识别预测 COPD 肺部恶化的痰液生物标志物。
Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD.
机构信息
Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.
出版信息
Chest. 2022 May;161(5):1239-1249. doi: 10.1016/j.chest.2021.10.049. Epub 2021 Nov 18.
BACKGROUND
Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets.
RESEARCH QUESTION
Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations?
STUDY DESIGN AND METHODS
We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations.
RESULTS
Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.
INTERPRETATION
Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT01969344; URL: www.
CLINICALTRIALS
gov.
背景
更好地理解与 COPD 气道病理生理特征相关的通路，将确定新的预测生物标志物和新的治疗靶点。
研究问题
COPD 患者气道中哪些生理通路发生改变，并可预测加重？
研究设计和方法
我们应用了与黏液水合和炎症相关的代谢组学生物标志物的质谱分析面板，对来自多中心亚人群和 COPD 中间结局研究的痰进行分析。评估 COPD 患者痰液中升高的生物标志物与 COPD 疾病严重程度的测量值及其预测未来加重的能力之间的关系。
结果
分析了 980 例患者的痰液上清液：77 例健康不吸烟者，341 例肺功能正常的吸烟者和 562 例 COPD 患者（178 例 Global Initiative on Chronic Obstructive Lung Disease [GOLD] 1 期疾病，303 例 GOLD 2 期疾病，81 例 GOLD 3 期疾病）。多个通路的生物标志物在 COPD 中升高，并与痰中性粒细胞计数相关。在最显著的分析物中（假发现率为 0.1）有唾液酸、次黄嘌呤、黄嘌呤、甲基硫代腺苷、腺嘌呤和谷胱甘肽。唾液酸和次黄嘌呤与疾病严重程度的测量值密切相关，这些生物标志物的升高与加重时间缩短和未来加重预测模型的改善相关。
解释
生物标志物评估提示与 COPD 气道病理生理特征相关的黏液水合、腺苷代谢、蛋氨酸回收和氧化应激通路。靶向这些通路的治疗方法可能对 COPD 有益，并且添加痰液可溶性相生物标志物的简单模型可改善对肺部加重的预测。
临床试验注册
ClinicalTrials.gov；编号：NCT01969344；网址：www.clinicaltrials.gov。
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