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

Abstract

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 wellcontrolled 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.

The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma

“…Where interleukin-5 is responsible for the maturation and survival of eosinophils. In non-allergic eosinophilic asthma, a response to prostaglandin D2, interleukin-33, interleukin-25, and thymic stromal lymphopoietin, is a production of interleukin-5 and interleukin-13, which are released after epithelial damage [14], [15].…”

“…High levels of neutrophils are produced from the release of cytokines from T helper 17 cells, T helper 1 cells, or type 3 innate lymphoid cells that are activated by macrophages and neutrophil chemokines like C-X-C motif chemokine ligand (CXCL)-8. In bronchiectasis, a common comorbidity of severe asthma in adults, an increased amount of neutrophils indicates that a bacterial colonization exists or is an effect of corticosteroids which promotes the survival of neutrophils and suppresses type 2 immunity [14], [15], [16], [17].…”