随访支气管热成形术一年后对重度哮喘患者气道炎症和促纤维化基因表达的影响
2026/09/09
摘要
背景：支气管热成形术（BT）可减轻重度哮喘患者的症状，但其作用机制尚不清楚。本初步研究旨在探究BT对支气管基因表达的影响及其与气道结构改变的关联。
方法：对10例重度哮喘患者在BT治疗前及治疗后12个月进行支气管镜检查，包括支气管内超声（EBUS）、支气管肺泡灌洗（BAL）和支气管内膜活检。我们评估了BAL细胞学、活检组织形态计量学，以及与免疫（如固有免疫或2型相关）和促纤维化反应相关基因的mRNA表达。
结果：BT治疗后，哮喘控制情况显著改善（哮喘控制测试[ACT]评分中位数从14提高到18，p = 0.0078），急性发作率降低（从5次降至1次，p = 0.0020）。肺功能检查显示气流阻塞指标无改善，但气体陷闭情况减轻（残气量/肺总量[RV/TLC]从0.47降至0.39，p = 0.0078）。BAL中嗜酸性粒细胞增多（从0.3%增至3.7%，p = 0.0020），主要见于全身使用糖皮质激素剂量大幅减少的患者。组织学分析显示气道平滑肌（ASM）质量显著减少，而基因表达数据仅显示与重塑相关的转录本（如COL3A1、GDNF）有适度上调。这些分子变化与支气管结构或肺功能指标无关，可能反映了局部炎症模式的改变。
结论：BT似乎并未从根本上改变治疗气道的免疫特征，但与ASM厚度减小和纤维化特征相关。这与BALF中嗜酸性粒细胞增多有关，提示BT对气道各部分的影响存在异质性，且随着临床症状改善减少糖皮质激素使用会进一步改变这种影响。
Effect of bronchial thermoplasty on airway inflammatory and profibrotic gene expression after one-year follow-up in severe asthma
Bogdan Jakiela, Stanislawa Bazan-Socha, Karolina Górka, Iwona Gross-Sondej, Sławomir Mikrut, Krzysztof Okoń, Piotr Sadowski, Anna Andrychiewicz, Tomasz Stachura, Marek Przybyszowski, Grażyna Bochenek, Krzysztof Sładek, Jerzy Soja
Abstract
Background: Bronchial thermoplasty (BT) reduces symptoms in severe asthma, but its mechanisms remain poorly understood. This preliminary study aimed to investigate the effect of BT on bronchial gene expression and its associations with airway structural changes.
Methods: Bronchoscopy with endobronchial ultrasound (EBUS), bronchoalveolar lavage (BAL), and endobronchial biopsies was performed in 10 patients with severe asthma before and 12 months after BT. We assessed BAL cytology, biopsy histomorphometry, and mRNA expression of genes related to immune (e.g., innate or type-2 related) and profibrotic responses.
Results: BT resulted in significant improvement in asthma control (ACT score increased from median 14 to 18, p = 0.0078) and a reduction in exacerbation rate (from 5 to 1, p = 0.0020). Spirometric measures of airflow obstruction did not improve, but air trapping decreased (RV/TLC from 0.47 to 0.39, p = 0.0078) after BT. An increase in BAL eosinophils was observed (from 0.3% to 3.7%, p = 0.0020), predominantly in patients with greater reductions in systemic corticosteroids. Histological analysis showed a significant reduction in the airway smooth muscle (ASM) mass, while gene-expression data demonstrated only moderate upregulation of remodeling-related transcripts (e.g., COL3A1, GDNF). These molecular changes were not associated with bronchial structural or spirometric parameters and likely reflect shifts in local inflammatory patterns.
Conclusion: BT does not appear to fundamentally alter the immunological profile in the treated airways but is associated with a decrease in ASM thickness along with features of fibrosis. This was associated with increased BALF eosinophilia, suggesting heterogeneous effect of BT across airway compartments, further modified by corticosteroid reduction accompanying clinical improvement.
背景：支气管热成形术（BT）可减轻重度哮喘患者的症状，但其作用机制尚不清楚。本初步研究旨在探究BT对支气管基因表达的影响及其与气道结构改变的关联。
方法：对10例重度哮喘患者在BT治疗前及治疗后12个月进行支气管镜检查，包括支气管内超声（EBUS）、支气管肺泡灌洗（BAL）和支气管内膜活检。我们评估了BAL细胞学、活检组织形态计量学，以及与免疫（如固有免疫或2型相关）和促纤维化反应相关基因的mRNA表达。
结果：BT治疗后，哮喘控制情况显著改善（哮喘控制测试[ACT]评分中位数从14提高到18，p = 0.0078），急性发作率降低（从5次降至1次，p = 0.0020）。肺功能检查显示气流阻塞指标无改善，但气体陷闭情况减轻（残气量/肺总量[RV/TLC]从0.47降至0.39，p = 0.0078）。BAL中嗜酸性粒细胞增多（从0.3%增至3.7%，p = 0.0020），主要见于全身使用糖皮质激素剂量大幅减少的患者。组织学分析显示气道平滑肌（ASM）质量显著减少，而基因表达数据仅显示与重塑相关的转录本（如COL3A1、GDNF）有适度上调。这些分子变化与支气管结构或肺功能指标无关，可能反映了局部炎症模式的改变。
结论：BT似乎并未从根本上改变治疗气道的免疫特征，但与ASM厚度减小和纤维化特征相关。这与BALF中嗜酸性粒细胞增多有关，提示BT对气道各部分的影响存在异质性，且随着临床症状改善减少糖皮质激素使用会进一步改变这种影响。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Front Immunol. 2026 Aug 7:17:1886894. doi: 10.3389/fimmu.2026.1886894.）
（Front Immunol. 2026 Aug 7:17:1886894. doi: 10.3389/fimmu.2026.1886894.）
Effect of bronchial thermoplasty on airway inflammatory and profibrotic gene expression after one-year follow-up in severe asthma
Bogdan Jakiela, Stanislawa Bazan-Socha, Karolina Górka, Iwona Gross-Sondej, Sławomir Mikrut, Krzysztof Okoń, Piotr Sadowski, Anna Andrychiewicz, Tomasz Stachura, Marek Przybyszowski, Grażyna Bochenek, Krzysztof Sładek, Jerzy Soja
Abstract
Background: Bronchial thermoplasty (BT) reduces symptoms in severe asthma, but its mechanisms remain poorly understood. This preliminary study aimed to investigate the effect of BT on bronchial gene expression and its associations with airway structural changes.
Methods: Bronchoscopy with endobronchial ultrasound (EBUS), bronchoalveolar lavage (BAL), and endobronchial biopsies was performed in 10 patients with severe asthma before and 12 months after BT. We assessed BAL cytology, biopsy histomorphometry, and mRNA expression of genes related to immune (e.g., innate or type-2 related) and profibrotic responses.
Results: BT resulted in significant improvement in asthma control (ACT score increased from median 14 to 18, p = 0.0078) and a reduction in exacerbation rate (from 5 to 1, p = 0.0020). Spirometric measures of airflow obstruction did not improve, but air trapping decreased (RV/TLC from 0.47 to 0.39, p = 0.0078) after BT. An increase in BAL eosinophils was observed (from 0.3% to 3.7%, p = 0.0020), predominantly in patients with greater reductions in systemic corticosteroids. Histological analysis showed a significant reduction in the airway smooth muscle (ASM) mass, while gene-expression data demonstrated only moderate upregulation of remodeling-related transcripts (e.g., COL3A1, GDNF). These molecular changes were not associated with bronchial structural or spirometric parameters and likely reflect shifts in local inflammatory patterns.
Conclusion: BT does not appear to fundamentally alter the immunological profile in the treated airways but is associated with a decrease in ASM thickness along with features of fibrosis. This was associated with increased BALF eosinophilia, suggesting heterogeneous effect of BT across airway compartments, further modified by corticosteroid reduction accompanying clinical improvement.
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