Omics in NSAID-Exacerbated Respiratory Disease: Current Evidence From the Upper and Lower Airways.

Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is a mainly type 2 inflammatory condition that combines asthma, nasal polyps, and hypersensitivity to NSAIDs. Its pathogenesis involves both upper and lower airways, yet most studies to date have examined these compartments separately. It remains unclear whether the molecular mechanisms in the nose, sinuses, and lungs are distinct or overlapping-an important gap, given that clinical manifestations of N-ERD involve both sites. In this review, we summarize available omics studies-transcriptomics, proteomics, metabolomics, and epigenomics-performed on upper and lower airways in patients with N-ERD. While omics approaches have revealed new molecular insights, comparisons across studies are limited by heterogeneity in design, controls, and methodology. We emphasize the need for integrated multi-omics analyses and standardized frameworks to better characterize the disease across airways. Such efforts are essential for identifying robust biomarkers and therapeutic targets and for moving toward a systems-level understanding of N-ERD.