Clinical and Translational Allergy · Published 2026-08-01 · DOI 10.1002/clt2.70182
Piotr Szatkowski, Lucyna Mastalerz
ABSTRACT NSAID‐exacerbated respiratory disease (N‐ERD) is a chronic inflammatory disorder characterized by asthma, chronic rhinosinusitis with nasal polyps and respiratory reactions to cyclooxygenase‐1 inhibiting nonsteroidal anti‐inflammatory drugs (NSAID). Its pathogenesis involves dysregulated arachidonic acid metabolism, epithelial barrier dysfunction and activation of multiple immune cell types, including eosinophils, mast cells, macrophages, basophils, and innate lymphoid cells. Recent genomic and transcriptomic analyses have revealed variants in genes linked to epithelial integrity and cellular interactions, metabolic and epigenetic reprogramming of monocyte‐derived macrophages that promotes persistent proinflammatory activity. Emerging biomarkers, such as 15‐oxo‐eicosatetraenoic acid (15‐oxo‐ETE), acylcarnitines, apolipoprotein E, oncostatin M, surfactant protein D, retinoic acid and glial cell line‐derived neurotrophic factor provide novel mechanistic insights. A recently proposed Aspirin Hypersensitivity Diagnostic Index, integrating urinary leukotriene E4 (LTE4) and 15‐oxo‐ETE with sinus computed tomography (CT) scoring, may offer a practical noninvasive diagnostic tool. Inflammatory endotyping highlights substantial heterogeneity in N‐ERD, encompassing T2‐dominant, T1‐, T3‐related and neutrophilic inflammatory patterns, which may coexist or vary across airway compartments and influence clinical presentation and treatment response. As therapeutic strategies evolve, biologic agents targeting T2 pathways are becoming increasingly central, while aspirin therapy after desensitization may be reserved for selected patients. This review aims to summarize current mechanistic insights into the immune, epithelial, and lipid pathways involved in N‐ERD, with a particular focus on emerging biomarkers and inflammatory endotypes relevant to diagnosis and personalized therapy.
Abstract from DOAJ. Public domain (CC0 1.0).
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Szatkowski, P., Mastalerz, L. (2026). Integrated Immune, Epithelial and Lipid Pathways in NSAID‐Exacerbated Respiratory Disease. Clinical and Translational Allergy. https://doi.org/10.1002/clt2.70182