Department of Medicine, Division of Respirology, McMaster University, Hamilton, Canada.
Respir Res. 2014 Apr 14;15(1):42. doi: 10.1186/1465-9921-15-42.
Chronic obstructive pulmonary disease (COPD) is known to greatly affect ventilation (V) and perfusion (Q) of the lung through pathologies such as inflammation and emphysema. However, there is little direct evidence regarding how these pathologies contribute to the V/Q mismatch observed in COPD and models thereof. Also, little is known regarding how smoking cessation affects V/Q relationships after inflammation and airspace enlargement have become established. To this end, we have quantified V/Q on a per-voxel basis using single photon emission computed tomography (SPECT) in mouse models of COPD and lung obstruction.
Three distinct murine models were used to investigate the impact of different pathologies on V/Q, as measured by SPECT. Lipopolysaccharide (LPS) was used to produce neutrophilic inflammation, porcine pancreatic elastase (PPE) was used to produce emphysema, and long-term cigarette smoke (CS) exposure and cessation were used to investigate the combination of these pathologies.
CS exposure resulted in an increase in mononuclear cells and neutrophils, an increase in airspace enlargement, and an increase in V/Q mismatching. The inflammation produced by LPS was more robust and predominantly neutrophilic, compared to that of cigarette smoke; nevertheless, inflammation alone caused V/Q mismatching similar to that seen with long-term CS exposure. The emphysematous lesions caused by PPE administration were also capable of causing V/Q mismatch in the absence of inflammation. Following CS cessation, inflammatory cell levels returned to those of controls and, similarly, V/Q measures returned to normal despite evidence of persistent mild airspace enlargement.
Both robust inflammation and extensive airspace enlargement, on their own, were capable of producing V/Q mismatch. As CS cessation resulted in a return of V/Q mismatching and inflammatory cell counts to control levels, lung inflammation is likely a major contributor to V/Q mismatch observed in the cigarette smoke exposure model as well as in COPD patients. This return of V/Q mismatching to control values also took place in the presence of mild airspace enlargement, indicating that emphysematous lesions must be of a larger volume before affecting the lung significantly. Early smoking cessation is therefore critical before emphysema has an irreversible impact on gas exchange.
慢性阻塞性肺疾病（COPD）已知通过炎症和肺气肿等病理学极大地影响肺部的通气（V）和灌注（Q）。然而，关于这些病理学如何导致 COPD 及其模型中观察到的 V/Q 不匹配，几乎没有直接证据。此外，关于吸烟停止后炎症和气腔扩大已经建立后如何影响 V/Q 关系知之甚少。为此，我们使用单光子发射计算机断层扫描（SPECT）在 COPD 和肺阻塞的小鼠模型中逐像素量化 V/Q。
使用三种不同的小鼠模型来研究不同病理学对 V/Q 的影响，方法是通过 SPECT 测量。脂多糖（LPS）用于产生中性粒细胞炎症，猪胰弹性蛋白酶（PPE）用于产生肺气肿，长期吸烟（CS）暴露和停止用于研究这些病理学的组合。
CS 暴露导致单核细胞和中性粒细胞增加，气腔扩大增加，V/Q 不匹配增加。与吸烟相比，LPS 产生的炎症更强烈且主要是中性粒细胞；然而，单独的炎症也导致类似于长期 CS 暴露的 V/Q 不匹配。PPE 给药引起的肺气肿病变也能够在没有炎症的情况下引起 V/Q 不匹配。CS 停止后，炎性细胞水平恢复到对照水平，同样，尽管存在持续的轻度气腔扩大，但 V/Q 测量也恢复正常。
强烈的炎症和广泛的气腔扩大本身就能够产生 V/Q 不匹配。由于 CS 停止导致 V/Q 不匹配和炎症细胞计数恢复到对照水平，因此肺部炎症可能是吸烟暴露模型以及 COPD 患者中观察到的 V/Q 不匹配的主要原因。V/Q 不匹配恢复到对照值也发生在轻度气腔扩大的情况下，这表明肺气肿病变必须具有更大的体积才能对肺部产生重大影响。因此，在肺气肿对气体交换产生不可逆转的影响之前，早期戒烟至关重要。
