哮喘中基底膜区增厚的临床与生物学特征
2025/04/06
摘要
背景：一部分哮喘患者的气道病理特征表现为上皮下基底膜区增厚（“BMZ增厚型哮喘”）。
目的：描述BMZ增厚型哮喘的临床特征，并确定BMZ增厚是否伴随气道上皮中特定的炎症模式。
方法：41名健康对照者的支气管内活检组织切片中的BMZ厚度进行定量分析，这些样本来自严重哮喘研究计划-3（Severe Asthma Research Program-3）的参与者，所有参与者均接受了肺功能检查和气道上皮刷检的基因表达谱分析。
结果：健康对照组中BMZ厚度的第90百分位数值为2.9 µM，而35%的哮喘患者的BMZ厚度超过这一上限。与BMZ较薄的哮喘患者相比，BMZ增厚的哮喘患者更年轻，血液中嗜酸性粒细胞数量和血清免疫球蛋白E（IgE）水平更高，且这些IgE对动物蛋白具有特异性。BMZ增厚患者的支气管扩张剂前FEV1（第一秒用力呼气量）显著低于BMZ较薄患者，但支气管扩张剂后FEV1无显著差异。在BMZ增厚患者的上皮刷检中，白细胞介素-13（IL-13）激活相关基因和肥大细胞的存在显著上调，而干扰素γ或白细胞介素-17（IL-17）激活的基因特征未显现。
结论：BMZ增厚标志着一部分年轻哮喘患者的特征，这些患者对动物气源性过敏原的IgE水平较高，且在IL-13激活的气道上皮细胞和肥大细胞浸润的背景下，支气管张力增加。
Clinical and Biological Features of a Thickened Basement Membrane Zone in Asthma.
Clarus, Leung; Monica, Tang; Walter E,
Abstrast
Background: A subset of asthma patients have airway pathology characterized by a thickened subepithelial basement membrane zone ("BMZ-thick asthma").
Objective: 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.
背景：一部分哮喘患者的气道病理特征表现为上皮下基底膜区增厚（“BMZ增厚型哮喘”）。
目的：描述BMZ增厚型哮喘的临床特征，并确定BMZ增厚是否伴随气道上皮中特定的炎症模式。
方法：41名健康对照者的支气管内活检组织切片中的BMZ厚度进行定量分析，这些样本来自严重哮喘研究计划-3（Severe Asthma Research Program-3）的参与者，所有参与者均接受了肺功能检查和气道上皮刷检的基因表达谱分析。
结果：健康对照组中BMZ厚度的第90百分位数值为2.9 µM，而35%的哮喘患者的BMZ厚度超过这一上限。与BMZ较薄的哮喘患者相比，BMZ增厚的哮喘患者更年轻，血液中嗜酸性粒细胞数量和血清免疫球蛋白E（IgE）水平更高，且这些IgE对动物蛋白具有特异性。BMZ增厚患者的支气管扩张剂前FEV1（第一秒用力呼气量）显著低于BMZ较薄患者，但支气管扩张剂后FEV1无显著差异。在BMZ增厚患者的上皮刷检中，白细胞介素-13（IL-13）激活相关基因和肥大细胞的存在显著上调，而干扰素γ或白细胞介素-17（IL-17）激活的基因特征未显现。
结论：BMZ增厚标志着一部分年轻哮喘患者的特征，这些患者对动物气源性过敏原的IgE水平较高，且在IL-13激活的气道上皮细胞和肥大细胞浸润的背景下，支气管张力增加。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Am J Respir Crit Care Med 2025 Feb 25;0(0);DOI: 10.1164/rccm.202408-1544OC. IF: 17.452）
Clinical and Biological Features of a Thickened Basement Membrane Zone in Asthma.
Clarus, Leung; Monica, Tang; Walter E,
Abstrast
Background: A subset of asthma patients have airway pathology characterized by a thickened subepithelial basement membrane zone ("BMZ-thick asthma").
Objective: 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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