1 Lung Investigation Unit, Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
2 Department of Respiratory Medicine, Royal Devon & Exeter Hospital, Exeter, United Kingdom.
Am J Respir Crit Care Med. 2019 May 15;199(10):1195-1204. doi: 10.1164/rccm.201810-1860SO.
The pathology and impact of chronic obstructive pulmonary disease (COPD) results from an abnormal inflammatory process resulting in tissue damage with ineffective repair in response to toxic inhalants (especially cigarette smoke). Identification of mechanisms provides the opportunity to develop new therapies and a personalized approach to management. The collection of multiple genetic and detailed biochemical data from small and large patient cohorts has led to an explosion of studies investigating biomarkers to achieve these aims. Despite widespread enthusiasm and many statistically significant associations, the interpretation of COPD biomarker results requires thought and leaves many questions unanswered. The present review assesses the importance of these associations, whether they represent cause or effect, reflect disease severity or activity, the complexity of the pathway to the final pathogenic and hence interventional step, and problems with interpreting cross-sectional studies without knowing individual disease trajectories. The complexity of biomarker specificity without sufficient clinical phenotype and endotype information contributes to problems of interpretation. A strategic change is needed to develop useful COPD biomarkers; this includes focusing on endotype biomarkers within specific clinical phenotypes, biomarkers in early COPD, exacerbation subtype biomarkers, and biomarkers to predict or measure drug effects.
慢性阻塞性肺疾病（COPD）的病理学和影响源于异常的炎症过程，导致组织损伤，对有毒吸入物（尤其是香烟烟雾）的反应无效修复。识别这些机制为开发新疗法和个性化管理方法提供了机会。从小型和大型患者队列中收集的多个遗传和详细生化数据，导致了大量研究生物标志物以实现这些目标的研究。尽管人们普遍对此充满热情，并发现了许多具有统计学意义的关联，但 COPD 生物标志物结果的解释需要深入思考，并且仍有许多问题尚未得到解答。本综述评估了这些关联的重要性，它们是因果关系的反映，反映疾病的严重程度或活动程度，还是反映了最终发病和干预步骤的途径的复杂性，以及在不了解个体疾病轨迹的情况下，解释横断面研究的问题。生物标志物特异性的复杂性，加上缺乏足够的临床表型和内型信息，导致解释困难。需要进行策略性改变以开发有用的 COPD 生物标志物；这包括专注于特定临床表型内的内型生物标志物、早期 COPD 生物标志物、加重亚型生物标志物以及预测或衡量药物效果的生物标志物。
