Identification of Phenotypic Clusters of Non-steroidal Anti-inflammatory Drugs Exacerbated Respiratory Disease

Abstract

Background

Clinical presentation of non-steroidal anti-inflammatory drugs exacerbated respiratory disease (NERD) is found to be heterogeneous. This study classified phenotypic clusters to determine NERD subtypes.

Methods

We performed 2-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 1 burst of intravenous steroid treatment and/or at least 2 bursts of oral steroid use (≥ 45 mg/3days) per year. The possession rate of anti-asthmatic medications was estimated during the follow-up period.

Results

There were 4 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 4 subtypes in the female proportion, baseline FEV1%, 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 ICS/LABA showed significant differences among the 4 subtypes. Metabolomic analysis showed that the 4 subtypes of NERD had a higher serum LTE4 level than those with aspirin-tolerant asthma. The patients with subtypes 1 and 3 had a higher urine LTE4 level than those with subtype 2.

Conclusion

We found 4 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.

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