Some decades after pioneering reports of obstructive sleep apnea in the Pickwickian syndrome, obstructive sleep apnea is a recognized common clinical problem with important consequences such as excessive daytime sleepiness and cerebrovascular or cardiovascular disease (stroke, hypertension, myocardial infarct, atrial fibrillation, and vascular dementia). In this article, the author provides information on historical notes and physiology of respiration during sleep as well as pathophysiology and clinical aspects of sleep-related breathing disorders, particularly obstructive sleep apnea syndrome. The article also summarizes diagnostic methodologies, describes the most common complications of obstructive sleep apnea and their pathogenetic mechanisms, and outlines available therapeutic approaches and their indications, suggesting issues for future research.
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• Obstructive sleep apnea syndrome is characterized by repeated upper airway obstructions leading to sleep fragmentation and oxygen desaturations in severe cases. Narrowing and closure of the upper airway, specifically the oropharynx, during sleep is the basis of the disease.
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• Obstructive sleep apnea occurs more frequently in men than in women, with important consequences such as excessive daytime sleepiness and a higher risk of cerebrovascular or cardiovascular disease (stroke, hypertension, myocardial infarct, atrial fibrillation, and vascular dementia).
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• Habitual snoring is the first stage of the disease, which may progress to high resistance in the obstructed area while breathing and eventually intermittent obstruction while asleep.
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• Obstructive sleep apnea syndrome (mild, moderate, and severe) tends to develop after body weight increases and age advances, with obesity being the most salient risk factor for the development of obstructive sleep apnea.
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• A nocturnal video-polysomnogram performed in a sleep laboratory is the gold standard for diagnosis of obstructive sleep apnea, but an easier approach, mainly when focusing on screening purposes, consists in the use of ambulatory devices recording various combinations of pulse oximetry, breathing effort, airflow, snoring, heart rate, EEG, or other measures.
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• The type of treatment for obstructive sleep apnea syndrome depends on the severity of the disorder. Treatment often includes losing weight, avoidance of alcohol and hypnotic drugs, and avoidance of the supine position during sleep. In moderate to severe obstructive sleep apnea, the treatment of choice is nasal continuous positive airway pressure (CPAP) application that functions as an air splint to maintain positive intraluminal pressure in the upper airway. There are variations in PAP devices such as Bilevel PAP, auto CPAP, and adaptive servo-ventilation. Oral appliances and surgical procedures (uvulopalatopharyngoplasty, tracheostomy, maxillofacial surgery) designed to maintain nocturnal airway patency are additional options to be considered in selected cases. Neurostimulators of the oropharyngeal dilator muscles are available for patients who do not tolerate or fail PAP therapy.
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• If uncontrolled, moderate to severe sleep apnea may be associated with brain structural lesions, pervasive sleepiness, and cognitive changes.
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• Sleep apnea is a risk factor for increased mortality in patients with COVID-19 infection.
Historical note and terminology
The first medical description of sleep apnea was made by Sidney Burwell and colleagues in 1956. Prior to that date there had been a few published cases of cardiopulmonary insufficiency with extreme obesity, periodic breathing, and hypersomnia or narcolepsy that were reviewed by Harvey Estes and colleagues in a 1957 article (50). Burwell and associates described a case of a sleepy, obese patient and used the eponym of Pickwickian syndrome. The term “Pickwickian” was derived from The Posthumous Papers of the Pickwick Club written by Charles Dickens, in which the boy Joe resembles “modern” patients with obstructive sleep apnea because he was excessively fat, a heavy snorer, red-faced, and sleepy during the day (43). The popular movie The Westerner filmed in 1940 starring Gary Cooper and Walter Brennan shows a scene depicting a most classical obstructive sleep apnea event after an evening of heavy alcohol drinking. This film was produced more than 20 years before sleep apnea made it to the medical literature, indicating that sleep apnea was known at the popular level but not recognized by the medical establishment.
Burwell attributed symptoms to obesity causing inefficient breathing (alveolar hypoventilation); the consequent rise in carbon dioxide level in blood resulted in drowsiness (23). However, Rodman and colleagues and Lawrence, studying non-obese subjects, attributed the alveolar hypoventilation to a primary hypoexcitability of the respiratory center (108; 165).
In 1965, Jung and Kuhlo described the characteristic repetitive interruptions of breathing during sleep in these patients. They showed that carbon dioxide narcosis was not the cause of hypersomnia because it could occur even in subjects whose gas analysis values were normal during wakefulness (87). At almost the same time, Gastaut and colleagues in France reported that the recurrent breathing arrests typical of the syndrome were mainly due to an obstruction of the upper airway (64).
In studies published in the “Bulletin de Physiopathologie Respiratoire,” Lugaresi and colleagues described the dramatic hemodynamic and respiratory consequences of sleep apnea using invasive monitoring of blood pressure in sleeping Pickwickian patients (34; 118).
In subsequent studies, the same authors highlighted the pathophysiological link between snoring and obstructive apneas, indicating the existence of a continuum of clinical conditions between snoring and the severest forms of obstructive sleep apnea syndrome (116; 115). Epidemiological studies showed that obstructive sleep apnea was an important risk factor for arterial hypertension, ischemic heart disease, and stroke (119).
Tracheostomy bypassing the pharyngeal obstruction appeared to be an efficacious therapy for obstructive sleep apnea (102; 117).
The introduction of nasal continuous positive airway pressure (CPAP) revolutionized the treatment of obstructive sleep apnea (188). The recognition that obstructive sleep apnea is a common disorder with disabling symptoms and substantial associated morbidity and mortality has had a profound impact on the field of sleep medicine. Despite the increased recognition of obstructive sleep apnea, moderate to severe obstructive sleep apnea remains underdiagnosed and undertreated.