Verbanck Sylvia A B, Foy Brody H
Respiratory Division, University Hospital (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Center for Systems Biology , Massachusetts General Hospital, Boston, Massachusetts.
J Appl Physiol (1985). 2022 Apr 1;132(4):947-955. doi: 10.1152/japplphysiol.00687.2021. Epub 2022 Feb 17.
We have previously identified bronchial generations 5-7 as the locus of maximum contribution to the convective portion of the phase III slope in computed tomography (CT)-based lung models of patients with asthma. In the present study, we examined how phase III slope is generated locally, by specifically interrogating at individual branch points, the necessary condition for a phase III slope to occur: some degree of convective flow sequencing between any two daughter branches that have a heterogeneity in gas washout concentration between them. Flow sequencing at individual branch points showed a wide range of values, including branch points where flow sequencing was such that phase III slopes were negative locally. Yet, the net effect in the 24 bronchial trees that we studied was that flow sequencing between pairs of less and better ventilated units most frequently drove positive phase III slopes in generations 5-7. By investigating the link of local flow sequencing between any two daughter branches to the corresponding heterogeneity of mechanical lung properties, heterogeneity of compliance was seen to be a major determinant of flow sequencing. In these bronchial structures, compliance heterogeneity was essentially brought about by volume asymmetry resulting from terminating pathways within the three-dimensional (3-D) confines of the lung contours. We conclude that the serial and parallel combination of lung mechanical properties at individual branch points in an asymmetrical branching network generates flow sequencing in mid-range conductive airways, leading to a positive at-mouth phase III slope. Conceptually, the simplest way to obtain a sloping phase III during a washout exhalation is when there is convective flow sequencing between two lung units, such that the better ventilated unit contributes relatively more to exhaled flow at the beginning of phase III in the exhalation. Here, we show how compliance heterogeneity across the serial and parallel arrangement of branch points in bronchial trees of patients with asthma leads to flow sequencing, and thus phase III slopes of positive sign at the patient's mouth.
我们之前已确定，在基于计算机断层扫描（CT）的哮喘患者肺部模型中，支气管第5 - 7级是对第三阶段斜率对流部分贡献最大的部位。在本研究中，我们通过专门研究各个分支点，来探究第三阶段斜率是如何在局部产生的，这是第三阶段斜率出现的必要条件：在任意两个气体洗脱浓度存在异质性的子分支之间存在一定程度的对流流动排序。各个分支点的流动排序显示出广泛的值，包括流动排序使得局部第三阶段斜率为负的分支点。然而，在我们研究的24个支气管树中，总体效果是通气较差和较好的单元对之间的流动排序最常导致第5 - 7级出现正的第三阶段斜率。通过研究任意两个子分支之间的局部流动排序与肺机械特性相应异质性的联系，发现顺应性异质性是流动排序的主要决定因素。在这些支气管结构中，顺应性异质性基本上是由肺轮廓三维（3 - D）范围内终止路径导致的体积不对称引起的。我们得出结论，不对称分支网络中各个分支点处肺机械特性的串联和并联组合在中等范围的传导气道中产生流动排序，导致口部出现正的第三阶段斜率。从概念上讲，在洗脱呼气过程中获得倾斜的第三阶段的最简单方法是当两个肺单元之间存在对流流动排序时，这样通气较好的单元在呼气第三阶段开始时对呼出气流的贡献相对更大。在这里，我们展示了哮喘患者支气管树中分支点的串联和并联排列上的顺应性异质性如何导致流动排序，从而在患者口部产生正号的第三阶段斜率。
