By Amber Luong, MD

 Obstructive Sleep Apnea
Obstructive breathing disorders include a spectrum of sleep abnormalities including primary snoring, upper airway resistance syndrome and obstructive sleep apnea (OSA). Polysomnography (PSG) emerged from all-night sleep research performed in the 1970's at Stanford University measuring respiratory and cardiac events during sleep (Holland, 1974). A key index derived from PSG was the apnea-hypoapnea index (AHI). This index has been utilized in the definition of different sleep-disordered breathing diagnoses. Patients with primary snoring have a normal AHI and no complaints of daytime somnolence. While upper airway resistance is characterized by a normal AHI but patients suffer from daytime somnolence. On the extreme of the spectrum, sleep apnea, which means "cessation of breath", is noted for an abnormal AHI of greater than 5, drops in oxygen saturation below 90% and daytime somnolence. There are two types of sleep apnea: central and obstructive. Central sleep apnea represents a neurologic dysfunction where no respiratory effort is generated, while the later is a mechanical obstruction in respiration anywhere along the respiratory pathway. This review will focus only on obstruction sleep apnea.

Pathophysiology
 The patency of the airway is dependent on the interaction of forces that collapse and open the lumen. Obstructive sleep apnea is the clinical manifestation that occurs when these forces are skewed towards the collapse of the airway lumen. Two principles of fluid flow, the Bernoulli principle and the Venturi effect, can be applied to the airway to understand causes of airflow obstruction. The Bernoulli principle describes fluid flow through a column. A partial vacuum exists between the column walls and the flowing fluid. The partial vacuum increases as the flow of the fluid increases. Applied to the airway, as the airflow increases, the increasing partial vacuum draws in the airway walls and narrow the lumen. The Venturi effect describes acceleration of airflow through a narrowed space. Together with the pliability of the airway, these two principles create a cycle of OSA that often requires arousal from sleep to be broken. 
 In addition to these principles acting within the airway, there are forces that also contribute to the narrowing of the lumen. The negative pressure generated from inspiration causes reduction of airway area. In patients with excess pharyngeal soft tissue compromising the airway patency, a minimal reduction in airway lumen can lead to obstruction. In addition, extralumenal pressure from excess tissue can also narrow the airway lumen.
 The pharynx has little bony or cartilaginous support especially between the choana and the epiglottis, but dilator muscles that include the genioglossus and tensor palatini provide an intrinsic stiffness to the pharynx. These muscles are activated during inspiration to counteract the negative intraluminal pressure. The activity of these dilators is modulated by both mechanoreceptors and respiratory neurons. Therefore, these muscles are activated in response to rise in intraluminal pressure and/or rise in carbon dioxide levels. These responses are present during sleep, although not as brisk as when awake (White 2005). The threshold level of activation is thought to vary among individuals. With a low threshold as in patients with OSA, arousal may result before REM sleep is obtained. In addition, the ability to recruit these muscles to overcome the pressures causing airway collapse can also differ. Therefore, it is hypothesized that OSA develops in individuals who have a lower threshold level of activation and are unable to generate enough counteracting dilator muscle activity during sleep (White 2005).
 The upper airway extends from the nasal vestibule to caudal end of the trachea. Obstruction can occur anywhere along the airway but the most common sites are retropalatal and retrolingual. These are the sites with little bony and cartilaginous support. Fujita classified patterns of collapse into retropalatal (type I), retropalatal and retrolingual (type II), and retrolingual only (type III) (Fujita 1985).
  
Effect on Health
 This is a very controversial topic with active ongoing research. The difficulty of finding the link between OSA and other health conditions such as cardiovascular disease lies in the shared risk factors. For example, obesity is a risk factor for both OSA and cardiovascular disease. 
 The Sleep Heart Health Study is currently being conducted to provide data to address the relationship between OSA and cardiovascular morbidity.  Shahar et al (2001) presented initial data from this study indicating an increased risk of coronary artery disease, congestive heart failure, and stroke in patients with severe OSA. Importantly, even a mild increase in AHI had a increase risk of cerebrovascular disease.
 In a recent study published in the New England Journal of Medicine, Gami et al (2005) compared the incidence of cardiac caused sudden death at various times of the day between people with PSG-documented OSA and those without. They found that OSA patients had a 2.6 relative risk of cardiac-caused sudden death between midnight and 6 in the morning. In addition, there was a direct correlation between the AHI and relative risk of sudden death.
 In addition, sleep-disordered breathing as defined by increase AHI > 5 had a 3 to 4 times relative risk for developing atrial fibrillation and nonsustained ventricular tachycardia, respectively (Mehra et al, 2006).

Diagnosis and Evaluation
 The diagnosis of OSA centers initially on the history. Again, OSA is a cessation of breath secondary to obstruction. A history of snoring, witnessed arousal during sleep, restless sleep and apneic episodes during sleep are all concerning for OSA. Other symptoms of sleep-disordered breathing include morning and nocturnal headaches, nocturnal enuresis, nocturnal sweating, morning fatigue and decreased cognitive function. Stratification of high-risk for OSA is based on the presence of 4 criteria: witnessed apnea episodes, body mass index greater than 35, habitual snoring and excessive daytime somnolence. The Epworth Sleepiness Scale is widely used to assess daytime somnolence. It questions patients about their tendency of falling asleep during various situations.  Seven scenarios are presented and the patient notes a 0 through 3 to indicate whether or not he or she would fall asleep. A score of 8 or less is considered normal. A score of 10 or higher is considered abnormal (Rowley JA and Lorenzo N, 2005).
 The primary purpose of the physical exam is to identify areas of possible obstruction starting from the nasal vestibule to the hypophaynx. Evaluation of the oral cavity and oropharynx should focus on the tonsils, the soft palate, the tongue and the anatomy of the mandible and its relative position to the maxilla. The key component of the physical exam is the fiberoptic nasopharyngoscopy. The Mueller maneuver can help describe the areas of obstruction. It is performed in either the supine or upright position. It describes the degree of collapse at various levels of the pharynx as the patient is inhaling with a closed mouth and nose. The most significant sites of obstruction are the retropalatal site and at the base of tongue.  Given its subjectiveness, there are significant limitations to this exam.
 As part of the physical exam, it is important to evaluate for extraluminal sources of possible airway obstruction including excess soft tissue within the neck. Also, a deviated septum can also interfere with airflow. Correction of a deviated septum can improve compliance with continuous positive airway pressure (CPAP), which is the primary nonsurgical method of treating OSA. It is important to evaluate the airway for sites of obstruction, both from within the airway and from extraluminal sources.
 There are a number of objective means to evaluate the airway. One such test is the lateral cephalometric radiograph. It provides a 2-dimensional evaluation of this 3-dimensional area. Despite this limitation, the posterior airway space measurement on the lateral cephalometric radiograph correlates to volume of hypopharyngeal airway on 3-D CT scans.
 Another method of objectively evaluating sleep disorders is the polysomnography (PSG). It is an overnight evaluation that is completed as an inpatient but recent devices have allowed home testing. The parameters measured are noted in Table I. The inpatient PSG can be split such that the first half of the night is the traditional sleep study and the second half is designed to titrate CPAP to determine parameters needed for treatment. Recently, a variety of portable sleep-study monitoring devices have been made available. Sleep monitoring devices are categorized by the number of variables tracked. Type 2 devices are comprehensive portable polysomnography with a minimum of seven channels. The type 3 devices have a minimum of 4 channels including airflow. Finally, the least sophisticated type 4 devices monitor 1 or 2 parameters, often oxygen saturation. The in-laboratory, technician-attended, overnight polysomnography is designated a Type 1 sleep monitor. Chesson et al. (2003) compared these types of portable sleep monitoring devices to the in-laboratory polysomnography and found that type 3 and 4 devices do not provide data to meet Medicare guidelines to either rule in or rule out OSA. These guidelines are based on specific sleep parameters such as number of apnea and hypoapnea episodes. In addition, unattended type 2 devices are not recommended to screen for OSA. In conclusion, the authors noted that additional studies focusing specifically on type 2 devices, outcomes, and cost-benefit analysis are needed.
 The most significant results from a PSG as it pertains to the diagnosis of OSA are the number of apnea and hypoapnea episodes. Apnea is defined as airway cessation for greater than 10 seconds. Hypoapnea has a more vague definition to include airway cessation of less than 10 seconds with a 50% decrease in tidal volume associated with a significant drop in oxygen saturation between 2 to 4%. These numbers are used to determine the apnea-hypoapnea index, which is the number of apnea and hypoapnea episodes in one hour, also referred to as the respiratory disturbance index. It is calculated as follows: (total apnes + total hypopneas)/ total sleep time in hours.
 Severity of obstructive sleep apnea is based on arbitrary cutoffs of AHI. OSA diagnosis is made with an AHI of greater than 5. Mild OSA is defined with an AHI of 5 to 15 per hour. Between 15 and 30 per hour is characterized as moderate and severe OSA has an AHI greater than 30 (Rowley JA and Lorenzo N, 2005).
 
Table I - Parameters measured for PSG
Electroencephalogram
Electrooculogram
Nasal and oral airflow monitors: thermistor or nasal prong pressure
Chin electromyogram
Body position monitors
Chest respiratory effort monitor
Abdominal respiratory effort monitor
Electrocardiogram
Pulse oximetry
Tracheal microphone
Anterior tibialis electromyogram
Optional: end-tidal carbon dioxide monitor, esophageal pressure monitor, nasal CPAP/bilevel positive airway pressure

Treatment
Non-surgical
 Continuous positive airway pressure (CPAP) is the primary non-surgical treatment for OSA. It is indicated for moderate and severe OSA. For patients with AHI less than 15, CPAP is recommended when clinical symptoms such as daytime somnolence are associated with the elevated AHI. CPAP is shown to eliminate apnea and hypoapnea episodes and prevent drops in desaturation. However, the primary problem with CPAP is compliance, quoted at approximately 50%. Compliance is better in patients with a severe problem, who perceive great benefit. Addressing nasal airway obstruction such as a deviated septum has been shown to improve tolerance to nasal mask.
 Continuous positive airway pressure can reduce baseline blood pressure in patients with hypertension and severe OSA. In addition, patients with congestive heart failure and OSA showed improved left ventricular ejection fraction while using CPAP (Kaneko et al, 2003). This study evaluated 24 patients with OSA and congestive heart failure(CHF) and randomized them to either medical therapy for CHF or to medical therapy with the addition of CPAP for one month. There was improvement in several cardiovascular parameters including systolic blood pressure and heart rate in addition to the increased ejection fraction.
 Oral appliances are another nonsurgical methods of increasing upper airway flow. There are several types that either advance the mandible, prevent the tongue from falling into the oropharynx or a combination.  Again, the primary disadvantage to these devices is patient compliance. These dental appliances are more effective in mild and moderate OSA than for the more severe forms.
 In addition, weight, diet and medications should all be evaluated. Weight loss may decrease the severity of the obstruction, primarily from extraluminal sources. However, weight loss only is unlikely to resolve OSA. Alcohol or sedating medications can decrease muscle tonicity and dampen oxygenating reflexes. These should be avoided.

Surgical Therapy
 Historically, the initial surgical treatment for OSA was tracheostomy. It remains the main surgical procedure that has proven essentially 100% success in the treatment of OSA. However, given the negative social aspects associated with a tracheotomy, it is not often recommended except in the most severe cases.
 Uvulopalatopharyngoplasty (UPPP) is the most common surgical procedure performed for OSA. However, the surgical success rate for UPPP as defined by a 50% reduction in AHI or RDI and an RDI below 20 ranges from 40% to 65%.  Many factors have been attributed to this poor success rate including multiple levels of obstruction, morbid obesity, poor surgical technique and severity of disease.  Complications to UPPP include velopharyngeal insufficiency, postoperative bleeding, nasopharyngeal stenosis, voice change, and vague foreign body sensation.
 The Stanford group designed an algorithm for surgical approach to OSA. In the Stanford Protocol, it emphasizes direct surgical treatment at all the suspected regions of obstruction. There are two phases in this algorithm with the first phase including nasal reconstruction, UPPP or uvulopalatal flap, and limited mandibular osteotomy with
genioglossus advancement. Overall success rate was reported at 60-80%. The increased success was partially attributed to the modified UPPP with an extended uvulopalatal flap procedure.  In this surgical method, submucosal adipose tissue is removed from the soft palate and supratonsillar region. If symptoms are persistent, then the patient is eligible for Phase II surgery, which involves maxillomandibular advancement osteotomy to treat refractory hypopharyngeal obstruction. The mandible is advanced at least 10 mm anteriorly. In a group of 175 patients who underwent subsequent maxillomandibular advancement between 1998 and 1995, the cure rate was 97% with a reduction of the mean RDI from 72.3 to 7.2.  Their 5-year long-term cure rates decrease to 85%, but still impressive.
 There are a number of relatively new techniques recently introduced to address retropalatal and retrolingual obstruction. Studies on their effectiveness are currently underway. Some procedures focused on the soft palate include the Pillar system, radiofrequency and chemical treatment of the soft palate. The goal of these procedures is to induce stiffness of the soft palate to reduce obstruction as well and vibrations, which manifest as snoring. The Pillar system involves implantation of 3 inserts into the soft palate during an office-clinic visit. With a similar goal of stiffening the soft palate, radiofrequency and chemical treatment of the soft palate has been performed in the office. Laser-assisted uvulopalatoplasty has also been touted as a clinic procedure. It involves the use of a laser to perform a uvulectomy and limited resection of the soft palate. For the retrolingual site, a number of procedures address the base of tongue. Again, radiofrequency treatment of the base of tongue can induce scarring and reduction in volume. A midline glossectomy aims to reduce the volume of the base of tongue. The effectiveness of these procedures is currently under investigation. 

References
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