CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease

D D Sin^1,2, L Wu², J A Anderson³, N R Anthonisen⁴, A S Buist⁵, P S Burge⁶, P M Calverley⁷, J E Connett⁸, B Lindmark⁹, R A Pauwels^10,, D S Postma¹¹, J B Soriano¹², W Szafranski¹³, J Vestbo¹⁴

¹ The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St Paul’s Hospital, Vancouver, British Columbia, Canada
² Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
³ Department of Medical Statistics, GlaxoSmithKline R&D, UK
⁴ Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
⁵ Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA
⁶ Heartlands Hospital NHS Trust, Birmingham, UK
⁷ University Hospital Aintree, Liverpool, UK
⁸ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
⁹ AstraZeneca R&D, Lund, Sweden
¹⁰ Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium
¹¹ Department of Pulmonology, University of Groningen, the Netherlands
¹² Fundación Caubcc-Cimera, Palma de Mallorca, Balearic Islands, Spain
¹³ Department of Lung Diseases, Voivodeship Specialist Hospital, Radom, Poland
¹⁴ South Manchester University Hospital NHS Trust, Wythenshawe Hospital, Manchester, UK

Correspondence to:
Dr D D Sin
James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, Canada, V6Z 1Y6; dsin{at}mrl.ubc.ca

Background: Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown.

Methods: A pooled analysis, based on intention to treat, of individual patient data from seven randomised trials (involving 5085 patients) was performed in which the effects of inhaled corticosteroids and placebo were compared over at least 12 months in patients with stable COPD. The end point was all-cause mortality.

Results: Overall, 4% of the participants died during a mean follow up period of 26 months. Inhaled corticosteroids reduced all-cause mortality by about 25% relative to placebo. Stratification by individual trials and adjustments for age, sex, baseline post-bronchodilator percentage predicted forced expiratory volume in 1 second, smoking status, and body mass index did not materially change the results (adjusted hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.55 to 0.96). Although there was considerable overlap between subgroups in terms of effect sizes, the beneficial effect was especially noticeable in women (adjusted HR 0.46; 95% CI 0.24 to 0.91) and former smokers (adjusted HR 0.60; 95% CI 0.39 to 0.93).

Conclusions: Inhaled corticosteroids reduce all-cause mortality in COPD. Further studies are required to determine whether the survival benefits persist beyond 2–3 years.

Keywords: corticosteroids; mortality; chronic obstructive pulmonary disease; pooled analysis

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