Depression in Older Asthmatics: Understanding Inflammatory and Behavioral Pathways

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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.