BACKGROUND AND OBJECTIVE:Bronchodilator reversibility (BDR) is common in smoking-related COPD, but the airway pathology underlying this has not been described. In particular, it is not known whether BDR is associated with underlying airway eosinophilia and whether BDR is predictive of a better response to inhaled corticosteroid (ICS) treatment. METHODS: A double-blind, placebo-controlled, randomized 2:1 study of fluticasone propionate (FP), 500 microg twice daily versus placebo over 6 months was performed in subjects with mild to moderate COPD. Subjects with a clinical history of asthma were excluded, but not on BDR criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were performed in 36 subjects at baseline, and 30 of these provided a second full set of samples (FP, n = 19; placebo, n = 11). RESULTS:Baseline BDR was not related to airway eosinophilia and did not predict response to ICS. Post-bronchodilator FEV(1) increased in the FP group compared with the placebo group (P = 0.05), and there were within-treatment group reductions in total symptom scores with FP (P < 0.05). Compared with placebo, FP reduced macrophage numbers but increased neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There were within-treatment group reductions in the numbers of EBB mast cells and CD8+ve lymphocytes with FP (P = 0.007). CONCLUSIONS: BDR was not related to any particular inflammatory phenotype or any clinical or anti-inflammatory response to ICS in these subjects with mild to moderate COPD.
RCT Entities:
BACKGROUND AND OBJECTIVE: Bronchodilator reversibility (BDR) is common in smoking-related COPD, but the airway pathology underlying this has not been described. In particular, it is not known whether BDR is associated with underlying airway eosinophilia and whether BDR is predictive of a better response to inhaled corticosteroid (ICS) treatment. METHODS: A double-blind, placebo-controlled, randomized 2:1 study of fluticasone propionate (FP), 500 microg twice daily versus placebo over 6 months was performed in subjects with mild to moderate COPD. Subjects with a clinical history of asthma were excluded, but not on BDR criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were performed in 36 subjects at baseline, and 30 of these provided a second full set of samples (FP, n = 19; placebo, n = 11). RESULTS: Baseline BDR was not related to airway eosinophilia and did not predict response to ICS. Post-bronchodilator FEV(1) increased in the FP group compared with the placebo group (P = 0.05), and there were within-treatment group reductions in total symptom scores with FP (P < 0.05). Compared with placebo, FP reduced macrophage numbers but increased neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There were within-treatment group reductions in the numbers of EBB mast cells and CD8+ve lymphocytes with FP (P = 0.007). CONCLUSIONS: BDR was not related to any particular inflammatory phenotype or any clinical or anti-inflammatory response to ICS in these subjects with mild to moderate COPD.
Authors: Amir Soltani; Sukhwinder Singh Sohal; David Reid; Steve Weston; Richard Wood-Baker; E Haydn Walters Journal: PLoS One Date: 2012-06-29 Impact factor: 3.240
Authors: Amir Soltani; Hans Konrad Muller; Sukhwinder S Sohal; David W Reid; Steve Weston; Richard Wood-Baker; Eugene Haydn Walters Journal: Histopathology Date: 2012-02-09 Impact factor: 5.087
Authors: Sukhwinder Singh Sohal; Amir Soltani; David Reid; Chris Ward; Karen E Wills; H Konrad Muller; Eugene Haydn Walters Journal: Int J Chron Obstruct Pulmon Dis Date: 2014-05-27
Authors: Sukhwinder Singh Sohal; David Reid; Amir Soltani; Steven Weston; Hans Konrad Muller; Richard Wood-Baker; Eugene Haydn Walters Journal: PLoS One Date: 2013-05-22 Impact factor: 3.240