Role of exercise in modulating airway inflammation

描述（由申请人提供）：在过去的20年里，哮喘的患病率、发病率和死亡率都有所增加。最近的报告表明，有氧运动可以改善呼吸系统疾病（包括哮喘）患者的整体健康状况；然而，记录的哮喘反应的改变以及这种改变背后的机制仍然不明确。众所周知，运动对免疫系统有深远的影响；这些影响包括运动介导的体内T淋巴细胞的再分布。越来越多的证据表明，T淋巴细胞在哮喘的发病机制中起着核心作用。据报道，运动也能诱导内源性糖皮质激素（GCs）的释放。内源性GCs通过与糖皮质激素受体（GR）结合并随后改变转录事件而发挥抗炎作用。基于本文提供的初步数据，本提案的假设是，中等强度有氧运动通过一种机制，包括调节T细胞反应和内源性糖皮质激素介导的作用，减轻特应性哮喘反应。拟开展的研究将：1)表征有氧运动对特应性哮喘肺内炎症反应和肺功能的影响；2)确定有氧运动对特应性哮喘肺内T细胞反应的影响；3)阐明内源性GCs在运动介导的特应性哮喘反应衰减中的作用。鉴于哮喘患病率的增加是一个主要的公共卫生问题，探索哮喘相关疗法的研究至关重要。预计这项研究将产生关于有氧运动在哮喘管理中的治疗潜力的新数据。

DESCRIPTION (provided by applicant): Asthma has increased in prevalence, morbidity and mortality over the past 20 years. Recent reports indicate that aerobic exercise improves the overall health of patients with respiratory diseases, including asthma; however, documented alterations in the asthmatic response as well as the mechanisms that underlie such alterations remain ill-defined. It is well appreciated that exercise profoundly influences the immune system; such effects include an exercise-mediated redistribution of T lymphocytes in vivo. Increasing evidence demonstrates that T lymphocytes play a central role in the pathogenesis of asthma. Exercise has also been reported to induce the release of endogenous glucocorticoids (GCs). Endogenous GCs act as anti-inflammatory agents through binding to the glucocorticoid receptor (GR) and subsequently altering transcriptional events. Based upon the preliminary data presented herein, the hypothesis of this proposal is that moderate intensity aerobic exercise attenuates the atopic asthmatic response via a mechanism that involves modulation of T cell responses and endogenous glucocorticoid-mediated actions. Proposed studies will: 1) Characterize the effect of aerobic exercise on inflammatory responses and pulmonary function within the atopic asthmatic lung; 2) Determine the effect of aerobic exercise on T cell responses within the atopic asthmatic lung; and 3) Delinate the role of endogenous GCs in the exercise-mediated attenuation of the atopic asthmatic response. Given that the increase in prevalence of asthma is a major public health concern, research that explores asthma-related therapies is vital. It is anticipated that this study will produce novel data regarding the therapeutic potential of aerobic exercise in the management of asthma.