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Cluster Analysis to Identify Distinct Asthma Phenotypes in the ATLANTIS Cohort
Pauline J M Kuks1,2, Tatiana Karp1,2, Jorine E Hartman1,2
1Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Allergy
|November 10, 2025
Summary
This study identified four asthma phenotypes using small airways dysfunction (SAD) and gene expression. SAD is linked to severe, poorly controlled asthma with high inflammation and frequent exacerbations.
Area of Science:
- Pulmonology
- Asthma Research
- Genetics
Background:
- Previous asthma subgroup analyses often excluded small airways dysfunction (SAD) and gene expression data.
- The ATLANTIS study investigated SAD prevalence and its impact on asthma control, exacerbations, and quality of life.
Purpose of the Study:
- To identify distinct asthma phenotypes beyond current severity classifications.
- To explore the role of small airways dysfunction (SAD) and gene expression in asthma heterogeneity.
Main Methods:
- Utilized data from 773 asthma patients (GINA 1-5) in the ATLANTIS study.
- Collected comprehensive data including symptoms, lung function (large and small airways), cell counts, and nasal gene expression.
- Applied Self-Organizing Map-Ward's clustering method to identify patient subgroups.
Main Results:
- Identified four distinct asthma clusters (A, B, C, D).
- Cluster A (8%) showed frequent exacerbations, SAD, and high eosinophils, linked to high asthma gene expression.
- Cluster B (27%) comprised atopic, early-onset asthma with uncontrolled symptoms and normal lung function.
- Cluster C (36%) included male former smokers with mild obstruction and high neutrophils.
- Cluster D (29%) presented with normal lung function and low eosinophils.
Conclusions:
- Four distinct asthma phenotypes were identified, highlighting the importance of SAD.
- Small airways dysfunction (SAD) is associated with high type-2 inflammation, reduced lung function, and frequent exacerbations.
- SAD may serve as a clinical marker for poorly controlled asthma and warrants consideration as a key trait.
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