支气管热成形术诱导重症哮喘气道壁细胞外基质的变化
2023/10/25
摘要
背景：气道重塑是哮喘的一个突出特征，包括气道平滑肌（ASM）质量增加和细胞外基质（ECM）组成改变。支气管热成形术（BT）是一种用于重症哮喘的支气管镜治疗方法，其目标是气道重塑。
目的：探讨BT对ECM组成的影响及其与临床疗效的关系。
方法：这是TASMA试验的一个子研究。30例重症哮喘患者接受BT治疗，其中13例患者在BT前接受了6个月的标准治疗（对照组）。收集人口统计学数据、临床数据，包括肺功能和支气管活检。通过组织学和免疫组织化学染色分析BT处理和未处理部位的活检。探讨了组织学与临床结果之间的关系。
结果：治疗6个月后，网状基底膜（RBM）厚度从7.28μm减少到5.74μm（相对减少21%），胶原阳性组织面积百分比从26.3%增加到29.8%（相对增加13%）。胶原结构分析显示纤维的弯曲频率降低。纤维蛋白-1和纤连蛋白阳性的百分比面积分别增加了2.5%和5.9%（相对增加了124%和15%）。弹性蛋白没有变化。胶原和纤维蛋白-1的变化与FEV1可逆性的变化呈负相关。
结论：与ASM减少相比，BT影响RBM厚度和ECM排列，其特征是胶原占据的组织面积增加，纤维组织密度降低。胶原和纤维蛋白-1均与FEV1可逆性的变化呈负相关。
Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma
Pieta C Wijsman, Annika W M Goorsenberg, Noa Keijzer, Julia N S d'Hooghe, Nick H T Ten Hacken, Pallav L Shah, Els J M Weersink, Jôse Mara de Brito, Natalia de Souza Xavier Costa, Thais Mauad, Martijn C Nawijn, Judith M Vonk, Jouke T Annema, Janette K Burgess, Peter I Bonta
Abstract
Background: Airway remodeling is a prominent feature of asthma, including increased airway smooth muscle (ASM) mass and altered extracellular matrix (ECM) composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets this airway remodeling.
Objective: To investigate the effect of BT on ECM composition and its association with clinical outcomes.
Methods: This is a sub-study of the TASMA trial. Thirty severe asthma patients were BT treated, of which 13 patients prior to BT were treated by six months of standard therapy (control group). Demographic data, clinical data including pulmonary function and bronchial biopsies were collected. Biopsies at BT treated and non-treated locations were analyzed by histological and immune-histochemical staining. Associations between histology and clinical outcomes were explored.
Results: Six months after treatment, reticular basement membrane (RBM) thickness was reduced from 7.28μm to 5.74μm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased with 2.5% and 5.9% respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1-reversibility.
Conclusion: Next to ASM reduction, BT impacts RBM thickness and the ECM arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1-reversibility.
背景：气道重塑是哮喘的一个突出特征，包括气道平滑肌（ASM）质量增加和细胞外基质（ECM）组成改变。支气管热成形术（BT）是一种用于重症哮喘的支气管镜治疗方法，其目标是气道重塑。
目的：探讨BT对ECM组成的影响及其与临床疗效的关系。
方法：这是TASMA试验的一个子研究。30例重症哮喘患者接受BT治疗，其中13例患者在BT前接受了6个月的标准治疗（对照组）。收集人口统计学数据、临床数据，包括肺功能和支气管活检。通过组织学和免疫组织化学染色分析BT处理和未处理部位的活检。探讨了组织学与临床结果之间的关系。
结果：治疗6个月后，网状基底膜（RBM）厚度从7.28μm减少到5.74μm（相对减少21%），胶原阳性组织面积百分比从26.3%增加到29.8%（相对增加13%）。胶原结构分析显示纤维的弯曲频率降低。纤维蛋白-1和纤连蛋白阳性的百分比面积分别增加了2.5%和5.9%（相对增加了124%和15%）。弹性蛋白没有变化。胶原和纤维蛋白-1的变化与FEV1可逆性的变化呈负相关。
结论：与ASM减少相比，BT影响RBM厚度和ECM排列，其特征是胶原占据的组织面积增加，纤维组织密度降低。胶原和纤维蛋白-1均与FEV1可逆性的变化呈负相关。
(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)
(J Allergy Clin Immunol. 2023 Oct 5:S0091-6749(23)01247-2. doi: 10.1016/j.jaci.2023.09.035.)
(J Allergy Clin Immunol. 2023 Oct 5:S0091-6749(23)01247-2. doi: 10.1016/j.jaci.2023.09.035.)
Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma
Pieta C Wijsman, Annika W M Goorsenberg, Noa Keijzer, Julia N S d'Hooghe, Nick H T Ten Hacken, Pallav L Shah, Els J M Weersink, Jôse Mara de Brito, Natalia de Souza Xavier Costa, Thais Mauad, Martijn C Nawijn, Judith M Vonk, Jouke T Annema, Janette K Burgess, Peter I Bonta
Abstract
Background: Airway remodeling is a prominent feature of asthma, including increased airway smooth muscle (ASM) mass and altered extracellular matrix (ECM) composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets this airway remodeling.
Objective: To investigate the effect of BT on ECM composition and its association with clinical outcomes.
Methods: This is a sub-study of the TASMA trial. Thirty severe asthma patients were BT treated, of which 13 patients prior to BT were treated by six months of standard therapy (control group). Demographic data, clinical data including pulmonary function and bronchial biopsies were collected. Biopsies at BT treated and non-treated locations were analyzed by histological and immune-histochemical staining. Associations between histology and clinical outcomes were explored.
Results: Six months after treatment, reticular basement membrane (RBM) thickness was reduced from 7.28μm to 5.74μm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased with 2.5% and 5.9% respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1-reversibility.
Conclusion: Next to ASM reduction, BT impacts RBM thickness and the ECM arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1-reversibility.
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ITGAM-巨噬细胞调控作为治疗中性粒细胞型哮喘的潜在策略：来自生物信息学分析和体内实验的见解
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NO暴露对哮喘小鼠气道炎症和氧化应激的影响
