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Principal Investigator: Jeremy Elliot Orr
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2024
Award: $169,893
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <Acetazolamide><Address><Adverse effects><Affect><American><Apnea><Ataxia><Ataxy><Award><Breathing><Brief Pain Inventory><CPAP><CPAP Ventilation><California><Caring><Cell Communication and Signaling><Cell Signaling><Central Alveolar Hypoventilation><Central Apnea><Central Sleep Apnea><Central Sleep Apnea Syndrome><Central Sleep-Disordered Breathing><Central Sleep-Disordered Breathings><Chest><Chronic><Clinical Research><Clinical Study><Clinical Trials><Complex><Continuous Positive Airway Pressure><Coordination Impairment><Critical Care><Cross-Over Trials><Crossover Trials><Data><Department of Health and Human Services><Development Plans><Development and Research><Disease><Disorder><Doctor of Medicine><Dose><Drug Therapy><Drugs><Dyssynergia><Event><Excess Mortality><Faculty><Failure><Fellowship><Foundations><Funding><Goals><Health><Hypoventilation><Impairment><Individual><Intracellular Communication and Signaling><Investigators><K23 Award><K23 Mechanism><K23 Program><Knowledge><Laboratories><Link><M.D.><Measures><Mediating><Medical><Medication><Medicine><Mentored Patient-Oriented Research Career Development Award><Mentored Patient-Oriented Research Career Development Award (K23)><Mentors><Moods><Morbidity><Morbidity - disease rate><NIH><NRSA><National Institutes of Health><National Research Service Awards><O element><O2 element><Ondine Syndrome><Opiate user><Opiates><Opioid><Opioid drug user><Overdose><Oxygen><PWUO><Pain><Painful><Pathogenesis><Patients><Persistent pain><Personalized medical approach><Pharmaceutical Preparations><Pharmacotherapy><Physicians><Physiology><Placebos><Pneumology><Pneumonology><Polysomnography><Public Health><Pulmonary Medicine><Pulmonology><QOL><Quality of life><R & D><R&D><Randomization trial><Randomized><Recreation><Research><Research Personnel><Research Support><Researchers><Respiration Disorders><Respiratory Aspiration><Respiratory Disorder><Respiratory Inspiration><Respiratory physiology><Risk><Science><Scientist><Sham Treatment><Signal Transduction><Signal Transduction Systems><Signaling><Sleep><Sleep Apnea><Sleep Apnea Syndromes><Sleep Hypopnea><Sleep Monitoring><Sleep disturbances><Sleep-Disordered Breathing><Societies><Somnography><Specialist><Supervision><Symptoms><Techniques><Thorace><Thoracic><Thorax><Treatment Failure><United States Department of Health and Human Services><United States Dept. of Health and Human Services><United States National Institutes of Health><Universities><aberrant sleep><adverse consequence><adverse outcome><biological signal transduction><breathing disorder><care as usual><career development><chronic pain><chronic pain patient><co-morbid><co-morbidity><comorbidity><comparative effectiveness><constant pain><customized therapy><customized treatment><death risk><determine efficacy><disrupted sleep><disturbed sleep><drug treatment><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><high risk group><high risk individual><high risk people><high risk population><impaired sleep><improve symptom><improved><improvement on sleep><indexing><individualized approach><individualized medicine><individualized patient treatment><individualized therapeutic strategy><individualized therapy><individualized treatment><inspiration><irregular sleep><lasting pain><licit opioid><member><mortality><mortality risk><on-going pain><ongoing pain><opiate consumption><opiate drug use><opiate intake><opiate medication><opiate use><opioid consumption><opioid drug use><opioid intake><opioid medication><opioid patient><opioid use><opioid user><patient centered><patient oriented><patient specific therapies><patient specific treatment><patient with chronic pain><patients who use opioids><people who use opioids><personalized approach><persons who use opioids><polysomnographic><poor health outcome><poor sleep><precision approach><prescribed opiate><prescribed opioid><prescription opiate><prescription opioid><primary outcome><professor><prospective><public health emergency><quality of sleep><randomisation><randomization><randomized trial><randomly assigned><reduced health outcome><research and development><respiratory><respiratory dysfunction><respiratory function><secondary outcome><sham therapy><sleep control><sleep disruption><sleep dysregulation><sleep improvement><sleep measurement><sleep physiology><sleep polysomnography><sleep quality><sleep regulation><sleep-related breathing disorder><statistics><symptom improvement><symptomatic improvement><tailored approach><tailored medical treatment><tailored therapy><tailored treatment><therapy failure><treatment as usual><treatment risk><treatment strategy><trial design><unique treatment><usual care><ventilation><worse health outcome>