Decoding Type 2 Asthma Heterogeneity: Cluster Analysis of Australasian Severe Asthma Network.

Authors

Yan Li Huang, Ji Wang, Ke Deng, Chang Yong Wang, Gang Liu, Peng Gao, Wei Jie Zhang, Alan Chen-Yu Hsu, Min Xie, Zhi Hong Chen, Ling Qin, Fang Wang, Jie Zhang, Feng Min Luo, Wei Min Li, Gang Wang

Published in

The journal of allergy and clinical immunology. In practice. Nov 10, 2026. Epub Nov 10, 2026.

Abstract

Variable clinical remission rates on biologics may reflect heterogeneity within type 2 (T2) asthma, but such heterogeneity remains largely unexplored.
To identify clinically distinct T2 asthma subtypes using multidimensional profiling and hierarchical clustering.
All T2 participants (n=764) were from the Australasian Severe Asthma Network, identified by elevated eosinophil levels, elevated FeNO, or allergic sensitization. Baseline clinical and inflammatory data were integrated to identify potential clusters in the training set using hierarchical clustering, followed by prospective assessment of exacerbation over 12 months. A random forest classifier was internally cross-validated and applied to a held-out validation set to assess profile consistency.
Three subtypes emerged as: Cluster 1 (n=241, 45.0%) represented a female-predominant, well-controlled allergic subtype; Cluster 2 (n=110, 20.6%) constituted older T2 asthma patients with overlapping non-T2 features, including increased sputum neutrophil counts, fixed airflow limitation, and multiple comorbidities, with higher severe exacerbation rates (incidence rate ratios [IRR]=2.54, P=0.025) and emergency visit rates (IRR=5.06, P=0.040); and Cluster 3 (n=184, 34.4%) showed multiple elevated T2 biomarkers, poor symptom control and increased severe exacerbation (IRR=2.49, P=0.007) and hospitalization risk (IRR=3.28, P=0.009). The classifier showed 83.6% agreement with the original cluster assignments (κ=0.738), with post-bronchodilator FEV₁/FVC, age, and BMI as leading discriminators.
T2 asthma encompasses distinct subtypes with prognostic and therapeutic implications. Our findings support a precision medicine approach for these subtypes: Cluster 3 patients may warrant early assessment for biologic therapy when eligible, while Cluster 2 may benefit from integrated strategies addressing non-T2 traits.

PMID:
43009016
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.

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