基底膜增厚型哮喘患者的临床和生物学特征
2025/07/15
背景：部分哮喘患者的气道病理特征表现为上皮下层基底膜区增厚（简称“BMZ增厚型哮喘”）。
目的：明确BMZ增厚型哮喘的临床特征，并探究基底膜增厚是否伴随气道上皮特定的炎症模式。
方法：采用基于设计的体视学方法，对来自SARP-3项目（the Severe Asthma Research Program-3）的109名哮喘患者和41名健康对照组的支气管活检组织切片进行BMZ厚度量化。所有参与者均接受肺功能检测及气道上皮刷检基因表达谱分析。
结果：健康人群中BMZ厚度的第90百分位值为2.9微米，35%的哮喘患者超过此临界值。与BMZ未增厚型患者相比，BMZ增厚型哮喘患者更年轻，血液嗜酸性粒细胞数量更多，且血清中针对动物蛋白的sIgE水平升高。支气管舒张剂使用前的平均第一秒用力呼气容积（FEV1）在BMZ增厚型患者中显著更低，但用药后FEV1无显著差异。BMZ增厚型患者的上皮刷检样本中，IL-13激活相关基因及肥大细胞标志基因显著上调，而γ干扰素或IL-17激活相关基因未见明显特征。
结论：基底膜增厚型哮喘是哮喘中的一个亚型，特征为：更年轻，对动物气源性过敏原的IgE水平升高，以及在IL-13激活的上皮细胞及肥大细胞浸润背景下出现的支气管张力增强。
（四川大学华西医院呼吸与危重症医学科 黄彦立1 王霁1 王刚1 译）
（Am J Respir Crit Care Med. 2025 Feb 25;211(5):759–69. doi: 10.1164/rccm.202408-1544OC. ）
Background: A subset of asthma patients have airway pathology characterized by a thickened subepithelial basement membrane zone ("BMZ-thick asthma").
Objectives: To characterize the clinical features of BMZ-thick asthma and to determine if BMZ thickness accompanies specific patterns of inflammation in the airway epithelium.
Methods: Design-based stereology was used to quantify BMZ thickness in endobronchial biopsy tissue sections from 109 asthma patients and 41 healthy controls from the Severe Asthma Research Program-3 whose participants had undergone spirometry and gene expression profiling in airway epithelial brushings.
Results: The upper 90th percentile value for BMZ thickness in the healthy cohort was 2.9 µM, and 35% of the asthma cohort had values above this upper limit. Compared to BMZ-thin asthma patients, BMZ-thick asthma patients were younger and had higher blood eosinophil numbers and serum immunoglobulin E levels that were specific to animal proteins. Mean pre-bronchodilator FEV1 was significantly lower in BMZ-thick than in BMZ-thin patients, but post-bronchodilator FEV1 was not. Upregulation of genes signifying interleukin-13 activation and presence of mast cells were evident in epithelial brushings in BMZ-thick patients, but gene signatures for activation by interferon gamma or interleukin-17 were not.
Conclusions: A thickened BMZ marks a subset of younger asthma patients characterized by higher IgE levels to animal aeroallergens and by increased bronchomotor tone occurring in the context of airway epithelial cells activated by interleukin-13 and infiltrated by mast cells.
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肺驻留记忆B细胞维持呼吸道过敏IgE应答
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