Association of Inhaled Corticosteroids with Incident Pneumonia and Mortality in COPD Patients; Systematic Review and Meta-Analysis

Abstract

Background Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They have been associated with increased risk of pneumonia but not with increased pneumonia-associated or overall mortality. Methods To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic. Results We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35-1.93, p<0.001; as well as in observational studies: OR 1.89; 95% CI 1.39-2.58, p<·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia case-fatality: RR 0.91; 95% CI 0.52-1.59, p=0.74; and OR 0.72; 95% CI 0.59-0.88, p=0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85-1.05, p=0.31; and OR 0.79; 95% CI 0.65-0.97, p=0.02, respectively. Conclusions Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.

Small airway inflammation and extrafine inhaled corticosteroids plus long-acting beta2-agonists formulations in chronic obstructive pulmonary disease

“…ICS use has been reported to be associated with an increased risk of pneumonia in some studies, although the risk of mortality due to pneumonia does not increase, and in fact, ICS treatment seems to be protective against this risk [77,114,115]. However, the risk factors for acquiring pneumonia are often the same as those that mandate the use of ICS combination treatment in patients with COPD [77,114,115]. In addition, severe acute exacerbations of COPD have an independent negative impact on patient prognosis.…”

When is dual bronchodilation indicated in COPD?

“… 63 , 64 Management of exacerbating patients has largely focused on maximizing bronchodilation, rather than prescribing an ICS-containing regimen. 1 , 65 Due to the increased risk of pneumonia with an ICS, 66 GOLD 2017 recommends that ICS withdrawal be considered if no benefit is seen. 1 This recommendation is based on findings from WISDOM, which demonstrated that ICSs can be withdrawn in COPD patients without increased risk of exacerbation, provided adequate bronchodilator therapy is in place.…”

Inhaled corticosteroids preventing pneumonia mortality: paradox or selection bias?

“…While there is good evidence that ICS increase the incidence of pneumonia and pneumonia-related mortality, several observational studies suggest that ICS use prior to a pneumonia event decreases mortality in patients with pneumonia [11,14,15]. A meta-analysis of these and other observational studies report a significant decrease in case-fatality with prior ICS use among patients with pneumonia (RR 0.72, 95% CI 0.59-0.88) [13].…”

“…A meta-analysis of several trials suggests that ICS are also associated with an increase in the incidence of pneumonia-related mortality (RR 1.50, 95% CI 0.85-2.67), although limited by few events [13]. An observational study also reported increased pneumonia-related mortality with ICS (RR 1.53, 95% CI 1.30-1.80) [10].…”