The Overlap Syndrome of COPD and OSA: Determinants of Health Status and Outcomes

描述（由申请人提供）：这是一份K23奖的申请，申请人是加州大学弗朗西斯科分校（UCSF）的肺病学家西奥多Omachi博士。大町博士致力于成为以患者为导向的慢性阻塞性肺疾病（COPD）和阻塞性睡眠呼吸暂停（OSA）重叠综合征的临床研究者。尽管COPD和OSA的病理生理学表明这两种疾病组合可能特别有害，但COPD-OSA重叠综合征对健康结果的影响尚未阐明。Omachi博士将利用他的主要导师目前资助的NHLBI R 01的现有基础设施，该项目正在跟踪通过Kaiser Permanente的综合卫生系统招募的1，202名COPD受试者。这些受试者已经仔细的特点与调查为基础的和生理测量。在计划的受试者重新评估中，Omachi博士提出的研究将增加对照睡眠研究以及其他针对重叠综合征的客观和基于调查的措施。在目标1中，Omachi博士将研究OSA在多大程度上导致COPD患者健康状况不佳，包括运动耐量降低和健康相关生活质量差。在目标2中，他将确定重叠综合征与不良健康结果、直接医疗费用和间接工作残疾费用的前瞻性关联。在目标3中，他将研究COPD-OSA重叠综合征对夜间低氧血症，昼夜高碳酸血症，全身炎症，白天嗜睡和睡眠质量的影响，并将进一步研究这些因素在重叠综合征中导致不良健康状况和结局的介导作用。该K23奖项将为大町博士提供必要的支持，以：（1）成为COPD和OSA重叠综合征的以患者为导向的专业临床研究人员，（2）发展拟议研究和独立研究者职业生涯所需的睡眠医学特定技能，（3）实施先进的生物统计方法，将转化医学纳入临床研究，（4）完善进行复杂经济分析所需的技能，（5）发展独立的临床研究生涯。为了实现这些目标，大町博士组建了一个指导团队，由一位主要导师，阻塞性肺病流行病学专家Mark Reynner博士和3位共同导师组成：Paul Blanc博士，著名的工作障碍研究员; Edward Yelin博士，卫生经济学专家; Steven Gregorich博士，生物统计分析专家。他的团队还包括4名科学顾问：Samuel Kuna博士，研究OSA的门诊管理; UCSF睡眠障碍中心主任大卫克拉曼博士; Patricia Katz博士，心理测量分析专家;和Michael Matthay博士，肺部转化医学技术专家。这支敬业的导师团队，加上严格的， 支持性的研究环境，将确保大町博士发展成为一个成功的独立研究者。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Theodore Omachi, a pulmonologist at the University of California, San Francisco (UCSF). Dr. Omachi is establishing himself as a patient-oriented clinical investigator of the overlap syndrome of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). Although the pathophysiology of COPD and OSA suggests that these two diseases may be particularly harmful in combination, the effects of the COPD-OSA overlap syndrome on health outcomes have not been elucidated. Dr. Omachi will leverage the existing infrastructure of his primary mentor's currently-funded NHLBI R01, which is following 1,202 COPD subjects recruited through Kaiser Permanente's integrated health system. These subjects have been carefully characterized with both survey-based and physiologic measurements. In planned subject reassessments, Dr. Omachi's proposed study will add controlled sleep studies as well as other objective and survey-based measures specific to the overlap syndrome. In Aim 1, Dr. Omachi will investigate the extent to which OSA contributes to poor health status, including reduced exercise tolerance and poor health-related quality of life, in COPD patients. In Aim 2, he will determine the prospective association of the overlap syndrome with adverse health outcomes, direct medical costs, and indirect work disability costs. In Aim 3, he will examine the impact of the COPD-OSA overlap syndrome on nocturnal hypoxemia, diurnal hypercapnia, systemic inflammation, daytime sleepiness, and sleep quality and will furthermore investigate the mediating role of these factors in contributing to poor health status and outcomes in the overlap syndrome. This K23 award will provide Dr. Omachi with the support necessary to: (1) become an expert patientoriented clinical researcher of the overlap syndrome of COPD and OSA, (2) develop skills specific to sleep medicine necessary both for the proposed research and his career as an independent investigator, (3) implement advanced biostatistical methods which incorporate translational medicine into clinical studies, (4) refine skills necessary to perform complex economic analyses, and (5) develop an independent clinical research career. To achieve these goals, Dr. Omachi has assembled a mentoring team comprised of a primary mentor, Dr. Mark Eisner, an expert in obstructive lung disease epidemiology, and 3 co-mentors: Dr. Paul Blanc, a renowned researcher of work disability; Dr. Edward Yelin, an expert in health economics; and Dr. Steven Gregorich, an expert in biostatistical analyses. His team also includes 4 scientific advisors: Dr. Samuel Kuna, who researches the ambulatory management of OSA; Dr. David Claman, Director of the UCSF Sleep Disorders Center; Dr. Patricia Katz, an expert in psychometric analyses; and Dr. Michael Matthay, an expert in pulmonary translational medicine techniques. This dedicated mentorship team, combined with a rigorous, supportive research environment, will ensure Dr. Omachi develops into a successful independent investigator.