Type 2 gene expression signature in severe asthma associates with more advanced airway remodeling
Abstract Background Asthma is a heterogeneous disease with various inflammatory subtypes, including the type‐2 (T2) endotype associated with airway eosinophilia. Severe asthma is linked to reduced ventilatory function due to airway structural changes. This study compared the extent of airway remodel...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-06-01
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| Series: | Clinical and Translational Allergy |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/clt2.70060 |
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| Summary: | Abstract Background Asthma is a heterogeneous disease with various inflammatory subtypes, including the type‐2 (T2) endotype associated with airway eosinophilia. Severe asthma is linked to reduced ventilatory function due to airway structural changes. This study compared the extent of airway remodeling in different immunological endotypes of asthma. Methods Severe asthma patients (n = 30) were stratified based on bronchial expression of T2 (e.g., CST1) and T3 (e.g., IL17A) immunity genes as T2‐high, T3‐high, or low‐inflammatory. We analyzed airway wall thickness using endobronchial ultrasound (EBUS), bronchial biopsy morphometry, and mRNA expression of remodeling genes. Bronchial epithelial cell cultures were used to assess cytokine responses. Results T2‐high asthma patients showed lower predicted FEV1 (59 vs. 74 % in low‐inflammatory variant, p = 0.049) and increased submucosa layer (L2) in EBUS (0.203 vs. 0.189 mm, p = 0.018). T2‐high asthma patients also had increased airway smooth muscle (ASM) mass (∼2‐fold, p = 0.018) and marginally thicker reticular basement membrane. T3‐high asthma showed only a trend toward thicker L2 (p = 0.055). Only patients with an eosinophilic signature in endobronchial biopsy demonstrated increased expression of remodeling genes, including TGFB1. A profibrotic profile was also induced in bronchial epithelium stimulated in vitro with IL‐13. Conclusion These data suggest that T2‐signature in severe asthma is associated with increased ASM mass and more pronounced airway obstruction. Overexpression of remodeling genes primarily occurred in patients with signs of eosinophilic infiltration in the bronchial mucosa, suggesting that remodeling may progress with uncontrolled airway inflammation. |
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| ISSN: | 2045-7022 |