchial epithelium and by decreasing ACh release from the epithelium.

[ATS] Improvement in lung function with indacaterol/glycopyrrolate (ind/gly) in

patientswith moderate to severe COPD from the Us: a subgroup alalysis from the Flight1 and

Flight2 studies Kerwin E, Mahler DA, FowlerTaylor A, Maitra S, Banerji D

Mesa 3

Introduction.-

IND/GLY 27,5/15,6 μg demostrated superior improvement in lung funtion along with rapid onset versus its monocomponents (IND27,5 μg and GLY 15,6 μg) and placebo in patients with moderate-to-severe COPD. Here we present the lung function data in the subgroup of patients from the US.

Methods.-- FLIGHT1 and FLIGHT2 were replicate, 12 week, multi-center.

Randomized, double-blind studies that evaluated the safety and efficacy of IND/GLY.

- Lung funtion was evaluated in terms of the area under the curve up to 12 h for forced expiratory volumen in 1 second (FEV1 AUC 0-12H),

TROUGH FEV1 and peak FEV1 during 4 hours post dose with IND/GLY

versus its monocomponents and placebo.

- Onset of action was evaluated by measuring the improvement in FEV1

at 5 min post-morning dose on Day1.

Results.- (I)

- Of 2038 patients from the overall pool, 1104 were fron the US an included in this analysis (IND/GLY, n=274; IND, n=256; GLY, n=292; placebo, n=278).

- IND/GLY showed superior improvement in lung function with a statistically significant (p>0,001) improvement in FEV1AUC0-12H at

week 12, compared with placebo, IND and GLY (Table 1).

Results.- (II)- Improvements in trough FEV1 and peak

FEV1 were also statistically significant with

IND/GLY versus placebo, and its monocompnents at Week 12 (all p<0,001).

- In addition, IND/GLY showed rapid onset of action as indicated by a statistically significant improvement in FEV1 at 5 min

post-dose on Day 1 versus placebo (p<0,001).

Conclusions.-

- In this post-hoc analysis, IND/GLY b.i.d. Demonstrated superior improvement in lung fuction with a rapid onset of action compared with monocponents and placebo.