NSAID-exacerbated respiratory disease, N-ERD, is associated with measurable changes in concentrations of lipid mediators involved in inflammation and pain modulation, a new study shows. Plasma concentrations of two key endocannabinoid-related lipids, arachidonoylethanolamide (AEA) and oleoylethanolamide (OEA), were significantly reduced in patients with N-ERD, compared to healthy controls.

In addition, even a very low dose of aspirin increased AEA and OEA levels in controls, but not in N-ERD patients. The study, conducted in collaboration between the University of Eastern Finland, the University of Helsinki and Helsinki University Hospital, was published in Clinical & Experimental Allergy.

N-ERD is a chronic syndrome in which nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, provoke asthma attacks and other respiratory symptoms. Patients typically suffer from severe asthma and chronic rhinosinusitis with nasal polyps, and the condition significantly impairs quality of life. Currently, there is no clinical laboratory test for N-ERD, and diagnosis requires a costly and risky aspirin challenge performed in a hospital setting. The disease mechanisms remain poorly understood, and optimal treatment strategies are still lacking.

This present study is the first to report changes in endocannabinoid signalling in patients with N-ERD, which may help explain chronic inflammation and heightened perception of pain associated with the condition. In addition to reduced concentrations of AEA and OEA, elevated concentrations of leukotriene E4 and other lipid mediators were also observed, possibly reflecting N-ERD associated inflammation.

“These changes in lipid metabolism, which affect the endocannabinoid system, may in the future open up new avenues for diagnosing N-ERD, and for developing targeted therapies,” Doctoral Researcher Viljami Salmi from the University of Helsinki notes.

Further research involving larger patient cohorts is needed. The present study included eight individuals diagnosed with N-ERD and seven healthy controls.

Research article:

V. E. Salmi, A. Lyly, M. Neuvonen, E. Saarentaus, M. Niemi, and S. Toppila-Salmi, “ Systemic N-Acylethanolamines and Other Lipid Mediators Are Associated With NSAID-Exacerbated Respiratory Disease,” Clinical & Experimental Allergy (2025): 1–4, https://doi.org/10.1111/cea.70145.