title: Steroid resistance in COPD? Overlap and differential anti-inflammatory effects in smokers and ex-smokers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands ; University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, The Netherlands.
authors: Susan J M
authors: SJ
authors: Hoonhorst
authors: University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands ; University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, The Netherlands.
authors: Nick H T
authors: NH
authors: ten Hacken
authors: University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, The Netherlands ; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
authors: Judith M
authors: JM
authors: Vonk
authors: University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, The Netherlands ; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
authors: Wim
authors: W
authors: Timens
authors: Leiden University Medical Center, Department of Pulmonology, Leiden, The Netherlands.
authors: Pieter S
authors: PS
authors: Hiemstra
authors: Leiden University Medical Center, Department of Pulmonology, Leiden, The Netherlands.
authors: Thérèse S
authors: TS
authors: Lapperre
authors: University of Amsterdam, Academic Medical Centre Amsterdam, Department of Pulmonary Diseases, Amsterdam, The Netherlands.
authors: Peter J
authors: PJ
authors: Sterk
authors: University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands ; University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, The Netherlands.
authors: Dirkje S
authors: DS
authors: Postma
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000368:Aged; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016540:Smoking Cessation; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones