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An overview of sleep disordered breathing for the otolaryngologist.

History and magnitude of the problem

The clinical entity currently referred to as obstructive sleep apnea syndrome (OSAS) might have been described as early as the 4th century BC. Dionysius, a tyrant during the time of Alexander the Great, was described as obese, as manifesting sleep-related breathing abnormalities suggestive of OSAS, and as hypersomnolent.

Clinical histories suggestive of sleep disordered breathing (SDB), including OSAS, are presented in 17th and 19th century medical reports. [1-3] Nonetheless, English novelist Charles Dickens is often given credit for the first description of OSAS in 1836. [4] His character, Joe the Fat Boy, had a voracious appetite and exhibited a complex of symptoms and findings suggestive of OSAS: loud snoring, hypersomnolence, bizarre personality, obesity, polycythemia, and congestive heart failure. In 1956, more than 100 years after Dickens published The Posthumous Papers of the Pickwick Club, the term "Pickwickian," alluding to Dickens' character, was used for the first time in the medical literature to describe an obese patient with periodic respiration, hypersomnolence, hypoxemia, polycythemia, and congestive heart failure. [5] It was assumed that the mechanical load on the respiratory system led to a blunted respiratory drive and hypoventilation during both sleep and wake states. Blood gas aberrations resulting from hypoventilation during both sleep and wakefulness were believed to b e responsible for the observed periodic respiration, polycythemia, and heart failure. Hypoxia and hypercapnia were felt to be the cause of hypersomnolence. [5]

But during the decade that followed, improved technology documented that only a small minority of obese and hypersomnolent patients were hypoxic or hypercapnic while they were awake. This group represents the true Pickwickian patient. Most obese and sleepy patients were found to have normal blood gases while they were awake. Their hypersomnolence was primarily the result of sleep fragmentation caused by SDB. [1]

Prevalence. Recent data suggest that the prevalence of SDB in the form of obstructive sleep apnea (OSA) is 24% for men and 9% for women between the ages of 30 and 60 years. [6] Approximately 4% of men and 2% of women in that age range have full-blown OSAS, the syndrome being defined by OSA that causes hypersomnolence. [6] Estimates of the incidence of OSA for elderly men range from 28 to 67% and for elderly women from 20 to 54%. [7-11] Of the approximately 75,000 patients seen annually in accredited sleep disorders centers, 75% are diagnosed with OSAS. Recent projections of the prevalence of OSAS in the United States range from 7 to 18 million people. people. [12]

Sequelae. Two primary health consequences are associated with OSAS. [12] One is the neuropsychiatric sequelae of chronic sleep disruption, which include depression, cognitive dysfunction, disruption of professional, family, and social life, and inattention that can result in automobile and industrial accidents. The second is the cardiovascular sequelae of chronic sleep-related hypoventilation, which include pulmonary and systemic hypertension, congestive heart failure, coronary heart disease, myocardial infarction, and stroke. Industrial safety and transportation authorities are currently focusing on hypersomnolence as a significant cause of industrial and mass transportation accidents, and the incidence of recurrent highway crashes is seven times greater for individuals with OSAS than for normal controls. [13,14]

Natural history studies demonstrate an association between snoring or OSA and hypertension, cardiac ischemia, myocardial infarction, and stroke. In many studies, the strength of these associations is diminished when findings are adjusted for the potentially confounding influences of obesity and smoking, which could both independently increase the risk of vascular disease, snoring, and SDB [15-19] In one case-control study that attempted to control for weight and smoking, the risk of myocardial infarction was four times higher among snorers than nonsnorers, while weight and smoking did not appear to be confounding factors. [18] Another study of patients with OSAS found that they had twice the prevalence of hypertension, three times the prevalence of coronary artery disease, and four times the prevalence of cerebrovascular disease than did the U.S. population in general as reported by the National Center for Health Statistics. [15]

In a report of a 5-year followup of 198 patients with OSAS, the overall mortality for patients who had been treated "conservatively"-that is, they were prescribed a weight loss regimen-was 11 11%. [20] By contrast, there were no deaths among patients in whom OSAS was eliminated by tracheostomy, despite the fact that the tracheostomized patients had been more severely affected. In a study of 385 OSAS patients with 8-year followup, overall mortality was five times higher in untreated patients whose apnea index was greater than 20 events per hour than for untreated patients whose index was less than 20 events per hour. There were no deaths among patients who were effectively treated with tracheostomy or nasal continuous positive airway pressure (CPAP). [21].

Most studies that have attempted to estimate OSAS mortality have been criticized for their small sample sizes, short followup, failure to control for confounding variables associated with obesity or smoking, and other shortcomings inherent in retrospective natural history studies. Changing patterns of treatment have complicated the assessment of the untreated disorder. The weaknesses of various reports in the literature were addressed in a recent epidemiologic review. [22] To put into perspective the strengths and limitations of existing data, which suggest that there are indeed significant mortality and morbidity from OSAS, the National Heart, Lung, and Blood Institute recently funded the Sleep Heart Health Study. This investigation is an extensive multi center, multiyear prospective study of the morbidity and mortality caused by OSA.

Varied manifestations of SDB

SDB encompasses a number of related respiratory disorders that are linked to the sleep state. They are characterized by recurrent episodes of cessation of ventilation (apneas) or respiratory efforts that result in abnormally diminished ventilation (hypopneas). Apnea might be the result of a lack of inspiratory effort, called central apnea, or of ineffective inspiratory effort against a collapsing upper airway, called obstructive apnea. Obstructive apnea that is characterized by an initial central component followed by a collapse of the upper airway at the onset of respiratory effort has been termed mixed apnea.

Hypopnea also might be central or obstructive in nature. The distinction between central and obstructive hypopnea is most effectively made by intraesophageal manometry, which is generally not performed during routine sleep studies. Definitions of hypopnea have varied, but all are based on the same parameters: a variably diminished airflow that results in a drop in oxygen saturation of a pre-established degree, a transient arousal, or both. Apnea and hypopnea both cause arousal. It was recently demonstrated that inspiratory effort in the face of increased upper airway resistance could result in transient arousal despite the maintenance of normal ventilation and oxygenation. The term respiratory effort-related arousal (RERA) can be applied to the phenomenon of inspiratory effort against increased upper airway resistance that results in transient arousal, even though it does not meet the ventilation criteria of either apnea or hypopnea. [23] RERAs are the pathognomonic events that define the upper airway resist ance syndrome (UARS), which is manifested by the hypersomnolence that is the result of frequent RERAs. [24]

Role of the ventilatory control system

There are state-related differences in respiratory control between the sleep and wake states and between the five stages of sleep, most predominantly between stages 1 through 4 non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Therefore, the transition from one of these states to another involves a shift in the neural and neuromuscular mechanisms that maintain alveolar ventilation. This modulation includes alterations in the complex feedback loops and reflexes that monitor the demands of the organism and control ventilation to meet its metabolic needs. It also involves state-specific changes in respiratory load compensation in the form of variations in the medullary motor output to primary and accessory respiratory muscles in response to upper airway resistance and changes in resistance. Breathing disturbances of a central, obstructive, or mixed nature can occur at the interface of two states (e.g., between wake and sleep or between different stages of sleep) in response to the changing state- specific nuances of respiratory control. The respiratory instability prevents the smooth passage from one state to another, thereby causing a volley of shifts back and forth across the two interfaces. This perpetuates instability in both respiration and the state. [25-30]

Wake and NREM sleep generally interface. Sleep is the more vulnerable condition with respect to the body's ability to adapt to metabolic demands. During wakefulness, the brain almost anticipates metabolic rate demands and provides rapid compensation for changes in breathing that are brought about by altered requirements for gas exchange. A strong functional component of the drive to breathe in wakefulness, referred to as the wakefulness drive, might reside within the reticular activating system of the forebrain. The wakefulness drive responds to visual, acoustic, and somatesthetic stimuli and is free of metabolic influence. It serves to boost the respiratory drive that is modulated by the chemoreceptor feedback system. The chemoreceptor system depends on the integration of input from the central pH and [PaCO.sup.2] chemoreceptors; the peripheral [PO.sup.2] and [PaCO.sup.2] chemoreceptors; the lung, chest wall, and upper airway mechanoreceptors; pressure receptors; and possibly flow receptors. The transition from wakefulness to sleep deactivates the wakefulness drive, thus making respiratory control more dependent on chemoreceptor feedback. This results in a diminished responsiveness to blood gas alterations. The absence of the wakefulness drive makes the body more vulnerable to ventilatory instability. [25-30]

The setpoint for [PaCO.sup.2] is higher during sleep than wakefulness, and the hypercapnic ventilatory response curve is shifted to the right throughout all stages of sleep as compared with wakefulness. The slope, or gain, of the ventilatory response to hypercapnia is diminished during sleep compared with wakefulness. These changes during sleep onset might actually reflect the reactivation of the chemoreceptor system, which is pre-empted during wakefulness by the wakefulness drive.

At the moment of sleep onset, the [PaCO.sup.2] setpoint is raised from the wake [PaCO.sup.2] setpoints to the higher sleep [PaCO.sup.2] set point. At the instant that the setpoint is reset, the static [PaCO.sup.2] remains transiently below the newly established sleep setpoint (at the level determined during the immediately ended period of wakefulness). The static [PaCO.sup.2], still at the lower wake level, is sensed as relative hypocapnia and triggers marked ventilatory inhibition. An apneic event ensues, during which the relative hypocapnia is corrected as [PaCO.sup.2] rises to meet the sleep setpoint. The apnea results in hypoxia, which triggers a vigorous respiratory response to correct the hypoxia. It also causes a brief arousal ("microarousal") that terminates the apnea. The microarousal instantly lowers the [PaCO.sup.2] set point back down to the wake setpoint. P in the ensuing breaths, is driven down to a level commensurate with the transiently reestablished wake state. As this occurs, sleep is reest ablished. The corrected once again is below the reestablished sleep setpoint, and respiratory inhibition and apnea recur. Similar transient decreases in [PaCO.sup.2] below its corresponding wake setpoint would not result in respiratory inhibition and apnea in the wake state because inhibition would be overridden by the wakefulness drive to breathe. However, because the relative hypocapnia occurs during transitions into sleep, when there is an absence of the wakefulness drive, significant respiratory inhibition to the point of apnea ensues.25-30

In summary, perpetuation of periodic breathing and central apnea or hypopnea occurs as a result of the mutual interaction of the dynamically changing sleep/wake states and the corresponding modulations in respiratory control that occur with shifts from one state to another. The cyclical shifts in state (from wake to sleep to wake and back) are brought about by respiratory control instability, which is set in motion by the initial shift from wake to sleep. Each apneic period is terminated by an arousal or microarousal (the latter is documented by electroencephalography; it is not usually consciously perceived by the individual). The breath immediately following the arousal is a large, compensatory breath that is stimulated 1) by the asphyxic stimulus (asphyxia resulting from the preceding apnea), 2) by the increased gain attributable to the shift in from its position below the sleep setpoint to its new position above the wake [PaCO.sup.2] setpoint, and 3) by the introduction of the wakefulness drive to breath e coincident with arousal. This large breath lowers Apnea does not occur during the brief epoch of wakefulness, but the microarousal terminates quickly with a rapid return to sleep. With the resumption of sleep, once a gain is below the sleep setpoint and apnea threshold. These constantly and cyclically shifting states-that is, from preapneic to postapneic, and from sleep to wakefulness, with the resultant switches in respiratory control setpoints and gains-perpetuate the cyclic apneas by preventing the respiratory control system from attaining and maintaining a state of equilibrium. This secondarily perpetuates state instability.

The transitions from wakefulness to sleep and from NREM to REM sleep also place the individual at risk for hypoventilation as a result of sleep-related impairment of strategies for compensating with upper airway load (upper airway resistance) compensation. The negative pressure required for inspiration is generated through an increase in chest cavity volume by actions of the diaphragm and intercostal muscles. Upper airway respiratory muscle activity provides compensatory "stiffening" of the upper airway to prevent a decrease in the size of the pharyngeal lumen and an increase in resistance to airflow. Reflex arcs involving these upper airway dilator muscles are integrated with the central mechanisms that control ventilation and breathing. The genioglossus muscle, for instance, responds to chemoreceptor stimuli by contracting in order to increase upper airway patency. Data suggest that there are several types of reflexes that control the upper airway musculature, with afferent input from chemoreceptor, postur al, and pressure receptors. This compensatory action is diminished during the sleep state compared with wakefulness. It is maximally diminished during REM sleep, when there is extreme skeletal muscle hypotonia or atonia. Although during wakefulness the intensity of motor output to the pharyngeal dilator muscles increases rapidly when needed to compensate for increasing upper airway resistance, sleep impairs the compensatory increase in neural drive, and REM sleep impairs it the most. The degree of alteration depends on the specific stage of sleep, with REM-related hypotonia more profound than NREM. It can be generalized that in normal sleep-related breathing, the pharyngeal airway is not fully protected from the effects of inspiratory negative pressure by compensatory upper airway muscle action. As a result, normal sleep triples the upper airway resistance compared with wakefulness. [30-35]

OSA represents the most extreme degree of lack of compensation for increased upper airway resistance, and it is characterized by upper airway collapse uncompensated by dilator muscle action. Collapse occurs in the pharynx. Collapse can occur in the retropalatal or retroglossal portions of the pharynx, or both. The site of pharyngeal obstruction varies among patients. Although airway resistance increases in normal persons during sleep as compared with wakefulness, the sleep-related increase is three times greater in individuals with OSA than in normals. An obstructive apnea results in an arousal or microarousal, with a return to the awake pattern of homeostasis. The wakefulness drive establishes adequate compensation for the increase in upper airway resistance through dilator muscle action, and the obstructive apnea terminates. [25-38]

Primary neurologic or neuromuscular pathology occasionally results in OSA; such pathologies include Chiari malformation, syringomyelobulbia, cerebral palsy, myotonic dystrophy, Shy-Drager syndrome, acquired nonprogressive dysautonomia, olivopontocerebellar degeneration, spinal cord injury, and bulbar stroke. However, in most cases of OSA, there is no identifiable neuromuscular dysfunction, and the problem relates primarily to the increase in upper airway resistance. [39]

Role of upper airway anatomy and structural variation in SDB

OSA has been associated with anatomic compromise resulting from neoplasia (benign or malignant), metabolic abnormality, and traumatic compromise. Inflammatory and metabolic disorders might cause diffuse enlargement of such structures as the tongue and pharyngeal lymphoid tissues, resulting in a compromise of the airway. [39] However, in the vast majority of cases, no specific focus of upper airway pathology can be identified. In one study of 200 patients with OSA, only three had a single pathological anatomic problem. [44] The rest demonstrated a combination of "disproportionate anatomic relationships" in the upper airway.

Anatomic abnormalities. Increased upper airway resistance and collapsibility in patients with OSA can be the result of an anatomic compromise. Pharyngeal resistance during wakefulness is increased in OSA patients compared with normal controls, and pharyngeal resistance correlates with OSA severity. [32-35] The pharynx of adults with OSA collapses when experimentally exposed to subatmospheric pressure during wakefulness, whereas that of normal controls does not. [40] The upper airway is anatomically smaller in apneics than in normals, especially at the retropalatal and retroglossal levels. [41-43] Pharyngeal cross-sectional area correlates inversely with OSA severity. [42]

Many well-defined craniofacial abnormalities can cause OSA. [39] The angles and distances within the upper airway (i.e., the dimensions and configuration of the pharyngeal airway) and the vectors of action of the airway's supporting muscles are determined by the dimensions and spatial relationships of the underlying craniofacial skeleton. Frequently, the anatomic basis for the upper airway obstruction is multifactorial, involving complex skeletal abnormalities translated into pharyngeal soft tissue abnormalities. Several abnormal patterns of craniofacial development have been recognized in adults who were previously considered to be morphologically normal but who manifested OSAS. [39] In a study of craniofacial bony landmarks in lateral cephalograms (radiologic studies of craniofacial skeletal and soft tissue structures) of patients with GSA, 153 of 155 patients had at least two abnormal landmarks. [45] There were many similarities between these findings and those in the population with specifically defined craniofacial syndromes. [39]

Obesity. The association between OSA and obesity is well recognized. Many (but not all) adults with OSA are somewhat obese. It has been demonstrated that patients with OSA who are not obese have more severe craniofacial abnormalities documented on cephalometry. Those who are morbidly obese tend to have few abnormal cephalometric measurements. The largest group of OSA patients has an intermediate level of obesity and an intermediate degree of cephalometric abnormality. [46]

It is well known that weight gain in a patient with OSA results in an increase in the severity of apnea. It has long been hypothesized, and later documented by MRI, that the region surrounding the collapsible segment of the pharynx in patients with OSA has a greater fat load than does the same region in equally obese patients who do not have OSA. [47] This finding--in 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 accumulation--suggests that the effect of obesity on OSA might be related to local parapharyngeal fat deposits. [46-49] Histopathologic studies of uvulas excised during uvulopalatopharyngoplasty for OSA demonstrated a higher amount of both fat and muscle mass compared with those seen during normal postmortem studies. [50]

It is hypothesized that OSA results in part from craniofacial dysmorphia of varying severity. The most severely dysmorphic patients, recognized early as having anomalous craniofacial development, present with airway obstruction at birth or during infancy. Those of this group who are the most severely affected have varying manifestations of airway obstruction while awake and asleep. Those who are less severely affected have only OSA. Mildly dysmorphic patients might develop OSA later in life, either as children when hypertrophic tonsils and adenoids tip the balance in favor of frank OSA, or as adults when weight and cervical fat deposition reach a critical point that converts incipient OSA (i.e., snoring or UARS) into frank OSA. [39]

The amount of muscle force needed to maintain airway patency in the face of negative pressure applied to the pharynx relates both to the degree of the negative pressure applied and to the dimensions and configuration of the pharynx. There are several interacting mechanisms by which a focus of upper airway narrowing predisposes to airway collapse, depending on the region of the upper airway that is compromised. A structural narrowing at the oropharyngeal or hypopharyngeal levels increases the tendency for airway collapse directly by increasing airway resistance. Maintenance of normal tidal volume in the face of increased upper airway resistance requires increased negative inspiratory pressure and increased velocity of air passing through the site of the narrowing. The latter further reduces intraluminal pressure (Bernoulli effect) and increases the tendency for pharyngeal collapse at the site of the narrowing. [35]

Recent data indicate that a pharyngeal configuration such that the anterior-posterior axis is longer than the lateral-lateral axis promotes airway collapse, although the mechanism has not been explained. [51,52] Stenosis of the nasal or nasopharyngeal airway exacerbates a tendency for OSA through a more complex mechanism of action. At rest, humans normally breathe through the nose. The mouth is held closed by the action of the medial pterygoids, masseter, and temporalis muscles. The normally high resistance of the nose in transnasal inspiration results in the introduction of subatmospheric intrapharyngeal pressure, and the transmural pressure of the pharynx tends to close the airway. If the nose is abnormally constricted, the resistance to airflow will be higher, and the pharyngeal negative pressure will be greater. This will more strongly tend to bring about pharyngeal occlusion. [35]

Many individuals who snore or have GSA 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 (atmospheric pressure to relatively negative pharyngeal pressure) is exerted across the soft palate, moving it dorsally and narrowing further the oropharyngeal lumen. [35,53,54] 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. [35] Furthermore, the nasal mucosa, which is bypas sed 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 OSA. [55,56] Several clinical studies confirm that nasal obstruction exacerbates a tendency toward OSA. [53-61] The larynx, the other high-resistance structure in the upper airway, can he the site of OSA when compromised by space-occupying lesions or abductor paralysis.

The efficiency of the action of upper airway dilating muscles--such as the genioglossus, geniohyoid, palatoglossus, palatopharyngeus, stylopharyngeus, and tensor palatini--depends on the proper coordination of their contraction with that of the diaphragm, the vector angles through which they act, and the linear distance through which they contract. The latter two parameters relate to the craniofacial skeletal anatomic attributes of the individual patient.

Anatomic compromise of the craniofacial skeleton and upper airway requires augmented activity from the dilating muscles of the upper airway to maintain airway patency. [28] It has been demonstrated in English bulldogs that upper airway compromise requires abnormally elevated levels of pharyngeal muscle activity to maintain pharyngeal patency during wakefulness. The normal decrease in muscle tone during sleep (down from the elevated levels during wakefulness) might be the mechanism by which OSA occurs in patients who have anatomic upper airway compromise. Although abnormally elevated muscle tone maintains airway patency during wakefulness, muted neuromuscular tone fails to maintain patency during sleep. [28,62]

Pathophysiology of OSA: The concept of Pcrit integrates the roles of central ventilatory control and upper airway structure in a model for SDB

One model of the upper airway in OSA likens it to a simple collapsible tube. The tendency of the upper airway to collapse can be expressed quantitatively in terms of a critical pressure (Pcrit), which is the pressure surrounding the area of collapse. If atmospheric pressure is designated zero, then airway collapse will occur whenever Pcrit is a positive number (indicating that it is higher than atmospheric pressure). When Pcrit is higher than atmospheric pressure, complete pharyngeal obstruction occurs in the form of obstructive apnea. Pcrit for an OSA patient can be defined as the lowest level of nasal CPAP at which airflow is maintained. OSA is the result of an abnormally elevated Pcrit during sleep. [31] In normals, Pcrit during sleep is -13 cm [H.sub.2]O. This means that during sleep, the atmospheric pressure is greater than the Pcrit, and the pharynx will not collapse. In patients who have frank airway collapse during sleep (i.e., OSA patients), Pcrit during sleep is +2.5 cm [H.sub.2]O. [31,47,63] Becaus e Pcrit exceeds atmospheric pressure (defined as zero), pharyngeal collapse will occur. Patients who have varying degrees of partial pharyngeal collapse have intermediate, but negative, levels of Pcrit during sleep: -6.5 cm [H.sub.2]O for asymptomatic snorers and -1.6 cm [H.sub.2]O for patients with hypopneas but no apneas. [31,63]

Pcrit levels are higher during sleep than during wakefulness in both normal individuals and OSA patients. In normals, Pcrit rises from awake values that are more negative than -41 cm [H.sub.2]O to sleep values of -13 cm [H.sub.2]O. [31,40,64] OSA patients, the spectrum of awake values of Pcrit ranges from -40 cm [H.sub.2]O to -17 cm [H.sub.2]O. [31,40] This means that the pharyngeal airway of OSA patients tends to be more collapsible than that of normals, although these values do not cross the critical line of zero (i.e., atmospheric pressure) except when the individual has sleep onset. The fact that both normals and apneic patients experience a substantial increase in upper airway collapsibility with sleep onset implies that sleep is a vulnerable state for the upper airway. [31] Although the cause of pharyngeal collapsibility in OSA is not clearly defined, it is probably multifactorial and reflects a combination of neuromuscular and anatomic variables or abnormalities. It appears clear that sleep-related de pression of neuromuscular function and alteration of reflex control of pharyngeal muscles result in marked increases in upper airway collapsibility and elevation in pharyngeal Pcrit in normals, snorers, and patients with OSA and UARS. [31,65-67]

Assessment and therapy for SDB: Mandate for a multidisciplinary team

Nonsurgical treatments for OSA and UARS include behavior modification, pharmacologic therapy, and the use of mechanical devices such as nasal CPAP and intraoral dental devices.

Behavior modification. Relevant forms of behavior modification include sleep hygiene to minimize exogenous sleep deprivation, avoidance of alcohol and sedative medications, efforts related to avoiding the supine sleep position, and efforts related to weight reduction. Sleep deprivation, alcohol, sedative medications, excess body weight, and the supine position all tend to exacerbate OSA and UARS. Sleep hygiene and avoidance of alcohol and drugs prevent exacerbation of OSA and UARS rather than treating the underlying disorder. Although weight reduction is curative in some obese patients with UARS or OSA of all degrees of severity, permanent loss of significant excess body weight by behavioral means alone is rarely successful. [68,69]

Pharmacologic therapy. Drug therapy is generally of limited value in the treatment of OSA. Although there are reports of limited improvement with acetazolamide, nicotine, and strychnine, none of these agents has proven to be of great value. [70] Of somewhat greater importance are medroxyprogesterone and the tricyclic antidepressant protriptyline, although both are still of limited clinical value. Medroxyprogesterone increases ventilatory response to both hypercapnia and hypoxia in normal men. Although it has been effective in improving oxygenation and correcting hypercapnia in patients with obesity hypoventilation syndrome, it has not proved to be clinically useful in the treatment of normocapnic OSA patients. [70,71] Protriptyline appears to ameliorate OSA via two mechanisms: 1) it tends to suppress REM sleep, the stage in which muscle hypotonia and OSA severity might be at their greatest, and 2) it increases pharyngeal neural activity and dilates the pharyngeal airway. [31,72]

Mechanical devices. Nasal CPAP is widely used as a therapy for OSA (and sometimes UARS), and it has been regarded as the mainstay of therapy for several years. Through the application of positive pressure to the pharynx via the nose, nasal CPAP has the potential to eliminate OSA. Proper application is based on overnight titration to the patient-specific effective pressure level. The major problem with nasal CPAP is relatively poor patient compliance. Early reports of nasal CPAP compliance were based solely on subjective patient reports, which suggested that long-term compliance rates were between 50 and 90%. [70] However, objective monitoring of patient compliance with nasal CPAP reveals significant discrepancies between it and subjective patient reporting and suggests that the level of compliance is much lower than what was previously accepted. In one study, 76% of patients exaggerated their nightly compliance. [73] Only 6% of them used the device for 7 hours per day on at least 5 days per week (i.e., on 70 % of nights), and only 46% of patients used nasal CPAP for at least 4 hours per day on at least 5 days per week.

There is a growing interest in devices that affect pharyngeal mechanics by altering the relative position of the maxilla, mandible, and tongue. Although the role of these appliances has not been adequately delineated, they are effective in diminishing snoring and apnea in some patients. [74,75]

Surgery. Surgical approaches to treat OSA fall into four categories. The first category includes surgical approaches that directly augment the compromised upper airway. These approaches include removal of tumors or masses, corrective nasal surgery, tonsillectomy, uvulopalato-pharyngoplasty, laser-assisted uvulopalatoplasty, laser lingual resection of the tongue and lingualplasty, genioglossal advancement, hyoid suspension, mandibular advancement, and maxillomandibular advancement. A new application of radiofrequency energy to ablate portions of the palate and tongue base has shown promise. The procedures must be applied based on a thoughtful analysis of the specific areas of anatomic compromise in each patient. In complex cases, multiple surgical corrections must be undertaken, either simultaneously or sequentially. This comprehensive approach, based on anatomic assessment, appears to have a high potential for correcting the compromised upper airway, thereby eliminating OSA. [76-80]

The second surgical approach entails surgery to bypass the upper airway obstruction (i.e., tracheostomy). Long regarded as the gold standard against which all other treatments were compared, tracheostomy remains a highly effective treatment. Its major limitations are the physical and psychosocial drawbacks of having a permanent tracheostomy.

The third approach is bariatric surgery (i.e., surgery for weight reduction). Bariatric surgery includes various forms of gastroplasty and gastric and intestinal bypass. For morbidly obese patients in whom the OSA appears to be at least in part secondary to obesity, these modalities of treatment might have a role as either a sole therapy or in conjunction with other surgical and nonsurgical approaches. Although some of the initial weight reduction tends to be reversed over time, there appears to be a significant long-term reduction in weight and a decrease in OSA severity. [81,82]

Finally, the fourth approach is surgery' to implant a pacemaker for pacing pharyngeal muscles (i.e., the genioglossus) to dilate the upper airway.83

The efficacy of various therapeutic approaches has been measured by the amount of improvement in polysomnographic parameters such as the respiratory disturbance index (apneas and hypopneas per hour) and the sleep fragmentation index (microarousals per hour). It is possible that the application of an indirect measure of efficacy, the Pcrit decrement, could have some clinical benefit in patient selection and treatment evaluation. In general, Pcrit must be below -5 cm 20 to eliminate SDB. [31] Three examples of the approximate decrement in Pcrit that can be achieved by different interventions are -6cm [H.sub.2O] through the loss of 15% of body weight; -3 to -4 cm [H.sub.2O] through protriptyline treatment; and -4 to -5 cm [H.sub.2O] through the avoidance of sleeping in the supine position. The decrement in Pcrit achieved by various surgical measures in specific clinical settings remains unknown, but it might provide useful information for patient and procedure selection. [31]

With the complexity of assessment and therapy for OSA, it seems clear that a multidisciplinary approach that coordinates input from diverse behavioral, medical, surgical, and dental specialists would be of value. As OSA is largely an upper airway disorder, there is a potential leadership role for the otolaryngologist, who is the recognized expert in assessment and treatment of disorders of the upper airway.

Abstract

Sleep disordered breathing was first described in ancient times. It is the result of a three-way interaction between the sleep/wake state-specific mechanisms of respiratory control, the interfacing of these mechanisms during times of state change, and the physical properties of the head and neck. Sleep disordered breathing results in pathological daytime sleepiness and is associated with significant cardiovascular morbidity. This paper reviews the history of the field, the physiologic and structural factors that result in sleep disordered breathing, and the implications of these factors for therapy.

From the Capital Region Sleep/Wake Disorders Center, the Capital Region OtolaryngologyuHead and Neck Group, and the Department of Surgery, Albany (NY) Medical College. Reprint requests: Aaron E. Sher, MD, 6 Executive Park Dr., Albany, NY 12203. Phone: (518) 482-9111; fax: (518) 482-6142.

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Publication:Ear, Nose and Throat Journal
Date:Sep 1, 1999
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