Clinical and Health Affairs
Obstructive Sleep Apnea
A Review and Update
By Inell C. Rosario, M.D.
■ Obstructive sleep apnea (OSA) is a common problem that plays a role in a number of other chronic health concerns including hypertension, atrial fibrillation, diabetes, and gastroesophageal reflux disease to name a few. In this article, we discuss the relationship between OSA and these conditions as well as how OSA is diagnosed and treated.
Sleep was once thought to be a static state of brain inactivity. Over the years, however, research has shown that it is actually a dynamic state during which an individual cycles through non-rapid eye movement and rapid eye movement (REM) stages. Some of the proposed functions of sleep include brain and body restoration, replenishment of cerebral glycogen, tissue synthesis and cell mitosis, protein synthesis, growth hormone release, energy conservation, regulation of noradrenergic activities, memory and information consolidation, brain development, and programming of abilities that may be genetically predetermined such as having an aptitude for math as opposed to literature. We are learning that lack of sleep can lead to short-term cognitive and physical dysfunction as well as development of long-term medical disorders.1
Experiments in animals clearly show that sleep is necessary for survival. The work of Rechtschaffen and colleagues, for example, showed that rats deprived of sleep died within 10 to 30 days after having experienced weight loss despite increased food intake and a loss of their ability to control their body temperature.2 Epidemiologic studies have shown increased mortality from coronary artery disease, cancer, and stroke in individuals who sleep fewer than four hours or more than nine hours a night, when compared with those who sleep an average of seven and a half hours a night.3,4
One of the main causes of sleep disturbances is sleep-disordered breathing, which can range from simple snoring to obstructive sleep apnea (OSA) and obesity hypoventilation syndrome. Obstructive sleep apnea is the cause of the majority of sleep-related morbidity. “Apnea,” which was first described by Guilleminault et al. in 1978, is a 90% or greater decrease in airflow that lasts for at least 10 seconds despite noted ongoing respiratory effort.5 ”Hypopnea” is a reduction of airflow of 30% from baseline with a 4% desaturation or 50% with a 3% desaturation or an arousal. Both apneas and hypopneas make up the apnea-hypopnea index (AHI), which is used to assess the severity of OSA. In general, an AHI score of <5 is considered normal; an AHI of >15 is considered critical, as this is the level at which many of the adverse consequences of OSA occur.
An estimated 24% of males and 9% of females in the United States have some form of sleep-disordered breathing (AHI >5). Four percent of males and 2% females are believed to have OSA (AHI >5 with excessive daytime sleepiness).1,6-8 This prevalence rate is higher among persons 65 years of age and older, persons with an elevated body mass index (>30), men with a neck girth greater than 17 inches and women with a neck girth greater than 16 inches, or persons with comorbidities such as hypertension, diabetes, stroke, depression, polycystic ovary syndrome, Parkinson’s disease, Down syndrome, multiple sclerosis, congestive heart failure, and atrial fibrillation.8-10 Punjabi and colleagues found OSA in 40% to 60% of overweight middle-aged men.11 Andreas et al. found more than 50% of patients with coronary artery disease also had OSA.12
The Relationship between OSA and Other Chronic Health Conditions
We have long been aware of the importance of sleep to safety. Many automobile crashes and a number of catastrophic accidents have been attributed to sleepiness and fatigue.13 More recently, we have become aware that lack of sleep is associated with a number of chronic health problems.
■ Hypertension
Obstructive sleep apnea has been shown to be an independent risk factor for the development of hypertension.8,9,14,15 Obstructive sleep apnea causes cyclical episodes of hypoxia and hypercapnia with augmented sympathetic discharge and vasoconstriction. Brooks et al. used canines with tracheotomies to show that with periodic closing of the stoma to create apneas, the animals developed systemic hypertension over time.16 Their hypertension was reversed when the periodic apneic episodes were discontinued. The Wisconsin Sleep Cohort Study, a random population sample study involving 5,000 state of Wisconsin employees 30 to 60 years of age, included a follow-up evaluation at four years that showed a 3.2 X odd ratio risk for development of hypertension in persons who had an AHI score >15 (adjusted for age, sex, smoking status, alcohol use, body mass index, and neck girth).15
The correlation between hypertension and OSA is in one way good news, as both conditions are treatable. Multiple studies have shown that a small drop in blood pressure can have a major impact on the severity of coronary artery disease.17,18 MacMahon et al. looked at the results from nine prospective studies involving 420,000 patients and found they consistently showed that a 5mm Hg decrease in diastolic blood pressure led to a 21% decrease in the incidence of coronary disease and a 34% decrease in the incidence of stroke over the mean study period of 10 years.17 A 10 mm Hg drop in diastolic pressure led to a 37% and 56% reduction in the rates of coronary artery disease and stroke, respectively. Notably, studies have shown that continuous positive airway pressure (CPAP) used in addition to medication also reduces blood pressure and, therefore, the cardiovascular risks associated with hypertension.19-22 A randomized double-blind controlled study by Pepperell et al. compared the use of sham CPAP (using masks with holes in them) with CPAP in 118 patients with OSA and excessive daytime sleepiness.19 Over the month-long study, the individuals treated with CPAP had an average decrease in their main arterial blood pressure of 5 mm Hg while those in the sham group had no change. Another study by Becker et al. comparing results from patients with therapeutic and subtherapeutic CPAP use showed that it was not just the use of CPAP but the effective reduction in AHI that was responsible for the blood pressure changes.21
■Atherosclerosis
Obstructive sleep apnea is thought to induce carotid artery atherosclerosis, with one assumed mechanism being intermittent, recurrent periods of hypoxia causing augmented sympathetic discharge and a release of proinflammatory mediators such as catecholamines, c-reactive protein, and various interleukins into the blood stream. Drager et al. randomized 24 patients who were matched for age and severity of OSA to either a CPAP group or a control group. Those in the CPAP group showed improvement in early signs of carotid artery atherosclerosis, with a noted decreased intima thickness. After four months of consistent CPAP use, those patients also saw a decrease in the above-mentioned mediators.23
■ Arrhythmias
Arrhythmias (most commonly tachy- and bradyarrhythmias) are also associated with OSA. Periods with multiple apneas lead to tachycardia with hyperventilation and increased sympathetic response. After the apnea, there is a calm or quiescent period of the respiratory cycle during which patients may experience bradycardia. Gami et al. on retrospective review found that the relative risk of sudden death for cardiac-related causes was highest among individuals with OSA between midnight and 6 a.m.24 One possible explanation for this is that REM sleep is more concentrated during the second half of the night, and it is during REM sleep that OSA is often most severe because of concomitant decreased muscle tone, decreased cardiac output, and increased heart rate variability.
■ Atrial Fibrillation
In a retrospective study, Gami and colleagues found that in subjects younger than 65 years of age, the frequency of atrial fibrillation was significantly correlated with the presence of OSA.25 An observational study by Kanagala et al. showed a >80% rate of recurrent atrial fibrillation in patients with untreated OSA compared with a 40% to 55% rate in those who did not have OSA.26
■ Diabetes
Although not well-understood, the incidence of OSA is exceedingly high in obese patients with type 2 diabetes. Viner et al. found the prevalence of OSA in this group of patients to be 86.6%.27 Punjabi et al. also found that OSA is associated with increased insulin resistance, glucose intolerance, and impairment in pancreatic B cell function.28 Moreover, Harsch et al. showed that with CPAP treatment, insulin resistance decreased.29
■ Nocturia
Obstructive sleep apnea is believed to exacerbate nocturia. During periods of apnea, arousal can lead to decreased bladder contraction and an urge to use the bathroom. The periods of apnea, which are associated with elevated blood pressure, lead to the release of the atrial naturetic peptide from the atrial myocytes. The release of this hormone by the heart cells in response to hypertension leads to vasodilation, increased glomerular filtration and salt excretion, and, therefore, increased urine production.1
■ Gastroesophageal Reflux Disease
Reflux symptoms, especially nocturnal regurgitation, may be caused or exacerbated by OSA. During an apnea, there is increased negative intrathoracic pressure as well as hyperventilation, both of which increase the risk of an episode of reflux. Reflux, in turn, contributes to persistent hoarseness, chronic cough, and chest and gastric discomfort.1
Identifying Patients with OSA
Diagnosing OSA requires a clinician to have a high index of suspicion when evaluating a patient. Traditionally, physicians suspected OSA in patients who were obese or who had certain anatomical features such as tonsillar hypertrophy, macroglossia, or retrognathia. Although these physical features do increase a person’s risk for OSA, physicians also need to consider sleep apnea in the patient who has difficulty controlling his or her blood pressure or diabetes; who has atrial fibrillation, polycystic ovary disease, cognitive dysfunction, multiple sclerosis, and Parkinson’s disease; or who shows signs of metabolic syndrome or complains of restlessness, morning headaches, depression, chronic fatigue, excessive daytime sleepiness, or insomnia. Physicians may need to pay particular attention to women, who may not present with the expected signs of sleep apnea such as excessive daytime sleepiness but instead may complain of insomnia or depression or decreased ability to multitask. In addition, physicians need to pay special attention to older patients, as age increases the risk for OSA.1,6-8, 27, 30-32
Obstructive sleep apnea is ideally diagnosed with an overnight polysomnogram. When an in-lab sleep study is impractical (eg, if the patient is a single parent), a home polysomnogram is an option. At-home testing is appropriate for the patient who has a high likelihood of having sleep apnea and has no other comorbidities. There are different types or levels of sleep studies. A Level I study is the most comprehensive. It typically involves using 16 or more channels monitoring EEG, EKG, EOG, EMG, airflow oximetry, nasal pressure, esophageal pressure, body position, snoring sounds, and rib cage and abdominal movements and is monitored by a sleep lab attendant. Level II, III, and IV studies are done in a patient’s home. Level III and IV studies are less comprehensive (eg, Level III studies monitor only two channels—heart rate and oximetry). In order for Medicare to pay for a study, it must monitor a minimum of three channels.
Treating Patients with OSA
Because we know there are significant health and safety risks associated with sleep apnea, it is important to diagnose and treat the condition in as many patients as possible. Unfortunately, there is no one-size-fits-all treatment for OSA. The treatments that are available do improve outcomes for the majority of patients. However, treatment needs to be patient-centered and often must be multidimensional. Patients should be advised to allow an adequate amount of time for sleep, generally seven to eight hours, and to minimize alcohol and caffeine use especially near bedtime. Some patients see significant benefit from positional therapy, which usually involves sleeping on their side to minimize posterior tongue collapse. For patients who are above their ideal body weight, weight loss and exercise can improve their condition. A cohort study showed that overweight individuals who reduced their weight by 10% reduced their AHI by 26%.33
■ Oral Appliances
Oral appliances are generally indicated for use in patients with mild to moderate sleep apnea, especially if the airway seems to collapse at the level of the tongue base. However, these devices are not recommended for patients with temporal mandibular joint disorders, who are unable to protrude their jaw 6 mm, who have multiple missing mandibular or maxillary teeth, or who have periodontal disease.
■ CPAP
Continuous positive airway pressure is universally accepted as the gold standard treatment for OSA and is often combined with a patient’s efforts to improve their sleep hygiene and lose weight. The first CPAP unit was introduced in 1981 by Colin Sullivan, and it revolutionized the treatment of sleep apnea. Before that, sleep apnea was often managed surgically, mostly with tracheotomy. A CPAP device delivers a positive stream of air pressure that essentially stents open the airway. This pressure can be varied or fixed. In addition, CPAP devices also can be used to deliver oxygen to patients with more severe OSA who may need oxygen supplementation. Depending on the severity of a patient’s sleep apnea, BIPAP or Bilevel positive airway pressure may be needed, especially if there are associated comorbidities such as neuromuscular dysfunction. The American Academy of Sleep Medicine recommends that initial CPAP titration be done in a lab to facilitate mask fitting, patient training, and desensitization as well as to document the point at which consolidated sleep occurs. Ideally, CPAP pressure is set once there is significant elimination of apnea and hypopneas (AHI <5) even during supine REM sleep. A variety of masks and nasal pillows can be used to deliver positive pressure. In addition, the newer CPAP machines are fairly quiet and much smaller, causing less disruption of sleep for the bed partner.
Consistent use of CPAP during the first two weeks of treatment is crucial for long-term compliance and success in resolving OSA, the likelihood of which is increased with use of additional heat and humidity. Therefore, prior to the polysomnogram and on follow up as well, it is important to educate patients about the importance of using their CPAP devices. Once they have adjusted to using the CPAP machine, patients should ideally be seen at least every six to 12 months to ensure ongoing adherence and to address any concerns.
■ Surgical Intervention
The goal of most surgeries for OSA is to reduce airway resistance. One procedure that has been used to treat sleep-disordered breathing and snoring is uvulopalatopharyngoplasty (UPPP), during which the uvula and a portion of the soft palate are removed (if tonsils are present, they are removed as well). Research has shown a 40% to 50% success rate of UPPP in decreasing AHI by 50%. A meta-analysis by Sher et al. found UPPP to have a success rate of 39% for curing sleep apnea.34 The fact that the success rate was only 39% is believed to be related to the fact that a large percentage of patients had co-existing, unrecognized hypopharyngeal obstruction. We now know UPPP is most indicated when the collapse of tissue is at the level of the retropalate. Because our ability to localize the level of airway obstruction has been improved with use of the Mueller maneuver during flexible nasal endoscopy in the clinic, cephalometric X-ray, and dynamic as well as static CT and MRI of the head and neck region, we can better identify patients who are more suitable candidates for UPPP. Other surgeries to improve sleep apnea include correcting obstructive nasal pathology such as septal deviation or turbinate hypertrophy, removal of adenoids, tongue-base reduction genioglossal advancement, thyrohyoid suspension, palatal advancement, and submental lipectomy. Depending on the exam findings, these procedures would be indicated for patients who cannot tolerate CPAP, who have subtherapeutic reduction of their AHI using CPAP alone, or who may not be able to use a CPAP machine because of their employment (eg, a soldier in the field).
In addition, there are some office-based procedures that have some efficacy in patients with mild to moderate OSA. Radiofrequency reduction of the turbinates, soft palate, and tongue base is an option. It delivers temperature-controlled submucosal heat to denature protein, which reduces the tissue volume and improves airflow and also stiffens the area being treated, which reduces snoring. Pillar implants have also gained some popularity but are mostly indicated for snoring or mild sleep apnea. During the procedure, three tiny Dacron inserts are placed in the soft palate to induce local soft-tissue reaction and fibrosis and thereby stiffen the soft palate, reducing its mobility and decreasing snoring.
Maxillomandibular advancement, which involves moving the mandible and maxilla anteriorly by as much as 15 mm, creates more physical space for the tongue and can resolve OSA in some patients. In a patient with craniofacial deficiencies, this also can result in cosmetic improvement. Most literature reviews show a 75% to almost 100% success rate of maxillomandibular advancement for treating OSA, with a long-term success rate of 90%. However, this surgery is not often recommended for a number a reasons including the fact that it may negatively affect a person’s appearance if they do not have a craniofacial deficiency. In addition, recovery can be prolonged, and trained surgeons may not be available within a given community.35
Tracheotomy is the definitive surgical treatment for sleep apnea, as it creates an opening in the neck to allow for breathing, bypassing the collapsed upper airway. Although it can be life- saving for patients with severe OSA who do not respond to CPAP or BIPAP treatment, it generally is considered the treatment of last resort, as it affects voice quality and cosmesis, and limits activities. In general, surgical options need to be explored and discussed when patients find they cannot or are unwilling to use CPAP or still have symptoms despite using CPAP. More studies are needed to objectively document the efficacy of surgical interventions and to determine their relative cost-effectiveness. As always, a big part of our job as physicians is to tailor care to the patient although at times the patient’s wishes may not be our first choice.
■ New Treatments
Hypoglossal nerve stimulation delivered by a device implanted in the intercostal space and tunneled subcutaneously to loop around the hypoglossal nerve, is currently being studied in Minnesota for the management of moderate sleep apnea. The device sends an impulse unilaterally to cranial nerve XII, which then causes the tongue’s protrusion and airway opening. Other treatments under development or being tested include robotic surgery for removal of the tonsils and tissues at the back of the throat. Approved in December for removal of head and neck cancers, robotic surgery is more precise and less invasive than manual techniques. Medications such as Qnexa are being tested to aid with weight loss.
Conclusion
Obstructive sleep apnea plays a role in a number of medical conditions that affect a person’s quality of life and their ability to interact with friends and family members and perform in the workplace. As we improve our understanding of the relationship between these conditions and OSA, we will be better able to provide effective therapeutic interventions for our patients. As in other areas of medicine, surgeons and sleep specialists will need to work together more often to treat patients who are not responding adequately to noninvasive therapies or who have persistent, bothersome symptoms despite compliance with the prescribed treatment. At the moment, however, we can celebrate the fact that we have made tremendous gains in our understanding of OSA and that patients have an array of options that can help them. MM
Inell Rosario is an otolaryngologist at Midwest Ear, Nose, and Throat Specialists in the Twin Cities.
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