"Defining Chronic Obstructive Pulmonary Disease in Older Persons"

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是世界范围内致残和死亡的主要原因，其定义是肺活量，仅基于1秒用力呼气量（FEV1）与用力肺活量（FVC）的降低比率，随后根据FEV1进行严重程度分期，以预测百分比（%Pred）表示。然而，在老年人中，目前COPD的肺活量测定指南存在问题，原因至少有三个。首先，确定FEV1/FVC降低的阈值仍然存在争议。其次，将FEV1表示为%Pred是有严重缺陷的，因为它不能解释参考组在整个生命周期中的变异性差异。第三，目前的肺活量测定指南尚未使用重要的临床指标（如死亡率和呼吸道症状）进行严格验证。作为回应，我们制定了一个两部分的肺活量测定策略来定义COPD，首先根据死亡风险确定FEV1/FVC的临界值；然后，在低于这个FEV1/FVC临界阈值的人群中，确定FEV1的切割点，以标准化残余百分位数（SR-tile）表示，并基于死亡风险和呼吸道症状。重要的是，SR-tile方法解释了参照组的可变性。本R03申请的目的是通过使用两项基于老年人的大型人群研究（健康、衰老和身体成分研究和心血管健康研究）的数据，相对于目前的指南，验证我们对COPD的肺活量测定定义。验证将基于与健康相关结果的纵向关联，包括住院和死亡率，以及与临床特征的横断面关联，包括呼吸道症状、身体表现和药物使用。我们的长期目标是评估老年人肺功能与健康相关结果之间关联的风险因素、宿主因素以及中介因素。这项R03申请是重要的一步，因为它将验证一种适合年龄的肺功能报告和COPD定义方法。

DESCRIPTION (provided by applicant): As a leading cause of disability and death worldwide, chronic obstructive pulmonary disease (COPD) is defined spirometrically, based solely on a reduced ratio of the forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), with severity subsequently staged according to the FEV1, expressed as percent predicted (%Pred). Among older persons, current spirometric guidelines for COPD are problematic, however, for at least three reasons. First, the threshold that establishes a reduced FEV1/FVC remains controversial. Second, expressing the FEV1 as %Pred is seriously flawed, because it does not account for differences in the variability of the reference group across the lifespan. Third, current spirometric guidelines have not been rigorously validated using important clinical measures such as mortality and respiratory symptoms. In response, we have developed a two-part spirometric strategy for defining COPD that first determines a cut-point for the FEV1/FVC based on mortality risk; and then, among persons below this critical FEV1/FVC threshold, determines cut-points for the FEV1, expressed as a standardized residual percentile (SR-tile)- and based on mortality risk and respiratory symptoms. Importantly, the SR-tile method accounts for variability of the reference group. The objective of this R03 application is to validate our spirometric definition of COPD, relative to current guidelines, by using data from two large population-based studies of older persons: the Health, Aging and Body Composition Study and the Cardiovascular Health Study. Validation will be based on longitudinal associations with health-related outcomes, including hospitalizations and mortality, and on cross-sectional associations with clinical features, including respiratory symptoms, physical performance, and medication use. Our long-term goal is to evaluate the risk and host factors, as well as the mediators, that underlie the association between pulmonary function and health-related outcomes, in older persons. This R03 application is an important step because it will validate an age-appropriate method for reporting pulmonary function and for defining COPD. PUBLIC HEALTH RELEVANCE: Among older persons, current spirometric guidelines may lead to misclassification (mainly over- diagnosis) of COPD and, in turn, potentially compromise patient care. We propose to validate a more evidence-based spirometric strategy that will avoid the misidentification of COPD among older persons. This could lead to more judicious use of COPD-specific pharmacotherapy and, as a result, reduce the frequency of medication-related adverse events.