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

描述（由申请人提供）：这是Theodore Omachi博士的K23奖申请，他是加州大学旧金山分校（UCSF）的肺病学家。Omachi博士是一名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。虽然COPD和OSA的病理生理学表明这两种疾病合并可能特别有害，但COPD-OSA重叠综合征对健康结果的影响尚未阐明。Omachi博士将利用其主要导师目前资助的NHLBI R01的现有基础设施，该项目正在跟踪通过Kaiser Permanente综合卫生系统招募的1202名COPD受试者。通过调查和生理测量对这些受试者进行了仔细的表征。在计划中的受试者重新评估中，大町博士提议的研究将增加对照睡眠研究，以及针对重叠综合征的其他客观和基于调查的测量。在Aim 1中，Omachi博士将调查OSA对COPD患者不良健康状况的影响程度，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之间的潜在关联。在Aim 3中，他将研究COPD-OSA重叠综合征对夜间低氧血症、日间高碳酸血症、全身性炎症、日间嗜睡和睡眠质量的影响，并进一步研究这些因素在导致重叠综合征的不良健康状况和结局中的中介作用。K23奖将为Omachi博士提供必要的支持，以便：(1)成为COPD和OSA重叠综合征的专家临床研究人员，(2)发展睡眠医学所需的技能，作为一名独立研究者，(3)实施先进的生物统计学方法，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事业。为了实现这些目标，Omachi博士组建了一个指导团队，其中包括一位主要导师，阻塞性肺病流行病学专家Mark Eisner博士，以及三位共同导师：著名的工作残疾研究员Paul Blanc博士；卫生经济学专家Edward Yelin博士；以及生物统计分析专家史蒂文·格雷戈里奇博士。他的团队还包括4名科学顾问：研究OSA门诊管理的Samuel Kuna博士；加州大学旧金山分校睡眠障碍中心主任David Claman博士；心理测量分析专家帕特里夏·卡茨（Patricia Katz）博士；以及肺转化医学技术专家迈克尔·马瑟博士。这个专门的指导团队，加上严格的，

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.