Obesity and Asthma: Unveiling Metabolic and Behavioral Pathways

 描述(由申请人提供)：肥胖与哮喘控制不佳以及更高的医疗保健利用率和成本有关。早期证据表明，肥胖，特别是在晚发哮喘患者(年龄12岁)中，通过促进呼吸道内的氧化应激而加重哮喘，这是一氧化氮(NO)代谢途径中L精氨酸减少和不对称二甲基精氨酸增加的结果。这一机制与特征更好的TH-2介导的炎症途径共存，后者是大多数慢性哮喘治疗的靶点。L-精氨酸/ADMA对肥胖成人哮喘活动度的相对贡献尚未得到充分研究，尚需评估以确定哮喘内型，以及L-精氨酸/ADMA是否适合作为肥胖性哮喘新疗法的靶点。但生物途径只是哮喘发病率的部分驱动因素。自我管理行为(SMB)，就像坚持服药一样，是哮喘控制和体重管理的关键，而在肥胖哮喘患者中，一系列潜在的相互冲突的看法和信念可能会阻碍各自的自我管理。让情况更加复杂的是，肥胖可能会损害认知功能，给SMB增加了另一个障碍。大多数关于SMB和健康结果的研究都集中在单一疾病上，而忽略了可能存在于影响共存医疗条件的信仰、行为和生物学之间的相互关系。在护理患有多种慢性疾病(如肥胖症和哮喘)的人方面，将通过考虑共病如何在所有这些层面上相互作用的战略来取得重大进展。我们的目标是通过研究肥胖哮喘患者之间的生物学和行为的相互作用来朝着这个目标前进，并最终改善他们的护理。研究的具体目的是：(1)比较迟发性哮喘肥胖者与(A)早发性哮喘肥胖者和(B)或(C)起病晚发的非肥胖性哮喘患者的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)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着时间的推移对这些疾病的管理的影响；(3)开发并试点测试三个基于理论的模块，这些模块整合了哮喘和肥胖症的咨询，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减肥的生活方式。我们将在纽约市和匹兹堡招募400名肥胖和非肥胖的成年哮喘患者，并在18个月内和哮喘加重后每6个月评估一次L精氨酸酶、ADMA和TH-2活性的标志物、哮喘和肥胖的疾病信念以及SMB、认知和哮喘发病率。对于目标3，我们将在自我调节模式的指导下，开发和测试整合的教育和咨询模块，对80名肥胖哮喘患者进行可行性和初步影响，以指导未来的综合自我管理支持计划。

 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.