The Impact of Sleep Disordered Breathing in People who use Opioids

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Project Summary/Abstract This proposal details a five-year research and career development plan for Jeremy E. Orr, M.D., a specialist in pulmonology and critical care medicine, and Assistant Professor of Medicine at the University of California, San Diego. His research has been supported by a National Research Service Award fellowship and currently an American Thoracic Society Foundation award. The overall focus of his research is understanding the importance of breathing issues during sleep in patients using chronic opioid medications, and identifying treatment strategies for these complex breathing issues that will improve health. This K23 award will provide necessary support for Dr. Orr to gain expertise in patient-oriented clinical research, applied physiology of sleep disordered breathing, and clinical trials. Dr. Orr has assembled a comprehensive team of mentors to support his research and career development. His primary mentor, Dr. Atul Malhotra, is a world expert in sleep disordered breathing (SDB) and applied respiratory physiology, with a strong track record of mentoring and promoting junior faculty to become independent investigators. Dr. Robert Owens is a NIH-funded physician-scientist with expertise in advanced techniques to measure SDB physiology, and will serve as a “hands-on” co-mentor. Additional members of the team are Dr. Sonia Jain (statistics and trials), Dr. Mark Wallace (opioids and pain), Dr. Shamim Nemati (signal analysis), and Dr. Frank Powell (control of breathing). Patients with chronic pain who use chronic opioids are at increased risk for poor health including ongoing pain, poor sleep, decreased quality of life, and an increased risk of mortality. Opioids are known to have effects on breathing which may lead to SDB, an under-recognized factor potentially contributing to adverse outcomes in these patients. SDB contributes to sleep disruption and impairments in oxygen levels, but has been little studied in this high-risk group of patients using opioids. In a broad group of subjects with chronic pain who use chronic opioids, this research will determine whether treatment of SDB with continuous positive airway pressure (CPAP) leads to improved sleep quality, as well as investigating other symptoms including pain in these patients (Aim 1). CPAP treatment may not be effective in some patients due to unstable breathing (due to opioids), so techniques to identify such individuals will be investigated, including new measures of breathing instability. For patients with persistent SDB despite CPAP, treatment options are limited. The research will evaluate whether a medication (acetazolamide) that helps to reduce the instability of breathing will help to resolve SDB (Aim 2). This research will provide Dr. Orr with a strong foundation to become an independent investigator studying the impact, pathogenesis and treatment of SDB in those using chronic opioids.