Nocturnal Deterusor Overactivity In Overactive Bladder Syndrome

描述(由申请人提供)：特发性膀胱过度活动症(OAB)是一种常见的疾病，与显著的发病率和经济负担有关。夜尿症的定义是睡眠中的空洞，它是OAB一些最重要的不良后果的原因。然而，对OAB患者的夜间生理学研究很少，相关夜尿症的机制也不清楚。此外，还不确定与白天OAB症状相关的机制是否与夜尿症有关，因为生理变化发生在睡眠中，而且OAB患者还有其他潜在的原因导致夜尿症，最明显的是夜间多尿(NP)。迫切需要建立OAB的夜尿症机制，因为夜尿症对治疗的反应不如白天OAB症状。这项申请提出了一项研究，旨在通过评估与OAB夜尿症相关的关键生理机制的有前景的生物标记物来解决这一需求。我们的重点是控制膀胱功能的两个系统之一：自主神经系统(ANS)。这项拟议的研究将检验这一假说，即OAB患者的夜尿可能反映了两个主要过程：1)逼尿肌不稳定导致ANS功能障碍，最终可能导致逼尿肌过度活动(DO)；2)夜间膀胱充盈增加，如NP，引发功能障碍。我们将通过在睡眠实验室中获得与多导睡眠图一致的模型关键组件(ANS的心率变异性评估，膀胱测速以指示DO，最大尿量作为逼尿肌不稳定的指标，以及夜间尿排率)的测量来验证这一假设：OAB伴夜尿症患者(N=76)；NP患者(N=56)；失眠患者(N=32)；以及对照组(N=25)。最终，这项工作可能导致OAB患者夜尿症病理过程的客观生物标志物的开发，用于未来的研究，并可能为改善这一重要但未得到充分治疗的公共卫生问题的患者的治疗提供基础。 公共卫生相关性：夜尿症是特发性膀胱过度活动综合征(OAB)的常见症状，也是其一些最重要的不良后果的来源，包括睡眠障碍、摔倒和日间嗜睡。然而，我们目前有效治疗OAB患者夜尿症的能力仍然有限。这至少部分是由于对OAB的夜尿症的病理生理学缺乏了解。通过更好地描述OAB相关夜尿症的生理机制，这项拟议的研究有可能导致开发更有效的治疗方法，从而改善许多OAB相关性夜尿症患者的生活。

DESCRIPTION (provided by applicant): Idiopathic overactive bladder syndrome (OAB) is a common disorder associated with significant morbidity and economic burden. Nocturia, defined by voids which disrupt sleep, is responsible for some of the most important adverse consequences of OAB. Yet, little research has been carried out on the nocturnal physiology of OAB patients and the mechanisms of the associated nocturia are poorly understood. Further, it remains uncertain whether mechanisms associated with daytime OAB symptoms are relevant to nocturia because changes in physiology occur with sleep and because there are other potential causes of nocturia in OAB patients, most notably nocturnal polyuria (NP). There is a pressing need to establish the mechanisms of nocturia in OAB because nocturia responds less well to treatment than daytime OAB symptoms. This application proposes a study which aims to address this need by evaluating promising biomarkers of key physiologic mechanisms associated with nocturia in OAB. Our focus is on one of the two systems which control bladder function: the autonomic nervous system (ANS). The proposed study will test the hypothesis that nocturia in OAB patients may reflect two primary processes: 1) detrusor muscle instability leading to ANS dysfunction which may culminate in detrusor overactivity (DO); and 2) increased nighttime bladder filling, such as occurs in NP, that triggers ANS dysfunction. We will test this hypothesis by obtaining measures of the key components of our model (heart-rate variability assessment of ANS, cystometrography to indicate DO, maximum void volume as an indicator of detrusor instability, and nocturnal urine production rate) coincident with polysomnography during a single night in the sleep laboratory in: OAB patients with nocturia (N=76); NP patients without OAB (N=56); insomnia patients (N=32); and controls (N=25). Ultimately, this work could lead to the development of objective biomarkers of the pathological processes of nocturia in OAB patients for future research and could provide a basis for improving the treatment of patients with this important but inadequately treated public health problem. PUBLIC HEALTH RELEVANCE: Nocturia is a common symptom of idiopathic overactive bladder syndrome (OAB) and the source of some of its most important adverse consequences including sleep disturbance, falls, and daytime sleepiness. Yet, our current capacity to effectively treat nocturia in OAB remains limited. This is due, at least in part, to a lack of understanding of the pathophysiology of nocturia in OAB. Through better characterizing the physiologic mechanisms of OAB-related nocturia, the proposed study has the potential to lead to the development of more effective treatments for this condition and thereby improve the lives of many patients with nocturia associated with OAB.