Cairncross Alvenia, Jones Robyn L, Elliot John G, McFawn Peter K, James Alan L, Noble Peter B
School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia.
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
J Appl Physiol (1985). 2020 Apr 1;128(4):757-767. doi: 10.1152/japplphysiol.00439.2019. Epub 2020 Feb 27.
The volume fraction of extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and/or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed ( = 12) or "fixed" obstructed ( = 6) on the basis of preoperative spirometry. The response to a DI, assessed by the ratio of isovolumic flows from maximal and partial inspirations (M/P), was also measured preoperatively. M/P was reduced in the obstructed group ( = 0.02). Postoperatively, bronchial segments were obtained from resected tissue, and luminal narrowing to acetylcholine and bronchodilation to simulated DI were assessed in vitro. Airway wall dimensions and the volume fraction of ECM within the ASM were quantified. Maximal airway narrowing to acetylcholine ( = 0.01) and the volume fraction of ECM within the ASM layer ( = 0.02) were increased in the obstructed group, without a change in ASM thickness. Whereas bronchodilation to simulated DI in vitro was not different between obstructed and unobstructed groups, it was correlated with increased M/P (bronchodilation/less bronchoconstriction) in vivo ( = 0.03). The volume fraction of ECM was inversely related to forced expiratory volume in 1 s FEV %predicted ( = 0.04) and M/P ( = 0.01). Results show that in subjects with fixed airflow obstruction the mechanical behavior of the airway wall is altered and there is a contemporaneous shift in the structural composition of the ASM layer. Cartilaginous airways from subjects with fixed airflow obstruction have an increase in the volume fraction of extracellular matrix within the airway smooth muscle layer. These airways are also intrinsically more reactive to a contractile stimulus, which is expected to contribute to airway hyperresponsiveness in this population, often attributed to geometric mechanisms. In view of these results, we speculate on how changes in extracellular matrix may impact airway mechanics.
在存在固定性气流受限的受试者中，气道平滑肌（ASM）层内细胞外基质（ECM）的体积分数增加。我们推测，ASM层内ECM的变化将在诱导收缩期间和/或响应诸如深吸气（DI）等外部施加的应力时影响力的传递。受试者为接受肺切除术的患者，根据术前肺活量测定将其分为无气流受限组（n = 12）或“固定性”气流受限组（n = 6）。术前还测量了通过最大吸气和部分吸气的等容流量之比（M/P）评估的对DI的反应。气流受限组的M/P降低（P = 0.02）。术后，从切除的组织中获取支气管节段，并在体外评估对乙酰胆碱的管腔狭窄和对模拟DI的支气管扩张情况。对气道壁尺寸和ASM内ECM的体积分数进行了量化。气流受限组对乙酰胆碱的最大气道狭窄（P = 0.01）和ASM层内ECM的体积分数（P = 0.02）增加，而ASM厚度无变化。虽然在体外模拟DI时气流受限组和无气流受限组之间的支气管扩张无差异，但它与体内M/P增加（支气管扩张/支气管收缩减轻）相关（P = 0.03）。ECM的体积分数与1秒用力呼气量占预计值的百分比（FEV1%predicted）（P = 0.04）和M/P（P = 0.01）呈负相关。结果表明，在存在固定性气流受限的受试者中，气道壁的力学行为发生改变，并且ASM层的结构组成同时发生变化。存在固定性气流受限的受试者的软骨性气道中，气道平滑肌层内细胞外基质的体积分数增加。这些气道对收缩刺激本质上也更具反应性，这预计会导致该人群的气道高反应性，而气道高反应性通常归因于几何机制。鉴于这些结果，我们推测细胞外基质的变化可能如何影响气道力学。
