Mohan Arjun, Sethi Sanjay
aDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University at Buffalo bDepartment of Veterans Affairs Western New York Healthcare System, Buffalo, New York, USA.
Curr Opin Pulm Med. 2014 Mar;20(2):146-52. doi: 10.1097/MCP.0000000000000032.
Despite the increasing awareness of their pathogenesis and clinical consequences, research on and clinical management of acute exacerbations of chronic obstructive lung disease (AECOPDs) have been hindered by the lack of a consistent and reliable definition. Symptom-based definitions of exacerbations are sensitive to events and account for unreported exacerbations. Event (healthcare utilization)-based definitions are somewhat more definitive but miss unreported events. Objective quantification of symptoms in AECOPD is now possible with the development of the Exacerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT-PRO), a patient-reported outcome (PRO) measure.
Several studies have revealed that unreported AECOPDs are more frequent than reported events and are associated with long-term adverse consequences. New antibiotic development for AECOPD has been hampered by the lack of validated measures for resolution of exacerbations. As a result of these observations, a unique collaborative effort between academia, industry and regulatory agencies resulted in the development of the EXACT-PRO. It consists of 14 questions that generate a score between 0 and 100, and it has been shown to have excellent reliability and validity.
In the absence of a reliable biomarker, the definition and measurement of exacerbations has been subjective and imprecise. PRO measures such as EXACT can provide much needed objectivity in assessing symptom-defined exacerbations, which may translate into a uniform outcome measure in clinical trials. With further development and validation, it may have a role in clinical practice in the earlier detection of exacerbations, stratification of an exacerbation severity and the assessment of clinical response to treatment.
尽管人们对慢性阻塞性肺疾病急性加重（AECOPD）的发病机制和临床后果的认识不断提高，但由于缺乏一致且可靠的定义，AECOPD的研究和临床管理受到了阻碍。基于症状的加重定义对事件敏感，并能涵盖未报告的加重情况。基于事件（医疗保健利用情况）的定义则更具确定性，但会遗漏未报告的事件。随着慢性阻塞性肺疾病加重工具（EXACT-PRO）的开发，一种患者报告结局（PRO）测量方法，现在可以对AECOPD的症状进行客观量化。
多项研究表明，未报告的AECOPD比报告的事件更为频繁，且与长期不良后果相关。由于缺乏用于评估加重情况缓解的有效措施，AECOPD新型抗生素的研发受到了阻碍。基于这些观察结果，学术界、产业界和监管机构之间进行了独特的合作，开发出了EXACT-PRO。它由14个问题组成，得分在0到100之间，已被证明具有出色的可靠性和有效性。
在缺乏可靠生物标志物的情况下，加重情况的定义和测量一直主观且不精确。像EXACT这样的PRO测量方法可以在评估基于症状定义的加重情况时提供急需的客观性，这可能转化为临床试验中统一的结局测量方法。随着进一步的开发和验证，它可能在临床实践中发挥作用，用于更早地检测加重情况、对加重严重程度进行分层以及评估临床治疗反应。
