Depression in Older Asthmatics: Understanding Inflammatory and Behavioral Pathways

这项研究的总体目标是调查与抑郁有关的生物和行为途径。 与老年人的哮喘结果有关。重度抑郁(MD)在老年哮喘患者中非常普遍， 尤其是在少数群体中，并与哮喘发病率的增加有关。MD导致系统功能增强 炎症(IL-1、IL-2、IL-6和肿瘤坏死因子-α水平升高)。其中一些 促炎细胞因子与更严重的哮喘表型有关，这可能解释了 MD与较差的哮喘预后的关系。然而，生物途径很可能只是 哮喘发病率的驱动因素。先前的研究表明，抑郁症一直与药物用量低有关。 在其他慢性病中的坚持。此外，理论和有限的经验证据表明，认知 抑郁症患者的情绪疾病表现可能导致适应不良的应对策略， 导致老年人对哮喘自我管理行为(SMB)的依从性较低，结果较差。 这项提案汇集了一个多学科的调查团队，以扩大对 MD与哮喘发病率增加有关的途径。具体目标是：1) 老年哮喘患者MD与呼吸道和全身炎症的关系及评价 与结果的纵向关联以及2)在MD和 老年人对哮喘SMB(服药依从性、避免触发和吸入器技术)的坚持 并找出连接他们的行为路径。我们将使用结构方程建模来评估 直接和间接致炎和行为通路的综合模型，探索 这种生物行为模型中关系的方向性，并评估特定路径对 老年MD患者的哮喘结局。我们将对400名英语和西班牙语学生进行纵向研究- 从3个不同种族招募的患有持续性哮喘的老年人(≥60岁)(约50%患有MD) 在纽约市的实践。研究对象将接受全面的面对面基线评估 并将使用精神病学面谈的黄金标准评估目前的MD障碍。我们会 还要采集外周血和诱导痰，用于呼吸道细胞因子和细胞表达的评估。 参与者将接受为期4周的监测，以获得对哮喘药物依从性的客观评估 使用电子设备。受试者将在6个月、12个月和18个月时进行前瞻性跟踪，并重复 MD、全身炎症标志物、SMB、疾病和用药信念以及哮喘的评估 结果。利用这些数据，我们将评估潜在的生物和行为途径的相互作用 MD与老年人哮喘发病率增加的关系。本研究的临床意义 包括潜在地确定可能受益于不同抗炎药物老年哮喘患者 治疗，并针对预测老年人哮喘的SMB的可改变的信念。

The overall objective of this study is to investigate the biological and behavioral pathways linking depression with asthma outcomes in older adults. Major depression (MD) is highly prevalent among older asthmatics, particularly in minorities, and is associated with increased asthma morbidity. MD leads to enhanced systemic inflammation (increased levels of interleukin [IL]-1, IL-2, IL-6, and tumor necrosis factor-α). Some of these pro-inflammatory cytokines have been linked to more severe asthma phenotypes, potentially explaining the relationship between MD and worse asthma outcomes. However, biological pathways are likely only part of the drivers of asthma morbidity. Prior studies show that depression is consistently linked with low medication adherence in other chronic diseases. Additionally, theory and limited empirical evidence suggest that cognitive and emotional illness representations in depressed patients may lead to maladaptive coping strategies that result in low adherence to asthma self-management behaviors (SMB) and poorer outcomes in older adults. This proposal brings together a multidisciplinary team of investigators to expand understanding of the pathways through which MD is associated with increased asthma morbidity. The Specific Aims are to: 1) Determine the relationship of MD with airway and systemic inflammation in older asthma patients and evaluate the longitudinal association with outcomes and 2) Establish the longitudinal association between MD and adherence to asthma SMB (medication adherence, trigger avoidance, and inhaler technique) among older adults and identify the behavioral pathways linking them. We will use structural equation modeling to assess an integrated model of the direct and indirect causal inflammatory and behavioral pathways, explore the directionality of relationships in this biobehavioral model, and evaluate the contributions of specific pathways to asthma outcomes in older patients with MD. We will conduct a longitudinal study of 400 English and Spanish- speaking older adults (≥60 years) with persistent asthma (~50% with MD) recruited from 3 racially diverse practices in New York City. Study subjects will undergo a comprehensive in-person baseline evaluation of their asthma and will be assessed for current MD disorder using the gold standard for psychiatric interviews. We will also collect peripheral blood and induced sputum for airway cytokine and cellular expression assessments. Participants will be monitored for 4 weeks to obtain objective assessment of asthma medication adherence using an electronic device. Subjects will be followed prospectively at 6, 12 and 18 months with repeated assessments of MD, systemic inflammatory markers, SMB, illness and medication beliefs, and asthma outcomes. Using these data, we will evaluate the interplay of biological and behavioral pathways underlying the relationship of MD with increases in asthma morbidity in older adults. The clinical implications of this study include potentially identifying older patients with asthma who may benefit from different anti-inflammatory treatments, and targeting modifiable beliefs that predict asthma SMB in older adults.