Respiratory Impairment in Aging Populations

老龄化人群的呼吸损伤

• 批准号: 8774110
• 负责人: Carlos A. Vaz Fragoso
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8774110
• 关键词: Accounting; Address; Affect; Age; Aging; American; Anatomy; Bronchodilator Agents; Chest; Chest wall structure; Chronic Obstructive Airway Disease; Data; Databases; Diagnosis; Diagnostic; Diffusion; Disease; Equation; Ethnic Origin; Exercise; Exposure to; Health; Height; Hospitalization; Impairment; Interstitial Lung Diseases; Knowledge; Lead; Lung; Measures; Methods; Modeling; Normal Statistical Distribution; Obstructive Lung Diseases; Outcome; Patients; Pattern; Performance; Pharmaceutical Preparations; Phenotype; Physiology; Population; Populations at Risk; Publishing; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Reference Values; Relative (related person); Research; Respiratory Therapy; Risk Factors; Severities; Smoker; Smoking; Societies; Symptoms; Testing; Time; Tobacco smoke; Toxic Environmental Substances; Veterans; Walking; Work; X-Ray Computed Tomography; age group; age related; aged; base; clinically relevant; health administration; high risk; interest; lung volume; never smoker; older patient; pressure; public health relevance; pulmonary function; respiratory; sex

DESCRIPTION (provided by applicant): Respiratory impairment is most often defined spirometrically as: 1) airflow limitation (e.g. COPD), based on a reduced FEV1/FVC, with severity then defined by FEV1 alone; or 2) restrictive-pattern (e.g. interstitial lung disease), based on a reduced FVC but normal FEV1/FVC. The diagnostic thresholds for FEV1/FVC and for FEV1 and FVC alone are usually established by the Global Initiative for Obstructive Lung Disease (GOLD) or the American Thoracic Society (ATS).5-7 These thresholds have serious age-related limitations, however, and will frequently misidentify respiratory impairment in aging populations.8-22 GOLD, for example, uses a threshold of 0.70 for FEV1/FVC, but an FEV1/FVC <0.70 frequently occurs in healthy, asymptomatic never-smokers, aged >50.6-15 GOLD additionally uses percent predicted (%Pred) thresholds for FEV1 and FVC but, because these do not account for the age-related variability in spirometric performance, a given %Pred threshold is not equivalent for all persons.9,16,17In contrast, the ATS sets thresholds for FEV1/FVC and FVC at the lower limit of normal (ATS-LLN5).5-7 This approach also has serious limitations, because the ATS-LLN5 is frequently calculated from regression equations that incorrectly assume a linear relationship between predictors and spirometric measures, and/or incorrectly assume that reference values have a normal distribution and constant variability across the lifespan.9 Otherwise, the ATS also uses %Pred thresholds for FEV1. Consequently, we propose an alternative approach for defining respiratory impairment, using spirometric Z- scores as calculated by Lambda-Mu-Sigma (LMS).1,9,10 The LMS-calculated Z-scores account for age-related changes, including variability in spirometric performance and skewness of reference data.9 Using this approach, we have shown that LMS-defined respiratory impairment is associated with multiple health outcomes,15,18-23 but our prior work did not address several gaps in knowledge. First, we evaluated only whites aged <80, because LMS-calculated Z-scores were not previously available for non-whites and those aged >80. This task is now possible because new LMS equations have been published for multiple ethnicities and age up to 95.10,24 Second, as health outcomes of interest, we did not evaluate exercise capacity, use of respiratory medications, or hospitalizations other than for COPD. Third, we did not evaluate "pulmonary phenotypes," specifically those defined by physiology or CT imaging. Lastly, we did not evaluate spirometric change over time. Accordingly, the objective of this proposal is to address these gaps in knowledge. Using new LMS equations and databases from multiple aging populations, including U.S. Veterans and a broad array of health outcomes and pulmonary phenotypes, we propose the following specific aims: Aim 1. To evaluate the association between respiratory impairment and health outcomes. We hypothesize that: 1) the LMS approach, compared to GOLD or ATS, will show a greater association between respiratory impairment and health outcomes; and 2) discordant designations of respiratory impairment (GOLD and ATS abnormal, respectively, but LMS normal) will not be associated with health outcomes. Aim 2. To evaluate the association between respiratory impairment and pulmonary phenotypes. We hypothesize that: 1) the LMS approach, compared to GOLD or ATS, will show a greater association between respiratory impairment and various pulmonary phenotypes; and 2) discordant designations of respiratory impairment (as defined in Aim 1) will not be associated with a pulmonary phenotype. Aim 3. To evaluate spirometric change over time, with FEV1 and FVC expressed as LMS-calculated Z- scores, %Pred, and absolute volumes (mL). These analyses will include group-based trajectory modeling and key time-varying risk factors that may affect spirometric trajectories. We hypothesize that: 1) aging is associated with declining trajectories of spirometri measures; and 2) LMS-calculated Z-scores, rather than %Pred and absolute volumes (mL), will show a greater association with time-varying risk factors.

描述（由申请人提供）： 呼吸障碍最常以刺激性定义为：1）基于降低的FEV1/FVC的气流限制（例如COPD），然后仅由FEV1定义了严重性；或2）基于FVC降低但FEV1/FVC的限制性图案（例如间质性肺疾病）。 FEV1/FVC和FEV1和FVC的诊断阈值通常是由全球阻塞性肺疾病（Gold）或美国胸腔学会（ATS）（ATS）建立的。5-7这些阈值具有严重的年龄相关局限性，具有严重的限制。并经常会误导衰老人群中的呼吸障碍。黄金还使用FEV1和FVC的预测百分比（％PRED）阈值，但由于这些阈值并不考虑与年龄相关的肺活量测定性能的可变性，因此给定的％PRED阈值并非所有人都等效。9,16,17in的对比度， FEV1/FVC和FVC在正常下限（ATS-LLN5）的ATS设置阈值。5-7此方法也具有严重的局限性，因为ATS-LLN5经常是根据回归方程式计算出的，该回归方程式错误地假设在错误地假设之间存在线性关系预测指标和肺活量测量和/或错误地假设参考值在整个寿命中具有正态分布和恒定变异性。9否则，ATS还使用FEV1的％PRED阈值。 因此，我们提出了一种定义呼吸障碍的替代方法，使用lambda-mu-sigma（LMS）计算的螺旋测量Z-得分.1,9,10。1,9,10LMS计算的Z分数对年龄相关的变化表示了变化，包括变化。在参考数据的肺活量测量表现和偏度中。9使用这种方法，我们表明LMS定义的呼吸障碍与多种健康结果相关，15,18-23，但我们先前的工作并未解决知识上的几个差距。首先，我们仅评估了<80岁的白人，因为以前不适合非白人和年龄> 80岁的白人。现在可以使用此任务，因为新的LMS方程已针对多个种族发布，并且年龄高达95.10,24秒，因为感兴趣的健康结果，我们没有评估运动能力，使用呼吸药物或COPD以外的其他住院治疗。第三，我们没有评估“肺表型”，特别是由生理学或CT成像定义的肺表型。最后，我们没有随着时间的推移评估肺活量测定变化。因此，该提议的目的是解决知识中的这些差距。 使用来自多个老龄化人群的新LMS方程和数据库，包括美国退伍军人以及广泛的健康结果和肺部表型，我们提出了以下特定目的：目标1。评估呼吸障碍和健康结果之间的关联。我们假设：1）与黄金或ATS相比，LMS方法将显示呼吸障碍与健康结果之间的更大关联； 2）呼吸损伤的不一致名称（分别为黄金和ATS异常，但正常LMS）与健康结果无关。 目的2。评估呼吸障碍与肺表型之间的关联。我们假设：1）与黄金或ATS相比，LMS方法将显示呼吸障碍与各种肺部表型之间的更大关联； 2）呼吸障碍的不一致名称（AIM 1中定义）将与肺表型无关。 AIM 3。为了评估肺活量变化，FEV1和FVC表示为LMS计算的Z-SCORES，％PRED和绝对体积（ML）。这些分析将包括基于组的轨迹建模和可能影响肺活量轨迹的关键时变风险因素。我们假设：1）衰老与螺旋层措施的轨迹下降有关； 2）LMS计算的Z分数，而不是百分比PRED和绝对体积（ML），将与随时间变化的危险因素显示出更大的关联。