? DESCRIPTION (provided by applicant): Obesity is associated with poor asthma control and greater healthcare utilization and costs. Early evidence suggests that obesity, especially among those with late onset asthma (>age 12 years), worsens asthma by promoting oxidative stress in the airway, a consequence of reduced L-arginine and increased asymmetric di- methyl arginine (ADMA) in the nitric oxide (NO) metabolic pathway. This mechanism coexists with the better characterized TH-2 mediated inflammatory pathways, which are the target of most chronic asthma therapeutics. The relative contribution of the L-arginine/ADMA to asthma activity in obese adults is understudied and evaluation is needed to determine asthma endotypes and whether L-arginine/ADMA is a suitable focus for new treatments for obese asthmatics. But biological pathways are only part of the drivers of asthma morbidity. Self-management behaviors (SMB), like medication adherence, are a key to asthma control and weight management, and in obese asthmatics an array of potentially conflicting perceptions and beliefs may impede self-management of each. Further complicating this picture, cognitive functioning can be impaired by obesity, adding another impediment to SMB. Most research on SMB and health outcomes focuses on single illnesses, ignoring the interrelationships that likely exist between the beliefs, behaviors, and biology that influence coexisting medical conditions. Major advances in care of people with multiple chronic medical conditions, such as obesity and asthma, will occur through strategies that consider how comorbidities interact on all these levels. Our goal is to move toward this end by examining the interaction of biology and behavior among obese asthmatics and ultimately improve their care. The Specific Aims are to: (1) compare the longitudinal relationship between L-arginine/ADMA balance and morbidity (lung function, asthma control, acute resource utilization, and quality of life) between obese adults with late onset asthma vs. (a) obese adults with early onset asthma and non-obese asthmatics with early (b) or late (c) onset disease; (2) evaluate the interrelationship between obesity- and asthma-related illness beliefs, and the impact of cognitive function, on patients' management of these conditions over time; (3) develop and pilot test three theory-based modules that integrate counseling for asthma and obesity to promote better SMB, including self-monitoring, adherence to asthma medications, and lifestyle changes for weight loss. We will recruit 400 obese and non-obese adult asthmatics in New York City and Pittsburgh and assess L-arginase, ADMA, and markers of TH-2 activity, asthma and obesity illness beliefs and SMB, cognition, and asthma morbidity every 6 months over 18 months and after asthma exacerbations. For Aim 3, we will develop and test the integrated education and counseling modules, guided by the Self-regulation Model, on 80 obese asthmatics for feasibility and preliminary impact to inform a future, comprehensive program of self-management support.

R01HL129198

2016-05-01

2021-04-30