The basic mechanism of OSA involves an imbalance between the factors that promote airway collapse and the factors that promote airway patency [15]. In predisposed individuals with a small airway and/or sleep-related pharyngeal neuromuscular dysfunction, the normal loss of upper airway dilator muscle (e.g., genioglossus muscle) tone results in upper airway collapse followed by an absence of airflow despite persistent inspiratory muscle efforts of the diaphragm and the accessory respiratory muscles of the chest and neck. The progressively increasing negative inspiratory pressures mounted to overcome the upper airway resistance/collapse induce so-called respiratory effort-related arousals (RERAs). The reestablishment of airway patency then allows for the compensatory ventilation to correct hypercapnia and hypoxemia. As the individual reenters sleep, the cycle of intermittent partial or complete upper airway obstruction reoccurs multiple times during the sleep period. The recurrent arousals associated with abnormal respiratory events result in sleep fragmentation, reduced sleep efficiency, and reduced rapid eye movement (REM) sleep, all leading to daytime neurocognitive dysfunction. The intermittent hypoxemia and arousals associated with these obstructive respiratory events enhance catecholamine release, oxidative damage, systemic inflammation, endothelial dysfunction, insulin resistance, and hypercoagulability, which may be the basis for the increased risk of cardiovascular comorbidities [coronary heart disease (CHD), stroke, congestive heart failure (CHF), and arrhythmia] and metabolic dysfunction [16]. Sleep stage and body position also influence the severity of OSA. The atonia of the oropharyngeal dilator muscles and the accessory respiratory muscles during REM sleep facilitates upper airway collapse and reduces tidal volumes, respectively. The supine position causes upper airway narrowing by facilitating the direct posterior displacement of the soft palate, tongue, and jaw, and it reduces tidal volumes by enhancing the upward displacement of the diaphragm, particularly in obese individuals with increased abdominal girth.

OSA disorders classically present with loud persistent snoring and breathing pauses during sleep, usually observed by a bed partner, roommate, or household member. The patient may report choking, gasping, gagging, and snoring causing awakenings. Unlike paroxysmal nocturnal dyspnea associated with CHF, asthma, or panic disorders, dyspnea following an obstructive apneic event resolves spontaneously within a few seconds. Neurocognitive manifestations include subjective and objective hypersomnolence as well as impairments in attention/vigilance, delayed long-term visual and verbal memory, visuospatial/constructional abilities, and executive function [17]. OSA increases the risk of motor vehicle accidents, especially in noncommercial drivers [18]. Symptoms of OSA disorders mimic those of clinical depression including depressed mood, irritability, reduced energy level, insomnia, impaired sex drive, etc. [19]. Nocturia may occur due to cardiac release of atrial natriuretic peptide in response to wide fluctuations in intrathoracic pressure during the obstructive apneic event [20]. Physical findings in OSAS include increased BMI (≥28 kg/m²), wide neck circumference (≥17 in. in men and ≥16 in. in women), and predisposing craniofacial features [Table 3.1]. The Mallampati score and Friedman tongue position score both correlate well with OSA severity [21]. Cardiopulmonary examination may reveal the presence of cardiovascular comborbidities such as CHF and COPD.

Cardiovascular complications that may develop during the course of untreated OSA disorders include systemic hypertension, CHD, CHF, arrhythmias, and stroke due to the resulting increased adrenergic activity (norepinephrine release), endothelial dysfunction (reduced flow-mediated dilation), increased pituitary–adrenal axis activity (increased serum ACTH and cortisol levels), systemic inflammation (elevated C-reactive protein and tumor necrosis factor-α levels), and hypercoagulability [16]. Diabetes mellitus type 2 commonly develops in up to 22–63 % of OSA patients depending upon the SRBD severity [22]. Other endocrine derangements associated with OSA include hypogonadism (reduced luteinizing hormone, total and free testosterone, and SHBG) [23, 24], hypercortisolism [25], and reduced plasma insulin-like growth factor (IGF-I) [26].

Various tools have been validated for screening patients for OSAS (e.g., Epworth Sleepiness Scale, STOP-BANG, Berlin questionnaire, etc.). The STOP-BANG questionnaire, which assigns a point for each risk factor present, surpasses the others in terms of performance characteristics and simplicity of use as a screening tool [27]. The ICSD-3 diagnostic criteria for OSAS require the presence of characteristic nocturnal symptoms, neurocognitive dysfunction, mood disorder, and/or cardiovascular comorbidities plus a polysomnogram documenting an elevated respiratory disturbance index (RDI ≥ 5/h), which is calculated as the number of obstructive apneas, hypopneas, and RERAs per hour of sleep [1, 28]. A higher cutoff (RDI ≥ 15/h) is designated for asymptomatic individuals with none of the comorbid conditions listed. While the definition of obstructive apneas is straightforward (i.e., complete cessation of airflow for ≥10 s), published criteria for scoring obstructive hypopneas vary but generally require a ≥30 % reduction of airflow accompanied by either a ≥3–4 % O₂ desaturation or an arousal [28]. RERAs reflect shifts in EEG waveform frequency to alpha, theta, or beta (except spindles) associated with <30 % reduction in airflow amplitude. Upper airway resistance syndrome (UARS) is a mild variant of OSA disorders characterized by the predominance of RERAs and the scarcity of obstructive apneas and hypopneas in a patient with daytime hypersomnolence. The diagnosis of UARS may require esophageal pressure monitoring, which can detect a series of progressively increasing negative inspiratory pressures leading to an arousal. [Note: The Center for Medicare and Medicaid Services, however, uses the AHI, which excludes RERAs, in determining whether OSAS therapies are reimbursed. The exclusion of RERAs may result in the underdiagnosis of OSAS, the underestimation of its severity, and, consequently, the undertreatment of its associated neurocognitive, cardiovascular, and metabolic dysfunction.] Meanwhile, home sleep testing (HST) using a type III portable monitoring device that records at least three respiratory parameters (i.e., airflow, respiratory effort, and oximetry) has been shown to have adequate diagnostic performance when administered in patients with a high pretest probability of moderate-to-severe OSA and with no significant comorbid cardiopulmonary, neurologic, or sleep disorders [29]. However, HST may miss milder forms of OSA including the UARS subtype, since RERAs cannot be detected without EEG monitoring. Peripheral arterial tonometry (PAT) analyzes the fluctuations in peripheral arterial blood flow, heart rate, and oxygen saturation associated with autonomic nervous system changes in response to sleep stage changes (REM vs. non-REM) and sleep-related breathing events. PAT technology has been validated in multiple studies using in-laboratory polysomnography as reference to have good diagnostic performance characteristics [30]. Overnight oximetry alone may be able detect the sawtooth desaturation pattern, or transient dips in SpO₂ returning to baseline, characteristic of OSA. Although the O₂ desaturation index (ODI, which is calculated as the number of times the oxygen saturation dips by 3–4 % divided by the number of hours of oximetry recording time) derived from an overnight oximetry correlates well with the severity of OSA, cases not associated with O₂ desaturations (e.g., UARS) may go undiagnosed.

CPAP is the treatment of choice for OSAS. CPAP functions as a mechanical splint which prevents airway collapse. To determine the optimal pressure level, the patient may either undergo an in-laboratory therapeutic PSG with CPAP titration or home auto-titrating CPAP therapeutic trial (Fig. 3.1). During the in-laboratory therapeutic CPAP titration, the technologist manually adjusts the pressure level to eliminate obstructive apneas, hypopneas, RERAs, and snoring detected via PSG (Fig. 3.2). Alternatively, the auto-titrating CPAP machine can detect apneas, airflow limitation, and snoring using a flow sensor and algorithmically adjust the pressure to eliminate them. Optimal CPAP levels obtained from manual vs. automatic CPAP titration are generally comparable. Meta-analytic studies seem to favor auto-CPAP over fixed CPAP in terms of adherence, sleep architectural changes, neurocognitive outcome (i.e., sleepiness), and patient preference [31, 32]. CPAP therapy has been associated with significant salutary effects on neurocognitive symptoms and cardiovascular complications [Table 3.2]. Despite its high efficacy, CPAP adherence rates are disappointingly low 30–60 % [33]. Barriers to CPAP adherence may include low confidence and motivation, cost, social stigma, lack of partner support, or adverse effects (e.g., poor mask fit, air leaks, facial skin irritation, claustrophobia, naso-oropharyngeal dryness, rhinitis, aerophagia, etc.).

In OSA patients who refuse or cannot tolerate CPAP, the efficacy, benefits, and risks of alternative therapies [e.g., positional, oral appliance (OA), nasal expiratory positive pressure (EPAP), oral pressure (OP), and surgical therapies] should be discussed [34]. Although less efficacious in normalizing the AHI, positional therapy, or avoidance of the supine position with the use of a device (e.g., t-shirt with tennis balls inserted in a back pocket), may be tried for those with positional OSA [35]. Positional OSA is characterized by a 50 % reduction in AHI from supine to non-supine position and a non-supine AHI <10 events/h. Poor long-term positional device adherence may limit its efficacy. There are two types of OA devices: mandibular advancing devices (MADs) and the tongue-retaining devices (TRDs). MADs mechanically protrude the jaw, thereby pulling the tongue and soft palate anteriorly and increasing the pharyngeal size [36]. TRDs suction the tongue anteriorly to prevent retrolingual space collapse. OA therapy is more effective for those who have mild-to-moderate OSA, positional OSA, and lower BMI, particularly if 50–75 % mandibular protrusion is achieved [37]. Nasal EPAP devices adhere to the nostrils during sleep and function as one-way valves that allow minimal impedance to inspiratory flow but provide some resistance to expiratory flow. Although initial clinical trials demonstrated significant reductions in AHI particularly in mild-to-moderate OSA with lower BMI [38, 39], a more recent trial of nasal EPAP on patients withdrawn from CPAP therapy revealed recurrence of hypersomnolence and sleep-disordered breathing [40]. OP therapy is a novel device consisting of a suction hose and a mouthpiece that provides gentle suction in the oral cavity during sleep. The negative pressure in the oral cavity pulls the soft palate anteriorly toward the tongue, thereby opening up the retropalatal and retrolingual spaces. Early clinical trials on OP therapy for CPAP-intolerant patients show modest yet significant improvements in the AHI [41]. Surgical therapies include various otorhinolaryngologic procedures [42] as well as bariatric surgery [43, 44]. Although adenotonsillectomy is the treatment of choice for children with OSAS, otorhinolaryngologic procedures have not been as effective in treating OSA in adults. Uvulopalatopharyngoplasty (UPPP), the most commonly performed surgical procedure in adults with OSA, involves the removal of the uvula, tonsils, and part of the soft palate and reduces the severity of OSA by only 33 % [45]. Maxillomandibular advancement more effectively reduces the AHI by 87 % but requires a Le Fort I with bilateral sagittal split ramus osteotomies [45]. Tracheostomy can cure OSA by bypassing the upper airway obstruction but is rarely performed for this indication. Bariatric surgery reduces the severity of OSAS in majority of patients, cures the disease in a minority [44], and likely reduces the CPAP level requirements. Medications that are supposed to enhance ventilator drive (e.g., theophylline and progesterone), respiratory muscle function (e.g., growth hormone and anabolic steroids), pharyngeal muscle tone (e.g., serotonin reuptake inhibitors), and weight loss (e.g., phentermine and topiramate) are not reliably effective in ameliorating the respiratory and neurocognitive abnormalities in OSA [46]. On the other hand, wakefulness-promoting agents such as modafinil and armodafinil may be prescribed as adjuncts for those patients who have persistent subjective (e.g., based on the Epworth sleepiness scale) hypersomnolence despite adequate CPAP adherence (defined as average CPAP use of ≥4 h/night for ≥70 % of the nights in a 30-day period) [47, 48]. O₂ therapy may improve nocturnal oxygenation but may also prolong the duration of respiratory events [49]. Sympathomimetic stimulants have cardiovascular side effects (e.g., tachycardia and hypertension) and are not approved for use in OSA. Exercise training [50] and playing wind instruments (e.g., didgeridoo [51]) achieved minimal to modest amelioration of OSA in unduplicated clinical trials. Further research on the efficacy of combining different modalities of non-CPAP therapies can determine whether this approach can improves outcomes in OSAS.