Obesity and Asthma: Unveiling Metabolic and Behavioral Pathways

肥胖和哮喘：揭示代谢和行为途径

• 批准号: 9127632
• 负责人: Alex D Federman
• 金额: $ 81.13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127632
• 关键词: 12 year old; Academic advising; Acute; Adherence; Adult; Arginine; Asthma; Behavior; Behavioral; Belief; Biological; Biology; Body Weight decreased; Breathing; Caring; Chronic; Cognition; Comorbidity; Conflict (Psychology); Counseling; Dietary intake; Dyspnea; Education; Equation; Equilibrium; Evaluation; Exercise; Fright; Future; Goals; Health; Health Care Costs; Health behavior outcomes; Impaired cognition; Inflammatory; Informal Social Control; Late-Onset Disorder; Life Style; Lung Inflammation; Mediating; Medical; Metabolic; Metabolic Pathway; Modeling; Monitor; Morbidity - disease rate; New York City; Nitric Oxide; Non obese; Obesity; Onset of illness; Outcome; Oxidative Stress; Pathway interactions; Patients; Perception; Pharmaceutical Preparations; Physical activity; Quality of life; Recruitment Activity; Research; Resources; Respiratory Signs and Symptoms; Respiratory physiology; Self Management; Steroids; Testing; Therapeutic; Time; Weight Gain; Weight maintenance regimen; arginase; asthmatic; base; cognitive function; diet and exercise; early onset; exercise adherence; health care service utilization; improved; medication compliance; novel; patient population; programs; public health relevance; theories

 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.

 描述（由申请人提供）：肥胖与哮喘控制不佳以及医疗保健利用率和成本较高有关。早期证据表明，肥胖，尤其是晚发性哮喘患者（> 12 岁），会通过促进气道氧化应激而加重哮喘，氧化应激是一氧化氮 (NO) 代谢途径中 L-精氨酸减少和不对称二甲基精氨酸 (ADMA) 增加的结果。这种机制与特征更明确的 TH-2 介导的炎症途径共存，后者是大多数慢性哮喘治疗的目标。 L-精氨酸/ADMA 对肥胖成人哮喘活动的相对贡献尚未得到充分研究，需要进行评估以确定哮喘内型以及 L-精氨酸/ADMA 是否适合肥胖哮喘患者的新治疗方法。但生物途径只是哮喘发病的部分驱动因素。自我管理行为（SMB），如药物依从性，是哮喘控制和体重管理的关键，而在肥胖哮喘患者中，一系列潜在相互冲突的观念和信念可能会阻碍每个人的自我管理。让情况变得更加复杂的是，认知功能可能会因肥胖而受损，这给中小型企业增加了另一个障碍。大多数关于中小企业和健康结果的研究都集中在单一疾病上，忽略了影响共存医疗状况的信念、行为和生物学之间可能存在的相互关系。通过考虑合并症如何在所有这些层面上相互作用的策略，将在治疗患有多种慢性疾病（例如肥胖和哮喘）的患者方面取得重大进展。我们的目标是通过研究肥胖哮喘患者生物学和行为的相互作用来实现这一目标，并最终改善他们的护理。具体目标是：(1) 比较患有晚发性哮喘的肥胖成人与 (a) 患有早发性哮喘的肥胖成人和患有早发型 (b) 或晚发 (c) 疾病的非肥胖哮喘患者之间 L-精氨酸/ADMA 平衡与发病率（肺功能、哮喘控制、急性资源利用和生活质量）之间的纵向关系； (2) 评估肥胖和哮喘相关疾病信念之间的相互关系，以及认知功能对患者随时间管理这些疾病的影响； (3) 开发并试点测试三个基于理论的模块，将哮喘和肥胖咨询结合起来，以促进更好的 SMB，包括自我监测、坚持哮喘药物治疗以及改变生活方式以减轻体重。我们将在纽约市和匹兹堡招募 400 名肥胖和非肥胖成人哮喘患者，并在 18 个月内以及哮喘恶化后每 6 个月评估 L-精氨酸酶、ADMA 和 TH-2 活性标记物、哮喘和肥胖疾病信念以及 SMB、认知和哮喘发病率。对于目标 3，我们将在自我调节模型的指导下，针对 80 名肥胖哮喘患者开发和测试综合教育和咨询模块，以了解可行性和初步影响，为未来全面的自我管理支持计划提供信息。