Haimerl P, Bernhardt U, Schindela S, et al. - Given that an aberrant arachidonic acid (AA) metabolism drives the NSAID-exacerbated respiratory disease (N-ERD), and macrophages are major generators of AA metabolites and subject to metabolic reprogramming, so researchers intended to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD. They found that N-ERD monocytes/ macrophages displayed an overall decrease in DNA methylation, aberrant metabolic profiles as well as an increased expression of chemokines, suggestive of a persistent pro-inflammatory activation. In N-ERD patients, increased acylcarnitines were detected in macrophages, sputum, nasal lining fluid and plasma samples. Upon inflammatory challenge, increased levels of acylcarnitines, pro-inflammatory AA metabolites, cytokines and chemokines were shown to be generated by N-ERD macrophages vs healthy macrophages. Overall, in N-ERD, a pro-inflammatory metabolic and epigenetic reprogramming of macrophages was deciphered by these data.