Identification of phenotypic clusters of nonsteroidal anti‐inflammatory drugs exacerbated respiratory disease

Background Clinical presentation of nonsteroidal anti‐inflammatory drugs exacerbated respiratory disease ( NERD ) is found to be heterogeneous. This study classified phenotypic clusters to determine NERD subtypes. Methods We performed two‐step cluster analysis using urticaria, chronic rhinosinusitis ( CRS ), and atopy, in a NERD cohort comprising 302 patients. Asthma exacerbation was defined as receiving at least one burst of intravenous steroid treatment and/or at least two bursts of oral steroid use (≥ 45 mg/3 days) per year. The possession rate of anti‐asthmatic medications was estimated during the follow‐up period. Results There were four subtypes: subtype 1 ( NERD with CRS /atopy and no urticaria), subtype 2 ( NERD with CRS and no urticaria/atopy), subtype 3 ( NERD without CRS /urticaria), and subtype 4 ( NERD with urticaria). Significant differences were found between the four subtypes in the female proportion, baseline FEV 1%, serum total IgE level, and sputum/peripheral eosinophil count. A higher frequency of asthma exacerbations was noted in subtype 1 compared to subtype 3. The possession rates of medium‐ to high‐dose inhaled corticosteroids/long‐acting beta 2 ‐agonists showed significant differences among the four subtypes. Metabolomic analysis showed that the four subtypes of NERD had a higher serum leukotriene E4 ( LTE 4) level than those with aspirin‐tolerant asthma. The patients with subtypes 1 and 3 had a higher urine LTE 4 level than those with subtype 2. Conclusion We found four distinct subtypes with different clinical/biochemical findings and asthma exacerbations in a NERD cohort. These findings suggest that stratified strategies by applying subtype classification may help achieve better outcomes in the management of NERD .