Risk of pneumonia associated with long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease: a critical review and update.

Abstract

The aim was to determine the effects of long-term inhaled corticosteroid use on pneumonia in patients with chronic obstructive pulmonary disease (COPD) via systematic searches of MEDLINE, EMBASE, ISI, regulatory documents and manufacturers' trial registries. Our updated meta-analysis of 24 long-term randomized controlled trials involving 23 096 participants shows a significantly increased risk of pneumonia with the use of inhaled corticosteroids in COPD (relative risk 1.57, 95% confidence interval 1.41-1.75, P < 0.0001). The increased risk of pneumonia is not accompanied by a corresponding increase in mortality. The elderly and those with more severe disease and lower forced expiratory volume in 1s are at the highest risk of pneumonia. The trials of currently available inhaled corticosteroids have included participants with varying duration of inhaled corticosteroid exposure and COPD severity, with apparent differences in the proportion of pneumonia ascertained among these trials. The absence of adequately powered long-term head-to-head trials precludes any definitive conclusions on intraclass differences in risk. Clinicians should consider the long-term risks of pneumonia with the use of inhaled corticosteroids in patients with COPD. Adequately powered long-term head-to-head trials with objective pneumonia definitions, active ascertainment and radiologic and microbiologic confirmation are needed to clarify any intraclass differences in the risk of pneumonia.