Nocturnal Deterusor Overactivity In Overactive Bladder Syndrome

描述（由申请人提供）：特发性膀胱过动综合征（OAB）是一种常见的疾病，具有显著的发病率和经济负担。夜尿症，指的是扰乱睡眠的空隙，是OAB的一些最重要的不良后果的原因。然而，关于OAB患者夜间生理的研究很少，相关夜尿的机制也知之甚少。此外，日间OAB症状的相关机制是否与夜尿症相关仍不确定，因为生理变化发生在睡眠中，而且OAB患者夜尿症还有其他潜在原因，最明显的是夜间多尿（NP）。由于夜尿症对治疗的反应不如白天的夜尿症好，因此迫切需要建立夜尿症的机制。本申请提出了一项研究，旨在通过评估与OAB夜尿相关的关键生理机制的有前途的生物标志物来满足这一需求。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）。该研究将验证OAB患者夜尿症可能反映两个主要过程的假设：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ANS功能障碍。我们将通过获得我们模型的关键组成部分（ANS的心率变异性评估、指示DO的膀胱造影、作为逼尿肌不稳定指标的最大空隙容积和夜间尿产率）在睡眠实验室的一个晚上与多导睡眠图相一致来检验这一假设：OAB夜尿症患者（N=76）；无OAB的NP患者（N=56）；失眠患者（N=32）；对照组（N=25）。最终，这项工作可能导致开发出OAB患者夜尿病理过程的客观生物标志物，用于未来的研究，并为改善这一重要但治疗不足的公共卫生问题患者的治疗提供基础。

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.