在体外进行计算机模拟实验以及在体内实验中验证支气管热成形术对急性气道平滑肌质量损伤的影响
2018/08/16
摘要
支气管热成形术是治疗哮喘的一种方法。目前尚不清楚，当气道壁暴露于可影响细胞存活的温度时，能对组织病理学产生怎样的影响。我们将气道平滑肌和支气管上皮细胞暴露于培养基（37-70℃）10秒以模拟热成形术。在体外计算机模拟实验中，我们开发了热成形术后气道热分布的数学模型。在体内实验中，我们研究了14名重症哮喘患者气道成形术前后的气道平滑肌质量和上皮完整性变化。将培养基加热至≥65℃时，体外气道平滑肌和上皮细胞数量显着减少。计算机模拟显示在大气道中热分布差异较大，其中低于10％的内半径约4毫米气道壁被加热至大于60摄氏度。在体内实验中，热成形术后6周，哮喘控制有所改善（通过哮喘控制问卷-6测量;MD0.7,95％CI 0.1-1.3; p = 0.03），气道平滑肌质量下降（绝对中位数减少5％，四分位数间距（IQR）0-10; p = 0.03）和上皮完整性增高（14％，IQR 6-29; p = 0.007）。后两种结果均表明其未改善哮喘控制。综合的体内和体外计算机模拟实验，表明热成形术后气道平滑肌的减少不能完全归因于快速加热，并且这种减少也不能使哮喘控制得到更多的改善。
In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss
Chernyavsky, I. L. et al. Eur Respir J. 2018 May 28.
Abstract
Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival. Airway smooth muscle and bronchial epithelial cells were exposed to media (37-70 degrees C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma. In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to >/=65 degrees C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60 degrees C in airways with an inner radius of approximately 4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1-1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0-10; p=0.03) and epithelial integrity increased (14%, IQR 6-29; p=0.007). Neither of the latter two outcomes was related to improved asthma control. Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control.
支气管热成形术是治疗哮喘的一种方法。目前尚不清楚，当气道壁暴露于可影响细胞存活的温度时，能对组织病理学产生怎样的影响。我们将气道平滑肌和支气管上皮细胞暴露于培养基（37-70℃）10秒以模拟热成形术。在体外计算机模拟实验中，我们开发了热成形术后气道热分布的数学模型。在体内实验中，我们研究了14名重症哮喘患者气道成形术前后的气道平滑肌质量和上皮完整性变化。将培养基加热至≥65℃时，体外气道平滑肌和上皮细胞数量显着减少。计算机模拟显示在大气道中热分布差异较大，其中低于10％的内半径约4毫米气道壁被加热至大于60摄氏度。在体内实验中，热成形术后6周，哮喘控制有所改善（通过哮喘控制问卷-6测量;MD0.7,95％CI 0.1-1.3; p = 0.03），气道平滑肌质量下降（绝对中位数减少5％，四分位数间距（IQR）0-10; p = 0.03）和上皮完整性增高（14％，IQR 6-29; p = 0.007）。后两种结果均表明其未改善哮喘控制。综合的体内和体外计算机模拟实验，表明热成形术后气道平滑肌的减少不能完全归因于快速加热，并且这种减少也不能使哮喘控制得到更多的改善。
（复旦大学附属中山医院呼吸内科 包晨 摘译 杨冬 审校）
（Chernyavsky, I. L. et al. Eur Respir J. 2018 May 28.）
（Chernyavsky, I. L. et al. Eur Respir J. 2018 May 28.）
In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss
Chernyavsky, I. L. et al. Eur Respir J. 2018 May 28.
Abstract
Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival. Airway smooth muscle and bronchial epithelial cells were exposed to media (37-70 degrees C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma. In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to >/=65 degrees C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60 degrees C in airways with an inner radius of approximately 4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1-1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0-10; p=0.03) and epithelial integrity increased (14%, IQR 6-29; p=0.007). Neither of the latter two outcomes was related to improved asthma control. Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control.
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嗜酸粒细胞性哮喘与非嗜酸粒细胞哮喘中穿透素水平
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哮喘患儿肺功能的整合转录组学和代谢组学研究
