年龄因素在重度未控制哮喘患者气道炎症与功能中的差异性影响
2026/02/25
摘要
背景：支气管镜下活检研究有助于对重度哮喘气道炎症和重塑的理解，但针对儿童与成人人群的直接比较仍十分有限。
目的：比较儿童与成人重度未控制哮喘患者的组织病理学和临床特征。
方法：我们评估了13例儿童和36例成人重度未控制哮喘患者的人口学资料、临床和实验室数据、肺功能、呼出气一氧化氮（FENO）以及支气管镜下活检标本。
结果：儿童组中男性比例较高，而成人组则以女性为主。儿童的肺功能优于成人（FEV1% 中位数：82% vs. 55%）。相反，在多个气道区室中，儿童的炎症细胞密度显著更高：上皮内层表现为嗜酸性粒细胞、糜酶（chymase）阳性肥大细胞和CD8+ T细胞水平升高；气道平滑肌层表现为中性粒细胞、类胰蛋白酶阳性肥大细胞和糜酶阳性肥大细胞水平升高；黏膜下层则表现为嗜酸性粒细胞、类胰蛋白酶（tryptase）阳性肥大细胞和糜酶阳性肥大细胞水平升高。相比之下，成人黏膜下层的CD4+ T细胞密度更高。两组之间的结构参数，包括基底膜和上皮厚度、胶原沉积以及气道平滑肌/总组织面积，均无显著差异。
结论：在存在相似结构重塑的情况下，患有重度哮喘的儿童表现出更显著的气道炎症，但肺功能维持优于成人。这些发现提示儿童群体中存在一个潜在的治疗窗口期，强调了在重度哮喘管理中需要采取针对不同年龄段的个体化治疗策略。
关键词： CD8(+) T细胞；重度哮喘；气道炎症；气道重塑；支气管镜下活检；肺功能；肥大细胞
Abstract
Background: Endobronchial biopsy studies have deepened our understanding of airway inflammation and remodeling in severe asthma, but direct comparisons between pediatric and adult populations remain scarce.
Objective: To compare the histopathological and clinical characteristics of children and adults with severe uncontrolled asthma.
Methods: Demographic, clinical, and laboratory data, lung function, Fractional Exhaled Nitric Oxide (FeNO) and endobronchial biopsies were evaluated from 13 children and 36 adults with severe uncontrolled asthma.
Results: The pediatric group had a higher proportion of males, while females predominated in adults. Children exhibited better lung function than adults (median FEV1% pred. 82% vs. 55%). In contrast, inflammatory cell densities were significantly higher in children across multiple airway compartments: elevated levels of eosinophils, chymase-positive mast cells, and CD8+ T cells in the intraepithelial (IE) layer; neutrophils, tryptase-positive mast cells, and chymase-positive mast cells in the airway smooth muscle (ASM) layer; and eosinophils, tryptase-positive mast cells, and chymase-positive mast cells in the submucosal (SM) layer. In contrast, CD4+ T cell density in the SM layer was higher in adults. Structural parameters, including basement membrane and epithelial thickness, collagen deposition, and ASM/total tissue area, were similar between groups.
Conclusion: Children with severe asthma exhibit greater airway inflammation yet maintain better lung function compared to adults with similar structural remodeling. These findings highlight a potential therapeutical window in the pediatric population, emphasizing the need for age-tailored management approaches in severe asthma.
Keywords: CD8(+) T cells; Severe asthma; airway inflammation; airway remodeling; endobronchial biopsy; lung function; mast cells.
背景：支气管镜下活检研究有助于对重度哮喘气道炎症和重塑的理解，但针对儿童与成人人群的直接比较仍十分有限。
目的：比较儿童与成人重度未控制哮喘患者的组织病理学和临床特征。
方法：我们评估了13例儿童和36例成人重度未控制哮喘患者的人口学资料、临床和实验室数据、肺功能、呼出气一氧化氮（FENO）以及支气管镜下活检标本。
结果：儿童组中男性比例较高，而成人组则以女性为主。儿童的肺功能优于成人（FEV1% 中位数：82% vs. 55%）。相反，在多个气道区室中，儿童的炎症细胞密度显著更高：上皮内层表现为嗜酸性粒细胞、糜酶（chymase）阳性肥大细胞和CD8+ T细胞水平升高；气道平滑肌层表现为中性粒细胞、类胰蛋白酶阳性肥大细胞和糜酶阳性肥大细胞水平升高；黏膜下层则表现为嗜酸性粒细胞、类胰蛋白酶（tryptase）阳性肥大细胞和糜酶阳性肥大细胞水平升高。相比之下，成人黏膜下层的CD4+ T细胞密度更高。两组之间的结构参数，包括基底膜和上皮厚度、胶原沉积以及气道平滑肌/总组织面积，均无显著差异。
结论：在存在相似结构重塑的情况下，患有重度哮喘的儿童表现出更显著的气道炎症，但肺功能维持优于成人。这些发现提示儿童群体中存在一个潜在的治疗窗口期，强调了在重度哮喘管理中需要采取针对不同年龄段的个体化治疗策略。
关键词： CD8(+) T细胞；重度哮喘；气道炎症；气道重塑；支气管镜下活检；肺功能；肥大细胞
（南方医科大学南方医院 凌嘉俊 赵文驱 赵海金）
（Mára de Brito J, J Allergy Clin Immunol. 2026 Jan 30:S0091-6749(26)00068-0. Online ahead of print.Age-Dependent Differences in Airway Inflammation and Function in Severe Uncontrolled Asthma）
（Mára de Brito J, J Allergy Clin Immunol. 2026 Jan 30:S0091-6749(26)00068-0. Online ahead of print.Age-Dependent Differences in Airway Inflammation and Function in Severe Uncontrolled Asthma）
Abstract
Background: Endobronchial biopsy studies have deepened our understanding of airway inflammation and remodeling in severe asthma, but direct comparisons between pediatric and adult populations remain scarce.
Objective: To compare the histopathological and clinical characteristics of children and adults with severe uncontrolled asthma.
Methods: Demographic, clinical, and laboratory data, lung function, Fractional Exhaled Nitric Oxide (FeNO) and endobronchial biopsies were evaluated from 13 children and 36 adults with severe uncontrolled asthma.
Results: The pediatric group had a higher proportion of males, while females predominated in adults. Children exhibited better lung function than adults (median FEV1% pred. 82% vs. 55%). In contrast, inflammatory cell densities were significantly higher in children across multiple airway compartments: elevated levels of eosinophils, chymase-positive mast cells, and CD8+ T cells in the intraepithelial (IE) layer; neutrophils, tryptase-positive mast cells, and chymase-positive mast cells in the airway smooth muscle (ASM) layer; and eosinophils, tryptase-positive mast cells, and chymase-positive mast cells in the submucosal (SM) layer. In contrast, CD4+ T cell density in the SM layer was higher in adults. Structural parameters, including basement membrane and epithelial thickness, collagen deposition, and ASM/total tissue area, were similar between groups.
Conclusion: Children with severe asthma exhibit greater airway inflammation yet maintain better lung function compared to adults with similar structural remodeling. These findings highlight a potential therapeutical window in the pediatric population, emphasizing the need for age-tailored management approaches in severe asthma.
Keywords: CD8(+) T cells; Severe asthma; airway inflammation; airway remodeling; endobronchial biopsy; lung function; mast cells.
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生物标志物在慢性气道疾病
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超越生物标志物：临床因素能否更好地预测重度哮喘的生物制剂疗效？
