title: Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids.
abstract: Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo. During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.In patients using ICS during GL1 and using ICS 0-50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+(fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87-3.84), CD4+(1.91, 95% CI 1.33-2.75) and CD8+cells (1.71, 95% CI 1.15-2.53), and mast cells (1.91, 95% CI 1.36-2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42-2.54), as did counts of macrophages (2.10, 95% CI 1.55-2.86), neutrophils (1.92, 95% CI 1.39-2.65) and lymphocytes (2.01, 95% CI 1.46-2.78).ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands L.I.Z.Kunz@lumc.nl.
authors.forename: Lisette I Z
authors.initials: LI
authors.lastname: Kunz
authors.affiliation: Dept of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: Ten Hacken
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.|Dept of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: Thérèse S
authors.initials: TS
authors.lastname: Lapperre
authors.affiliation: Dept of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Dept of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Huib A M
authors.initials: HA
authors.lastname: Kerstjens
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: van Schadewijk
authors.affiliation: Dept of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.affiliation: Dept of Medical Decision Making, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Sont
authors.affiliation: Dept of Medical Decision Making, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jiska B
authors.initials: JB
authors.lastname: Snoeck-Stroband
authors.affiliation: Dept of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000368:Aged; D001980:Bronchi / Q000473:pathology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage*; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009504:Neutrophils / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D013183:Sputum / Q000166:cytology; D028761:Withholding Treatment
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D000068297:Fluticasone-Salmeterol Drug Combination; D000068298:Fluticasone