Jeremy E. Orr, MD is a fellow in the Division of Pulmonary and Critical Care Medicine at the University of California San Diego. He has a background in Internal Medicine, Pulmonary and Critical Care Medicine, and Sleep Medicine. Most recently, he has been interested in the role of unstable ventilatory control as a potential mechanism for sleep disordered breathing (SDB). Under the mentorship of Dr. Atul Malhotra and Dr. Robert Owens, his research program will investigate the hypothesis that increased time delay between the lungs and neural control centers for breathing (termed circulatory delay) results in instability, which in turn causes SDB. The study will look at patients with pulmonary arterial hypertension (PAH), who may have right ventricular failure, but lack other known predisposition to SDB. Subjects will undergo sleep testing to determine the presence and characteristics of SDB in this group. The study will then utilize clinically available hemodynamic data and quantitative analysis of sleep study data to determine the relationship between circulatory delay, control stability, and sleep disordered breathing. Many subjects will subsequently be treated clinically for their pulmonary hypertension with selective pulmonary vasodilator therapy, which is expected to improve pulmonary artery pressures and right ventricular function. Follow up study visits will determine the effect of this treatment on SDB, and whether any change is attributable to improvements in circulatory delay and control stability. Thus, this study seeks to move past correlation to a causal pathway between circulatory delay and sleep disordered breathing. Although the proposed study is focused on a specific group, the results will be applicable to a broader category of patients - particularly those with right heart failure and/or low cardiac output - and could help determine management of sleep disordered breathing in such patients. This research will help to advance a more comprehensive model of SDB, allowing clinicians and patients to move beyond the one-size-fits-all approach using CPAP to more individualized treatment.

Public Health Relevance

Sleep disordered breathing (SDB) is a highly prevalent disease with known deleterious effects, but adherence to first-line treatment with positive airway pressure (CPAP) is poor. A growing body of research suggests that a variety of mechanisms, such as unstable control of breathing, may drive SDB in different patients, and that a better understanding may lead to more personalized treatment options. This research program will determine the effect of a circulatory delay, a component of unstable ventilatory control, in the development of SDB, and therefore may be relevant for future management of sleep disordered breathing.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Laposky, Aaron D
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University of California, San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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Orr, Jeremy E; Sands, Scott A; Edwards, Bradley A et al. (2018) Measuring Loop Gain via Home Sleep Testing in Patients with Obstructive Sleep Apnea. Am J Respir Crit Care Med 197:1353-1355
Orr, Jeremy E; Malhotra, Atul; Sands, Scott A (2017) Pathogenesis of central and complex sleep apnoea. Respirology 22:43-52