支气管哮喘气道平滑肌重塑的异质性
2023/02/01
摘要
背景：支气管哮喘通气功能障碍具有异质性，可能代表气道平滑肌（ASM）重塑的分布情况。
目的：确定轻重度哮喘患者ASM重塑的分布情况。
方法：在非致死性哮喘（n=30）和致死性哮喘患者（n=20）的3条支气管通路中的9个气道水平上测量ASM面积，并与无哮喘的对照组（n=30）进行比较。计算气道内和气道之间ASM面积的相关性。根据大气道或小气道中存在或不存在ASM重塑（对照组平均ASM面积>2SD，n=86），对有12个大气道和12个小气道可用的哮喘病例（n=42）进行分类。
结果：ASM重塑在非致死性哮喘病例内和病例之间差异很大，在致死性哮喘患者中更为广泛和融合，且更为显著。在相同或不同的支气管通路内，ASM水平之间的相关性很弱，但未观察到可预测的重塑模式。通过平均数据，44%的哮喘病例被分为大气道或小气道中无ASM重塑，尽管ASM重塑的气道数量增加了3-10倍，81%的哮喘病例在至少1个大气道和小气道中有ASM重塑。
结论：ASM重塑与哮喘严重程度相关，但个体内部和个体之间存在异质性，可能导致支气管哮喘功能障碍存在异质性。这些发现支持ASM重塑患者特异性靶向的需要。
Heterogeneity of Airway Smooth Muscle Remodelling in Asthma.
James AL, Donovan GM, Green FHY, Mauad T, Abramson MJ, Cairncross A, Noble PB, Elliot JG
Abstract
BACKGROUND:Ventilatory defects in asthma are heterogeneous and may represent the distribution of airway smooth muscle (ASM) remodelling.
OBJECTIVES: To determine the distribution of ASM remodelling in mild-severe asthma.
METHODS:The ASM area was measured in 9 airway levels in 3 bronchial pathways in cases of nonfatal (n=30) and fatal asthma (n=20) and compared with controls without asthma (n=30). Correlations of ASM area within and between bronchial pathways were calculated. Asthma cases with 12 large and 12 small airways available (n=42) were classified based on the presence or absence of ASM remodelling (>2SD of mean ASM area of controls n=86) in the large or small airways or both.
RESULTS:ASM remodelling varied widely within and between cases of nonfatal asthma and was more widespread and confluent, and more marked, in fatal cases. There were weak correlations of ASM between levels within the same or separate bronchial pathways however, predictable patterns of remodelling were not observed. Using mean data, 44% of all asthma cases were classified as having no ASM remodelling in either the large or small airways, despite a 3-10 fold increase in the number of airways with ASM remodelling and 81% of asthma cases having ASM remodelling in at least 1 large and small airway.
CONCLUSIONS:ASM remodelling is related to asthma severity but is heterogenous within and between individuals and may contribute to the heterogenous functional defects observed in asthma. These findings support the need for patient-specific targeting of ASM remodelling.
背景：支气管哮喘通气功能障碍具有异质性，可能代表气道平滑肌（ASM）重塑的分布情况。
目的：确定轻重度哮喘患者ASM重塑的分布情况。
方法：在非致死性哮喘（n=30）和致死性哮喘患者（n=20）的3条支气管通路中的9个气道水平上测量ASM面积，并与无哮喘的对照组（n=30）进行比较。计算气道内和气道之间ASM面积的相关性。根据大气道或小气道中存在或不存在ASM重塑（对照组平均ASM面积>2SD，n=86），对有12个大气道和12个小气道可用的哮喘病例（n=42）进行分类。
结果：ASM重塑在非致死性哮喘病例内和病例之间差异很大，在致死性哮喘患者中更为广泛和融合，且更为显著。在相同或不同的支气管通路内，ASM水平之间的相关性很弱，但未观察到可预测的重塑模式。通过平均数据，44%的哮喘病例被分为大气道或小气道中无ASM重塑，尽管ASM重塑的气道数量增加了3-10倍，81%的哮喘病例在至少1个大气道和小气道中有ASM重塑。
结论：ASM重塑与哮喘严重程度相关，但个体内部和个体之间存在异质性，可能导致支气管哮喘功能障碍存在异质性。这些发现支持ASM重塑患者特异性靶向的需要。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2022 Nov 18. doi: 10.1164/rccm.202111-2634OC.)
(Am J Respir Crit Care Med. 2022 Nov 18. doi: 10.1164/rccm.202111-2634OC.)
Heterogeneity of Airway Smooth Muscle Remodelling in Asthma.
James AL, Donovan GM, Green FHY, Mauad T, Abramson MJ, Cairncross A, Noble PB, Elliot JG
Abstract
BACKGROUND:Ventilatory defects in asthma are heterogeneous and may represent the distribution of airway smooth muscle (ASM) remodelling.
OBJECTIVES: To determine the distribution of ASM remodelling in mild-severe asthma.
METHODS:The ASM area was measured in 9 airway levels in 3 bronchial pathways in cases of nonfatal (n=30) and fatal asthma (n=20) and compared with controls without asthma (n=30). Correlations of ASM area within and between bronchial pathways were calculated. Asthma cases with 12 large and 12 small airways available (n=42) were classified based on the presence or absence of ASM remodelling (>2SD of mean ASM area of controls n=86) in the large or small airways or both.
RESULTS:ASM remodelling varied widely within and between cases of nonfatal asthma and was more widespread and confluent, and more marked, in fatal cases. There were weak correlations of ASM between levels within the same or separate bronchial pathways however, predictable patterns of remodelling were not observed. Using mean data, 44% of all asthma cases were classified as having no ASM remodelling in either the large or small airways, despite a 3-10 fold increase in the number of airways with ASM remodelling and 81% of asthma cases having ASM remodelling in at least 1 large and small airway.
CONCLUSIONS:ASM remodelling is related to asthma severity but is heterogenous within and between individuals and may contribute to the heterogenous functional defects observed in asthma. These findings support the need for patient-specific targeting of ASM remodelling.
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