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Common exacerbation-prone phenotypes across asthma and chronic obstructive pulmonary disease (COPD)
Kentaro Hyodo1,2, Hironori Masuko1, Hisayuki Oshima1
1Department of Pulmonary Medicine, University of Tsukuba, Ibaraki, Japan.
Plos One
|March 21, 2022
Summary
This study identified five patient clusters for chronic inflammatory airway diseases, revealing that the IL4RA gene polymorphism rs8832 is linked to type 2 inflammation-driven exacerbations. These findings support a treatable traits approach for managing asthma and COPD exacerbations.
Area of Science:
- Pulmonology and Genetics
- Investigating the genetic underpinnings of complex respiratory diseases.
- Understanding endotypes in chronic inflammatory airway diseases.
Background:
- Chronic inflammatory airway diseases like asthma and COPD present complex, heterogeneous symptoms.
- Exacerbations in these conditions share common risk factors, suggesting overlapping pathophysiological mechanisms.
- The role of specific gene polymorphisms, such as IL4RA, in exacerbation phenotypes requires further clarification.
Purpose of the Study:
- To identify exacerbation-prone phenotypes in asthma and COPD beyond diagnostic labels.
- To investigate the association of the IL4RA gene polymorphism (rs8832) with these phenotypes.
- To explore the genetic influence of rs8832 in specific asthma subgroups.
Main Methods:
- Cluster analysis of patients with asthma, COPD, and asthma-COPD overlap (ACO) based on exacerbation risk factors.
- Multinomial logistic regression to assess the association of IL4RA rs8832 with identified clusters, using healthy adults as controls.
- Genetic analysis of rs8832 in asthma patients with allergic rhinitis and no exacerbation history.
Main Results:
- Five distinct clusters were identified, not strictly aligned with asthma, COPD, or ACO diagnoses.
- Clusters were characterized by factors like high eosinophils, smoking with impaired lung function, GERD, non-allergic females, and allergic rhinitis with elevated IgE.
- The IL4RA rs8832 polymorphism showed a significant association with the allergic rhinitis/elevated IgE cluster (Cluster 5) and type 2 exacerbation-prone phenotypes (Clusters 1 and 5).
Conclusions:
- Clinical heterogeneity in exacerbations may stem from common endotypes across asthma and COPD.
- The IL4RA rs8832 polymorphism is a potential genetic marker for type 2 inflammation-driven exacerbations.
- Findings support a treatable traits approach for personalized exacerbation prevention in chronic inflammatory airway diseases.
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