School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, Perth, Western Australia, Australia.
J Appl Physiol (1985). 2013 May 15;114(10):1460-71. doi: 10.1152/japplphysiol.01489.2012. Epub 2013 Mar 14.
The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma (n = 5) or had no history of asthma (n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM (P = 0.014), greater maximal airway narrowing under static conditions (P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer (r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group (P = 0.0001) and the group with a history of asthma (P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing (P = 0.02; r = -0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.
本研究初步探讨了气道壁的结构/功能异常与既往哮喘患者气道过度狭窄和深吸气（DI）时支气管扩张反应降低的关系。支气管节段取自接受手术的患者，这些手术主要是为了切除肺部肿瘤。研究对象报告有既往医生诊断的哮喘（n = 5）或无哮喘病史（n = 8）。通过乙酰胆碱刺激评估离体气道狭窄反应，以确定最大支气管收缩和敏感性，分别在静态条件下和模拟潮气量和 DI 操作下进行。固定气道节段用于测量气道壁尺寸，特别是气道平滑肌（ASM）层。既往哮喘史患者的气道 ASM 增加（P = 0.014），静态条件下最大气道狭窄增加（P = 0.003），但敏感性无变化。最大气道狭窄与 ASM 层面积呈正相关（r = 0.58，P = 0.039）。在周期性振荡气道中，DI 可使对照组（P = 0.0001）和既往哮喘组（P = 0.001）气道产生支气管扩张。虽然随着气道狭窄的增加，DI 时的支气管扩张作用减弱（P = 0.02；r = -0.64），但当气道狭窄程度相匹配时，两组间 DI 时的支气管扩张程度无差异。结果表明，哮喘中 ASM 质量增加导致体内气道过度狭窄。相比之下，哮喘时的气道壁在 DI 期间可能对机械拉伸有正常的反应。我们提出，哮喘中最大气道狭窄增加和 DI 时支气管扩张反应降低是独立的。
