Dubsky S, Zosky G R, Perks K, Samarage C R, Henon Y, Hooper S B, Fouras A
Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Victoria, Australia;
School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
J Appl Physiol (1985). 2017 Mar 1;122(3):503-510. doi: 10.1152/japplphysiol.00476.2016. Epub 2016 Dec 29.
Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo. Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.
为了解肺部的区域反应，需要有关原位支气管收缩期间气道直径分布的详细信息。先前使用计算机断层扫描（CT）的成像研究测量了气道直径以及对支气管收缩剂的反应变化，但所采用的手动测量方法严重限制了每个受试者测量的气道数量。因此，气道反应的详细分布和异质性尚不清楚。我们开发并应用了动态成像和先进的图像处理方法，以在体内量化和比较数百条气道。基于CT的该方法应用于静脉注射乙酰甲胆碱（MCh）期间对屋尘螨致敏的小鼠和对照小鼠。在MCh激发前后测量气道直径，比较结果显示了机械通气期间整个肺部气道反应的分布。采用强迫振荡测试来测量肺力学的整体反应。我们发现反应存在明显的异质性，所有气道大小均出现气道反常扩张。气道反常扩张的概率随基线气道直径减小而降低，且不受先前存在的炎症影响。结果证实了将肺视为一个完整的相互连接系统而非独立单元集合的重要性。希望反应分布测量有助于阐明体内导致气道反应异质性的机制。有关原位支气管收缩期间气道直径分布的信息对于理解肺部的区域反应至关重要。我们开发了一种成像方法，用于在小鼠支气管收缩期间在体内量化和比较数百条气道的大小。结果显示气道收缩和反常扩张均存在很大的异质性，证实了将肺视为相互连接系统而非独立单元集合的重要性。
