Centre for Animal Biotechnology, Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia.
PLoS One. 2011;6(12):e28740. doi: 10.1371/journal.pone.0028740. Epub 2011 Dec 12.
There is increasing evidence that the small airways contribute significantly to the pathophysiology of asthma. However, due to the difficulty in accessing distal lung regions in clinical settings, functional changes in the peripheral airways are often overlooked in studies of asthmatic patients. The aim of the current study was to characterize progressive changes in small airway function in sheep repeatedly challenged with house dust mite (HDM) allergen.
METHODOLOGY/PRINCIPAL FINDINGS: Four spatially separate lung segments were utilized for HDM challenges. The right apical, right medial, right caudal and left caudal lung segments received 0, 8, 16 and 24 weekly challenges with HDM respectively. A wedged-bronchoscope technique was used to assess changes in peripheral resistance (R(p)) at rest, and in response to specific and non-specific stimuli throughout the trial. Allergen induced inflammatory cell infiltration into bronchoalveolar lavage and increases in R(p) in response to HDM and methacholine were localized to treated lung segments, with no changes observed in adjacent lung segments. The acute response to HDM was variable between sheep, and was significantly correlated to airway responsiveness to methacholine (r(s) = 0.095, P<0.01). There was no correlation between resting R(p) and the number of weeks of HDM exposure. Nor was there a correlation between the magnitude of early-phase airway response and the number of HDM-challenges.
Our findings indicate that airway responses to allergic and non-allergic stimuli are localized to specific treated areas of the lung. Furthermore, while there was a decline in peripheral airway function with HDM exposure, this decrease was not correlated with the length of allergen challenge.
越来越多的证据表明,小气道对哮喘的病理生理学有重要贡献。然而,由于在临床环境中难以进入远端肺部区域,哮喘患者的外周气道功能变化在研究中经常被忽视。本研究的目的是描述绵羊反复接受屋尘螨(HDM)变应原挑战时小气道功能的进行性变化。
方法/主要发现:使用 4 个空间上分离的肺段进行 HDM 挑战。右尖段、右中段、右后段和左后段肺段分别接受 0、8、16 和 24 次每周的 HDM 挑战。使用楔形支气管镜技术评估整个试验过程中休息时和对特定和非特定刺激时外周阻力(R(p))的变化。HDM 和乙酰甲胆碱引起的炎性细胞浸润到支气管肺泡灌洗液和 R(p)的增加局限于治疗的肺段,相邻肺段没有变化。HDM 的急性反应在绵羊之间是可变的,并且与乙酰甲胆碱的气道反应性显著相关(r(s) = 0.095,P<0.01)。HDM 暴露的休息时 R(p)与 HDM 暴露的周数之间没有相关性。早期气道反应的幅度与 HDM 挑战的次数之间也没有相关性。
我们的发现表明,气道对变应原和非变应原刺激的反应局限于肺部的特定治疗区域。此外,虽然 HDM 暴露后外周气道功能下降,但这种下降与变应原暴露时间无关。