Dyspnea on Exertion in Obesity: Effects of Exercise Training and Weight Loss

描述（由申请人提供）：肥胖是美国的一个流行病问题，是21世纪世纪最重要的健康挑战之一。肥胖的主要后果是心脏病、高血压、糖尿病、睡眠呼吸障碍和代谢综合征的死亡率和发病率增加。许多肥胖的成年人经历劳力性呼吸困难，不能锻炼。因此，肥胖成人劳力性呼吸困难不仅是一个重要的和多产的临床问题，它是预防和治疗肥胖和肥胖相关的合并症的障碍。虽然大多数肥胖的成年人在运动时呼吸困难通常被认为是失调，我们的初步数据挑战这一传统的智慧。例如，在运动时呼吸困难的女性中，我们发现呼吸的氧气消耗（即，呼吸功）显著增加，并与劳力性呼吸困难高度相关。因此，目前尚不清楚肥胖者的劳累性呼吸困难是由于心血管失调（运动训练将显着有益），还是由于与肥胖相关的呼吸力学变化（在运动训练之前可能需要采取积极的减肥措施）。可以忍受。本申请的总体目的是研究在其他方面健康的肥胖成年人中的劳力性呼吸困难是否可以通过耐力运动训练（即，心血管调节的增加），或体重减轻（即，减少肥胖相关的呼吸限制，特别是呼吸的氧气消耗）。我们假设，在其他方面健康的肥胖成人劳力性呼吸困难不会改善耐力运动训练，因为劳力性呼吸困难的肥胖成人没有去适应，单独的运动训练不太可能减少肥胖相关的呼吸限制，特别是呼吸的氧气消耗。与此相反，我们假设劳力性呼吸困难将改善体重减轻，因为体重减轻应减少肥胖相关的呼吸限制，特别是呼吸的氧气成本。在本申请中，我们将利用两种干预措施来研究我们的建议：1）没有减肥的耐力运动训练，以及2）没有耐力运动训练的减肥。具体目标：为了实现总体目标，将检验以下假设：1）耐力运动训练不会改善伴有劳力性呼吸困难的肥胖成人的劳力性呼吸困难; 2）体重减轻，尤其是胸壁脂肪减少，将改善伴有劳力性呼吸困难的肥胖成人的劳力性呼吸困难。我们的长期目标是研究肥胖成年人劳力性呼吸困难的机制，并提供新的临床相关结果，这些结果可能会改变预防肥胖、治疗肥胖和降低肥胖患者心脏病、高血压和代谢综合征风险的干预方法。 公共卫生相关性：在美国，肥胖成年人运动时呼吸困难（呼吸短促）是一种常见的健康问题。病因目前尚不清楚，在许多情况下，劳力性呼吸困难是预防和治疗肥胖症和共存疾病的障碍。我们的研究将探讨这种不适的机制，以及运动训练和减肥在减少运动性呼吸困难方面的有效性。这项研究的结果可能会改变预防肥胖、治疗肥胖和降低肥胖患者心脏病风险的干预方法。因此，这些结果将对肥胖和肥胖相关合并症的治疗具有广泛和直接的临床意义。

DESCRIPTION (provided by applicant): Obesity is an epidemic problem in the United States and is among the most important health challenges of the 21st Century. The major consequences of obesity are increased rates of mortality and morbidity from heart disease, hypertension, diabetes, sleep-disordered breathing, and the metabolic syndrome. Many obese adults experience exertional dyspnea and are unable to exercise. Therefore, exertional dyspnea in obese adults is not only an important and prolific clinical concern it is an obstacle to the prevention and treatment of obesity and obesity-related comorbidities. Although most obese adults with dyspnea on exertion are generally considered to be deconditioned, our preliminary data challenge this conventional wisdom. For example, in women with dyspnea on exertion, we have found the oxygen cost of breathing (i.e., work of breathing) to be markedly increased and highly associated with exertional dyspnea. Thus, it is presently unclear if exertional dyspnea in obesity is due to cardiovascular deconditioning, in which exercise training would be dramatically beneficial, or to obesity-related changes in respiratory mechanics, in which aggressive weight loss measures may be necessary before exercise training can be tolerated. The overall objective of this application is to investigate whether exertional dyspnea in otherwise healthy obese adults can be ameliorated by endurance exercise training (i.e., increase in cardiovascular conditioning), or by weight loss (i.e., decrease in obesity related-respiratory limitations, specifically, the oxygen cost of breathing). We hypothesize that exertional dyspnea in otherwise healthy obese adults will not improve with endurance exercise training since obese adults with exertional dyspnea are not deconditioned, and exercise training alone is unlikely to decrease obesity-related respiratory limitations, specifically the oxygen cost of breathing. In contrast, we hypothesize that exertional dyspnea will be ameliorated with weight loss, since weight loss should decrease obesity related-respiratory limitations, in particular, the oxygen cost of breathing. In this application, we will utilize two interventions to investigate our proposals: 1) endurance exercise training without weight loss, and 2) weight loss without endurance exercise training. Specific Aims: To accomplish the overall objective, the following hypotheses will be tested: 1) Endurance exercise training will not ameliorate exertional dyspnea in obese adults with dyspnea on exertion; and 2) Weight loss, especially loss of chest wall fat, will ameliorate exertional dyspnea in obese adults with dyspnea on exertion. Our long-term objective is to investigate the mechanism of exertional dyspnea in obese adults and provide novel and clinically relevant results that could potentially alter interventional approaches for preventing obesity, treating obesity, and reducing the risk of heart disease, hypertension, and the metabolic syndrome in obese patients. PUBLIC HEALTH RELEVANCE: Dyspnea (shortness of breath) on exertion in obese adults is a common health problem in America. The cause is currently unknown, and in many instances exertional dyspnea is an obstacle to the prevention and treatment of obesity and coexisting diseases. Our research will investigate the mechanisms of this discomfort and the effectiveness of exercise training and weight loss in reducing dyspnea on exertion. The results of this research could potentially alter interventional approaches for preventing obesity, treating obesity, and reducing the risk of heart disease in obese patients. Thus, these results will have broad and immediate clinical relevance to the treatment of obesity and obesity-related comorbidities.