Airway Mucin Concentration as a Marker of Chronic Bronchitis.
Airway Mucin Concentration as a Marker of Chronic Bronchitis.
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DOI：
10.1056/nejmoa1701632
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发表时间：
2017-09-07
期刊：
影响因子：
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通讯作者：
Boucher RC
中科院分区：
文献类型：
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作者：
Kesimer M;Ford AA;Ceppe A;Radicioni G;Cao R;Davis CW;Doerschuk CM;Alexis NE;Anderson WH;Henderson AG;Barr RG;Bleecker ER;Christenson SA;Cooper CB;Han MK;Hansel NN;Hastie AT;Hoffman EA;Kanner RE;Martinez F;Paine R 3rd;Woodruff PG;O'Neal WK;Boucher RC
慢性阻塞性肺疾病（COPD）的特点是慢性支气管炎和肺气肿成分。在一个生物物理模型中，假设气道表面黏液的浓度是控制健康人黏液运输与黏液阻塞性肺疾病患者黏液运输停止的关键变量。在这个模型下，假设高黏液蛋白浓度产生痰和疾病进展，这是慢性支气管炎的特征。我们通过对参与者进行问卷调查、胸部断层扫描、肺活量测定和诱导痰检查，对来自COPD研究亚群和中间结果测量（SPIROMICS）的917名参与者的COPD状态进行了表征。用排色层析和折射法测定痰液中总粘蛋白浓度。在148名参与者中，呼吸道分泌的粘蛋白MUC5AC和MUC5B通过质谱法进行了定量。来自慢性支气管炎问卷调查的数据和痰中总粘蛋白浓度的数据也在一个独立的94名参与者队列中进行了分析。目前或曾经吸烟的严重慢性阻塞性肺病患者的平均（±SE）总粘蛋白浓度高于从未吸烟的对照组（3166±402比1515±152 μg /毫升），每年两次或两次以上呼吸恶化的参与者的平均（±SE）总粘蛋白浓度高于无呼吸恶化的参与者（4194±878比2458±113 μg /毫升）。重度COPD患者中MUC5B和MUC5AC的绝对浓度分别是从未吸烟的对照组的3倍和10倍。对总黏液蛋白浓度与慢性支气管炎诊断之间的相关性进行受体-工作特征曲线分析，SPIROMICS队列的曲线下面积为0.72(95%可信区间[CI]， 0.65至0.79)，独立队列的曲线下面积为0.82（95%可信区间[CI]， 0.73至0.92）。气道粘蛋白浓度可能定量慢性支气管炎病理生理级联反应的一个关键组成部分，该级联反应产生痰并介导疾病严重程度。旨在探索痰中总粘蛋白浓度作为慢性支气管炎的诊断生物标志物和治疗靶点的研究似乎是有必要的。（由国家心脏、肺和血液研究所等机构资助。）
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis. We characterized the COPD status of 917 participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) using questionnaires administered to participants, chest tomography, spirometry, and examination of induced sputum. Total mucin concentrations in sputum were measured with the use of size-exclusion chromatography and refractometry. In 148 of these participants, the respiratory secreted mucins MUC5AC and MUC5B were quantitated by means of mass spectrometry. Data from chronicbronchitis questionnaires and data on total mucin concentrations in sputum were also analyzed in an independent 94-participant cohort. Mean (±SE) total mucin concentrations were higher in current or former smokers with severe COPD than in controls who had never smoked (3166±402 vs. 1515±152 μg per milliliter) and were higher in participants with two or more respiratory exacerbations per year than in those with zero exacerbations (4194±878 vs. 2458±113 μg per milliliter). The absolute concentrations of MUC5B and MUC5AC in current or former smokers with severe COPD were approximately 3 times as high and 10 times as high, respectively, as in controls who had never smoked. Receiver-operating-characteristic curve analysis of the association between total mucin concentration and a diagnosis of chronic bronchitis yielded areas under the curve of 0.72 (95% confidence interval [CI], 0.65 to 0.79) for the SPIROMICS cohort and 0.82 (95% CI, 0.73 to 0.92) for the independent cohort. Airway mucin concentrations may quantitate a key component of the chronic bronchitis pathophysiologic cascade that produces sputum and mediates disease severity. Studies designed to explore total mucin concentrations in sputum as a diagnostic biomarker and therapeutic target for chronic bronchitis appear to be warranted. (Funded by the National Heart, Lung, and Blood Institute and others.)