TY - JOUR
T1 - Steroid resistance in COPD? Overlap and differential anti-inflammatory effects in smokers and ex-smokers
AU - Hoonhorst, Susan J. M.
AU - ten Hacken, Nick H. T.
AU - Vonk, Judith M.
AU - Timens, Wim
AU - Hiemstra, Pieter S.
AU - Lapperre, Thérèse S.
AU - Sterk, Peter J.
AU - Postma, Dirkje S.
PY - 2014
Y1 - 2014
N2 - Inhaled corticosteroids (ICS) reduce exacerbation rates and improve health status but can increase the risk of pneumonia in COPD. The GLUCOLD study, investigating patients with mild-to-moderate COPD, has shown that long-term (2.5-year) ICS therapy induces anti-inflammatory effects. The literature suggests that cigarette smoking causes ICS insensitivity. The aim of this study is to compare anti-inflammatory effects of ICS in persistent smokers and persistent ex-smokers in a post-hoc analysis of the GLUCOLD study. Persistent smokers (n = 41) and persistent ex-smokers (n = 31) from the GLUCOLD cohort were investigated. Effects of ICS treatment compared with placebo were estimated by analysing changes in lung function, hyperresponsiveness, and inflammatory cells in sputum and bronchial biopsies during short-term (0-6 months) and long-term (6-30 months) treatment using multiple regression analyses. Bronchial mast cells were reduced by short-term and long-term ICS treatment in both smokers and ex-smokers. In contrast, CD3⁺, CD4⁺, and CD8⁺ cells were reduced by short-term ICS treatment in smokers only. In addition, sputum neutrophils and lymphocytes, and bronchial CD8⁺ cells were reduced after long-term treatment in ex-smokers only. No significant interactions existed between smoking and ICS treatment. Even in the presence of smoking, long-term ICS treatment may lead to anti-inflammatory effects in the lung. Some anti-inflammatory ICS effects are comparable in smokers and ex-smokers with COPD, other effects are cell-specific. The clinical relevance of these findings, however, are uncertain
AB - Inhaled corticosteroids (ICS) reduce exacerbation rates and improve health status but can increase the risk of pneumonia in COPD. The GLUCOLD study, investigating patients with mild-to-moderate COPD, has shown that long-term (2.5-year) ICS therapy induces anti-inflammatory effects. The literature suggests that cigarette smoking causes ICS insensitivity. The aim of this study is to compare anti-inflammatory effects of ICS in persistent smokers and persistent ex-smokers in a post-hoc analysis of the GLUCOLD study. Persistent smokers (n = 41) and persistent ex-smokers (n = 31) from the GLUCOLD cohort were investigated. Effects of ICS treatment compared with placebo were estimated by analysing changes in lung function, hyperresponsiveness, and inflammatory cells in sputum and bronchial biopsies during short-term (0-6 months) and long-term (6-30 months) treatment using multiple regression analyses. Bronchial mast cells were reduced by short-term and long-term ICS treatment in both smokers and ex-smokers. In contrast, CD3⁺, CD4⁺, and CD8⁺ cells were reduced by short-term ICS treatment in smokers only. In addition, sputum neutrophils and lymphocytes, and bronchial CD8⁺ cells were reduced after long-term treatment in ex-smokers only. No significant interactions existed between smoking and ICS treatment. Even in the presence of smoking, long-term ICS treatment may lead to anti-inflammatory effects in the lung. Some anti-inflammatory ICS effects are comparable in smokers and ex-smokers with COPD, other effects are cell-specific. The clinical relevance of these findings, however, are uncertain
U2 - https://doi.org/10.1371/journal.pone.0087443
DO - https://doi.org/10.1371/journal.pone.0087443
M3 - Article
C2 - 24505290
SN - 1932-6203
VL - 9
SP - e87443
JO - PLOS ONE
JF - PLOS ONE
IS - 2
ER -