Can diet- & exercise-induced weight loss improve asthma control in obese adults?

描述（由申请人提供）：项目总结关于肥胖和哮喘之间关系的科学证据不断积累。最近的研究越来越关注这种关系的本质，而不是试图确定这种关系是否存在。许多（尽管不是全部）流行病学研究报告肥胖和哮喘之间存在暂时正确的剂量-反应关系。动物研究支持这两种疾病之间的因果关系；然而，人类的因果途径仍有待了解。在新的NIH哮喘诊断和管理指南中，肥胖首次被明确承认为一种重要的合并症，基于有限的研究，肥胖的治疗被认为对哮喘控制有潜在的益处。虽然目前关于减肥对哮喘结果的影响的证据是令人鼓舞的，但还远远没有定论。该随机对照试验（RCT）的总体目标是研究循证生活方式减肥干预对肥胖成人哮喘控制的效果。干预将包括饮食和身体活动的改变以及行为的改变。这种方法在预防和控制众所周知的与肥胖相关的合并症，如糖尿病和高血压方面已被证明有效。我们将从北加州Kaiser Permanente （KPNC）的4个医疗中心（一个大型群体模式的健康维护组织）的约20,000名可能符合条件的哮喘患者中随机选取324名年龄在18-70岁、控制欠佳、持续性哮喘、体重指数为30.0至39.9 kg/m2的患者。随机化前，所有参与者将与现场KPNC哮喘护理经理完成一次办公室访问和一次电话咨询，随机化后，所有参与者将继续接受KPNC医生的标准护理。那些被随机分配到实验组的人将接受综合生活方式减肥干预。主要结果将是12个月时Juniper哮喘控制问卷的总得分。具体目的是：1)确定干预措施是否改善了与哮喘相关的现有损害（哮喘症状、肺活量肺功能、活动限制、抢救药物使用和哮喘相关的生活质量）；2)确定干预措施是否改善了与哮喘相关的未来风险指标（哮喘加重和哮喘药物不良反应）；3)在控制哮喘药物效力和依从性后，研究干预效果的潜在机制，重点关注体重、身体活动和饮食组成变化的相对贡献；4)探索潜在的影响修饰因素，如性别、种族/民族、教育程度和其他基线特征。这个项目将有助于提高目前对肥胖-哮喘关系本质的理解。如果减肥干预被证明可以改善哮喘的结果，它将增加其他可用的医疗和环境策略来管理肥胖成人的哮喘，这反过来可能导致降低与哮喘和肥胖相关的发病率和死亡率。公共卫生相关性：尽管潜在的机制尚不清楚，但越来越多的科学证据表明，肥胖的儿童和成人患哮喘的风险较高，或者对于那些已经患有哮喘的人来说，症状更严重。新的国家哮喘管理指南建议临床医生考虑建议超重或肥胖的哮喘患者减肥，这是基于非常有限的研究表明，除了其他已知的健康益处外，减肥还可能改善哮喘控制。目前的研究旨在严格调查减肥，通过推荐的饮食调整、身体活动和行为改变策略，是否对肥胖成人哮喘的管理有显著的临床益处。如果成功，该项目将有助于推进目前治疗肥胖成人哮喘的临床指南，这反过来可能导致与哮喘和肥胖相关的发病率和死亡率降低。

DESCRIPTION (provided by applicant): Project Summary Scientific evidence continues to accumulate on the relation between obesity and asthma. More recent efforts are increasingly focused on the nature of the relation, as opposed to trying to determine whether such a relation exists. Many, although not all, epidemiological studies report a temporally correct and dose-response relationship between obesity and asthma. Animal studies support a causal link between the two disorders; however, the causal pathway remains to be understood in humans. In the new NIH asthma diagnosis and management guidelines, obesity is explicitly recognized, for the first time, as an important co-morbidity, and treatment of obesity is deemed to have potential benefits on asthma control based on limited studies. Although current evidence of the effects of weight loss on asthma outcomes is encouraging, it is far from being conclusive. The overall goal of the proposed randomized controlled trial (RCT) is to investigate the efficacy of an evidence-based lifestyle weight loss intervention on asthma control among obese adults. The intervention will involve a combination of dietary and physical activity changes and behavioral modification. This approach has demonstrated efficacy in preventing and controlling well-recognized obesity-related co- morbidities such as diabetes and hypertension. We will randomize 324 patients ages 18-70 years who have suboptimally controlled, persistent asthma and a body mass index of 30.0 to 39.9 kg/m2 from ~20,000 potentially eligible asthma patients at four medical centers of Kaiser Permanente in Northern California (KPNC), a large, group-model health maintenance organization. All participants will complete an office visit and a phone consultation, pre-randomization, with an on-site KPNC asthma care manager, and all will continue to receive KPNC standard of care from their physician post-randomization. Those randomly assigned to the experimental group will receive the comprehensive lifestyle weight loss intervention. The primary outcome will be the overall score at 12 months on the Juniper Asthma Control Questionnaire. The specific aims are to: 1) Determine whether the intervention improves measures of current impairment associated with asthma (asthma symptoms, spirometric lung function, activity limitations, rescue medication use, and asthma-related quality of life); 2) Determine whether the intervention improves measures of future risk associated with asthma (asthma exacerbations and adverse effects of asthma medication); 3) Examine potential mechanisms of intervention effects, focusing on the relative contributions of changes in weight, physical activity, and diet composition, after controlling for asthma medication potency and adherence; and 4) Explore potential effect modifiers, e.g. sex, race/ethnicity, education, and other baseline characteristics. This project will help advance current understanding of the nature of obesity-asthma relationship. If the weight loss intervention is proven to improve asthma outcomes, it will add to the other medical and environmental strategies available to manage asthma in obese adults, which may, in turn, lead to reduced morbidity and mortality associated with asthma and obesity. PUBLIC HEALTH RELEVANCE: Although the underlying mechanisms remain unclear, growing scientific evidence suggests that children and adults who are obese are at elevated risk of developing asthma or, for those who already have the disease, having worse symptoms. The new national asthma management guidelines recommend that clinicians consider advising asthma patients who are overweight or obese to lose weight, based on very limited studies showing that weight loss may improve asthma control, in addition to its other known health benefits. The current study aims to rigorously investigate whether weight loss, through recommended strategies for dietary modification, physical activity, and behavioral change, has significant clinical benefits for the management of asthma in obese adults. If successful, this project will help advance the current clinical guidelines for treating obese adults with asthma, which, in turn, may lead to reduced morbidity and mortality associated with asthma and obesity.