Dr. Cao is board certified in pulmonary medicine, critical care medicine, and sleep medicine. Dr. Cao's clinical expertise includes complex sleep apnea syndromes, advanced modes of PAP therapy, neuromuscular disease and home mechanical ventilation. She sees patients at the Sleep Center and the Neuromuscular Clinic. Her research interests include advanced positive airway pressure devices for complex sleep disordered breathing, opioid induced central sleep apnea, and sleep education.
- Pulmonary and sleep related breathing disorders in neuromuscular disease
- Home Mechanical Ventilation
- Central Sleep Apnea
- Pulmonology and Sleep Disorders
- Sleep Medicine
Clinical Associate Professor, Neurology & Neurological Sciences
Clinical Associate Professor, Psychiatry and Behavioral Sciences - Stanford Center for Sleep Sciences and Medicine
Boards, Advisory Committees, Professional Organizations
Vice Chair, American Academy of Sleep Medicine; Sleep Technologist & Respiratory Therapist Education Committee (2020 - Present)
Committee Member, American College of Chest Physicians - Council of NetWorks (2020 - Present)
Chair, American College of Chest Physicians - Home Mechanical Ventilation and Neuromuscular Disease NetWork (2019 - Present)
Committee Member, American College of Chest Physicians - Scientific Presentations and Awards Committee (2018 - Present)
Member, American Thoracic Society (2008 - Present)
Fellow, American Academy of Sleep Medicine (2007 - Present)
Fellow, American College of Chest Physicians (2004 - Present)
Medical Education: Western University of Health Sciences College of Osteopathic Medicine of the Pacific (2000) CA
Fellowship: Stanford University - CAPS (2008) CA
Fellowship, Harbor-UCLA Medical Center, Pulmonary and Critical Care (2007)
Residency: Loma Linda University - School of Medicine (2003) CA
Board Certification: American Board of Internal Medicine, Pulmonary Disease (2006)
Board Certification: American Board of Internal Medicine, Critical Care Medicine (2007)
Board Certification: American Board of Internal Medicine, Sleep Medicine (2009)
Current Research and Scholarly Interests
Positive Airway Pressure devices for central sleep apnea
Graduate and Fellowship Programs
Sleep Medicine (Fellowship Program)
Noninvasive Ventilator Devices and Modes.
Sleep medicine clinics
2020; 15 (4): 545–55
Noninvasive ventilation has become an increasingly common treatment strategy for patients with diverse conditions involving chronic respiratory failure. An intimate understanding of various advanced respiratory devices and modes is essential in the management of these patients. Pressure-limited modes of ventilation are more commonly used than volume modes for noninvasive ventilation owing to enhanced patient comfort and synchrony with the ventilator, as well as improved leak compensation. Common pressure modes include spontaneous/timed and pressure control, with volume-assured pressure support being an additive feature available on certain devices. Evidence guiding the optimal mode of ventilation for specific diseases is limited.
View details for DOI 10.1016/j.jsmc.2020.08.005
View details for PubMedID 33131664
Consensus-Based Care Recommendations for Pulmonologists Treating Adults with Myotonic Dystrophy Type 1.
Respiration; international review of thoracic diseases
Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects approximately 1 in 2,500 individuals globally [Ashizawa et al.: Neurol Clin Pract 2018;8(6):507-20]. In patients with DM1, respiratory muscle weakness frequently evolves, leading to respiratory failure as the main cause of death in this patient population, followed by cardiac complications [de Die-Smulders et al.: Brain 1998;121(Pt 8):1557-63], [Mathieu et al.: Neurology 1999;52(8):1658-62], [Groh et al.: Muscle Nerve 2011;43(5):648-51]. This paper provides a more detailed outline on the diagnostic and management protocols, which can guide pulmonologists who may not have experience with DM1 or who are not part of a neuromuscular multidisciplinary clinic. A group of neuromuscular experts in DM1 including pulmonologists, respiratory physiotherapists and sleep specialists discussed respiratory testing and management at baseline and during follow-up visits, based on their clinical experience with patients with DM1. The details are presented in this report.Myotonic recruited 66 international clinicians experienced in the treatment of people living with DM1 to develop and publish consensus-based care recommendations targeting all body systems affected by this disease [Ashizawa et al.: Neurol Clin Pract. 2018;8(6):507-20]. Myotonic then worked with 12 international respiratory therapists, pulmonologists and neurologists with long-standing experience in DM respiratory care to develop consensus-based care recommendations for pulmonologists using a methodology called the Single Text Procedure. This process generated a 7-page document that provides detailed respiratory care recommendations for the management of patients living with DM1. This consensus is completely based on expert opinion and not backed up by empirical evidence due to limited clinical care data available for respiratory care management in DM patients. Nevertheless, we believe it is of relevance for professionals treating adults with myotonic dystrophy because it addresses practical issues related to respiratory management and care, which have been adapted to meet the specific issues in patients with DM1.The resulting recommendations are intended to improve respiratory care for the most vulnerable of DM1 patients and lower the risk of untoward respiratory complications and mortality by providing pulmonologist who are less experienced with DM1 with practical indications on which tests and when to perform them, adapting the general respiratory knowledge to specific issues related to this multiorgan disease.
View details for DOI 10.1159/000505634
View details for PubMedID 32299079
The Effect of Obstructive Sleep Apnea on Absolute Risk of Central Serous Chorioretinopathy.
American journal of ophthalmology
To determine the incidence of central serous chorioretinopathy (CSC) stratified by age, sex, and diagnosis with obstructive sleep apnea (OSA), and to determine whether some patients with newly diagnosed CSC may be candidates for OSA evaluation.Retrospective cohort study.We used the IBM Marketscan database to select 59,016,145 commercially-insured patients in the United States between 2007 and 2016. We identified patients' first diagnosis with CSC, and defined patients as having OSA if they had a diagnosis following a sleep study. We specified Cox proportional hazard models with interactions between age, sex, and OSA status to determine patients' risk of developing CSC. We estimated the positive predictive value (PPV) that a new diagnosis of CSC would have in predicting a subsequent diagnosis of OSA.Risk of CSC increased with age in years (HR=1.030, p<.001) and OSA diagnosis (HR=1.081, p=.033), and was lower in women (HR=0.284, p<.001). We estimated the annual incidence of CSC was 9.6 and 23.4 per 100,000 women and men, respectively. Incidence was higher in women and men with OSA (17.2 and 40.8 per 100,000). The PPV of CSC diagnosis as a predictor of OSA was highest in the fifth decade of life.The incidence of CSC in our patient sample is higher than previously reported. Risk of CSC is higher in men than in women, and OSA increases risk of CSC in both men and women. Some patients, particularly older males, may be good candidates for OSA evaluation following a CSC diagnosis.
View details for DOI 10.1016/j.ajo.2020.05.040
View details for PubMedID 32574769
NEUROMUSCULAR RESPIRATORY FAILURE IN THE ICU: AN "UNWEANABLE" PATIENT AND A NOVEL TIERED PROTOCOL
LIPPINCOTT WILLIAMS & WILKINS. 2020
View details for Web of Science ID 000530000201212
- Chronic opioid use on sleep and respiration: scratching the surface. Sleep medicine 2019
Effects of Chronic Opioid Use on Sleep and Wake
SLEEP MEDICINE CLINICS
2018; 13 (2): 271-+
Chronic use of opioids negatively affects sleep on 2 levels: sleep architecture and breathing. Patients suffer from a variety of daytime sequelae. There may be a bidirectional relationship between poor sleep quality, sleep-disordered breathing, and daytime function. Opioids are a potential cause of incident depression. The best therapeutic option is withdrawal of opioids, which proves difficult. Positive airway pressure devices are considered first-line treatment for sleep-related breathing disorders. New generation positive pressure servo ventilators are increasingly popular as a treatment option for opioid-induced sleep-disordered breathing. Treatments to improve sleep quality, sleep-related breathing disorders, and quality of life in patients who use opioids chronically are discussed.
View details for PubMedID 29759277
Sleep and Health: Medical Students' Perspectives and Lessons Learned
2017; 41 (5): 679–81
View details for PubMedID 28929351
- Factors Influencing Noninvasive Ventilation Initiation in Amyotrophic Lateral Sclerosis ELSEVIER SCIENCE BV. 2017: 187A
- Survey of Sleep Education Offered by US Pulmonary and Critical Care Fellowship Training Programs ELSEVIER SCIENCE BV. 2017: 554A
Continuous positive airway pressure therapy in obstuctive sleep apnea: benefits and alternatives
EXPERT REVIEW OF RESPIRATORY MEDICINE
2017; 11 (4): 259-272
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 PubMedID 28287009
The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.
Nature and science of sleep
2016; 8: 81-86
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
View details for PubMedCentralID PMC4803263
A Novel Adaptive Servoventilation (ASVAuto) for the Treatment of Central Sleep Apnea Associated with Chronic Use of Opioids.
Journal of clinical sleep medicine
2014; 10 (8): 855-861
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
View details for PubMedCentralID PMC4106939
- Central Sleep Apnea: Effects on Stroke Volume in Heart Failure AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2013; 187 (4): 340-341
- Sleep-Disordered Breathing, Heart Failure, and Phrenic Nerve Stimulation CHEST 2012; 142 (4): 821-823
- Acute and Chronic Sleep Loss: Implications on Age-Related Neurocognitive Impairment SLEEP 2012; 35 (7): 901-902
NEUROHORMONES AND SLEEP
VITAMINS AND HORMONES: SLEEP HORMONES, VOL 89
2012; 89: 1-17
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
2011; 17 (15): 1476-1482
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 PubMedID 21476951
Hypocretin and Its Emerging Role as a Target for Treatment of Sleep Disorders
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
2011; 11 (2): 227-234
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 PubMedID 21170610
Advances in the pharmacological approach to sleep disorders.
Current pharmaceutical design
2011; 17 (15): 1416-1417
View details for PubMedID 21476950
Obstructive Sleep Apnea and Chronic Opioid Use
2010; 188 (6): 459-468
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 PubMedID 20658143
Families with sleepwalking
2010; 11 (7): 726-734
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 PubMedID 20598633
Advances in Narcolepsy
MEDICAL CLINICS OF NORTH AMERICA
2010; 94 (3): 541-?
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 2009; 13 (2): 107-110
- Sleep and breathing: The impact of mechanical ventilation on the quality of sleep CRITICAL CARE MEDICINE 2008; 36 (6): 1960-1962
- Sleep difficulties and behavioral outcomes in children ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE 2008; 162 (4): 385-389
- Maxillomandibular advancement surgery for obstructive sleep apnea Minerva Pneumologica 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
2004; 17 (4): 211-216
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