Optimal management of sleep-disordered breathing depends on accurate diagnosis and institution of appropriate therapeutic modalities.
Screening studies in the United States, Europe, and Australia have shown that a substantial proportion of the adult population has mild-to-moderate sleep-disordered breathing (SDB),1,2 a condition characterized by repeated episodes of apnea and hypopnea during sleep. According to the American Lung Association, as many as 18 million Americans suffer from SDB.3 Men are more susceptible than women, and SDB clusters have been observed within families.3 Obesity appears to be a predisposing factor.
The terms SDB and sleep apnea are often used interchangeably. Apnea and hypopnea cause temporary elevations in blood pressure in association with blood-oxygen desaturation, arousal, and sympathetic activation, and may cause elevated blood pressure during the daytime and, ultimately, sustained hypertension. People with SDB are therefore at risk for hypertension and, possibly, heart disease.4
People who suffer from severe SDB may lose so much sleep that their level of alertness during wakefulness is seriously impaired. Such a lack of alertness may pose a serious hazard if they are operating heavy machinery or driving a car. In fact, numerous investigators have found a strong correlation between SDB and the risk of traffic accidents.5-8
Pathogenesis and Clinical Manifestations
Despite the prevalence of SDB, the pathogenetic mechanisms of this disorder remain not completely understood. The occurrence of upper airway obstruction during sleep and not wakefulness implicates the removal of the wakefulness stimulus to breathe as a key factor underlying upper airway obstruction during sleep. Most of the data on sleep effect are derived from studies during nonrapid eye movement (NREM) sleep, given the difficulty in achieving REM during invasive studies in the laboratory environment.
The reduction of tonic upper airway dilating muscle activity caused by sleep is associated with reduced upper airway caliber and increased pharyngeal wall compliance.9 The mechanical corollary of decreased caliber is an increase in upper airway resistance.10 In addition to increased resistance, increased pharyngeal wall compliance during sleep in snorers is manifested by the occurrence of inspiratory flow limitation as flow plateaus during inspiration.10
The combination of increased resistance and inspiratory flow limitation leads to an increased work of breathing, hypoventilation, and frequent arousals from sleep, and ensuing excessive daytime sleepiness. This has been described as a distinct clinical entity referred to as the upper airway resistance syndrome.11
The ability of the ventilatory control system to compensate for added loads is essential for the preservation of chemoreceptor homeostasis; however, immediate compensation for added loads is compromised during NREM sleep. Therefore, resistive loading results in decreased tidal volume and minute ventilation and, consequently, alveolar hypoventilation with subsequent elevation of arterial Paco2.12 Furthermore, NREM sleep abolishes the ability of upper airway dilating muscles to respond to negative pressure.
In awake humans and animals, application of negative pressure to the upper airway elicits a reflex activation of the genioglossus muscle, presumably dilating the upper airway. The fact that this reflex is absent during NREM sleep suggests that sleep eliminates a protective reflex that maintains upper airway patency in the face of narrowing or deformation.13,14 The mechanical consequences of such reflex activation have not yet been determined.
In summary, the failure of immediate load compensation in people with SDB results in hypoventilation and a subsequent increase in respiratory muscle activity.
Determinants of Upper Airway Patency During Sleep
Upper Airway Size and Shape
Some studies have suggested that the pharyngeal airway is smaller during wakefulness in patients with SDB relative to that of normal people.15 In addition, the airway in patients with SDB has an anterior-posterior configuration unlike the horizontal configuration in normal persons.15 The implications of the observed lateral narrowing to the pathogenesis of upper airway obstruction during sleep are yet to be determined.
Pharyngeal patency is a function of the transmural pressure across the pharyngeal wall as well as the compliance of the pharyngeal wall.16 The inspiratory reduction in intraluminal pressure during inspiration is associated with decreased pharyngeal cross-sectional area.15,17 The magnitude of inspiratory narrowing is more pronounced during NREM sleep relative to wakefulness, in patients with SDB relative to normal persons, and in obese patients relative to thin patients.16
Negative intraluminal pressure is thought to induce upper airway obstruction in patients with SDB.17 The collapsing subatmospheric intraluminal pressure during inspiration is generated by thoracic pump muscle activity. In addition, when inspiratory narrowing during sleep occurs, the ensuing increase in air velocity results in decreased intraluminal pressure.16 Subsequently, intraluminal pressure becomes more negative and, hence, more collapsing to the upper airway.
The compliance of the pharyngeal wall is an important determinant of the effect of transmural pressure.16 A stiff pharyngeal wall (as during wakefulness) remains patent even with a significant collapsing transmural pressure. In contrast, a compliant upper airway (as in patients with SDB during sleep) is closed even at atmospheric pressure.
The intrinsic stiffness of the pharyngeal wall is attributed to neuromuscular and nonneuromuscular factors. Upper airway dilating muscles such as the genioglossus muscle are presumed to be critical to the preservation of upper airway patency; however, there is conflicting evidence regarding the effect of upper airway muscles on pharyngeal compliance.
Thoracic Caudal Traction
The upper airway is connected to the thoracic cage and the mediastinum by several structures. Increased lung volume during inspiration is associated with upper airway caliber in awake persons, probably because of thoracic inspiratory activity providing caudal traction on the upper airway, independent of upper airway dilating muscle activity.18 Caudal traction may transmit subatmospheric pressure through the trachea and ventrolateral cervical structures to the soft tissues surrounding the upper airway, increasing transmural pressure and thereby dilating the pharyngeal airway. This mechanism has been shown in sleeping subjects by reduced upper airway resistance and increased retropalatal airway size when end-expiratory lung volume was increased by passive inflation.19 Caudal traction may either dilate or stiffen the pharyngeal airway.18
Patients with SDB may be more dependent on the effects of increased lung volume because dilatation and/or stiffening may be more prominent in a highly compliant upper airway.
The Role of Anatomic Abnormalities, Obesity, and Snoring in the Pathogenesis of SDB
Increased upper airway resistance and collapsibility in patients with SDB can be the result of an anatomic compromise. Pharyngeal resistance during wakefulness is increased in patients with SDB compared with normal individuals, and pharyngeal resistance correlates with the severity of SDB.20 The pharynx of adults with SDB collapses when experimentally exposed to subatmospheric pressure during wakefulness, whereas that of normal controls does not.21 The upper airway is anatomically smaller in patients with SDB than in normal individuals, particularly at the retropalatal and retroglossal levels. Pharyngeal cross-sectional area correlates inversely with SDB severity.22
SDB has been associated with anatomic compromise resulting from neoplasia (benign or malignant), metabolic abnormalities, and traumatic compromise. Inflammatory disorders may cause diffuse enlargement of structure such as the tongue and pharyngeal lymphoid tissues (tonsillitis), resulting in a compromise of the airway; however, in the majority of patients with SDB, no specific focus of upper airway pathology can be identified.
The association between obesity and SDB is well recognized. Weight gain in patients with SDB usually results in an increase in the severity of apnea. It has long been hypothesized, and later documented by magnetic resonance imaging, that the region surrounding the collapsible segment of the pharynx in patients with SDB has a greater fat load than does the same region in equally obese patients who do not have SDB. This findingin conjunction with the finding of an increase in airway resistance and a decrease in airway stability documented when applying lard-filled bags to the neck to simulate cervical fat accumulationsuggests that the effect of obesity on SDB might be related to local parapharyngeal fat deposits.23 Histopathologic studies of uvulas excised during uvulopalatopharyngoplasty (UPPP) for SDB have demonstrated higher amounts of both fat and muscle mass compared with those seen during normal postmortem studies.22,24
Many people who snore or have SDB mouth-breathe during sleep. Although this has not been systematically investigated, increased nasal or nasopharyngeal resistance might explain it. The open-mouth posture unfavorably alters the pharyngeal airway by creating a relatively unstable passage. With the mouth open, the tongue and soft palate are exposed to atmospheric pressure. This releases the anterior part of the tongue, producing a dorsal motion of the belly of the genioglossus, and decreases the dimensions of the oropharyngeal lumen. The entire transmural pressure of the pharynx is exerted across the soft palate, moving it dorsally and narrowing further the oropharyngeal lumen.
Open-mouth posture further compromises the pharyngeal airway by diminishing the length of the axis of action of the genioglossus and, therefore, its efficacy in pulling the tongue forward out of the airway. Furthermore, the nasal mucosa, which is bypassed in mouth breathing, might have receptors that respond to airflow and serve as afferent stimuli for the neural regulatory mechanisms of respiration. Eliminating this afferent input to reflex arcs involving upper airway muscles could predispose to SDB.
Clinical studies have confirmed that nasal obstruction exacerbates a tendency toward SDB.22 The larynxthe other high-resistance structure in the upper airwaycan be the site of SDB when compromised by space-occupying lesions or abductor paralysis.
Management of SDB
Nonsurgical approaches to the management of SDB include behavioral modification, drug therapy, and use of mechanical devices. Behavioral modifications include avoidance of alcohol and sedative medications, alteration of sleep position, avoidance of sleep deprivation, and weight loss. Drug therapy for SDB is of limited clinical value, with the exception of thyroxine replacement in patients with hypothyroidism.25
Nasal continuous positive airway pressure (nCPAP) is the initial treatment of choice for SDB in adults and can reduce mortality associated with SDB.26 CPAP allows progressive restoration of air flow, as the pressure applied exceeds the airway opening pressure. Appropriate CPAP can resolve SDB in many patients. CPAP works by pneumatically splinting the collapsible upper airway. Although effective, CPAP is uncomfortable or intolerable for some patients, and variable patient compliance remains a significant problem. Studies have found that up to 25% of patients discontinue CPAP therapy.27,28
There are surgical options for the management of severe SDB. Tracheostomy was the initial surgical procedure performed for SDB and is effective in decreasing the morbidity and mortality of SDB. Because tracheostomy bypasses the collapsible upper airway, it is the definitive surgical treatment for SDB. This procedure, however, is associated with complications and significant emotional and physical morbidity.29 From the patients perspective, tracheostomy is aesthetically and socially undesirable. Nevertheless, tracheostomy remains an important surgical option in patients with severe SDB who cannot tolerate CPAP, and for whom other interventions are ineffective or unacceptable.
Uvulopalatopharyngoplasty is currently the most commonly performed surgical procedure for the treatment of SDB.30 UPPP is a procedure that enlarges the retropalatal upper airway by excising a portion of the posterior soft palate and uvula with trimming and reorientation of the tonsillar pillars. The tonsils, if present, are excised as well. Historically, UPPP has been considered effective in about 50% of patients with SDB.129,20 These suboptimal results are due largely to unresolved obstruction of the upper airway in sites other than the retropalatal region. Preoperative screening studies are now used to identify patients in whom the retropalate is the primary site of obstruction and in whom UPPP is more likely to be effective. Significant weight gain after UPPP may also contribute to suboptimal results.
Laser-assisted uvulopalatoplasty (LAUP) has been developed for the treatment of snoring and SDB. It is performed under local anesthesia on an outpatient basis. LAUP is a multistaged procedure that involves carbon dioxidelaser excision of the uvula and a small portion of the soft palate at each stage. The goal of staging is to excise the least amount of palatal tissue needed to reduce snoring effectively while reducing the risk of velopharyngeal insufficiency. LAUP has been reported to reduce morbidity, such as pain and bleeding, as compared to traditional UPPP.31 LAUP is also less expensive and may require less time off from work.
Additional surgical procedures used in selected patients with severe SDB, all of which are designed to enlarge the retropalatal airway, include uvulopalatopharyngoglossoplasty; linguoplasty; laser midline glossectomy; inferior sagittal mandibular osteotomy and genioglossal advancement with hyoid myotomy and suspension (GAHM); and maxillomandibular osteotomy (MMO). Laser midline glossectomy involves laser extirpation of a portion of the posterior midline tongue. Laser lingual tonsillectomy, reduction of the aryepiglottic folds, and partial epiglottectomy may be performed in selected patients. Linguoplasty involves additional extirpation of posterior and lateral tongue tissue. In GAHM, the glenoid tubercle of the mandible (the anterior attachment of the tongue) is advanced by a limited osteotomy of the mandible. MMO enlarges the retrolingual airway maximally and provides some enlargement of the retropalatal airway as well. The major drawback of MMO is that it is a complex procedure limited to only a few institutions, and is associated with significant postoperative morbidity.
The consequences of SDB can be significant for those affected as well as bed partners and family members. Although many patients try to self-manage their symptoms, most will eventually seek treatment if symptoms are unrelenting and/or progressive. Optimal management depends on accurate diagnosis, which includes identification of possible triggers, and institution of the appropriate therapeutic modalities.
John D. Zoidis, MD, is a contributing writer for Sleep Review.
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