Toward precision medicine in NSAID-exacerbated respiratory disease

Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is a distinct clinical syndrome characterized by moderate-to-severe asthma and a high prevalence of chronic rhinosinusitis with nasal polyps and asiprin/NSAID intolerance. The primary pathogenesis of N-ERD includes the dysregulation of arachidonic acid metabolism with subsequent cysteinyl leukotriene overproduction and persistent type 2/eosinophilic inflammation in the upper and lower airways. N-ERD has considerably heterogeneous clinical features and courses, emphasizing the necessity for classifying its phenotypes and/or endotypes to enable early diagnosis and individualized treatment approaches. However, the lack of reliable and standardized tests and biomarkers can cause diagnostic delays, leading to inadequate management and more severe disease progression in affected individuals. Current treatments for N-ERD include NSAID avoidance, aspirin desensitization, and the use of leukotriene modifiers and corticosteroids. Recently, biologics targeting interleukin (IL)-4, IL-5, IL-13, and IgE have been suggested as treatment options, particularly for patients with high type 2 inflammatory burden. However, the treatment responses in this patient population remain variable, highlighting the need for individualized therapeutic strategies. In this review, we summarize recent insights into the pathogenic mechanisms, clinical manifestations, and phenotype classification of N-ERD, evaluate emerging biomarkers, and explore the potential of targeted therapies within the framework of precision medicine.