James B. Skatrud

The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults

BACKGROUND Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health. METHODS A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score (> or = 5, > or = 10, and > or = 15); we used logistic regression to investigate risk factors. RESULTS The estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for women and 24 percent for men. We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome (an apnea-hypopnea score of 5 or higher and daytime hypersomnolence). Male sex and obesity were strongly associated with the presence of sleep-disordered breathing. Habitual snorers, both men and women, tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher. CONCLUSIONS The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women. Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence.

Prospective Study of the Association between Sleep-Disordered Breathing and Hypertension

BACKGROUND Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies. We performed a prospective, population-based study of the association between objectively measured sleep-disordered breathing and hypertension (defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications). METHODS We analyzed data on sleep-disordered breathing, blood pressure, habitus, and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study (and after eight years of follow-up in the case of 184 of these participants). Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing, as defined by the apnea-hypopnea index (the number of episodes of apnea and hypopnea per hour of sleep). The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status, body-mass index, neck and waist circumference, age, sex, and weekly use of alcohol and cigarettes. RESULTS Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line, the odds ratios for the presence of hypertension at follow-up were 1.42 (95 percent confidence interval, 1.13 to 1.78) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none, 2.03 (95 percent confidence interval, 1.29 to 3.17) with an apnea-hypopnea index of 5.0 to 14.9 events per hour, and 2.89 (95 percent confidence interval, 1.46 to 5.64) with an apnea-hypopnea index of 15.0 or more events per hour. CONCLUSIONS We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.

Sleep Apnea and Hypertension: A Population-based Study

Transient, nocturnal elevations of blood pressure have been observed during apneic episodes in the sleep apnea syndrome and may be caused by the acute consequences of sleep-disordered breathing such as arousals, high negative intrathoracic pressures, nocturnal desaturation of oxyhemoglobin, hypercapnia, or increased sympathetic nerve activity [1]. However, the mechanism by which these intermittent nocturnal events contribute to sustained, daytime hypertension is not known. It has been postulated that repetitive hemodynamic oscillations caused by frequent apneic episodes occurring in rapid succession may prevent systemic blood pressures from returning to baseline levels and that this may in turn result in neurohumoral or vascular changes leading to elevated waking pressures and sustained hypertension [2]. Several casecontrol and cross-sectional studies suggest that hypertension is highly prevalent (50% to 90%) in patients with the sleep apnea syndrome [1-5]. Sleep apnea has also been reported to occur frequently (22% to 62%) in patients with essential hypertension [6-9]. However, in these studies blood pressure readings were collected at one time of day in the clinic [6, 9] or from records of reported hypertension [7, 8] in highly selected patient populations such as patients with severe obstructive sleep apnea [1-5]. Some studies found a strong association between sleep apnea and hypertension whereas others failed to do so. Inconsistencies in the results are probably caused by nonuniform definitions of hypertension and apnea, differences in methods and populations studied, lack of appropriate control participants, and failure to control for confounding factors such as age, sex, and obesity. Self-reported habitual, heavy snoring has also been associated with hypertension [10-13]. Because most people with sleep apnea snore, however, polysomnographic data are needed to separate participants with sleep apnea and to assess the association with snoring alone. In the earlier surveys, no objective data on breathing during sleep were available, so it was not possible to determine if any or all of the measured association was caused by the inclusion of apneic persons among snorers. In recent epidemiologic studies that included polysomnographic data, it was found that once sleep apnea was incorporated into the analysis, snoring did not contribute independently to the prediction of hypertension [14]. The most compelling evidence that sleep apnea can cause sustained high blood pressure comes from studies that have shown a reduction in blood pressure after sleep apnea was treated [6, 15-22]. However, interpretation of these intervention studies is difficult because of the confounding effect of weight loss that occurred in several studies [17-19, 22] or lack of data on weight change [6, 12, 16, 20, 23]. Weight loss alone has been shown to reduce blood pressure [23]. Collectively, these studies suggest the hypothesis that sleep-disordered breathing plays a causal role in hypertension. In view of recent estimates of sleep apnea prevalence of 9% for women and 24% for men [24], there is a clear need to investigate how sleep-disordered breathing at the milder end of the severity spectrum, including habitual snoring without sleep apnea, is related to blood pressure. Our purpose was to determine how ambulatory blood pressure measurements obtained during an entire 24-hour period, while awake and asleep, differed among people with and without sleep-disordered breathing in the general population. To avoid previous problems of relying on casual blood pressure measurements, of difficulty in separating effects of snoring from those of sleep apnea, and of selection bias between groups, we studied 147 employed adults enrolled in a long-term study of risk factors, natural history, and health consequences of sleep-disordered breathing using 24-hour ambulatory blood pressure monitoring and overnight polysomnography. Methods One hundred and forty-seven persons were recruited from the Wisconsin Sleep Cohort Study, an ongoing prospective study of sleep-disordered breathing. The details of the design and sampling scheme for the Sleep Cohort Study have been described previously [24]. We used a two-stage sampling scheme designed to yield a cohort of men and women with a wide range of sleep-disordered breathing. For the first stage, all state employees, aged 30 to 60 years, from four large agencies were surveyed on sleep characteristics, health history, and sociodemographics by mailed questionnaire. For the second stage, all survey participants reporting habitual (almost every night) snoring, snorting, or breathing pauses, or extremely loud snoring (designated snorers) and a random sample of the remaining participants (designated nonsnorers) were recruited for laboratory sleep studies, with an overall ratio of one nonsnorer for every two snorers. During a 1-year period, 163 employees consecutively studied by overnight polysomnography in the Sleep Research Laboratory at the University of Wisconsin Clinical Research Center were asked to participate in the blood pressure study: Of these, 147 participants agreed and were successfully studied (90% response rate). The protocol was approved by the Human Subjects Committee at the University of Wisconsin Hospital and Clinics, and all participants gave written, informed consent. Data Collection Overnight polysomnography conducted in our sleep laboratory consisted of electroencephalography, electro-oculography, and electromyography to identify sleep stages [25]; measurements of nasal and oral airflow by end-tidal carbon dioxide detection and thermistry; oximetry for arterial oxyhemoglobin saturation; and inductance plethysmography to detect respiratory effort. Body weight and height were measured on all participants to calculate body mass index (kg/m2). Data on sleep problems, sociodemographics, and health history were collected via a structured questionnaire and personal interview. The complete sleep study protocol has been previously reported [24]. Criteria for Sleep Apnea and Habitual Snoring An abnormal breathing event was defined as either a complete cessation of airflow lasting 10 seconds or more (apnea) or a decrease in airflow accompanied by a 4% or greater decrease in arterial oxygen saturation (hypopnea). The average number of abnormal events per hour of sleep (apneahypopnea index) for each person was used as a measure of sleep apnea. For categorical data analysis, cut points were used to represent mild or worse sleep apnea (apneahypopnea index 5) and little or no sleep apnea (apneahypopnea index < 5). Participants with little or no sleep apnea were further categorized as snorers or nonsnorers based on self-reported habitual snoring (every night or almost every night). Criteria for Sleep-Disordered Breathing We categorized participants as participants with sleep-disordered breathing (those with apneahypopnea index 5 and nonapneic snorers with apneahypopnea index < 5) and participants with no sleep-disordered breathing (nonsnorers with apneahypopnea index < 5). Ambulatory Blood Pressure Measurements These measurements were obtained with the Accutracker II (Suntech Medical Instruments/Eutectics Electronics, Raleigh, North Carolina), a 24-hour blood pressure monitoring device that uses a modified auscultatory method of blood pressure measurement. The system consists of a portable two.25-kg console that is connected to three electrocardiographic leads, a cuff, and a microphone positioned over the left brachial artery. The console initiates inflation of the cuff. During the deflation of the cuff set at a rate of 3 mm Hg per second, the persons R-wave complex triggers the microphone to listen for Korotkoff sounds during a window period after a brief pulse-propagation delay. This system, called R-wave gating, reduces the effect of muscle artifact or amount of artifactual sound encountered in noisy environments outside of the office setting. Special computer software identifies the cuff pressures at the onset and disappearance of Korotkoff sounds for each cuff deflation cycle as systolic and diastolic pressures, respectively. At the beginning of all ambulatory blood pressure monitor placements, three seated and three standing pressures were obtained on each participant and calibrated to within 5 mm Hg of a standard mercury sphygmomanometer using a T-tube assembly. Blood pressures were measured at random intervals of 15 to 20 minutes during waking hours and every 30 minutes during periods of sleep. The deflation rate was set at 3 mm Hg per second. All measurements were done with the display monitor off to prevent anticipation of the readings by the participants. Ambulatory pressures while awake included those taken during activities of daily living such as sitting, standing, walking, and eating. Detailed diaries of activity, posture, bedtime, and time on awakening from sleep were kept by all the participants. Participants were instructed to refrain from vigorous exercises and arm movements during inflations. Specific information relevant to blood pressure such as data on history of hypertension and use of antihypertensive medications were obtained at the time of placement of the 24-hour blood pressure monitor. The ambulatory pressure data record for each person included individual readings of systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate at random intervals. The blood pressure data were edited using predetermined criteria and without knowledge of the sleep data. Criteria for deleting individual blood pressure readings included a pulse pressure that was greater than 120 mm Hg or less than 15 mm Hg (biologically implausible), an inconsistent increase or decrease in systolic or diastolic blood pressure greater than 30 mm Hg from previous or subsequent reading occurring during test codes indicating major arm movement, or weak Korotkoff sounds. The reproducibility of t

Mechanisms of hypoxia‐induced periodic breathing during sleep in humans.

Ventilation was studied during wakefulness and sleep in six healthy humans in normoxia (mean barometric pressure (PB) = 740 torr), and in hypobaric hypoxia (PB = 455 torr). Hypoxia caused hyperventilation and hypocapnic alkalosis (delta Pa,CO2 = ‐7 torr) during wakefulness and in all sleep states. Periodic breathing was the predominant pattern of breathing in all stages of non‐rapid eye movement (non‐r.e.m.) sleep in hypoxia, but was rarely observed during wakefulness or r.e.m. sleep. Periodic breathing was composed of repetitive oscillations of reproducible cycle length characterized by clusters of breaths with augmented inspiratory effort (VT/TI) and highly variable distribution of breath‐to‐breath minute ventilation (VE) and tidal volume (VT), which alternated regularly with prolongations of the expiratory pause of the last breath of each cluster (apnea duration = 5‐18 sec). Hypoxia‐induced periodic breathing was eliminated by: (a) acute restoration of normoxia coincident with a 3‐6 torr increase in Pa,CO2; and (b) augmented FI,CO2 (at constant arterial oxygen saturation) which rapidly and reversibly eliminated apneas and stabilized breathing pattern with a less than 2 torr increase in Pa,CO2. If hypocapnia was prevented (by augmented FI,CO2) during acute induction of hypoxia in non‐r.e.m. sleep, periodic breathing was also prevented. We propose that the genesis of hypoxia‐induced periodic breathing requires the combination of hypoxia and hypocapnia. Periodicity results from oscillations in CO2 about a CO2‐apnea threshold whose functional expression is critically linked to sleep state.

The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep

Sleep unmasks a highly sensitive hypocapnia‐induced apnoeic threshold, whereby apnoea is initiated by small transient reductions in arterial CO2 pressure (PaCO2) below eupnoea and respiratory rhythm is not restored until PaCO2 has risen significantly above eupnoeic levels. We propose that the ‘CO2 reserve’ (i.e. the difference in PaCO2 between eupnoea and the apnoeic threshold (AT)), when combined with ‘plant gain’ (or the ventilatory increase required for a given reduction in PaCO2) and ‘controller gain’ (ventilatory responsiveness to CO2 above eupnoea) are the key determinants of breathing instability in sleep. The CO2 reserve varies inversely with both plant gain and the slope of the ventilatory response to reduced CO2 below eupnoea; it is highly labile in non‐random eye movement (NREM) sleep. With many types of increases or decreases in background ventilatory drive and PaCO2, the slope of the ventilatory response to reduced PaCO2 below eupnoea remains unchanged from control. Thus, the CO2 reserve varies inversely with plant gain, i.e. it is widened with hyperventilation and narrowed with hypoventilation, regardless of the stimulus and whether it acts primarily at the peripheral or central chemoreceptors. However, there are notable exceptions, such as hypoxia, heart failure, or increased pulmonary vascular pressures, which all increase the slope of the CO2 response below eupnoea and narrow the CO2 reserve despite an accompanying hyperventilation and reduced plant gain. Finally, we review growing evidence that chemoreceptor‐induced instability in respiratory motor output during sleep contributes significantly to the major clinical problem of cyclical obstructive sleep apnoea.

Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans

An important determinant of [H+] in the environment of the central chemoreceptors is cerebral blood flow. Accordingly we hypothesized that a reduction of brain perfusion or a reduced cerebrovascular reactivity to CO2 would lead to hyperventilation and an increased ventilatory responsiveness to CO2. We used oral indomethacin to reduce the cerebrovascular reactivity to CO2 and tested the steady‐state hypercapnic ventilatory response to CO2 in nine normal awake human subjects under normoxia and hyperoxia (50% O2). Ninety minutes after indomethacin ingestion, cerebral blood flow velocity (CBFV) in the middle cerebral artery decreased to 77 ± 5% of the initial value and the average slope of CBFV response to hypercapnia was reduced to 31% of control in normoxia (1.92 versus 0.59 cm−1 s−1 mmHg−1, P < 0.05) and 37% of control in hyperoxia (1.58 versus 0.59 cm−1 s−1 mmHg−1, P < 0.05). Concomitantly, indomethacin administration also caused 40–60% increases in the slope of the mean ventilatory response to CO2 in both normoxia (1.27 ± 0.31 versus 1.76 ± 0.37 l min−1 mmHg−1, P < 0.05) and hyperoxia (1.08 ± 0.22 versus 1.79 ± 0.37 l min−1 mmHg−1, P < 0.05). These correlative findings are consistent with the conclusion that cerebrovascular responsiveness to CO2 is an important determinant of eupnoeic ventilation and of hypercapnic ventilatory responsiveness in humans, primarily via its effects at the level of the central chemoreceptors.

Role of Respiratory Motor Output in Within-Breath Modulation of Muscle Sympathetic Nerve Activity in Humans

We measured muscle sympathetic nerve activity (MSNA, peroneal microneurography) in 5 healthy humans under conditions of matched tidal volume, breathing frequency, and end-tidal CO(2), but varying respiratory motor output as follows: (1) passive positive pressure mechanical ventilation, (2) voluntary hyperventilation, (3) assisted mechanical ventilation that required the subject to generate -2.5 cm H(2)O to trigger each positive pressure breath, and (4) added inspiratory resistance. Spectral analyses showed marked respiratory periodicities in MSNA; however, the amplitude of the peak power was not changed with changing inspiratory effort. Time domain analyses showed that maximum MSNA always occurred at end expiration (25% to 30% of total activity) and minimum activity at end inspiration (2% to 3% of total activity), and the amplitude of the variation was not different among conditions despite marked changes in respiratory motor output. Furthermore, qualitative changes in intrathoracic pressure were without influence on the respiratory modulation of MSNA. In all conditions, within-breath changes in MSNA were inversely related to small changes in diastolic pressure (1 to 3 mm Hg), suggesting that respiratory rhythmicity in MSNA was secondary to loading/unloading of carotid sinus baroreceptors. Furthermore, at any given diastolic pressure, within-breath MSNA varied inversely with lung volume, demonstrating an additional influence of lung inflation feedback on sympathetic discharge. Our data provide evidence against a significant effect of respiratory motor output on the within-breath modulation of MSNA and suggest that feedback from baroreceptors and pulmonary stretch receptors are the dominant determinants of the respiratory modulation of MSNA in the intact human.

Mechanisms of the cerebrovascular response to apnoea in humans

We measured ventilation, arterial O2 saturation, end‐tidal CO2 (PET,CO2), blood pressure (intra‐arterial catheter or photoelectric plethysmograph), and flow velocity in the middle cerebral artery (CFV) (pulsed Doppler ultrasound) in 17 healthy awake subjects while they performed 20 s breath holds under control conditions and during ganglionic blockade (intravenous trimethaphan, 4.4 ± 1.1 mg min−1 (mean ±s.d.)). Under control conditions, breath holding caused increases in PET,CO2 (7 ± 1 mmHg) and in mean arterial pressure (MAP) (15 ± 2 mmHg). A transient hyperventilation (PET,CO2−7 ± 1 mmHg vs. baseline) occurred post‐apnoea. CFV increased during apnoeas (by 42 ± 3 %) and decreased below baseline (by 20 ± 2 %) during post‐apnoea hyperventilation. In the post‐apnoea recovery period, CFV returned to baseline in 45 ± 4 s. The post‐apnoea decrease in CFV did not occur when hyperventilation was prevented. During ganglionic blockade, which abolished the increase in MAP, apnoea‐induced increases in CFV were partially attenuated (by 26 ± 2 %). Increases in PET,CO2 and decreases in oxyhaemoglobin saturation (Sa,O2) (by 2 ± 1 %) during breath holds were identical in the intact and blocked conditions. Ganglionic blockade had no effect on the slope of the CFV response to hypocapnia but it reduced the CFV response to hypercapnia (by 17 ± 5 %). We attribute this effect to abolition of the hypercapnia‐induced increase in MAP. Peak increases in CFV during 20 s Mueller manoeuvres (40 ± 3 %) were the same as control breath holds, despite a 15 mmHg initial, transient decrease in MAP. Hyperoxia also had no effect on the apnoea‐induced increase in CFV (40 ± 4 %). We conclude that apnoea‐induced fluctuations in CFV were caused primarily by increases and decreases in arterial partial pressure of CO2 (Pa,CO2) and that sympathetic nervous system activity was not required for either the initiation or the maintenance of the cerebrovascular response to hyper‐ and hypocapnia. Increased MAP or other unknown influences of autonomic activation on the cerebral circulation played a smaller but significant role in the apnoea‐induced increase in CFV; however, negative intrathoracic pressure and the small amount of oxyhaemoglobin desaturation caused by 20 s apnoea did not affect CFV.

Effect of hypoxia on the hypopnoeic and apnoeic threshold for CO2 in sleeping humans

1 Rhythmic breathing during sleep requires that PCO2 be maintained above a sensitive hypocapnic apnoeic threshold. Hypoxia causes periodic breathing during sleep that can be prevented or eliminated with supplemental CO2. The purpose of this study was to determine the effect of hypoxia in changing the difference between the eupnoeic PCO2 and the PCO2 required to produce hypopnoea or apnoea (hypopnoea/apnoeic threshold) in sleeping humans. 2 The effect of hypoxia on eupnoeic end‐tidal partial pressure of CO2 (PET,CO2) and hypopnoea/apnoeic threshold PET,CO2 was examined in seven healthy, sleeping human subjects. A bilevel pressure support ventilator in a spontaneous mode was used to reduce PET,CO2 in small decrements by increasing the inspiratory pressure level by 2 cmH2O every 2 min until hypopnoea (failure to trigger the ventilator) or apnoea (no breathing effort) occurred. Multiple trials were performed during both normoxia and hypoxia (arterial O2 saturation, Sa,O2= 80 %) in a random order. The hypopnoea/apnoeic threshold was determined by averaging PET,CO2 of the last three breaths prior to each hypopnoea or apnoea. 3 Hypopnoeas and apnoeas were induced in all subjects during both normoxia and hypoxia. Hypoxia reduced the eupnoeic PET,CO2 compared to normoxia (42.4 ± 1.3 vs. 45.0 ± 1.1 mmHg, P < 0.001). However, no change was observed in either the hypopnoeic threshold PET,CO2 (42.1 ± 1.4 vs. 43.0 ± 1.2 mmHg, P > 0.05) or the apnoeic threshold PET,CO2 (41.3 ± 1.2 vs. 41.6 ± 1.0 mmHg, P > 0.05). Thus, the difference in PET,CO2 between the eupnoeic and threshold levels was much smaller during hypoxia than during normoxia (‐0.2 ± 0.2 vs. ‐2.0 ± 0.3 mmHg, P < 0.01 for the hypopnoea threshold and ‐1.1 ± 0.2 vs. ‐3.4 ± 0.3 mmHg, P < 0.01 for the apnoeic threshold). We concluded that hypoxia causes a narrowing of the difference between the baseline PET,CO2 and the hypopnoea/apnoeic threshold PET,CO2, which could increase the likelihood of ventilatory instability.

Impaired Vascular Regulation in Patients with Obstructive Sleep Apnea: Effects of Continuous Positive Airway Pressure Treatment

RATIONALE Impaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases. OBJECTIVES To test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea. METHODS We exposed 20 patients with moderate to severe sleep apnea and 20 control subjects, to isocapnic hypoxia and hyperoxic hypercapnia. A subset of 14 patients was restudied after treatment with continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS Cerebral flow velocity (transcranial Doppler), forearm blood flow (venous occlusion plethysmography), arterial pressure (automated sphygmomanometry), oxygen saturation (pulse oximetry), ventilation (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas analysis) were measured during three levels of hypoxia and two levels of hypercapnia. Cerebral vasodilator responses to hypoxia (-0.65 +/- 0.44 vs. -1.02 +/- 0.72 [mean +/- SD] units/% saturation; P = 0.03) and hypercapnia (2.01 +/- 0.88 vs. 2.57 +/- 0.89 units/mm Hg; P = 0.03) were smaller in patients versus control subjects. Hypoxic vasodilation in the forearm was also attenuated (-0.05 +/- 0.09 vs. -0.10 +/- 0.09 unit/% saturation; P = 0.04). Hypercapnia did not elicit forearm vasodilation in either group. Twelve weeks of continuous positive airway pressure treatment enhanced hypoxic vasodilation in the cerebral circulation (-0.83 +/- 0.32 vs. -0.46 +/- 0.29 units/% saturation; P = 0.01) and forearm (-0.19 +/- 0.15 vs. -0.02 +/- 0.08 units/% saturation; P = 0.003), and hypercapnic vasodilation in the brain showed a trend toward improvement (2.24 +/- 0.78 vs. 1.76 +/- 0.64 units/mm Hg; P = 0.06). CONCLUSIONS Vasodilator responses to chemical stimuli in the cerebral circulation and the forearm are impaired in many patients with obstructive sleep apnea. Some of these impairments can be improved with continuous positive airway pressure.