肺计算模型和小气道在哮喘中的作用
2019/06/13
摘要
背景：哮喘以小气道内的疾病为特征。一些研究表明强迫振荡技术在5Hz减去20Hz（R5-R20）时导出的电阻用于测量小气道疾病，但迄今为止对该测量方法仍有待验证。
方法：基于患者的完整传导气道模型通过CT扫描生成，以模拟气道树的不同水平上的不同程度的气道狭窄对强迫振荡R5-R20（n = 31）的影响。计算模型与哮喘队列（n = 177）中的回归模型相结合，以模拟小气道狭窄对哮喘控制和生活质量的影响。利用两个相似设计的随机安慰剂对照生物学试验（n = 137）的汇总数据，使用计算模型预测2型靶向生物制剂对小气道狭窄的影响。
结果：模拟结果表明，小气道变窄对R5-R20的影响比大气道变窄的影响更大，并且与哮喘控制和哮喘生活质量明显恶化相关（超过约40％的狭窄阈值），高于最小临床重要差异。在合并试验中观察到的对R5-R20的治疗效果相当于等于预测的约40％的小气道狭窄逆转。
结论：我们已经通过计算模型证明，强迫振荡R5-R20是对小气道解剖狭窄的直接测量，小气道狭窄对哮喘控制和生活质量都有显著影响，并且可能被生物制剂修改。
Lung Computational Models and the Role of the Small Airways in Asthma.
Foy BH, Soares M, Bordas R, Richardson M, Bell A, Singapuri A, Hargadon B, Brightling C, Burrowes K, Kay D, Owers-Bradley J, Siddiqui S.
Abstract
BACKGROUND:Asthma is characterised by disease within the small airways. Several studies have suggested that forced oscillation technique derived resistance at 5Hz minus 20Hz (R5-R20) is measure of small airways disease, however there has been limited validation of this measurement to date.
METHODS:Patient based complete conducting airway models were generated from CT scans to simulate the impact of different degrees of airway narrowing at different levels of the airway tree on forced oscillation R5-R20 (n=31). The computational models were coupled with regression models in an asthmatic cohort (n=177), to simulate the impact of small airway narrowing on asthma control and quality of life. The computational models were used to predict the impact on small airway narrowing of type-2 targeting biologics using pooled data from two similarly design randomised placebo control biologic trials (n=137).
RESULTS:Simulations demonstrated that narrowing of the small airways had a greater impact on R5-R20 than narrowing of the larger airways and was associated (above a threshold of approximately 40% narrowing) with marked deterioration in both asthma control and asthma quality of life, above the minimal clinical important difference. The observed treatment effect on R5-R20 in the pooled trials equated to a predicted small airway narrowing reversal of approximately 40%.
CONCLUSIONS:We have demonstrated using computational modelling that forced oscillation R5-R20 is a direct measure of anatomical narrowing in the small airways, that small airway narrowing has a marked impact on both asthma control and quality of life and may be modified by biologics.
背景：哮喘以小气道内的疾病为特征。一些研究表明强迫振荡技术在5Hz减去20Hz（R5-R20）时导出的电阻用于测量小气道疾病，但迄今为止对该测量方法仍有待验证。
方法：基于患者的完整传导气道模型通过CT扫描生成，以模拟气道树的不同水平上的不同程度的气道狭窄对强迫振荡R5-R20（n = 31）的影响。计算模型与哮喘队列（n = 177）中的回归模型相结合，以模拟小气道狭窄对哮喘控制和生活质量的影响。利用两个相似设计的随机安慰剂对照生物学试验（n = 137）的汇总数据，使用计算模型预测2型靶向生物制剂对小气道狭窄的影响。
结果：模拟结果表明，小气道变窄对R5-R20的影响比大气道变窄的影响更大，并且与哮喘控制和哮喘生活质量明显恶化相关（超过约40％的狭窄阈值），高于最小临床重要差异。在合并试验中观察到的对R5-R20的治疗效果相当于等于预测的约40％的小气道狭窄逆转。
结论：我们已经通过计算模型证明，强迫振荡R5-R20是对小气道解剖狭窄的直接测量，小气道狭窄对哮喘控制和生活质量都有显著影响，并且可能被生物制剂修改。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2019 May 18. doi: 10.1164/rccm.201812-2322OC. [Epub ahead of print])
(Am J Respir Crit Care Med. 2019 May 18. doi: 10.1164/rccm.201812-2322OC. [Epub ahead of print])
Lung Computational Models and the Role of the Small Airways in Asthma.
Foy BH, Soares M, Bordas R, Richardson M, Bell A, Singapuri A, Hargadon B, Brightling C, Burrowes K, Kay D, Owers-Bradley J, Siddiqui S.
Abstract
BACKGROUND:Asthma is characterised by disease within the small airways. Several studies have suggested that forced oscillation technique derived resistance at 5Hz minus 20Hz (R5-R20) is measure of small airways disease, however there has been limited validation of this measurement to date.
METHODS:Patient based complete conducting airway models were generated from CT scans to simulate the impact of different degrees of airway narrowing at different levels of the airway tree on forced oscillation R5-R20 (n=31). The computational models were coupled with regression models in an asthmatic cohort (n=177), to simulate the impact of small airway narrowing on asthma control and quality of life. The computational models were used to predict the impact on small airway narrowing of type-2 targeting biologics using pooled data from two similarly design randomised placebo control biologic trials (n=137).
RESULTS:Simulations demonstrated that narrowing of the small airways had a greater impact on R5-R20 than narrowing of the larger airways and was associated (above a threshold of approximately 40% narrowing) with marked deterioration in both asthma control and asthma quality of life, above the minimal clinical important difference. The observed treatment effect on R5-R20 in the pooled trials equated to a predicted small airway narrowing reversal of approximately 40%.
CONCLUSIONS:We have demonstrated using computational modelling that forced oscillation R5-R20 is a direct measure of anatomical narrowing in the small airways, that small airway narrowing has a marked impact on both asthma control and quality of life and may be modified by biologics.
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低于冰点空气及多种触发因素与慢性咳嗽中哮喘发作密切相关
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成纤维细胞形成的纤维胶原组织缺陷有助于哮喘患者气道重塑
