Efficacy and mechanisms of a behavioral therapy for insomnia coexisting with COPD

描述(申请人提供)：入睡困难、保持入睡或睡眠质量差(失眠)在慢性阻塞性肺病患者中很常见。失眠与更高的死亡率有关，睡眠时间为300分钟的人死亡风险是前者的四倍。失眠还与更高的发病率有关，与没有失眠的人相比，医疗费用高出75%。然而，由于潜在的不良反应，在COPD中使用失眠药物时要谨慎。COPD的常见特征，如呼吸困难、慢性炎症、焦虑和抑郁也会影响失眠，并可能干扰治疗结果。失眠认知行为疗法(CBT-I)是一种指导人们改变与睡眠相关的无益观念和行为的疗法，对原发性失眠症和其他慢性病患者有效，但这种疗法对COPD患者的疗效和作用机制尚不清楚。缺乏这些知识是一个重要的问题，因为如果没有这些知识，卫生保健提供者将仍然没有能力管理患有慢性阻塞性肺病和失眠的患者。长期目标是帮助开发安全有效的非药物干预措施，以最大限度地减少COPD患者的失眠及其后果。这里的目标是严格测试失眠治疗的两个组成部分-CBT-I和COPD教育(COPD-ED)-在患有失眠症和COPD的患者中的有效性，并确定影响治疗结果的机制。中心假设是CBT-I和COPD-ED对失眠和疲劳都有积极的、持久的影响。这一假设与申请人提供的初步数据是一致的。这项拟议研究的基本原理是，一旦了解CBT-I和COPD-ED的疗效和机制，就可以开发新的创新方法来治疗失眠，从非药物角度将失眠和疲劳降至最低，从而为COPD患者带来更长、更高质量和更有成效的生活，并降低由失眠引起的社会成本。在强有力的初步数据的指导下，中心假设将通过CBT-I、COPD-ED和非COPD、非睡眠健康教育注意控制(AC)的随机对照平行分组比较，采用高效的4组设计进行检验。ARM 1包括每周6次CBT-I+AC；ARM 2=6次COPD-ED+AC；ARM 3=CBT-I+COPD-ED；ARM 4=AC。这项设计将允许完成以下具体目标：1.确定CBT-I和COPD-ED单独治疗成分对失眠和疲劳的疗效。2.明确CBT-I和COPD-ED后预后的机制因素。这项研究是开发有效的非药物治疗慢性阻塞性肺疾病并发肺炎的必要的重要步骤。目标1和目标2中提出的工作将为治疗与慢性阻塞性肺疾病共存的失眠的新方法的有效性和成分的机制提供系统的证据。预计结果将具有重大的公共卫生意义和积极影响，因为已确定的机制极有可能为COPD失眠和疲劳的预防和治疗干预提供新的方法。

DESCRIPTION (provided by applicant): Difficulty falling asleep, staying asleep or poor quality sleep (insomnia) is common in people with chronic ob- structive pulmonary disease. Insomnia is related to greater mortality, with four times the risk of mortality for sleep times < 300 minutes. Insomnia is also related to greater morbidity, with 75% greater health care costs than people without insomnia. However, insomnia medications are used with caution in COPD due to potential adverse effects. Common features of COPD such as dyspnea, chronic inflammation, anxiety and depression also affect insomnia and can interfere with therapy outcomes. While cognitive behavioral therapy for insomnia (CBT-I), a therapy that provides guidance on changing unhelpful sleep-related beliefs and behavior, is effective for people with primary insomnia and people with other chronic illnesses, the efficacy and mechanisms of ac- tion of such a therapy are yet unclear in people with COPD. Lack of such knowledge is an important problem, because without it, health care providers will remain ill-equipped to manage patients with both COPD and in- somnia. The long-term goal is to help develop safe and effective non-pharmacological interventions to mini- mize insomnia and its consequences in people with COPD. The objective here is to rigorously test efficacy of two components of insomnia therapy - CBT-I and COPD education (COPD-ED) - in people with coexisting in- somnia and COPD, and to identify mechanisms responsible for therapy outcomes. The central hypothesis is that both CBT-I and COPD-ED will have positive, lasting effects on insomnia and fatigue. This hypothesis is consistent with preliminary data produced by the applicant. The rationale for the proposed study is that once the efficacy and mechanisms of CBT-I and COPD-ED are known, new and innovative approaches for insomnia can be developed to nonpharmacologically minimize insomnia and fatigue, thereby leading to longer, higher quality and more productive lives for people with COPD, and reduced societal cost due to insomnia. Guided by strong preliminary data, the central hypothesis will be tested using a randomized controlled parallel-groups comparison of CBT-I, COPD-ED and non-COPD, non-sleep health education attention control (AC) using a highly efficient 4-group design. Arm 1 comprises 6 weekly sessions of CBT-I+AC; Arm 2=6 sessions of COPD- ED+AC; Arm 3=CBT-I+COPD-ED; and Arm 4=AC. This design will allow completion of the following Specific Aims: 1. Determine the efficacy of individual treatment components, CBT-I and COPD-ED, on insomnia and fatigue. 2. Define mechanistic contributors to the outcomes after CBT-I and COPD-ED. The proposed re- search is a significant, necessary step in the development of effective non-pharmacologic therapies for insom- nia coexisting with COPD. The work proposed in Aims 1 and 2 will provide systematic evidence of efficacy and mechanisms of components of a novel approach to insomnia coexisting with COPD. Results are expected to have great public health significance and positive impact because the identified mechanisms are highly likely to provide new approaches for preventive and therapeutic interventions for insomnia and fatigue in COPD.