Sleep-Disordered Breathing and CPAP

Updated: Apr 16, 2018
  • Author: Vittorio Rinaldi, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Overview

Background

Upper-airway obstruction occurring during sleep—that is, sleep-disordered breathing (SDB)—was first demonstrated in the 1960s. SDB represents a group of physiopathologic conditions that are characterized by an abnormal respiratory pattern during sleep that can be isolated or can coexist with other respiratory, nervous, cardiovascular, or endocrine diseases. SDB is now known to be widely prevalent in the general population, and it is responsible for or contributes to numerous problems, ranging from fragmented sleep patterns to hypertension to traffic accidents. [1, 2]

SDB includes obstructive sleep apnea (OSA), which consists of breathing cessations of at least 10 seconds occurring in the presence of inspiratory efforts during sleep. Central sleep apnea (CSA) consists of similar apneas, but these instead take place in the absence of inspiratory efforts. [3, 4, 5, 6, 7]

OSA syndrome (OSAS) is a potentially disabling condition characterized by excessive daytime sleepiness, [8]  disruptive snoring, repeated episodes of upper-airway obstruction during sleep, and nocturnal hypoxemia. It is defined by an apnea-hypopnea index (the total number of episodes of apnea and hypopnea per hour of sleep), or respiratory disturbance index (RDI), of 5 or higher in association with excessive daytime somnolence.

Risk factors for sleep apnea include obesity, increased neck circumference, craniofacial abnormalities, hypothyroidism, and acromegaly. Daytime consequences include not only excessive sleepiness but also impaired cognitive performance and disturbed moods with a reduced quality of life. Excessive daytime sleepiness is reported to be associated with a higher risk of motor vehicle accidents and work place injuries or poor work performance .

In general, everyone with SDB snores, but not everyone who snores has SDB. Snoring in the absence of SDB is termed primary or simple snoring. However, some evidence indicates that snoring is one end of a clinical continuum, with severe OSA at the opposite end. Some health problems may be associated even with primary snoring. The relation between snoring sounds and severity of OSAS has been widely investigated. [9]

Upper-airway resistance syndrome (UARS) is characterized by snoring with increased resistance in the upper airway, resulting in arousals during sleep. This can disturb sleep architecture to the point of causing daytime somnolence. No distinct diagnostic criteria exist for this entity. Patients with UARS can be treated with continuous positive airway pressure (CPAP)—specifically, nasal CPAP (n-CPAP). [10, 11]

Treatment involves elimination of contributing factors and provision of n-CPAP. n-CPAP is effective in improving sleep quality and reducing daytime sleepiness. Long-term treatment with n-CPAP reduces both mortality and the acute blood pressure elevation that occurs with SDB. [12]  Over time, a trend develops toward baseline blood pressure reduction in hypertensive patients with SDB. Medical and surgical interventions may also be indicated.

Go to Obstructive Sleep ApneaChildhood Sleep ApneaCentral Sleep Apnea SyndromesObstructive Sleep Apnea and Home Sleep MonitoringSurgical Approach to Snoring and Sleep ApneaOral Appliances in Snoring and Obstructive Sleep Apnea, and Upper Airway Evaluation in Snoring and Obstructive Sleep Apnea for more information of these topics.

For patient education information, see the Sleep Disorders Center, as well as Snoring and Narcolepsy.

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Pathophysiology

Any factors that decrease upper-airway size or patency during sleep can lead to intermittent obstruction during inspiration, despite inspiratory effort. If the obstruction is sufficiently prolonged, blood oxygen levels drop. Then, the patient arouses or awakens. The arousals disrupt normal sleep architecture. These, together with the oxygenation drops, are responsible for the more severe accompaniments of SDB, including hypertension, arrhythmias, and death. [13]

Factors affecting upper-airway size or patency include numerous anatomic variants and abnormalities (eg, nasal obstruction, retrognathia, macroglossia), obesity, alcohol or sedative intake, and body position during sleep.

Obesity contributes to SDB by changing pharyngeal size and shape. Fat storage in the neck may be particularly associated with risk for SDB, though a subset of patients with SDB are of normal body weight. Many of these patients have a family history of snoring or SDB.

Alcohol intake near bedtime can cause or worsen SDB by reducing the activity of the upper-airway dilating muscles. Alcohol increases both the number and duration of apneic or hypopneic events.

Racial studies and chromosomal mapping, familial studies, and twin studies have provided evidence for a possible link between OSAS and genetic factors. Genetic factors associated with craniofacial structure, body fat distribution, and neural control of the upper-airway muscles likely interact to produce the OSAS phenotype. [14, 15, 16]

Although the role of specific genes that influence the development of OSAS has not yet been identified, some research, especially in animal models, suggests that several genetic systems may be important.

Human leukocyte antigen (HLA)-DQB1*0602 allele, a well-known genetic risk factor for narcolepsy, has been described as a potential genetic factor influencing sleep physiology in individuals diagnosed with OSAS. [17]

Polymorphisms in the serotonin (5-HT) receptor gene can alter its transcription, affecting the number of receptors in the serotoninergic system, contributing to OSAS. [18]

A number of inflammatory factors, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), can be found in high concentrations in persons with OSAS and may serve as biologic markers of this disease. The concentration of these cytokines contributes to weight gain in patients with OSAS and can also modify the risk of obesity-related metabolic disorders, especially insulin resistance. [19]

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Etiology

Important clinical risk factors for SDB are as follows:

  • Nasal obstruction
  • Craniofacial abnormalities
  • Mandibular retrognathia
  • Micrognathia
  • Narrowed, tapered, and short maxillary arch
  • Overbite
  • Long soft palate
  • Modified Mallampati grade III or IV
  • Macroglossia
  • Tonsillar hypertrophy
  • Neck circumference more than 17 in. for men and more than 16 in. for women
  • Obesity

Other problems that can contribute to or exacerbate SDB are sedative or alcohol use and poor sleep hygiene.

A very small percentage of patients with SDB have CSA rather than OSA. CSA can be caused by various neurologic disorders or can be idiopathic.

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Epidemiology

All the epidemiological studies indicate that sleep apnea is more common in men than in women (male-to-female ratio, 2-3:1). Sleep apnea occurs in 4% of men and 2% of women aged 30-60 years. A retrospective study on 830 patients with OSAS reported a male-to-female ratio (M:F) that increases with the gravity of the disease: 2.2:1 in mild OSAS and 7.9:1 in severe OSAS. [20, 21]  Hypersomnolence is reported with a percentage of 16% in men and 22% in women; 24% of men and 9% of women have an apnea-hypopnea index of at least 5.

The discrepancy between the lower prevalence of OSA, the greater frequency of obesity, and the smaller airway size in women compared with men suggests that a gender difference underlies this condition.

Men tend to have a larger but more collapsible airway during mandibular movement than women and this, in part, may play a role in the positional dependency and severity of OSA in men.

Another possible reason for the lower prevalence of OSAS may be reluctance on the part of many women to report symptoms mostly considered inappropriate, like snoring; this reluctance may cause a clinical underestimation of the problem in females.

The gender-related protective effect decreases in females who are postmenopausal and not on hormone replacement therapy. [22, 23]

The association between age and OSA is complex. Several studies have shown a higher prevalence of OSA in elderly persons than in middle-aged persons, although daytime symptoms may be less common with advancing age.

The Sleep Heart Health Study demonstrated that the influence of male sex and body mass index (BMI) on OSA tends to wane with age. For unclear reasons, the overall prevalence of OSA plateaus after age 65 years. [24]

The prevalence of OSAS among African-American persons seems to be at least equal to and possibly greater than that among white persons. The prevalence among men in urban India and men and women in Korea is similar to that observed in Western countries. Some researchers have noticed an increased incidence of OSA in persons of Asian origin.

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Prognosis

Excessive daytime sleepiness resulting from SDB can impact focus and concentration, causing decreased work effectiveness. Even mild-to-moderate SDB increases reaction time, causing performance decreases similar to alcohol intoxication. This can lead to motor vehicle accidents and other serious accidents in situations where alertness is required for safety (eg, heavy machinery operators).

Moderate-to-severe OSA is associated with earlier death. The cardiovascular sequelae of untreated OSA include hypertension, cor pulmonale, arrhythmias, and increased risk of myocardial infarction or stroke. [25, 26, 27, 28, 29] SDB is associated with higher levels of IL-6, a marker of myocardial infarction risk and mortality. [30] Adiposity may mediate the increased levels of C-reactive protein (CRP), fibrinogen, intercellular adhesion molecule (ICAM)-1, and P-selectin observed in SDB. [30]

OSA is associated with difficult-to-control hypertension. [31] CPAP also reduces markers of hypercoagulability, and this is a potential mechanisms by which it can reduce the rate of cardiovascular morbidity and mortality in OSAS patients. [32]

In heart failure patients with sleep apnea, studies have not shown the use of PAP to reduce the risks of cardiovascular outcomes or death; however, such therapy has been associated with some improvements in OSA symptoms. [33]

Treatment of OSA may reduce new first-time cerebrovascular events and recurrences. [34]  A study by Gupta et al suggested that in patients with stroke and OSA, CPAP treatment can yield significantly better stroke outcomes and statistically nonsignificant favorable outcomes in terms of recurrence of vascular events. [35]

Many of the studies examining the relation between OSA and glucose tolerance have shown a direct and independent relation between OSA and diabetes. The Wisconsin Sleep Study Cohort showed a greater prevalence of diabetes in subjects with increasing levels of OSA. [36]  Several studies have shown a beneficial effect of CPAP therapy on insulin resistance or glucose levels. [37, 38, 39]

The probable mechanisms connecting OSA with glucose tolerance and type 2 diabetes mellitus includes increased sympathetic activity, sympathovagal dysfunction, alterations in neuroendocrine function (especially in growth hormone [GH] and cortisol levels), and a high inflammatory state with an increase in the release of proinflammatory cytokines. [40, 38, 39, 41, 42]

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