Obesity and Asthma: Unveiling Metabolic and Behavioral Pathways

 描述（由申请人提供）：肥胖与哮喘控制不良和更高的医疗保健利用率和成本相关。早期的证据表明，肥胖，尤其是在晚发性哮喘患者（> 12岁）中，通过促进气道中的氧化应激而使哮喘恶化，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（ADMA）增加的结果。这种机制与TH-2介导的炎症通路共存，后者是大多数慢性哮喘治疗的靶点。L-精氨酸/ADMA对肥胖成年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源性，以及L-精氨酸/ADMA是否适合作为肥胖哮喘新治疗的重点。但生物学途径只是哮喘发病率的部分驱动因素。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，在肥胖哮喘患者中，一系列潜在冲突的感知和信念可能会阻碍自我管理。使这一情况进一步复杂化的是，肥胖会损害认知功能，这给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，忽略了影响共存医疗条件的信念，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，将在患有多种慢性疾病（如肥胖和哮喘）的人的护理方面取得重大进展。我们的目标是通过研究肥胖哮喘患者的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L-精氨酸/ADMA平衡与发病率之间的纵向关系（肺功能、哮喘控制、急性资源利用和生活质量）之间的比较。（a）肥胖成人早发性哮喘和非肥胖哮喘患者早发性（B）或晚发性（c）疾病;（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推移对这些疾病的管理的影响;（3）开发和试点测试三个理论为基础的模块，整合咨询哮喘和肥胖，以促进更好的SMB，包括自我监测，坚持哮喘药物，生活方式的改变减肥。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个月内每6个月和哮喘急性发作后评估L-丝氨酸蛋白酶、ADMA和TH-2活性标志物、哮喘和肥胖疾病信念、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，在80名肥胖哮喘患者身上开发和测试综合教育和咨询模块，以了解其可行性和初步影响，为未来的自我管理支持综合计划提供信息。

 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.