On the Cutting Edge of Obstructive Sleep Apnea: Where Next?

Led by Dr. Atul Malhotra, a prominent researcher, clinician, and thought leader in sleep apnea syndromes, this review paper1 discusses the latest in definitions, epidemiology, pathogenesis, diagnosis, and treatment of obstructive sleep apnea (OSA).


The authors highlight the shortcomings of the traditional metric, the apnea-hypopnea index (AHI), that is used to define OSA and its severity. As a frequency-based variable, the AHI does not measure or account for the degree or severity of hypoxemia, which, depending upon the outcome of interest, might represent a serious shortcoming in predicting risk of sequelae and complications of OSA. For example, the AHI, as a good measure of sleep fragmentation related to disordered breathing events, is predictive of sleepiness and motor vehicle crashes but not reliably associated with cardiovascular or metabolic outcomes. Further adding to the issue is the controversy surrounding what degree of oxyhemoglobin desaturation (2%, 3%, or 4%) best represents an event.


The seminal work coming out of the Wisconsin Sleep Cohort in 1993 and again in 2013 has been cited often for prevalence data on OSA. However, a new European cohort study that uses more contemporary definitions and ascertainment methods has shown a strikingly higher prevalence of moderate to severe OSA (23.4% in women and 49.7% in men). These trends are related in part to the increasing epidemic of obesity, more sensitive diagnostic techniques, and higher recognition of OSA among clinicians.


The traditional construct of the pathophysiology of OSA has focused on simple tube mechanics of an upper airway overcome by collapsing forces related to adipose tissue infiltration. More recent data suggest more complex interactions. Hypotheses include those related to neuropathic compromise of pharyngeal dilator muscles, destabilization of ventilatory control, and dysregulation of the mechanisms governing arousal from sleep consequent to disordered-breathing events. Further elucidation of these pathways could lead the way for more personalized approaches to treatment.


Although third-party economic pressures are driving the inexorable transition from laboratory-based polysomnography to out-of-center (home) sleep testing for most cases of uncomplicated OSA, it is important to highlight some of its shortcomings. First, most of what we know today regarding to important outcomes in OSA is derived from in-laboratory testing. Translating to strictly portable monitoring may be fraught with imprecision. Second, home sleep testing generally does not detect rapid eye movement (REM) sleep and therefore lacks the ability to determine the role of REM in any given patient's OSA, which may be of clinical importance. Third, home sleep testing does not measure brain waves to detect arousal from sleep, which is a critical determinant of the daytime effects of OSA. Finally, the authors highlight the potential drawbacks of the coupling of auto-titrating positive airway pressure (PAP) therapy, which is now the standard treatment pathway, to home sleep testing.


The authors highlight the interactions between OSA and chronic obstructive pulmonary disease (COPD), referred to as the "overlap syndrome," which is highly prevalent and associated with mortality increased over that seen in COPD alone. There is also increasing interest in the potential role of high bi-level pressure therapy in patients with hypercapnic COPD and OSA, though more research is needed to determine generalizability of published findings suggesting improved outcomes.


Continuous PAP remains the irrefutably effective "gold standard" therapy for OSA, but the quest remains for alternative treatments for those who cannot tolerate or will not entertain PAP therapy, to the point of avoiding diagnostic testing. An uncontrolled, open-label trial of hypoglossal nerve therapy has suggested efficacy in a subset of patients, but further work is needed to prove safety and to predict those who might benefit. Work continues on oral appliance therapy, both with negative pressure to displace the tongue and with various devices to advance the mandible. Further work is also needed to better define the role of upper-airway surgical procedures in subsets of patients with OSA.


  1. Malhotra A, Orr JE, Owens RL. On the cutting edge of obstructive sleep apnoea: where next? Lancet Respir Med 2015;3:397-403.

Clinical Topics: Heart Failure and Cardiomyopathies, Sleep Apnea

Keywords: Adipose Tissue, Brain Waves, Cohort Studies, Comorbidity, Continuous Positive Airway Pressure, Hypoglossal Nerve, Mandible, Obesity, Oxyhemoglobins, Polysomnography, Prevalence, Pulmonary Disease, Chronic Obstructive, Research Personnel, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Sleep Deprivation, Sleep Stages, Sleep, REM

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