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 133 patients with
N-ERD. Sixty six patients (49.6%) 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.