Cardiopulmonary correlates of cognitive function in SLE

描述(由申请人提供)：认知功能障碍在自身免疫性疾病患者中很常见，如系统性红斑狼疮(SLE)。这些缺陷可以影响广泛的活动，更好地了解其性质和发病机制对于开发有效的治疗方法至关重要。尽管先前对SLE患者的自身免疫和血管异常与脑功能障碍相关的研究很多，但还没有一个具体的潜在机制出现。系统性红斑狼疮是一种多器官疾病，高达60%的系统性红斑狼疮患者有肺部受累。在一小部分SLE受试者中，我们发现了与认知功能障碍有关的意想不到的肺部异常，我们在这项研究中的首要目标是比较更大规模的SLE受试者和对照组受试者的肺功能和运动能力，并评估肺功能、运动能力和认知之间的关系。该模型是基于先前对慢性阻塞性肺疾病(COPD)患者的研究，在COPD患者中，认知缺陷与肺功能、运动能力和抑郁有关。考虑到SLE表现的异质性，我们将尽量减少某些因素(即年龄、诊断时间、疾病严重程度和药物使用)的差异。我们还旨在评估和验证简单的自我报告锻炼措施的使用，这些措施很容易获得，适用和有效于这一人群。这将为未来的研究开发更大、更具成本效益的治疗方案。最后，我们的目标是检验运动是否改善了具有既定病程的轻度疾病中年SLE患者的认知功能。如果注意到改善，我们将探索其他人群共同的预测因素(即肺功能、运动能力和抑郁)以及自身免疫性SLE疾病特征特有的因素作为变化机制。最终，我们的目标是利用这项先导性研究来评估心肺锻炼作为干预措施的可行性和有效性，并指导更大规模试验的设计，这些试验将检验这种干预措施在治疗SLE患者认知功能障碍和其他风湿性自身免疫性疾病方面的有效性。 公共卫生相关性：系统性红斑狼疮(SLE)患者的认知功能障碍很常见，但机制仍不清楚，治疗选择有限。这项初步研究将调查导致SLE认知功能障碍的基本肺部问题和/或运动限制。它还将检查针对这一群体的锻炼计划是否可行，并证明认知能力有所改善。开发治疗系统性红斑狼疮认知功能障碍的新疗法可能会对这些和其他自身免疫患者的公共健康产生积极影响。

DESCRIPTION (provided by applicant): Cognitive dysfunction is common in patients with autoimmune disorders such as systemic lupus erythematosus (SLE). These deficits can impact a wide range of activities and a better understanding of the nature and pathogenesis is critical to developing effective treatment approaches in these patients. Despite many prior investigations into autoimmune and vascular abnormalities associated with brain dysfunction in SLE, no one specific underlying mechanism has emerged. SLE is a multi-organ disease and pulmonary involvement has been identified in up to 60% of SLE patients. In a small sample of SLE subjects we found unexpected pulmonary abnormalities related to cognitive dysfunction and our first aim in this study is to compare lung function and exercise capacity in a larger cohort of SLE and control subjects, and evaluate the relationship between lung function, exercise capacity and cognition. The model is based on prior studies in patients with chronic obstructive pulmonary disease (COPD) where cognitive deficits have been associated with poor lung function, exercise capacity and depression. Given the heterogeneity of SLE manifestations we will minimize diversity in some factors (i.e. age, length of diagnosis, disease severity and medication use). We also aim to evaluate and validate the use of brief self-report measures of exercise that are easy to obtain, applicable and valid for this population. This will allow development of larger, cost-effective treatment protocols for future investigations. Finally, we aim to examine whether or not exercise improves cognitive function in a small sample of mildly diseased middle aged SLE patients with established disease duration. If improvement is noted we will explore predictors common to other populations (i.e. lung function, exercise capacity and depression) as well as factors specific to autoimmune SLE disease characteristics as mechanisms of change. Ultimately, we aim to use this pilot study to evaluate the feasibility and utility of cardiopulmonary exercise as an intervention and to guide the design of larger trials that will examine the effectiveness of such an intervention in treating cognitive dysfunction in patients with SLE and possibly other rheumatic autoimmune disorders. PUBLIC HEALTH RELEVANCE: Cognitive dysfunction in patients with systemic lupus erythematosus (SLE) is common, and yet mechanisms remain unclear and treatment options limited. This pilot study will investigate basic pulmonary problems and/or exercise limitations contributing to cognitive dysfunction in SLE. It will also examine whether an exercise program for this group is feasible and demonstrates improvement on cognitive ability. Developing novel treatments for cognitive dysfunction in SLE could have positive effects for public health in these and other autoimmune patients.