Heterogeneity of NSAID-Exacerbated Respiratory Disease: has the time come for subphenotyping?

NSAID-Exacerbated Disease (N-ERD) is a chronic eosinophilic inflammatory disorder of the respiratory tract occurring in patients with asthma and/or rhinosinusitis with nasal polyps, whose symptoms are exacerbated by NSAIDs. The purpose of this review is to provide an update on clinical characteristics, pathophysiology, and management of N-ERD, and to emphasize heterogeneity of this syndrome.

Growing evidence indicates that N-ERD, which has been considered a separate asthma phenotype, is heterogenous, and can be divided in several subphenotypes varying in clinical characteristics. Pathophysiology of N-ERD is complex and extends beyond abnormalities in the arachidonic acid metabolism. Heterogeneity of pathophysiological mechanisms underlying development of airway inflammation seems to be associated with variability in response to both anti-inflammatory and disease-specific treatments (e.g., with aspirin after desensitization).

Progress in understanding of the pathophysiology of N-ERD leads to discovery and validation of new biomarkers facilitating diagnosis and predicting the response to treatment of the chronic inflammation underlying upper (CRSwNP) and lower airway (asthma) symptoms. Better characterization of the immunophysiopathological heterogeneity of N-ERD (identification of endotypes) may allow more personalized, endotype-driven approach to treatment in the future.