Elevation in lung volume and preventing catastrophic airway closure in asthmatics during bronchoconstriction

BackgroundAsthma exacerbations cause lung hyperinflation, elevation in load to inspiratory muscles, and decreased breathing capacity that, in severe cases, may lead to inspiratory muscle fatigue and respiratory failure. Hyperinflation has been attributed to a passive mechanical origin; a respiratory system time-constant too long for full exhalation. However, because the increase in volume is also concurrent with activation of inspiratory muscles during exhalation it is unclear whether hyperinflation in broncho-constriction is a passive phenomenon or is actively controlled to avoid airway closure.MethodsUsing CT scanning, we measured the distensibility of individual segmental airways relative to that of their surrounding parenchyma in seven subjects with asthma and nine healthy controls. With this data we tested whether the elevation of lung volume measured after methacholine (MCh) provocation was associated with airway narrowing, or to the volume required to preventing airway closure. We also tested whether the reduction in FVC post-MCh could be attributed to gas trapped behind closed segmental airways.FindingsThe changes in lung volume by MCh in subjects with and without asthma were inversely associated with their reduction in average airway lumen. This finding would be inconsistent with hyperinflation by passive elevation of airway resistance. In contrast, the change in volume of each subject was associated with the lung volume estimated to cause the closure of the least stable segmental airway of his/her lungs. In addition, the measured drop in FVC post MCh was associated with the estimated volume of gas trapped behind closed segmental airways at RV.ConclusionsOur data supports the concept that hyperinflation caused by MCh-induced bronchoconstriction is the result of an actively controlled process where parenchymal distending forces on airways are increased to counteract their closure. To our knowledge, this is the first imaging-based study that associates inter-subject differences in whole lung behavior with the interdependence between individual airways and their surrounding parenchyma.背景：哮喘急性加重可引发肺过度充气、吸气肌负荷升高及呼吸能力下降，严重时可导致吸气肌疲劳与呼吸衰竭。既往认为过度充气源于被动机械机制：呼吸系统时间常数过长，无法完成完全呼气。但由于呼气过程中吸气肌也会被激活，目前尚不清楚支气管收缩时的肺过度充气究竟属于被动现象，还是为避免气道闭合而主动调控的过程。 方法：本研究纳入7名哮喘患者与9名健康对照者，利用计算机断层扫描（CT，Computed Tomography）测量了个体节段性气道与其周围肺实质的顺应性差异。基于该实验数据，我们检验了乙酰甲胆碱（MCh，methacholine）激发试验后测得的肺容积升高，是否与气道狭窄相关，抑或是与预防气道闭合所需的容积有关。同时我们还验证了MCh激发后用力肺活量（FVC，forced vital capacity）的下降是否可归因于闭合节段气道后方潴留的气体。 结果：无论哮喘患者还是健康对照者，MCh诱导的肺容积变化与平均气道管腔内径的缩小呈负相关。这一发现与气道阻力被动升高导致的过度充气现象不符。与之相反，每名受试者的肺容积变化，与其可导致肺部最不稳定节段气道闭合的预估肺容积显著相关。此外，MCh激发后测得的FVC下降值，与残气量（RV，residual volume）水平下闭合节段气道后方预估潴留的气体体积相关。 结论：本研究数据支持如下观点：MCh诱导的支气管收缩所引发的过度充气，是一种主动调控的过程——通过增强气道周围肺实质的牵张力，以对抗气道闭合。据我们所知，本研究是首个基于影像学手段，将全肺行为的个体间差异与单个气道及其周围肺实质的相互依存关系相关联的研究。