Abstract
Background The decline in lung function can be reduced by long-term inhaled corticosteroid (ICS) treatment in subsets of patients with chronic obstructive pulmonary disease (COPD).We aimed to identify which clinical, physiological and non-invasive inflammatory characteristics predict the benefits of ICS on lung function decline in COPD. Methods Analysis was performed in 50 steroid-naive compliant patients with moderate to severe COPD (postbronchodilator forced expiratory volume in one second (FEV1), 30-80% of predicted, compatible with GOLD stages II-III), age 45-75 years, >10 packyears smoking and without asthma. Patients were treated with fluticasone propionate (500 μg bid) or placebo for 2.5 years. Postbronchodilator FEV1, dyspnea and health status were measured every 3 months; lung volumes, airway hyperresponsiveness (PC20), and induced sputum at 0, 6 and 30 months. A linear mixed effect model was used for analysis of this hypothesis generating study. Results Significant predictors of attenuated FEV1-decline by fluticasone treatment compared to placebo were: fewer packyears smoking, preserved diffusion capacity, limited hyperinflation and lower inflammatory cell counts in induced sputum (p<0.04). Conclusions Long-term benefits of ICS on lung function decline in patients with moderate-to-severe COPD are most pronounced in patients with fewer packyears, and less severe emphysema and inflammation. These data generate novel hypotheses on phenotype-driven therapy in COPD.
| Original language | English |
|---|---|
| Article number | 0143793 |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 1 Dec 2015 |
| Externally published | Yes |
Bibliographical note
Funding Information:The study was an investigator-initiated trial (registered as NCT00158847). The protocol was written by the GLUCOLD Study Group, and all procedures and analyses were carried out by the investigators only. The authors were fully independent from the sponsors of the study [the Netherlands Organization for Scientific Research (NWO) in a collaborative program with the Netherlands Asthma Foundation (grant 3.4.93.96.3), by GlaxoSmithKline (The Netherlands), and by the University Medical Center Groningen (UMCG) and the Leiden University Medical Center (LUMC)]. Therefore, the corresponding author has full access to all the data in the study and has final responsibility for the decision to submit for publication. The Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) was an investigator-initiated trial (registered as NCT00158847). The protocol was written by the GLUCOLD Study Group, and all procedures and analyses were carried out by the investigators only. We thank the patients for their cooperation in our study. The GLUCOLD Study Group consists of: H.F. Kauffman, D. de Reus, Dept. of Allergology; H.M. Boezen, D.F. Jansen, J.M. Vonk, Dept. of Epidemiology and Statistics; M.D.W. Barentsen, W. Timens, M. Zeinstra-Smit, Dept. of Pathology; A.J. Luteijn, T. van der Molen, G. ter Veen, Dept. of General Practice; M.M.E. Gosman, N.H.T. ten Hacken, H.A.M. Kerstjens, M.S. van Maaren, D.S. Postma, C.A. Veltman, A. Verbokkem, I. Verhage, H.K. Vink-Klooster, Dept. of Pulmonology; University of Groningen & University Medical Center Groningen, Groningen, The Netherlands. M.M.E. Gosman, Dept. of Neurology, Martini ziekenhuis Groningen, Groningen, The Netherlands; H. Thiadens, Dept. of General Practice; J.B. Snoeck-Stroband, J.K. Sont, Dept. of Medical Decision Making; J. Gast-Strookman, P.S. Hiemstra, K. Janssen, T.S. Lapperre, K.F. Rabe, A. van Schadewijk, J.A. Schrumpf, J. Smit-Bakker, J. Stolk, A.C.J.A. Tiré, H. van der Veen, M.M.E. Wijffels and L.N.A. Willems, Dept. of Pulmonology; Leiden University Medical Center, Leiden; P.J. Sterk, Dept. of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam The Netherlands; T. Mauad, University of Sao Paulo, Sao Paulo, Brazil.
Publisher Copyright:
© 2015 Snoeck-Stroband et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.