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

描述(由申请人提供)：这是为加州大学旧金山分校(UCSF)的肺科医生Theodore Omachi博士申请K23奖项。Omachi博士将自己确立为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员。虽然COPD和OSA的病理生理学研究表明，这两种疾病联合起来可能特别有害，但COPD-OSA重叠综合征对健康结局的影响尚未阐明。Omachi博士将利用他的主要导师目前资助的NHLBI R01的现有基础设施，该R01是通过Kaiser Permanente的综合健康系统招募的1202名COPD受试者。这些受试者已经被仔细地描述了基于调查和生理测量的特征。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受控睡眠研究，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博士将调查OSA在多大程度上导致COPD患者的健康状况不佳，包括运动耐力下降和与健康相关的生活质量下降。在目标2中，他将确定重叠综合征与不良健康结果、直接医疗成本和间接工作残疾成本之间的预期关联。在目标3中，他将研究COPD-OSA重叠综合征对夜间低氧血症、日间高二氧化碳、全身炎症、日间嗜睡和睡眠质量的影响，并将进一步调查这些因素在导致重叠综合征不良健康状况和预后方面的中介作用。这一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家临床研究人员，(2)发展拟议研究和他作为独立研究员职业生涯所必需的睡眠医学特定技能，(3)实施将转化医学纳入临床研究的先进生物统计学方法，(4)完善进行复杂经济分析所需的技能，以及(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，由主要导师、阻塞性肺疾病流行病学专家Mark Eisner博士和3名共同导师组成：著名的工作障碍研究人员Paul Blanc博士、卫生经济学专家Edward Yelin博士和生物统计分析专家Steven Gregorich博士。他的团队还包括4名科学顾问：研究阻塞性睡眠呼吸暂停综合征门诊管理的塞缪尔·库纳博士；加州大学旧金山分校睡眠障碍中心主任大卫·克拉曼博士；心理测量学分析专家帕特里夏·卡茨博士；以及肺部转化医学技术专家迈克尔·马泰博士。这支敬业的导师团队，与严格的、 支持性的研究环境，将确保Omachi博士发展成为一名成功的独立研究员。

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.