Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.

Keywords: community-acquired pneumonia; non-steroidal anti-inflammatory drugs; pleural effusion.

Figure 1

During pneumonia, NSAIDs may interfere with acute inflammation response and resolution. Invading pathogens within the alveolar air space induce an innate immune response, which involves cyclooxygenases (COX) to generate lipid mediators of inflammation such as prostaglandins (PG) E2 and I2 (1). NSAIDs may alter the subsequent recruitment of polymorphonuclear neutrophils through both COX-dependent and COX-independent effects. NSAIDs also alter their intrinsic functions such as phagocytosis and degranulation (2). The acute phase response is followed by a lipid mediator class switching (3), which leads to the biosynthesis of pro-resolving mediators such as lipoxins and resolvins (4). By inhibiting this stop signal through COX-2 inhibition, NSAIDs may limit the local recruitment of monocytes, which act through efferocytosis to resolve exudate, and subsequently hamper the resolution of inflammation (5). Abbreviations: COX-D = Cyclooxygenase-dependent; COX-iD = Cyclooxygenase-independent; COX2-D = Cyclooxygenase 2-dependent. Adapted from Serhan et al. [34].