CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Effect of salmeterol/fluticasone propionate on airway inflammation in COPD: a randomised controlled trial

Jean Bourbeau¹, Pota Christodoulopoulos¹, Francois Maltais², Yasuhiro Yamauchi³, Ronald Olivenstein¹, Qutayba Hamid³

¹ Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre, Montréal, Quebec, Canada
² Centre de recherche, Hôpital Laval, Institut Universitaire de cardiologie et de pneumologie, Université Laval, Québec, Canada
³ Meakins Christie Laboratories, McGill University, Montréal, Quebec, Canada

Professor Qutayba Hamid, Meakins Christie Laboratories, McGill University, 3626 St Urbain Street, Montreal, Quebec, Canada H2X 2P2; qutayba.hamid{at}mcgill.ca

Background: Airway inflammation in chronic obstructive pulmonary disease (COPD) is characterised by infiltration of CD8+ T cells and CD68+ macrophages and an increased number of neutrophils, whereas few studies have described the presence of eosinophils. Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear, recent studies suggest that combination therapy could be beneficial. A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate (SFC) and fluticasone propionate (FP) alone on inflammatory cells in the airways of patients with COPD.

Methods: Patients were treated in a randomised, double blind, parallel group, placebo-controlled trial with either a combination of 50 µg salmeterol and 500 µg FP twice daily (SFC, n = 19, 19 men, mean age 62 years), 500 µg FP twice daily (n = 20, 15 men, mean age 64 years) or placebo (n = 21, 17 men, mean age 66 years) for 3 months. At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8+ T lymphocytes, CD68+ macrophages, neutrophils and eosinophils were measured.

Results: CD8+ cells were significantly reduced by SFC compared with placebo (difference –98.05 cells/mm²; 95% CI –143.14 to –52.9; p<0.001). Such a marked effect was not seen with FP alone (–44.67 cells/mm²; 95% CI –90.92 to 1.57; p = 0.06). CD68+ macrophages were also reduced by SFC compared with placebo (difference –31.68 cells/mm²; 95% CI –61.07 to –2.29; p = 0.03) but not by FP. SFC did not significantly change neutrophils and eosinophils compared with placebo.

Conclusions: SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone.

Abbreviations: BAL, bronchoalveolar lavage; COPD, chronic obstructive pulmonary disease; CRQ, Chronic Respiratory Questionnaire; FEV₁, forced expiratory volume in 1 s; FP, fluticasone propionate; FVC, forced vital capacity; SFC, salmeterol xinafoate/fluticasone propionate; TLCO, carbon monoxide transfer factor

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