Depression in Older Asthmatics: Understanding Inflammatory and Behavioral Pathways

老年哮喘患者的抑郁症：了解炎症和行为途径

• 批准号: 10164846
• 负责人: PAULA J BUSSE
• 金额: $ 82.6万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164846
• 关键词: Acute Disease; Address; Adherence; Anti-Inflammatory Agents; Asthma; Behavior; Behavior Therapy; Behavioral; Behavioral Mechanisms; Belief; Biological; C-reactive protein; Chronic Disease; Clinical; Cognitive; Cohort Studies; Cytometry; Data; Elderly; Electronics; Emotional; Equation; Evaluation; Gold; High Prevalence; Hospitals; Inflammation; Inflammatory; Informal Social Control; Inhalators; Interleukin-1; Interleukin-1 beta; Interleukin-2; Interleukin-6; Interleukin-8; Interview; Knowledge; Lead; Link; Literature; Longitudinal Studies; Major Depressive Disorder; Measures; Mediating; Medical; Medical center; Mental Depression; Methods; Minority; Modeling; Monitor; Morbidity - disease rate; Neutrophilia; New York City; Outcome; Participant; Pathway interactions; Patients; Peripheral; Persons; Pharmaceutical Preparations; Phenotype; Populations at Risk; Research Personnel; Risk; Secondary to; Self Efficacy; Self Management; Sputum; Structure; Study Subject; TNF gene; Techniques; Testing; Time; Vulnerable Populations; airway inflammation; asthmatic; asthmatic patient; behavioral outcome; biobehavior; coping; cytokine; depressed patient; disorder control; health care service utilization; improved; improved outcome; inflammatory marker; inner city; medication compliance; multidisciplinary; neutrophil; novel; older patient; peripheral blood; prospective; racial diversity; recruit; response; systemic inflammatory response; targeted treatment; theories; therapy development

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.

本研究的总体目标是探讨抑郁症的生物和行为途径 与老年人哮喘的关系重度抑郁症（MD）在老年哮喘患者中非常普遍， 特别是在少数民族中，并与哮喘发病率增加有关。MD导致增强的系统性 炎症（白细胞介素[IL]-1 β、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与哮喘恶化的关系然而，生物学途径可能只是其中的一部分。 哮喘发病率的驱动因素。先前的研究表明，抑郁症始终与低药物治疗有关 在其他慢性疾病中的应用。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征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。 这项建议汇集了一个多学科的调查小组，以扩大对 MD与哮喘发病率增加相关的途径。具体目标是：1） 确定老年哮喘患者MD与气道和全身炎症的关系，并评估 与结果的纵向关联和2）建立MD与 老年人哮喘SMB依从性（药物依从性、触发避免和吸入器技术） 成年人，并确定联系他们的行为途径。我们将使用结构方程模型来评估一个 直接和间接因果炎症和行为途径的综合模型，探索 在这个生物行为模型的关系的方向性，并评估具体途径的贡献， 老年MD患者的哮喘转归。我们将对400名英国人和西班牙人进行纵向研究- 从3个不同种族招募的患有持续性哮喘（约50%患有MD）的会说话的老年人（≥60岁） 在纽约市开业。研究受试者将接受全面的面对面基线评估， 哮喘，并将使用精神病学访谈的黄金标准评估当前的MD疾病。我们将 还收集外周血和诱导痰用于气道细胞因子和细胞表达评估。 将对受试者进行为期4周的监测，以客观评估哮喘药物依从性 使用电子设备。将在6、12和18个月时对受试者进行前瞻性随访， 评估MD、全身炎症标志物、SMB、疾病和用药信念以及哮喘 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。这项研究的临床意义 包括潜在地识别可能受益于不同抗炎药的老年哮喘患者， 治疗，并针对预测老年人哮喘SMB的可改变信念。