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.

Public Health Relevance

Improving our understanding of poor outcomes and their determinants in the overlap syndrome of COPD and OSA is critical to developing methods of improving health in this common disorder. The research proposed in this K23 application will better inform clinicians as to the potential harm of OSA in COPD patients and, conversely, the potential benefits of screening for and treating OSA in COPD patients. Moreover, the findings from this research will provide greater understanding of the extent to which behavioral and pathophysiologic abnormalities in the overlap syndrome contribute to poor outcomes and thus lay the groundwork for interventional trials targeting the overlap syndrome.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (F1))
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Twery, Michael
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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Peñaloza, Renée A; Sarkar, Urmimala; Claman, David M et al. (2013) Trends in on-label and off-label modafinil use in a nationally representative sample. JAMA Intern Med 173:704-6
Omachi, Theodore A; Gregorich, Steven E; Eisner, Mark D et al. (2013) Risk adjustment for health care financing in chronic disease: what are we missing by failing to account for disease severity? Med Care 51:740-7
Omachi, Theodore A; Sarkar, Urmimala; Yelin, Edward H et al. (2013) Lower health literacy is associated with poorer health status and outcomes in chronic obstructive pulmonary disease. J Gen Intern Med 28:74-81
Omachi, Theodore A; Blanc, Paul D; Claman, David M et al. (2012) Disturbed sleep among COPD patients is longitudinally associated with mortality and adverse COPD outcomes. Sleep Med 13:476-83
Zutler, Moshe; Singer, Jonathan P; Omachi, Theodore A et al. (2012) Relationship of obesity with respiratory symptoms and decreased functional capacity in adults without established COPD. Prim Care Respir J 21:194-201
Katz, Patricia; Chen, Hubert; Omachi, Theodore A et al. (2011) The role of physical inactivity in increasing disability among older adults with obstructive airway disease. J Cardiopulm Rehabil Prev 31:193-7
Omachi, Theodore A (2011) Measures of sleep in rheumatologic diseases: Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI), and Pittsburgh Sleep Quality Index (PSQI). Arthritis Care Res (Hoboken) 63 Suppl 11:S287-96
Eisner, Mark D; Iribarren, Carlos; Blanc, Paul D et al. (2011) Development of disability in chronic obstructive pulmonary disease: beyond lung function. Thorax 66:108-14
Chen, Hubert; Cisternas, Miriam G; Katz, Patricia P et al. (2011) Evaluating quality of life in patients with asthma and rhinitis: English adaptation of the rhinasthma questionnaire. Ann Allergy Asthma Immunol 106:110-118.e1
Omachi, Theodore A; Eisner, Mark D; Rames, Alexis et al. (2011) Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency. Respir Res 12:35