Division of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom.
Royal Brompton Hospital, Respiratory Medicine, London, United Kingdom.
Am J Physiol Lung Cell Mol Physiol. 2021 Jan 1;320(1):L73-L83. doi: 10.1152/ajplung.00099.2020. Epub 2020 Nov 4.
Despite advances in the pathophysiology of chronic obstructive pulmonary disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD, but their association to COPD disease severity remains unknown. We analyzed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from 62 patients with mild to very severe COPD (51% male; mean age: 65.9 yr). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, and exercise testing), and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF [leukocyte, polymorphonuclear leukocyte (PMN; i.e., neutrophil), monocyte, epithelial, and platelet MVs] and plasma (leukocyte, PMN, monocyte, and endothelial MVs) and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including forced expiratory volume in 1 s, modified Medical Research Council dyspnea score, 6-min walk test, hyperinflation, and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically relevant disease severity indexes. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.
尽管在慢性阻塞性肺疾病（COPD）的病理生理学方面取得了进展，但仍然缺乏有助于临床管理的生化标志物。微泡（MVs）已被牵连到包括 COPD 在内的炎症性疾病的病理生理学中，但它们与 COPD 疾病严重程度的关联尚不清楚。我们分析了来自 62 名轻度至重度 COPD 患者（51%为男性；平均年龄：65.9 岁）的血浆和支气管肺泡灌洗液（BALF）中的不同 MV 群体。这些患者接受了全面的临床评估（症状评分、肺功能和运动测试），并评估了 MV 作为疾病严重程度的临床标志物的能力。我们成功地在 BALF 中鉴定了各种 MV 亚型群体[白细胞、多形核白细胞（PMN；即中性粒细胞）、单核细胞、上皮细胞和血小板 MV]和血浆（白细胞、PMN、单核细胞和内皮 MV），并将每种 MV 群体与疾病严重程度进行了比较。BALF 中性粒细胞 MV 是唯一与临床评估评分相关的群体，包括 1 秒用力呼气量、改良医学研究委员会呼吸困难评分、6 分钟步行试验、过度充气和气体转移。BALF 中性粒细胞 MV 与 BODE 指数也有强烈的相关性，而不是中性粒细胞数量。我们首次对 COPD 患者 BALF/血浆中的 MV 谱进行了全面评估。我们证明，BALF 中性粒细胞衍生的 MV 水平与许多关键的功能和临床相关的疾病严重程度指标相关，这是独特的。我们的研究结果表明，BALF 中性粒细胞 MV 具有成为 COPD 生物标志物的潜力，它将 COPD 的一个关键病理生理学机制（肺泡内中性粒细胞激活）与临床严重程度/结局紧密联系起来。
