Michelle Cao

All Publications

• Continuous positive airway pressure therapy in obstuctive sleep apnea: benefits and alternatives EXPERT REVIEW OF RESPIRATORY MEDICINE Cao, M. T., Sternbach, J. M., Guilleminault, C. 2017; 11 (4): 259-272

  Abstract

  Obstructive sleep apnea (OSA) is a highly prevalent condition affecting persons of all age with an increasing public health burden. It is implicated in cardiovascular disease, metabolic syndrome, neurocognitive impairment, reductions in quality of life, and increased motor vehicle accidents. The goals of OSA treatment are to improve sleep and daytime symptoms, and minimize cardiovascular risks.Areas covered: Continuous positive airway pressure (CPAP) is considered the gold standard therapy that delivers pressurized air into the upper airway to relieve obstruction during sleep. Although CPAP is an effective modality of treatment for OSA, adherence to therapy is highly variable. This article highlights the benefits of CPAP therapy, along with alternative treatment options including oral appliance, implantable and wearable devices, and surgery. Expert commentary: CPAP therapy is the gold standard treatment option and should continue to be offered to those who suffer from OSA. Alternative options are available for those who are unable to adhere to CPAP or choose an alternative treatment modality. The most interesting advances have been incorporating orthodontic procedures in conjunction with myofunctional therapy in prepubertal children, raising the possibility of OSA prevention by initiating treatment early in life.

  View details for DOI 10.1080/17476348.2017.1305893

  View details for Web of Science ID 000399464000002

  View details for PubMedID 28287009

• The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress. Nature and science of sleep Chow, M., Cao, M. 2016; 8: 81-86

  Abstract

  Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.

  View details for DOI 10.2147/NSS.S76711

  View details for PubMedID 27051324

• A Novel Adaptive Servoventilation (ASVAuto) for the Treatment of Central Sleep Apnea Associated with Chronic Use of Opioids. Journal of clinical sleep medicine Cao, M., Cardell, C., Willes, L., Mendoza, J., Benjafield, A., Kushida, C. 2014; 10 (8): 855-861

  Abstract

  To compare the efficacy and patient comfort of a new mode of minute ventilation-targeted adaptive servoventilation (ASVAuto) with auto-titrating expiratory positive airway pressure (EPAP) versus bilevel with back-up respiratory rate (bilevel-ST) in patients with central sleep apnea (CSA) associated with chronic use of opioid medications.Prospective, randomized, crossover polysomnography (PSG) study. Eighteen consecutive patients (age ≥ 18 years) who had been receiving opioid therapy (≥ 6 months), and had sleep disordered breathing with CSA (central apnea index [CAI] ≥ 5) diagnosed during an overnight sleep study or positive airway pressure (PAP) titration were enrolled to undergo 2 PSG studies-one with ASVAuto and one with bilevel-ST. Patients completed 2 questionnaires after each PSG; Morning After Patient Satisfaction Questionnaire and PAP Comfort Questionnaire.Patients had a mean age of 52.9 ± 15.3 years. PSG prior to randomization showed an apnea hypopnea index (AHI) of 50.3 ± 22.2 and CAI of 13.0 ± 18.7. Titration with ASVAuto versus bilevel-ST showed that there were significant differences with respect to AHI and CAI. The AHI and CAI were significantly lower on ASVAuto than bilevel-ST (2.5 ± 3.5 versus 16.3 ± 20.9 [p = 0.0005], and 0.4 ± 0.8 versus 9.4 ± 18.8 [p = 0.0002], respectively). Respiratory parameters were normalized in 83.3% of patients on ASVAuto versus 33.3% on bilevel-ST. Patients felt more awake and alert on ASVAuto than bilevel-ST based on scores from Morning After Patient Satisfaction Questionnaire (p = 0.0337).The ASVAuto was significantly more effective than bilevel-ST for the treatment of CSA associated with chronic opioid use.Cao M, Cardell CY, Willes L, Mendoza J, Benjafield A, Kushida C. A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids. J Clin Sleep Med 2014;10(8):855-861.

  View details for DOI 10.5664/jcsm.3954

  View details for PubMedID 25126031

• Central Sleep Apnea: Effects on Stroke Volume in Heart Failure AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Cao, M., Guilleminault, C., Lin, C. 2013; 187 (4): 340-341

  View details for DOI 10.1164/rccm.201212-2250ED

  View details for Web of Science ID 000315075800004

  View details for PubMedID 23418326

• Sleep-Disordered Breathing, Heart Failure, and Phrenic Nerve Stimulation CHEST Cao, M., Guilleminault, C. 2012; 142 (4): 821-823

  View details for DOI 10.1378/chest.12-0591

  View details for Web of Science ID 000317153200004

  View details for PubMedID 23032447

• Acute and Chronic Sleep Loss: Implications on Age-Related Neurocognitive Impairment SLEEP Cao, M., Guilleminault, C. 2012; 35 (7): 901-902

  View details for DOI 10.5665/sleep.1944

  View details for Web of Science ID 000305997300004

  View details for PubMedID 22754034

• NEUROHORMONES AND SLEEP VITAMINS AND HORMONES: SLEEP HORMONES, VOL 89 Frenette, E., Lui, A., Cao, M. 2012; 89: 1-17

  Abstract

  Mutual interactions between neurohormones, sleep, and the circadian system have been extensively studied. Hormonal secretion is either influenced by sleep and is independent of circadian timing or is closely coupled with the light-dark cycle, although both processes ultimately interact with each other. Sleep has a strong effect on the levels of some hormones (e.g., growth hormone) but little effect on others that are primarily regulated by the circadian system (e.g., melatonin). The exact mechanisms through which sleep affects circulating hormonal levels are not well understood. Much more is known about how the circadian system influences the secretion of hormones. Under normal circumstances, behaviors and the circadian system are synchronized with an optimal phase relationship, and consequently, hormonal systems are exquisitely regulated. Every bit of information constitutes but one small component of a broader, more global neurohormonal picture. In this review, we attempt to divide this analysis into sections including the pineal gland, adenohypophysis, neurohypophysis, describing the reciprocal influence regarding sleep and various neurohormones.

  View details for DOI 10.1016/B978-0-12-394623-2.00001-9

  View details for Web of Science ID 000306815900001

  View details for PubMedID 22640605

• Hypocretin Antagonists in Insomnia Treatment and Beyond CURRENT PHARMACEUTICAL DESIGN Ruoff, C., Cao, M., Guilleminault, C. 2011; 17 (15): 1476-1482

  Abstract

  Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.

  View details for Web of Science ID 000295455800009

  View details for PubMedID 21476951

• Hypocretin and Its Emerging Role as a Target for Treatment of Sleep Disorders CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Cao, M., Guilleminault, C. 2011; 11 (2): 227-234

  Abstract

  The neuropeptides hypocretin-1 and -2 (orexin A and B) are critical in the regulation of arousal and maintenance of wakefulness. Understanding the role of the hypocretin system in sleep/wake regulation has come from narcolepsy-cataplexy research. Deficiency of hypocretin results in loss of sleep/wake control with consequent unstable transitions from wakefulness into non-rapid eye movement (REM) and REM sleep, and clinical manifestations including daytime hypersomnolence, sleep attacks, and cataplexy. The hypocretin system regulates sleep/wake control through complex interactions between monoaminergic/cholinergic wake-promoting and GABAergic sleep-promoting neuronal systems. Research for the hypocretin agonist and the hypocretin antagonist for the treatment of sleep disorders has vigorously increased over the past 10 years. This review will focus on the origin, functions, and mechanisms in which the hypocretin system regulates sleep and wakefulness, and discuss its emerging role as a target for the treatment of sleep disorders.

  View details for DOI 10.1007/s11910-010-0172-9

  View details for Web of Science ID 000287926100016

  View details for PubMedID 21170610

• Advances in the pharmacological approach to sleep disorders. Current pharmaceutical design Cao, M. 2011; 17 (15): 1416-1417

  View details for PubMedID 21476950

• Obstructive Sleep Apnea and Chronic Opioid Use LUNG Guilleminault, C., Cao, M., Yue, H. J., Chawla, P. 2010; 188 (6): 459-468

  Abstract

  The use of opioids has been associated with development of sleep-disordered breathing, including central apneas, nocturnal oxygen desaturations, and abnormal breathing patterns. We describe sleep-disordered breathing and its subsequent treatment in a group of obstructive sleep apneic patients on chronic opioid therapy. Clinical evaluation followed by diagnostic overnight polysomnogram was performed in subjects on chronic opioid therapy who met the study criteria. All subjects had an initial CPAP titration followed by a repeat clinical evaluation. Subjects with an apnea-hypopnea index (AHI) ≥ 5 continued to report symptoms and had follow-up titration with bilevel positive therapy; then bilevel positive-pressure therapy with a back-up rate was then performed. Age-, sex-, and disease-severity-matched obstructive sleep apnea patients served as controls. Forty-four study participants, including a large group of women (50%), and 44 controls were enrolled in the study. Opioid subjects had AHI = 43.86 ± 1.19, with a central apnea index of 0.64 ± 1.36. Two abnormal breathing patterns were seen, including decreased inspiratory effort during an obstructive event and longer than expected pauses in breathing. Despite adequate titration with CPAP and bilevel positive-pressure therapy, nocturnal awakenings and central apnea awakenings persisted (AHI and central apnea indices of 13.81 ± 2.77 and 11.52 ± 2.12, respectively). Treatment with bilevel positive-pressure therapy with a back-up rate controlled the problem. Nonobese OSA patients with opioid intake have obstructive breathing with a different pattern. In this study, bilevel positive-pressure therapy with a back-up rate was the most effective treatment.

  View details for DOI 10.1007/s00408-010-9254-3

  View details for Web of Science ID 000285104200002

  View details for PubMedID 20658143

• Families with sleepwalking SLEEP MEDICINE Cao, M., Guilleminault, C. 2010; 11 (7): 726-734

  Abstract

  Studies on families with sleepwalking are uncommonly published but can give further information on the phenotype of patients with chronic sleepwalking.Out of 51 individuals referred for chronic sleepwalking during a 5-year period, we obtained sufficient information on 7 families with direct relatives who reported sleepwalking with or without sleep terrors. Among 70 living direct family members, we obtained questionnaire responses from 50 subjects and identified 34 cases with a history of sleepwalking. Of the 50 subjects, 16 completed only questionnaires, while all the others also completed a clinical evaluation and nocturnal sleep recordings.There was a positive history of sleepwalking on either the paternal or maternal side of the family over several generations in our 7 families. Thirty-three clinically evaluated subjects had evidence of sleep-disordered breathing (SDB), with associated craniofacial risk factors for SDB (particularly maxillary and/or mandibular deficiencies). There was a complete overlap with the report of parasomnias and the presence of SDB. In cases with current sleepwalking, treatment of SDB coincided with clear improvement of the parasomnia.All of our subjects with parasomnias presented with familial traits considered as risk factors for SDB. These anatomical risk factors are present at birth and even subtle SDB can lead to sleep disruption and instability of NREM sleep. The question raised is: are factors leading to chronic sleep disruption the familial traits responsible for familial sleepwalking?

  View details for DOI 10.1016/j.sleep.2010.01.011

  View details for Web of Science ID 000280914500019

  View details for PubMedID 20598633

• Advances in Narcolepsy MEDICAL CLINICS OF NORTH AMERICA Cao, M. 2010; 94 (3): 541-?

  Abstract

  Narcolepsy with cataplexy is a rare but life-long and challenging disorder. Current insight into the pathophysiology of this condition seems to be autoimmune-mediated postnatal cell death of hypocretin neurons occurring by organ-specific autoimmune targeting with HLA-T-cell receptor interactions. The hypocretin system seems to have an influence on multiple organ systems beyond its wake-promoting mechanisms. The recent availability of cerebrospinal fluid hypocretin-1 analysis has led to definitive diagnostic criteria for narcolepsy with cataplexy. Pharmacologic first-line treatments for excessive daytime sleepiness and cataplexy is sodium oxybate, with modafinil for daytime sleepiness, in adults and children. Other investigative agents and treatment modalities hold promise in future directions for narcolepsy.

  View details for DOI 10.1016/j.mcna.2010.02.008

  View details for Web of Science ID 000278853600008

  View details for PubMedID 20451031

• Pediatric sleep disorders: How can sleep-medicine make a difference? SLEEP MEDICINE REVIEWS Cao, M., Guilleminault, C. 2009; 13 (2): 107-110

  View details for DOI 10.1016/j.smrv.2008.11.002

  View details for Web of Science ID 000264943400001

  View details for PubMedID 19233696

• Sleep and breathing: The impact of mechanical ventilation on the quality of sleep CRITICAL CARE MEDICINE Cao, M., Sarinas, P. S. 2008; 36 (6): 1960-1962

  View details for DOI 10.1097/CCM.0b013e3181761260

  View details for Web of Science ID 000256513000042

  View details for PubMedID 18520652

• Sleep difficulties and behavioral outcomes in children ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Cao, M., Guilleminault, C. 2008; 162 (4): 385-389

  View details for Web of Science ID 000254752200014

  View details for PubMedID 18391149

• Maxillomandibular advancement surgery for obstructive sleep apnea Minerva Pneumologica Cao M, Li KK, Guilleminault C 2008; 47: 203-12
• The dual-wave bolus feature in continuous subcutaneous insulin infusion pumps controls prolonged post-prandial hyperglycaemia better than standard bolus in Type 1 diabetes DIABETES NUTRITION & METABOLISM Lee, S. W., Cao, M., Sajid, S., Hayes, M., Choi, L., Rother, C., de Leon, R. 2004; 17 (4): 211-216

  Abstract

  The dual-wave bolus delivers a combination of an immediate normal pre-meal insulin bolus (approximately 3 min) followed by an extended (or square-wave) bolus that is evenly delivered over several hr as programmed by the patient. The purpose of this study was to compare post-prandial glycaemic excursions following a high-fat meal after administration of insulin by normal vs dual-wave bolus. During this prospective, cross-over, repeated measures study, subjects with diabetes and treated with insulin pump therapy were evaluated using the continuous glucose monitoring system (CGMS) following three combinations of meal and bolus type. A control meal or a high-fat meal was given in place of the evening meal on three separate occasions and comparisons were made between: a) the control meal with normal insulin bolus delivery, b) the high-fat meal with normal insulin bolus delivery, and c) the high-fat meal with dual-wave insulin bolus delivery. Although mean baseline CGMS values were similar in each of the three combinations of meal and bolus type (p=0.54) and in the three hr immediately following the meal (p=0.64, p=0.83, p=1.0), when compared to the control meal/normal bolus and high-fat meal/dual-wave bolus combinations, CGMS profiles disclosed significantly elevated post-prandial glucose in hr 5 through 14 (p<0.05) following the high-fat/normal bolus combination. Prolonged post-prandial glycaemic excursions are identified using the CGMS. Treating post-prandial hyperglycaemia with dual-wave insulin delivery may help manage chronic hyperglycaemia in patients with diabetes.

  View details for Web of Science ID 000224974200002

  View details for PubMedID 15575341