Non-Steroidal Anti-Inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review.

Sodhi, Mohit; Khosrow-Khavar, Farzin; FitzGerald, J Mark; Etminan, Mahyar

There have been concerns regarding the safety of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with respiratory infections. However, to date the quality of the evidence has not been systematically assessed. The purpose of this systematic review was to evaluate the role of NSAIDs on pneumonia complications. OVID MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Google Scholar were searched. Studies that examined pneumonia complications in patients who had taken NSAIDs prior to onset of symptoms were identified. Quality assessment was conducted using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) assessment tool, which was adapted to include biases that were pertinent to this question. The search strategy identified 1,721 potential studies through the five primary databases and searching reference lists. Of these, ten studies met the inclusion criteria including: five nested case-control studies, two population-based case-control studies, and three cohort-studies. In total, 59,724 adults were included from four of the studies (range 57-59,250) and 1,217 children from five studies (range 148-540). All studies demonstrated a positive association; in adults (Odds Ratio/Risk Ratio range: 1.8-8.1) and children (Odds Ratio/Risk Ratio range: 1.9-6.8). Studies were limited by moderate or serious risk of confounding bias, exposure misclassification, and protopathic biases and sparse data bias. The results of this review demonstrate that published studies on the effect of NSAIDs use and risk of pneumonia complications are subject to a number of biases. These results should not be extrapolated as evidence of harm for NSAIDs, including ibuprofen, in respiratory ailments but highlight the need for more methodologically robust studies to evaluate this potential relationship.