Non‐steroidal Anti‐inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review

Abstract

There have been concerns regarding the safety of nonsteroidal antiinflammatory 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 before 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 1721 potential studies through the 5 primary databases and searching reference lists. Of these, 10 studies met the inclusion criteria, including 5 nested case‐control studies, 2 population‐based case‐control studies, and 3 cohort studies. In total, 59,724 adults were included from 4 of the studies (range = 57–59,250) and 1217 children from 5 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.

Coronavirus disease 2019: A comprehensive review on recent clinical updates and management tools for pharmacists

“…The current evidence at-hand is not indicative in showing a link between ibuprofen causing harm in patients with COVID-19, depicted in Table 2 38,39,[42][43][44][45][46] . However, with the theoretical mechanisms and previous implications, some patients and health care providers may be hesitant in choosing an NSAID to treat the fever or pain related to COVID-19.…”

FEVER in children – recommendations for primary care doctors – FEVER COMPASS

“…Pre-hospitalisation NSAID exposure has also been identified as an independent risk factor of paediatric pleural empyema and other pleural complications in other studies [79,82]. A review of 10 studies in children and adults where the risk of parenchymal and pleural pneumonia complications, as well as long-term hospitalisation, was assessed did not reveal a risk of NSAID administration, including ibuprofen, due to a possibility of pneumonia complications, highlighting a need for further observational studies [83]. Therefore, there is a suggestion that the necessity and the number of prehospitalisation NSAID doses may be markers rather than reasons of pulmonary or pleural complications in the hospital setting.…”

Host-informed therapies for the treatment of pneumococcal pneumonia

“…However, studies point to newly discovered antibacterial activities of NSAIDs, making them promising therapeutics to treat bacterial infections [46][47][48]. It has recently been established that the evidence against the use of NSAIDs has not been systematically assessed [49]. A comprehensive review examining the risk of pneumonia complications in pediatric and adult patients treated with NSAIDs [49] indicated that the conclusion of risks of NSAIDs in treating infection could be due to bias intrinsic to small data sets.…”

“…It has recently been established that the evidence against the use of NSAIDs has not been systematically assessed [49]. A comprehensive review examining the risk of pneumonia complications in pediatric and adult patients treated with NSAIDs [49] indicated that the conclusion of risks of NSAIDs in treating infection could be due to bias intrinsic to small data sets. Altogether, NSAIDs still hold potential and warrant further exploration as a general anti-inflammatory adjuvant therapy for bacterial infections.…”