Non‐eosinophilic asthma in nonsteroidal anti‐inflammatory drug exacerbated respiratory disease

BACKGROUND: The cellular inflammatory pattern of nonsteroidal anti‐inflammatory drug–exacerbated respiratory disease (N‐ERD) is heterogeneous. However, data on the heterogeneity of non‐eosinophilic asthma (NEA) with aspirin hypersensitivity are scanty. By examination of N‐ERD patients based on clinical data and eicosanoid biomarkers we aimed to identify NEA endotypes potentially guiding clinical management. METHODS: Induced sputum was collected from patients with N‐ERD. Sixty six patients (49.6% of 133 N‐ERD) with NEA were included in the hierarchical cluster analysis based on clinical and laboratory data. The quality of clustering was evaluated using internal cluster validation with different indices and a practical decision tree was proposed to simplify stratification of patients. RESULTS: The most frequent NEA pattern was paucigranulocytic (PGA; 75.8%), remaining was neutrophilic asthma (NA; 24.2%). Four clusters were identified. Cluster #3 included the highest number of NEA patients (37.9%) with severe asthma and PGA pattern (96.0%). Cluster #1 (24.2%) included severe only asthma, with a higher prevalence of NA (50%). Cluster #2 (25.8%) comprised well‐controlled mild or severe asthma (PGA; 76.5%). Cluster #4 contained only 12.1% patients with well‐controlled moderate asthma (PGA; 62.5%). Sputum prostaglandin D(2) levels distinguished cluster #1 from the remaining clusters with an area under the curve of 0.94. CONCLUSIONS: Among identified four NEA subtypes, clusters #3 and #1 represented N‐ERD patients with severe asthma but a different inflammatory signatures. All the clusters were discriminated by sputum PGD(2) levels, asthma severity, and age of patients. The heterogeneity of non‐eosinophilic N‐ERD suggests a need for novel targeted interventions.