Clinical and translational allergy · 2025
Type 2 gene expression signature in severe asthma associates with more advanced airway remodeling.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jakiela Bogdan, Górka Karolina, Gross-Sondej Iwona, Mikrut Sławomir, Okoń Krzysztof, Sadowski Piotr, Andrychiewicz Anna, Plutecka Hanna, Stachura Tomasz, Bochenek Grażyna, Bazan-Socha Stanisława, Sładek Krzysztof, Soja Jerzy
Аннотация
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.
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.