General
Incidence
Mortality
Cardiovascular Consequences

General
Myocardial infarction
Stroke
Systemic Hypertension
Pulmonary Hypertension
Arrythmias

Neurocognitive Dysfunction
Sleep Disorders and Accidents
CPAP Effects on Outcomes
Neuropsychological/Quality of Life Outcome Tools
Healthcare utilization in Obstructive Sleep Apnea
CPAP Compliance
Oral Appliance Therapy

Obstructive Sleep Apnea.
Strollo PJ Jr. And Rogers RM.

[No abstract available]

New Eng J Med 1996; 334: 99-104.

Sleep Apnea in 81 Ambulatory Male Patients with Stable Heart Failure – Types and Their Prevalences, Consequences and Presentations
Javaheri S, Parker TJ, Liming JD, Corbett WSW, Nishiyama H, Wexler L, Roselle GA.

ABSTRACT: BACKGROUND: Heart failure is a highly prevalent disorder that continues to be associated with repeated hospitalizations, high morbidity, and high mortality. Sleep-related breathing disorders with repetitive episodes of asphyxia may adversely affect heart function. The main aims of this study were to determine the prevalence, consequences, and differences in various sleep-related breathing disorders in ambulatory male patients with stable heart failure.

METHODS AND RESULTS: This article reports the results of a prospective study of 81 of 92 eligible patients with heart failure and a left ventricular ejection fraction < 45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4 +/- 4; group 1) and 41 patients with (51% of all patients; hourly rate of apnea/hypopnea, 44 +/- 19; group 2) sleep apnea. Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in group 2 than in group 1. Forty percent of all patients had central sleep apnea, and 11% had obstructive sleep apnea. The latter patients had significantly greater mean body weight (112 +/- 30 versus 75 +/- 16 kg) and prevalence of habitual snoring (78% versus 28%). However, the hourly rate of episodes of apnea and hypopnea (36 +/- 10 versus 47 +/- 21), episodes of arousal (20 +/- 14 versus 23 +/- 11), and desaturation (lowest saturation, 72 +/- 11% versus 78 +/- 12%) were similar in patients with these different types of apnea.

CONCLUSIONS: Fifty-one percent of male patients with stable heart failure suffer from sleep- related breathing disorders: 40% from central and 11% from obstructive sleep apnea. Both obstructive and central types of sleep apnea result in sleep disruption and arterial oxyhemoglobin desaturation. Patients with sleep apnea have a high prevalence of atrial fibrillation and ventricular arrhythmias.

Circulation 1998; 97: (2) 2154-2159

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Recognition of Obstructive Sleep Apnea
Strohl K and Redline S.

[No Abstract Available]

Am J Resp Crit Care Med 1996; 154: 279-289.

Positive pressure therapy.
Strollo PJ Jr, Sanders MH, Atwood CW

Continuous positive airway pressure (CPAP), bilevel positive airway pressure, and variable (auto- CPAP) pressure, their mechanisms of action, benefits, and complications are examined. A perspective on the future of positive airway pressure therapy for OSDB is provided.

In: Clin Chest Med (1998 Mar) 19(1):55-68 ISSN: 0272-5231 Positive airway pressure in the treatment of obstructive sleep- disordered breathing (OSDB) is reviewed.

The Occurrence of Sleep-Disordered Breathing Among Middle-Aged Adults.
Young T, Palta M, Dempsey J, Skatrud J, Weber S and Badr S.

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.

New Eng J Med 1993; 328:1230-1235.

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Estimation of the Clinically Diagnosed Proportion of Sleep Apnea Syndrome in Middle-Aged Med and Women.
Young T, Evans L, Finn M, Palta M.

The proportion of sleep apnea syndrome (SAS) in the general adult population that goes undiagnosed was estimated from a sample of 4,925 employed adults. Questionnaire data on doctor-diagnosed sleep apnea were followed up to ascertain the prevalence of diagnosed sleep apnea. In-laboratory polysomnography on a subset of 1,090 participants was used to estimate screen-detected sleep apnea. In this population, without obvious barriers to health care for sleep disorders, we estimate that 93% of women and 82% of men with moderate to severe SAS have not been clinically diagnosed. These findings provide a baseline for assessing health care resource needs for sleep apnea.

Sleep 1997; 20: (9) 705-706.

Diagnosis and Treatment of Sleep Apnea within the community – The Walla Walla Project.
Ball EM, Simon RD, Tall AA, Banks MB, NinoMurcia G, Dement WC.

BACKGROUND: Patients with sleep disorders are common in primary care, yet most physicians lack training in the diagnosis and treatment of such patients. OBJECTIVES: To enhance recognition of sleep disorders by community physicians and transfer the diagnostic testing and care of such patients from tertiary care centers to the local community. To present our polysomnogram experience relevant to sleep apnea. METHODS: Sleep disorders specialists provided a community with education, diagnostic equipment, and ongoing support as sleep disorders expertise was established locally. Outcomes for a 2-year period were assessed by chart review, patient questionnaire, tabulation of polysomnographic data, and comparison with published reports from specialized centers. RESULTS: Referral for sleep testing increased by almost 8-fold in patients at the Walla Walla Clinic in Walla Walla, Wash, from 0.27% (2 of 752 cases reviewed) to 2.1% (294 of 14330 internal medicine patients). Data were collected from all community physicians for a 2-year period on 360 new patients who underwent polysomnogram testing. This resulted in the diagnosis of sleep-related breathing disorders in 81% and periodic leg movements of sleep in 18%. Nasal continuous positive airway pressure treatment was given to 228 patients (average baseline apnea index of 19.1), representing a higher volume of patients than at many traditional sleep centers, yet compliance with continuous positive airway pressure was comparable. CONCLUSIONS: Sleep apnea is significantly underrecognized by primary care physicians. As a result of the intervention, local sleep expertise was established and large numbers of patients were discovered and treated in the community. Thus, a significant public health problem is identified and a solution established.

Archives of Int Med 1997 157:(4) 419-424.

Mortality and Apnea Index in Obstructive Sleep Apnea.
He J, Kryger MH, Zorick F J, Conway W, Roth T.

Although obstructive sleep apnea (OSA) has been studied in detail for over a decade, the mortality of this disorder is unclear. We calculated cumulative survival in 385 male OSA patients. We found that those with an apnea index (AI) greater than 20 had a much greater mortality than those with AI = less than 20. The probability of cumulative eight-year survival was .96 +/- 0.02 (SE) for AI = less than 20 vs. 63 +/- 0.17 for AI greater than 20 (p less than .05). This difference in mortality related to AI was particularly true in the patients less than 50 years of age in whom mortality from other causes is not common. None of the patients treated with tracheostomy or nasal CPAP died. Eight of the patients treated with uvulopalatopharyngoplasty (UPPP) died and the cumulative survival of the UPPP-alone treated group was not different from the survival curve of untreated OSA patients with an apnea index of greater than 20. We conclude that OSA patients with an apnea index of greater than 20 have a greater mortality than those below 20 and that UPPP patients be restudied after therapy. If the latter patients are found not to have marked amelioration of their AI, then they should be treated by nasal CPAP or tracheostomy.

Chest 1988; 94: 9-14.

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Mortality in Sleep Apnea Patients: A Multivariate Analysis of Risk Factors.
Lavie P, Herer P, Peled R, Berger J, Yoffe N., Zomer J. and Rubin A-HE.

During 1976-1988 we diagnosed sleep apnea syndrome (SAS) in 1,620 adult men and women monitored in the Technion sleep laboratories. Their age at the time of diagnosis ranged between 21 and 79 years. Fifty-seven patients (53 men and 4 women) had died by 1990, 53% due to respiratory-cardiovascular causes. The observed/expected (O/E) mortality rates, calculated for men only, revealed excess mortality of patients under 70 years old. Excess mortality was significant in the fourth and fifth decades (3.33, p < 0.002; 3.23, p < 0.0002, respectively). In patients older than 70 O/E was 0.33 (p < 0.0007). Hierarchical multivariate analysis with four fixed variables [age, body mass index (BMI), hypertension and apnea index] and four additional variables added manually one at a time (heart disease, lung disease, diabetes, apnea duration) was used to determine the predictors of death from all causes, cardiopulmonary causes and from myocardial infarction (MI). All four major variables were found to be significant predictors of mortality from all causes, in addition to lung disease and heart disease. Only age and BMI were significant predictors of cardiopulmonary deaths in addition to lung disease. Age, BMI and hypertension predicted MI deaths in addition to lung disease. These results were interpreted to suggest that SAS affects death indirectly, most probably by being a risk factor for hypertension. Comment in: Sleep 1997 May;20(5):377-80

Sleep 1995. 18 (3): 149-157.

Snoring and Risk of Cardivascular Disease in Women.
Hu FB; Willet WC; Manson JE; Colditz GA; Rimm EB; Spiezer FE; Hennekens CH; Stampfer MJ.

OBJECTIVES: To examine prospectively the association between snoring and incidence of cardiovascular disease (CVD) in women. BACKGROUND: Whether snoring increases risk of CVD remains unclear; most previous studies have been small, not prospective and limited to men. METHODS: Seventy-one thousand seven hundred seventy-nine female nurses 40 through 65 years of age and without previously diagnosed CVD or cancer at baseline in 1986 were followed up for eight years. Frequency of snoring was assessed using mailed questionnaires at baseline. RESULTS: During eight years of follow-up, we documented 1,042 incident cases of major CVD events (644 coronary heart disease [CHD] and 398 stroke). Compared with nonsnorers, the age-adjusted relative risks (RRs) of CVD were 1.46 (95% confidence interval 1.23 to 1.74) for occasional snorers and 2.02 (1.62 to 2.53) for regular snorers. The age-adjusted RRs of CHD were 1.43 (1.15 to 1.77) for occasional snorers and 2.18 (1.65 to 2.87) for regular snorers. The age-adjusted RRs of stroke were 1.60 (1.21 to 2.12) and 1.88 (1.29 to 2.74), respectively. After further adjustment for smoking, body mass index (BMI) and other covariates, the positive association between snoring and CVD was attenuated but remained statistically significant (RRs of CVD were 1.20 [1.01 to 1.43] for occasional snorers and 1.33 [1.06-1.67] for regular snorers. CONCLUSIONS: These data suggested that snoring is associated with a modest but significantly increased risk of CVD in women, independent of age, smoking, BMI and other cardiovascular risk factors. While further study is needed to elucidate the biological mechanism underlying this association, snoring may help clinicians identify individuals at higher risk for CVD.

J Am Coll Cardiology 2000 Feb; 35(2):308-313.

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Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea
H. Schneider, C. D. Schaub, C. A. Chen, K. A. Andreoni, A. R. Schwartz, P. L. Smith, J. L. Robotham, and C. P. O'Donnell

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model (n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 ± 1.7% decrease after apnea with arousal (P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 ± 1.0 vs. 4.1 ± 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 ± 2.3 mmHg vs. 10.3 ± 1.6 mmHg, REM vs. non-REM, respectively, P < 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation. J

Appl Physiol 2000 88: 1084-1092.

Association of Sleep Apnea with Myocardial Infarction in Men.
Hung J, Whitford EG, Parson RW, Hillman DR.

To examine the hypothesis that sleep apnoea is a risk factor for ischaemic heart disease, overnight polysomnography was performed in 101 unselected male survivors of acute myocardial infarction (MI) aged less than 66 yr and in 53 male subjects of similar age without evidence of ischaemic heart disease. The apnoea index (AI, number of apnoea episodes per hour of sleep) was 6.9 (SEM 1.2) in the MI patients versus 1.4 (0.3) in the control subjects. After adjustment for age, body mass index, hypertension, smoking, and cholesterol level, multiple logistic regression analysis identified the top quartile of AI (greater than 5.3) as an independent predictor of MI patients. The relative risk for myocardial infarction between the highest and lowest quartiles of AI was 23.3 (95% confidence interval 3.9-139.9). Comment in: Lancet 1990 Oct 6;336(8719):888 Comment in: Lancet 1990 Dec 1;336(8727):1378-9

Lancet 1990; 336: 261-264.

Sleep-Disorders Breathing in Men with Coronary Artery Disease.
Mooe T, Rabben T, Wiklund U, Franklin KA, Eriksson P.

OBJECTIVE: To examine the occurrence of sleep apnea and nocturnal hypoxemia in men with symptomatic coronary artery disease (CAD) and to evaluate the relationship between disordered breathing and coronary artery disease. DESIGN: Case-control study. Cases were randomly selected from men undergoing coronary angiography because of angina pectoris. Controls were age matched and selected from the population registry. Pulse oximetry, oronasal thermistors, body position indicator, and recording of body and respiratory movements were used to quantify desaturations and apneas. SETTING: Norrland University Hospital, a referral center for northern Sweden. SUBJECTS: One hundred forty-two men with angina pectoris and angiographically verified CAD and 50 controls without known heart disease. MAIN OUTCOME MEASURES: The number of arterial oxygen desaturations of 4% or more per hour of sleep, oxygen desaturation index (ODI), and the number of apneas or hypopneas per hour of sleep, apnea-hypopnea index (AHI). RESULTS: Men with CAD had a high occurrence of sleep- disordered breathing measured as ODI of 5 or more, 39% (n=55), or AHI of 10 or more, 37% (n=50), while, the same proportions in controls were 22% (n=11, p<0.05) and 20% (n=10, p<0.05). Mean values of ODI in cases and controls were 6.4 and 2.7, respectively (p<0.001). Multiple logistic regression analysis identified ODI, AHI, body mass index, and hypertension as significant predictors of CAD (p<0.05). CONCLUSION: Sleep- disordered breathing is common in men with CAD. A significant association between sleep apnea with nocturnal hypoxemia and CAD remains after adjustment for age, hypertension, body mass index, diabetes, and smoking.

Chest 1996; 109 (3): 659-663.

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Linking Sleep Disorders and Heart Failure.
Kales D,.

J. for Resp Care Pract 1999; Feb/Mar:59-65.

Investigating the Relationship between Stroke and Obstructive Sleep Apnea.
Dyken ME, Somers VK, Yamada T, Ren Z-Y, Zimmerman MB.

BACKGROUND AND PURPOSE: We aimed to prospectively determine whether the incidence of obstructive sleep apnea in patients with recent stroke was significantly different from that of a sex- and age- matched control group with no major medical problems. METHODS: We prospectively performed overnight polysomnography in 24 patients with a recent stroke (13 men and 11 women; mean age [+/- SD], 64.6 +/- 10.4 years) and 27 subjects without stroke (13 men and 14 women; mean age, 61.6 +/- 8.8 years). Patients with either ischemic or hemorrhagic stroke were entered into this study. Polysomnographic evaluations were performed within approximately 2 to 5 weeks after each patient's stroke. RESULTS: Obstructive sleep apnea was found in 10 of 13 men with stroke (77%) and in only 3 of 13 male subjects without stroke (23%) (P=.0169). Seven of 11 women with stroke (64%) had obstructive sleep apnea, while only 2 of 14 female subjects without stroke (14%) had obstructive sleep apnea (P=.0168). For men with stroke, the mean apnea/hypopnea index (+/- SE) was 21.5 +/- 4.2 events per hour, while for male subjects without stroke it was 4.8 +/- 1.8 events per hour (P=.0014). For women with stroke the mean apnea/hypopnea index was 31.6 +/- 8.8 events per hour, while for female subjects without stroke it was 2.9 +/- 1.6 events per hour (P=.0024). The 4-year mortality for patients with stroke was 20.8%. All patients with stroke who died had obstructive sleep apnea. CONCLUSIONS: Patients with stroke have an increased incidence of obstructive sleep apnea compared with normal sex- and age-matched control subjects. Hypoxia and hemodynamic responses to obstructive sleep apnea may have predisposed these patients to stroke.

Stroke 1996. 27: (3) 401-407.

Snoring and the Risk of Ischemic Brain Infarction.
Palomaki H.

To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers.

Stroke 1991; 22:1021-1025.

Sleep disordered Breathing and Poor Functional Outcome after Stroke
Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S.

BACKGROUND AND PURPOSE: We objectively evaluated patients with recent stroke to determine the prevalence of sleep-disordered breathing (SDB) and whether SDB was associated with unfavorable clinical outcomes. METHODS: Forty-seven patients with recent ischemic stroke (median, 13 days) were studied with computerized overnight oximetry for evidence of arterial oxyhemoglobin desaturation (SaO2). Polysomnography was also performed on 19 patients. Medical history, sleep history, location of stroke, and severity of neurological deficit were recorded, and patients were observed by staff for evidence of snoring and excessive daytime sleepiness. Functional abilities were measured with the use of the Barthel Index (BI). Outcome variables included ability to return home at discharge, continued residence at home at 3 and 12 months, BI at discharge, BI at 3 and 12 months, and death from any cause at 12 months. RESULTS: Mean SaO2 during oximetry was 94.0 +/- 1.7%, and percentage of recording time spent at < 90% SaO2 was 4.3 +/- 5.7%. The number of desaturation events per hour of recording time (desaturation index [DI]) was 9.5 +/- 9.67, with 15 of 47 (32%) having DI > 10 and 6 of 47 (13%) having DI > 20. Oximetry measures of SDB correlated with lower BI scores at discharge and lower BI at 3- and 12-month follow- ups (P < or = .05, Pearson coefficients). Oximetry measures correlated with return home after discharge, but the association between oximetry measures and living at home was lost at 12 months. Two oximetry variables correlated with death at 1 year. Brain stem location correlated with higher DI and time at < 90% SaO2, but patients with hemispheric stroke and oximetry abnormalities also had worse functional outcome. No correlation was found between oximetry values and sex, age, preexisting medical conditions (except previous stroke), or severity of neurological deficit. Oximetry abnormalities were associated with a history of snoring. Polysomnography on 19 patients confirmed oximetry evidence of severe SDB. Eighteen of 19 patients (95%) had an apnea-hypopnea index (AHI) of > 10 events per hour of recording, 13 of 19 (68%) had an AHI > 20, and 10 of 19 (53%) had an AHI > 30. Desaturation events were largely due to obstructive apneas. CONCLUSIONS: SDB accompanied by arterial oxyhemoglobin desaturation is common in patients undergoing rehabilitation after stroke and is associated with higher mortality at 1 year and lower BI scores at discharge and at 3 and 12 months after stroke. SDB may be an independent predictor of worse functional outcome. Obstructive sleep apnea appeared to be the most common form of SDB, and the frequent history of snoring suggests that SDB preceded the stroke in most patients.

Stroke 1996; 27: (2) 252-259.

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Sleep Apnea in Patients with Transient Ischemic Attack and Stroke: A Prospectice Study of 59 Patients.
Bassetti C, Aldrich M, Chrvin R, Quint D.

Although sleep apnea (SA) appears to be a cardiovascular risk factor, little is known about its frequency in patients with transient ischemic attack (TIA) and stroke. We prospectively studied 59 subjects (26 women and 33 men; mean age, 62 years) with stroke (n = 36) or TIA (n = 23) with the use of a standard protocol that included assessment of snoring and daytime sleepiness (Epworth Sleepiness Score [ESS]), a validated SA score (Sleep Disorders Questionnaire [SDQ-SA]), and a severity of stroke score (Scandinavian Stroke Scale [SSS]). SA was considered clinically probable (P-SA) when habitual snoring was associated with an ESS of > 10 or when SDQ-SA score was > or = 32 in women and > or = 36 in men. Polysomnography (PSG) was obtained in 36 subjects (group 1) a mean of 12 days after TIA or stroke. In 23 subjects (group 2), PSG was not available (n = 11), refused (n = 10), or inadequate (n = 2). Clinical and PSG data were compared with those obtained in 19 age- and gender-matched control subjects. Groups 1 and 2 were similar in mean age (61 versus 64 years), type of event (36% versus 44% TIA), reported habitual snoring (58% versus 52%), and P-SA (58% versus 50%). PSG showed SA (Apnea- Hypopnea Index [AHI], > or = 10) in 25 of 36 subjects (69%). The proportion of subjects with SA was similar in the TIA and stroke groups (69% versus 70%) and was well above the frequency found in our control group (15%). An AHI of > or = 20 and a minimal oxygen saturation of < 85% were each found in 20 of 36 subjects (55%). Gender and age did not correlate with severity of SA. Subjects with habitual snoring, P-SA, or severe stroke (SSS of < 30) had a significantly higher AHI (p < 0.05). The sensitivity of P-SA for SA was 64%, and the specificity was 67%. We conclude that SA has a high frequency in patients in the acute phase of TIA and stroke and SA cannot be predicted reliably on clinical grounds alone but is more likely in patients with habitual snoring, abnormal SDQ-SA, or severe stroke.

Neurology 1996; 47: (5) 1167-73.

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.
Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D'Agostino RB, Newman AB, Lebowitz MD, Pickering TG

CONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both. OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons. DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998. PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female). MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion accompanied by a > or = 4% drop in oxyhemoglobin saturation), obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication. RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring. CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.JAMA 2000 Apr 12;283(14):1880-1

Obstructive Sleep Apnea Syndrome As a Risk Factor for Hypertension: Population Study
Lavie P; Herer P; Hoffstein V.

OBJECTIVE: To assess whether sleep apnoea syndrome is an independent risk factor for hypertension. DESIGN: Population study. SETTING: Sleep clinic in Toronto. PARTICIPANTS: 2,677 adults, aged 20-85 years, referred to the sleep clinic with suspected sleep apnoea syndrome. OUTCOME MEASURES: Medical history, demographic data, morning and evening blood pressure, and whole night polysomnography. RESULTS: Blood pressure and number of patients with hypertension increased linearly with severity of sleep apnoea, as shown by the apnoea-hypopnoea index. Multiple regression analysis of blood pressure levels of all patients not taking antihypertensives showed that apnoea was a significant predictor of both systolic and diastolic blood pressure after adjustment for age, body mass index, and sex. Multiple logistic regression showed that each additional apnoeic event per hour of sleep increased the odds of hypertension by about 1%, whereas each 10% decrease in nocturnal oxygen saturation increased the odds by 13%. CONCLUSION: Sleep apnoea syndrome is profoundly associated with hypertension independent of all relevant risk factors.

BMJ 2000; 320 (7233): 479-482

Sleep Apnea and Hypertension: A Population-based Study.
Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB and Depmsey J.

OBJECTIVE: To measure the independent association of sleep-disordered breathing (sleep apnea and habitual snoring) and hypertension in a healthy adult population. DESIGN: A cross-sectional study of blood pressure during wakefulness and sleep among participants with and without sleep-disordered breathing. SETTING: Community-based study. PARTICIPANTS: 147 men and women, aged 30 to 60 years, selected from Wisconsin State employees enrolled in the Wisconsin Sleep Cohort Study, an ongoing, prospective, epidemiologic study of sleep- disordered breathing. MEASUREMENTS: Sleep and medical history interview, nocturnal polysomnography, and 24-hour ambulatory blood pressure monitoring in all participants. RESULTS: Mean blood pressures were significantly higher among participants with sleep apnea (> or = 5 apneas or hypopneas per hour of sleep) compared with those without (131/80 +/- 1.7/1.1 mm Hg compared with 122/75 +/- 1.9/1.2 mm Hg during wakefulness and 113/66 +/- 1.8/1.1 mm Hg compared with 104/62 +/- 2/1.3 mm Hg during sleep, respectively; P < 0.05). The variability of the blood pressure during sleep was significantly greater in participants with sleep apnea or a history of snoring compared with those without (P < 0.05). After controlling for obesity, age, and sex, sleep apnea was significantly associated with hypertension in a dose-response fashion, with odds ratios ranging from 2.0 for 5 apneic or hypopneic episodes per hour of sleep to 5.0 for 25 apneic or hypopneic episodes. CONCLUSIONS: Our data indicate an association between hypertension and sleep apnea independent of obesity, age, and sex in a nonselected, community- based adult population.

Ann Intern Med 1994; 120: 383-388.

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Population Based Study of Sleep Disordered Breathing as a Risk factor for Hypertension
Young T, Pappard P, Palta M, Hla KM, Finn L, Morgan B, Skatrud J.

BACKGROUND: Clinical observations have linked sleep-disordered breathing, a condition of repeated apneas and hypopneas during sleep, with hypertension but evidence for an independent association has been lacking. Understanding this relationship is important because the prevalence of sleep-disordered breathing is high in adults. OBJECTIVE: To test the hypothesis that sleep-disordered breathing is related to elevated blood pressure independent of confounding factors. METHODS: The sample included 1060 employed women and men aged 30 through 60 years who had completed an overnight protocol as part of the Wisconsin Sleep Cohort Study. In-laboratory polysomnography was used to determine sleep-disordered breathing status, quantified as the number of apneas and hypopneas per hour of sleep (apnea-hypopnea index). Blood pressure was measured on the night polysomnography was performed. RESULTS: Blood pressure increased linearly with increasing apnea-hypopnea index (P = .003 for systolic, P = .01 for diastolic, adjusted for confounding factors). The magnitude of the linear association increased with decreasing obesity. At a body mass index (weight in kilograms divided by the square of the height in meters) of 30 kg/m2, an apnea-hypopnea index of 15 (vs 0) was associated with blood pressure increases of 3.6 mm Hg for systolic (95% confidence interval, 1.3-6.0) and 1.8 mm Hg for diastolic (95% confidence interval, 0.3-3.3). The odds ratio for hypertension associated with an apnea-hypopnea index of 15 (vs 0) was 1.8 (95% confidence interval, 1.3-2.4). CONCLUSIONS: There is a dose- response relationship between sleep-disordered breathing and blood pressure, independent of known confounding factors. If causal, the high prevalence of sleep-disordered breathing could account for hypertension in a substantial number of adults in the United States.

Archive of Int Med 1997; 157:(15) 1746-1752

The Relationship Between Systemic Hypertension and Obstructive Sleep Apnea: Facts and Theory.
Fletcher E.

This article provides an in-depth overview of the relationship between primary hypertension and adult obstructive sleep apnea syndrome. The background data and research are taken from the English- language literature through 1993. Primary hypertension is a common cause of major medical illnesses, including stroke, heart disease, and renal failure, in middle-aged males. Its prevalence in the United States is around 20%, with the rate of newly diagnosed hypertensive patients being about 3% per year. Sleep apnea syndrome is common in the same population. It is estimated that up to 2% of women and 4% of men in the working population meet criteria for sleep apnea syndrome. The prevalence may be much higher in older, non-working men. Many of the factors predisposing to hypertension in middle age, such as obesity and the male sex, are also associated with sleep apnea. Recent publications describe a 30% prevalence of occult sleep apnea among middle-aged males with so called "primary hypertension." Is this association fortuitous, related to a high prevalence of both diseases in the same population, or is it caused by a factor common to both diseases, such as obesity? Should the diagnosis of apnea be actively sought with sleep studies in hypertensive populations? If a diagnosis of "asymptomatic" sleep apnea is made in a hypertensive person, should the apnea be treated? Current research data provide only partial answers to these and other questions regarding the association of apnea and hypertension. Logic dictates that clinically symptomatic patients in hypertensive clinics should receive appropriate evaluation for apnea, but broad populations of hypertensive individuals should not be referred for sleep studies.

Am J of Med 1995; 98: 118-128.

Obstructive Sleep Apnea as a Cause of Systemic Hypertension: Evidence from a Canine Model.
Brooks D, Horner RL, Kozar LF , Render- Teixeira L and Phillipson EA.

Several epidemiological studies have identified obstructive sleep apnea (OSA) as a risk factor for systemic hypertension, but a direct etiologic link between the two disorders has not been established definitively. Furthermore, the specific physiological mechanisms underlying the association between OSA and systemic hypertension have not been identified. The purpose of this study was to systematically examine the effects of OSA on daytime and nighttime blood pressure (BP). We induced OSA in four dogs by intermittent airway occlusion during nocturnal sleep. Daytime and nighttime BP were measured before, during, and after a 1-3-mo long period of OSA. OSA resulted in acute transient increases in nighttime BP to a maximum of 13.0+/- 2.0 mmHg (mean+/-SEM), and eventually produced sustained daytime hypertension to a maximum of 15.7+/-4.3 mmHg. In a subsequent protocol, recurrent arousal from sleep without airway occlusion did not result in daytime hypertension. The demonstration that OSA can lead to the development of sustained hypertension has considerable importance, given the high prevalence of both disorders in the population.

J Clin Invest 1997; 99 (1): 106-109.

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The Relationship Between the Severity of Sleep Apnea Syndrome and 24-h Blood Pressure Values in Patients with Obstructive Sleep Apnea.
Lavie P, Yoffe N, Berger I and Peled R.

Automated ambulatory 24-h BP monitoring was made in 38 patients with obstructive sleep apnea syndrome. Stepwise multiple regression analysis revealed that diastolic, systolic, and mean BP values during sleep as well as during wakefulness were significantly related to apnea/hypopnea index and age. Minimal arterial O2 saturation and total sleep time also significantly contributed to diastolic and mean BP values during sleep. Body mass index did not significantly contribute to any of the BP values. These results support a causal relationship between the severity of sleep apnea syndrome and systemic hypertension.

Chest 1993; 103 (3): 717-721.

Role of Daytime Hypoxemia in the Pathogenesis of Right Heart Failure in the Obstructive Sleep Apnea Syndrome.
Bradley TD, Rutherford R, Grossman RF, Lue F, Zamel N, Moldofsky H and Phillipson EA.

Although right heart failure is a recognized complication of obstructive sleep apnea, the incidence and pathogenesis of this complication have not been established. We therefore studied 50 consecutive patients with obstructive sleep apnea to determine the incidence of right heart failure and the factors involved in its development. Six patients (12%) were found to have right heart failure. There were no differences in the number of apneas between those with right heart failure (mean +/- SE, 30 +/- 10 per h sleep) and those without right heart failure (33 +/- 4 per h sleep). In contrast, mean nocturnal oxygen saturation was lower in patients with right heart failure (76 +/- 3%) than in those without right heart failure (90 +/- 1%; p less than 0.001). Furthermore, patients with right heart failure also had a substantially lower awake arterial PO2 (52 +/- 4 mmHg versus 75 +/- 2 mmHg; p less than 0.001) and a higher PCO2 (51 +/- 2 mmHg versus 36 +/- 1 mmHg; p less than 0.001) than those without right heart failure. Severe nocturnal hypoxemia in the absence of diurnal hypoxemia was not associated with right heart failure. Daytime hypoxemia in the patients with right heart failure was associated with a higher residual volume (p less than 0.001) and lower forced expiratory volume in one second (p less than 0.001) than in the patients without right heart failure. The findings suggest that sustained hypoxemia and/or hypercapnia over a 24-h period is a necessary prerequisite for the development of right heart failure in patients with obstructive sleep apnea, and that diffuse airway obstruction plays a major role in causing such hypoxemia.

Am Rev Respir Dis 1985; 131: 835-839.

Pulmonary Hypertension and Hypoxemia in Obstructive Sleep Apnea Syndrome.
Sajkov D, Cowie RJ, Thornton AT, Espinoza HA and McEvoy RD.

To determine whether pulmonary hypertension (PH) can occur in obstructive sleep apnea syndrome (OSAS) in the absence of lung or primary cardiac disease, we studied 27 patients (26 males, mean age 49 +/- 10 yr) with OSAS (respiratory disturbance index [RDI] > 10 events/h) in whom clinically significant lung or cardiac diseases were excluded. Pulsed Doppler measurements of pulmonary hemodynamics, pulmonary function tests, arterial blood gas analysis, and polysomnography were performed. A total of 11 OSAS patients (41%) were found to have pulmonary hypertension. The levels of PH were relatively mild (Ppa < or = 26 mm Hg). There were no differences between PH and non-PH patients in body mass index (BMI), smoking history, or lung function. PH patients were more hypoxemic when awake than non-PH patients (PaO2 = 72.2 +/- 7.6 versus 77.6 +/- 7.3 mm Hg, respectively; p < 0.05) but did not differ in severity of sleep apnea (RDI = 51.9 +/- 25.1 versus 56.8 +/- 26.2 events/h, respectively; p = NS) or indices of sleep desaturation. The hypoxemia in PH patients could not be explained by impairment of lung function, greater body mass, or a higher prevalence of smoking, and PaO2 in the study population was significantly correlated with Ppa (r = -0.46, p < 0.02) but not with FEV1 or BMI. We conclude that lung disease is not a prerequisite for PH in OSAS.We conclude that lung disease is not a prerequisite for PH in OSAS. We speculate that the development of PH in OSAS patients depends more on individual differences in the response of the pulmonary circulation to the episodic alveolar hypoxia and respiratory acidosis associated with sleep apneas than on differences in the frequency or severity of the apneas. Repetitive elevation of Ppa during sleep into the PH range may lead to pulmonary vascular remodeling in "responders" and thereby daytime PH and hypoxemia.

Am J Respir Crit Care Med 1994; 149. 416-422.

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Cardiac Arrhythmias, Snoring and Sleep Apnea.
Hoffstein V and Mateika S.

We investigated the frequency of cardiac arrhythmias in patients suspected of having sleep apnea, and related them to the severity of apnea, snoring, and nocturnal hypoxemia. We prospectively studied 458 patients who had nocturnal polysomnography which included objective measurement of snoring (quantified by the number of snores per hour of sleep [snoring index (SI)] and maximum nocturnal sound intensity [(dBmax)], as well as examination of the electrocardiogram (modified lead 2). We found 58 percent prevalence of arrhythmias in patients with sleep apnea (apnea/hypopnea index = AHI > 10), vs 42 percent in nonapneic controls (chi 2 = 16.7, p < 0.0001). Patients with arrhythmias had more severe apnea and nocturnal hypoxemia, but not snoring, than patients without arrhythmias. To examine separately the relationship between the prevalence of arrhythmias and snoring, nocturnal oxygenation, and apnea--we selected subgroups of patients "at the opposite ends of the spectrum" with respect to the severity of snoring, hypoxemia, and apnea. We found that 38 percent of light snorers had arrhythmias vs 39 percent of heavy snorers, 82 percent of patients with mean nocturnal oxygen saturation < 90 percent had arrhythmias vs 40 percent of patients with mean nocturnal oxygen saturation > 90 percent (chi 2 = 7.4, p = 0.006), and 70 percent of patients with AHI > or = 40 had arrhythmias vs 42 percent with AHI < or = (chi 2 = 9.2, p = 0.002). We conclude that patients with sleep apnea as a group have higher prevalence of cardiac arrhythmias than nonapneic patients and that snoring alone, without concomitant sleep apnea, is not associated with increased frequency of cardiac arrhythmias.

Chest 1994; 106: 466-471.

Factors Impairing Daytime Performance in Patients with Sleep Apnea/Hypopnea Syndrome.
Cheshire K, Engleman H, Deary I, Shapiro C, Doliglas NJ.

Patients with sleep apnea/hypopnea syndrome commonly demonstrate impaired daytime performance. In a prospective study, 29 patients with sleep apnea/hypopnea syndrome were assessed polysomnographically to determine the relationship of cognitive performance and daytime sleepiness with sleep disruption, hypoxemia, and mood. Deterioration of cognitive performance correlated significantly with increasing severity of nocturnal breathing irregularity, magnitude of nocturnal hypoxemia, and extent of sleep disruption. Multiple regression analysis identified frequency of apneas plus hypopneas and of arousal and the extent of nocturnal hypoxemia as the variables most strongly associated with cognitive deficits. Anxiety and depression also contributed to this impairment. Objective daytime sleepiness was not significantly associated with nocturnal variables. This study showed that the frequency of breathing irregularities and the extent of both sleep disruption and nocturnal hypoxemia are important in determining daytime function in patients with sleep apnea/hypopnea syndrome. All of these factors should be considered when deciding which patients require treatment.

Arch Intern Med 1992; 152: 538-541.

Neuropsychological Dysfunction in Sleep Apnea.
Greenberg GD, Watson RK and Deptula D.

To evaluate the effect of intermittent hypoxemia on neuropsychological functioning, neuropsychological tests were administered to 14 sleep apnea patients, a control group of 10 patients with other disorders of excessive somnolence, and another control group of 14 healthy volunteers. The sleep disorder groups were matched on two measures of sleepiness. It was found that sleep apnea patients performed significantly worse than both controls on 7 of 14 neuropsychological measures and on a rating of global neuropsychological impairment. The overall level of performance reflected only moderate impairment. Within the sleep apnea group, hypoxemia severity was significantly correlated with deficits on measures of motor and perceptual-organizational ability.

Sleep 1987. 10 (3): 254-262.

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Sleep Disordered Breathing and neuropsychological Deficits – A Population-Based Study.
Kim HC, Young T, Mathews CG, Weber SM, Woodard AR, Palta M.

The relationship of sleep-disordered breathing (SOB) to neuropsychological deficits was investigated with cross-sectional data from the Wisconsin Sleep Cohort Study, a population-based study of the natural history of SDB. A sample of 841 employed men and women ages 30 to 60 yr was studied by overnight polysomnography to assess the frequency of apneas and hypopneas per hour of sleep (apnea- hypopnea index, AHI). Prior to overnight polysomnography, the participants were given a battery of neuropsychological tests for functionally important capacities including motor skills, attention, concentration, information processing, and memory. Principal factor analysis of all the neuro-psychological test data revealed a psychomotor efficiency and a memory factor. Multiple regression analysis showed a significant negative association between logarithmically transformed AHI (LogAHI) and psychomotor efficiency score independent of age, gender, and educational status (p = 0.017). The relationship was not explained by self-reported sleepiness. No significant relationship was seen between LogAHI and memory score. In assessing the clinical significance of mild SDB, we estimate that an AHI of 15 is equivalent to the decrement in psychomotor efficiency associated with 5 additional yr of age, or to 50% of the decrement associated with hypnosedative use.

Am J of Resp and Crit care 1997; 156: (6) 1813-1819.

The Behavioral Morbidity of Obstructive Sleep Apnea.
Day R; Garhardstein R; Lumley A; Roth T; Rosentahl L. Prog

The behavioral morbidity associated with obstructive sleep apnea (OSA) includes symptoms of excessive daytime sleepiness (EDS), neurocognitive deficits, psychological problems, and possibly an increased chance of accidents. EDS is among the most frequently reported symptoms in patients diagnosed with OSA. The available data suggest that the primary cause of EDS is sleep fragmentation. The subjective measures of sleepiness include the sleep wake activity inventory and the epworth sleepiness scale. Sleepiness can also be evaluated objectively in the sleep laboratory using the multiple sleep latency test or the maintenance of wakefulness test. The neurocognitive manifestations of OSA include impairments in vigilance, concentration, memory, and executive function. There is no agreed on consensus as to how to best quantify neurocognitive deficits in this population. Symptoms consistent with depression or personality changes have also been described, but are likely to be correlates of EDS and/or the chronicity of the disorder. Manifestations of the behavioral morbidity of OSA are reversible, but dependent on the degree of normalization in sleep-disordered breathing and the individual's sleep habits.

Cardiovascular Dis 1999; 41(5): 341-354.

Hypersomnolence and Neurocognitive Performance in Sleep Apnea (editorial)
Roth T; Roehrs T; Rosenthal L

Two symptom clusters are prominent obstructive sleep apnea syndrome: excessive daytime sleepiness and neurocognitive difficulties. This article reviews studies that have attempted to determine the etiology and interrelation of these two symptom clusters. The research has clearly determined that the cause of the daytime sleepiness of obstructive sleep apnea syndrome is the fragmentation of sleep by the brief arousals that terminate each apneic event rather than the nocturnal hypoxemia that also occurs in obstructive sleep apnea syndrome. However, the daytime sleepiness and nocturnal hypoxemia appear to both contribute to the neurocognitive impairments of obstructive sleep apnea syndrome, and each seems to affect specific aspects of neurocognitive performance. The extent to which treatment reverses the neurocognitive impairments of obstructive sleep apnea syndrome is yet to be fully determined. The initial study suggests that the impairments are not completely reversed with treatment.

Curr Opin Pulm Med 1995; 1(6): 488-490.

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Automobile Accidents Involving Patients with Obstructive Sleep Apnea.
Findley LJ, Unverzagt ME and Suratt PM.

Although patients with obstructive sleep apnea often report falling asleep while driving, the frequency of auto accidents involving these patients has not been rigorously studied. Therefore, we compared the driving records of 29 patients with obstructive sleep apnea with those of 35 subjects without sleep apnea. The patients with sleep apnea had a sevenfold greater rate of automobile accidents than did the subjects without apnea (p less than 0.01). The percentage of persons with one or more accidents was also greater in the patients with apnea than in the control subjects without apnea (31% versus 6%, p less than 0.01). The percentage of persons having one or more accidents in which they were at fault was also greater in the patients with apnea than in the control subjects (24% versus 3%, p less than 0.02). The automobile accident rate of the patients with sleep apnea was 2.6 times the accident rate of all licensed drivers in the state of Virginia (p less than 0.02). In addition, 24% of patients with sleep apnea reported falling asleep at least once per week while driving. We conclude that patients with obstructive sleep apnea have a significantly higher frequency of auto accidents than do subjects without apnea. Impaired drivers with sleep apnea may cause many preventable auto accidents.

Am Rev Respir Dis 1988; 138: 337-340.

Sleep Disordered Breathing and Motor Vehicle Accidents in a Population Based Sample of Employed Adults.
Young T, Blustein J, Finn L, Palta M.

Studies have consistently shown that sleep apnea patients have high accident rates, but the generalizability of the association beyond clinic populations has been questioned. The goal of this investigation was to determine if unrecognized sleep-disordered breathing in the general population, ranging from mild to severe, is associated with motor vehicle accidents. The sample comprised 913 employed adults enrolled in an ongoing study of the natural history of sleep-disordered breathing. Sleep-disordered breathing status was determined by overnight in-laboratory polysomnography and motor vehicle accident (MVA) history was obtained from a statewide data base of all traffic violations and accidents from 1988 to 1993. Men with five or more apneas and hypopneas per hour of sleep [apnea-plus- hypopnea index (AHI) > 5], compared to those without sleep-disordered breathing, were significantly more likely to have at least one accident in 5 years (adjusted odds ratio = 3.4 for habitual snorers, 4.2 for AHI 5-15, and 3.4 for AHI > 15). Men and women combined with AHI > 15 (vs. no sleep-disordered breathing) were significantly more likely to have multiple accidents in 5 years (odds ratio = 7.3). These results, free of clinic selection bias, indicate that unrecognized sleep-disordered breathing in the general population is linked to motor vehicle accident occurrence. If the association is causal, unrecognized sleep-disordered breathing may account for a significant proportion of motor vehicle accidents.

Sleep 1997; 20: (8) 608-613.

Population and Occupational Screening for Obstructive Sleep Apnea: Are we There Yet?
Baumel MJ, Maislin G, Pack AI.

Several features of obstructive sleep apnea (OSA) suggest that it may be an appropriate disease for screening programs for general populations and more specific high-risk groups. Preliminary data suggest that OSA represents an important health problem in terms of high prevalence, increased levels of morbidity and mortality, and increased public safety risk. Furthermore, the chronicity of the disease and the relatively low levels of recognition of the disorder in the medical community suggest a potential for lead-time gains for screening programs. Specific groups that might be considered for screening programs include commercial vehicle operators, hazardous duty personnel, and certain groups of medical patients. The purpose of this clinical commentary is to consider the issues of population and specific group screening for OSA by reviewing the general principles of screening for chronic disease and then applying these principles specifically in the case of OSA. More extensive outcomes data relating levels of severity of the disorder to its potential adverse outcomes are needed and will assist in tailoring appropriate screening programs and determining the cost-effectiveness of screening various populations.

Am J of Resp and and Crit Care Med 1997; 155: (1) 9-14.

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The Association Between Sleep Apnea and the Risk of Traffic Accidents.
Teran-Santos J, Jimenez-Gomez A, Cordero-Guevara J.

BACKGROUND AND METHODS: Drowsiness and lack of concentration may contribute to traffic accidents. We conducted a case-control study of the relation between sleep apnea and the risk of traffic accidents. The case patients were 102 drivers who received emergency treatment at hospitals in Burgos or Santander, Spain, after highway traffic accidents between April and December 1995. The controls were 152 patients randomly selected from primary care centers in the same cities and matched with the case patients for age and sex. Respiratory polygraphy was used to screen the patients for sleep apnea at home, and conventional polysomnography was used to confirm the diagnosis. The apnea-hypopnea index (the total number of episodes of apnea and hypopnea divided by the number of hours of sleep) was calculated for each participant. RESULTS: The mean age of the participants was 44 years; 77 percent were men. As compared with those without sleep apnea, patients with an apnea-hypopnea index of 10 or higher had an odds ratio of 6.3 (95 percent confidence interval, 2.4 to 16.2) for having a traffic accident. This relation remained significant after adjustment for potential confounders, such as alcohol consumption, visual-refraction disorders, body-mass index, years of driving, age, history with respect to traffic accidents, use of medications causing drowsiness, and sleep schedule. Among subjects with an apnea-hypopnea index of 10 or more, the risk of an accident was higher among those who had consumed alcohol on the day of the accident than among those who had not. CONCLUSIONS: There is a strong association between sleep apnea, as measured by the apnea-hypopnea index, and the risk of traffic accidents.

The New England J of Medicine 1999; 340(11): 847-851.

Effect of Continuous Positive Airway Pressure Treatment on Daytime Function in Sleep Apnoea/Hypopnoea Syndrome.
Engleman HM, Martin SE, Deary IJ, Douglas NJ.

Continuous positive airway pressure (CPAP) is the treatment of choice for the sleep apnoea/hypopnoea syndrome (SAHS); it is usually given with the aim of improving daytime cognitive function, mood, and sleepiness. However, its efficacy has not been validated by controlled trials. We have carried out a randomised, placebo- controlled, crossover study of objective daytime sleepiness, symptoms, cognitive function, and mood in a consecutive series of 32 SAHS patients with a median apnoea plus hypopnoea frequency of 28 (range 7-129) per hour slept. Patients were treated with 4 weeks each of CPAP and an oral placebo, which they were told might improve upper airway muscle function during sleep. Assessments on the last day of each treatment included a multiple sleep latency test and tests of symptom scores, mood profiles, and cognitive performance. The patients had significantly less daytime sleepiness on CPAP than during the placebo period (mean sleep latency 7.2 [SE 0.7] vs 6.1 [0.7] min, p = 0.03). There were also improvements with CPAP in symptom ratings (2.1 [0.2] vs 4.3 [0.3], p < 0.001), mood (p < 0.05 for several measures), and cognitive performance, which showed improved vigilance (obstacles hit in Steer Clear "driving" test 76 [5] vs 81 [6], p < 0.01), mental flexibility (trail-making B time 66 [5] vs 75 [5] s, p < 0.05), and attention (p < 0.05). Objectively monitored CPAP use averaged only 3.4 (0.4) hours per night, but this study provides evidence of improved cognitive performance even at this low level of CPAP compliance.

Lancet 1994; 343: 572-575.

Daytime Sleepiness, Cognitive Performance and Mood after Continuous Positive Airway Pressure for the Sleep Apnoea/Hypopnoea Syndrome.
Engleman HM, Cheshire KE, Deary IJ, Douglas NJ.

BACKGROUND--Patients with the sleep apnoea/hypopnoea syndrome often receive continuous positive airway pressure to improve their symptoms and daytime performance, yet objective evidence of the effect of this treatment on cognitive performance is lacking. METHODS--A prospective parallel group study was performed comparing the change in objective daytime sleepiness as assessed by multiple sleep latency, cognitive function, and mood in 21 patients (mean (SE) number of apnoeas and hypopnoeas/hour 57 (6)) who received continuous positive airway pressure for three months and 16 patients (49(6) apnoeas and hypopnoeas/hour) who received conservative treatment for a similar period. RESULTS--Both groups showed significant within group changes in cognitive function between baseline and three months, but when comparisons were made between groups the only significant difference was a greater improvement in multiple sleep latency with continuous positive airway pressure. However, the improvement in sleep latency with continuous positive airway pressure was relatively small (3.5 (0.5) to 5.6 (0.7) min). The group treated with continuous positive airway pressure was divided into those who complied well with treatment (> 4.5 hours/night) and those who did not. Those who complied well (n = 14) showed significant improvement in mean sleep latency and also in depression score compared with the controls but no greater improvement in cognitive function. CONCLUSION--This study confirms significant improvements in objective sleepiness and mood with continuous positive airway pressure, but shows no evidence of major improvements in cognitive function.

Thorax 1993. 48: 911-914.

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Neuropsychologic Symptoms in Obstructive Sleep Apnea Improve after Treatment with Nasal Continuous Positive Airway Pressure.
Derderian SS, Bridenbatigh RH and Rajagopal KR.

To describe the affective changes associated with sleep restoration we assessed psychologic symptoms using the Profile of Mood States questionnaire before and two months after treatment with nasal continuous positive airway pressure (NCPAP) in seven men with obstructive sleep apnea (OSA). The results were compared with those of a control group of patients with OSA who did not receive NCPAP. Two of six mood factors, depression and fatigue, improved significantly following treatment with NCPAP. Total Mood Disturbance (TMD) score was used to assess global mood differences. The mean TMD score for the patients before treatment was 1.7 and during treatment decreased to -7.6 (p less than 0.05). This mean decrease of 9.3 in the TMD score implies generalized improvement in mood. These findings support the opinion that sleep fragmentation and abnormalities of respiration during sleep are at least partially responsible for affective changes seen in sleep apnea. These psychologic disturbances improve after treatment with NCPAP.

Chest 1988; 94 (5) 1023-1027.

Nasal CPAP and Weight Loss in Hypertensive Patients with Obstructive Sleep Apnea.
Rauscher H, Formanek D, Popp W, Zwick H.

BACKGROUND--The high prevalence of obstructive sleep apnoea (OSA) in patients with systemic hypertension and of hypertension in patients with OSA suggests a causal link between the two disorders. This study was carried out to determine whether nasal continuous positive airway pressure (CPAP) and weight loss affect daytime hypertension in OSA. METHODS--Sixty hypertensive patients with OSA took part in the study; 33 accepted nasal CPAP and used their machine for 5.7 (0.2) hours per night, and the remaining 27 patients refused nasal CPAP and upper airway surgery so the only therapeutic intervention was a recommendation of weight loss. A significant change in hypertension during follow up was defined as either a change in mean blood pressure of at least 10 mm Hg (or more than 8%) without a change in drug treatment, or a reduction in drug dosage with mean blood pressure within these limits. Weight loss was defined as a body mass index of at least 5% below the baseline value. RESULTS--After 512 (41) days, hypertension had become less severe in seven of 12 patients (58%) treated with weight loss only, in eight of 28 patients (29%) with nasal CPAP only, in two of five patients with nasal CPAP and weight loss, and in one of 15 patients without nasal CPAP or weight loss. Multivariate analysis of variance with the outcome of hypertension at follow up as the dependent variable revealed that only the percentage change in body mass index significantly contributed to the course of hypertension. CONCLUSION--The course of hypertension in OSA is more closely linked to weight loss than to elimination of sleep apnoea by nasal CPAP.

Thorax 1993; 48: 529-533.

Reduced Hospitalization with Cardiovascular and Pulmonary Disease in Obstructive Sleep Apnea Patients on Nasal CPAP Treatment.
Peker Y, Hender J, Jhanson A, Bende M.

Cardiovascular and pulmonary disease (CVPD) is common in patients with obstructive sleep apnea syndrome (OSAS). This retrospective study addressed the accumulated in-hospital time during 2 years prior to treatment with nasal continuous positive airway pressure (nCPAP) as compared to 2 years after initiating of nCPAP in patients with OSAS and CVPD. A cohort representing all patients (n = 88) receiving nCPAP during the period 1988-1994 at the Skovde Central Hospital, Skovde, Sweden, was studied. Data collection was based on interviews with patients as well as reviews of clinic charts. All hospitalizations and diagnostic codes by any type were thereby successfully gathered for the whole group. Six patients with confounding serious diseases were excluded from the analysis. A CVPD diagnosis (ICD-9, codes 401-435 and 490-496) was found in 54 out of 82 patients (66%), of whom 36 of 58 were nCPAP users (62%) and 18 of 24 were nonusers (75%). In 54 sleep apneics with CVPD, 31 were hospitalized acutely under one or more of these diagnostic codes during the study period of 4 years. The total number of in-hospital days due to CVPD in the nCPAP users (n = 19) before nCPAP prescription was 413 days (median 10, range 3-66) compared to 54 days (median 0, range 0-25) after nCPAP (p < 0.0001). The corresponding values for the nonuser group (n = 12) was 137 days (median 8.5, range 0-42) before and 188 days (median 9.5, range 0-47) after the nCPAP prescription (ns). We conclude that nCPAP treatment reduces the need for acute hospital admission due to CVPD in patients with OSAS. This reduction of concomitant health care consumption should be taken into consideration when assessing the cost-benefit evaluation of nCPAP therapy.

Sleep 1997; 20: (8) 645-653.

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A French Survey of 3,225 Patients Treated with CPAP for Obstructive Sleep Apnea: Benefits, Tolerance, Compliance and Quality of Life.
Meslier N, Lebrun T, Grillier-Lanoir V, Rolland N, Hendrerick C, Sailly JC, Racineux JL.

The aim of this study was to investigate in a large population of patients with obstructive sleep apnoea and on long-term treatment with continuous positive airway pressure (CPAP) the patients' perception of symptomatic improvement, side-effects and quality of life. Questionnaires were mailed via local respiratory homecare associations to 5,339 French patients who had been treated at home for at least 6 months with CPAP machines and who continued their treatment. In total, 3,225 questionnaires were analysable. More than 80% of the responding patients reported that CPAP treatment had greatly improved their symptoms. Despite discomfort related to nasal problems and excess noise from the blower, the mean rate of use for the whole population was 6 h 36 min+/-2 h 15 min. The perceived health evaluated by the Nottingham Health Profile was good (mean score <50) for at least 75% of the patients in each dimension explored. The perceived health was significantly related to the improvement in symptoms, the overall satisfaction and the objective compliance. This retrospective study indicates that patients who continued continuous positive airway pressure treatment for more than 6 months felt a great improvement in their symptoms, were satisfied with the treatment and had a relatively good perception of their health.

European Resp J 1998; 12: (1) 185-192.

Long term Use of CPAP Therapy for Sleep Apnea / Hypopnea Syndrome.
McArdle N; Devereux G; Heidarnejad H; Engleman HM; Macakay TW; Douglas NJ.

Patients with the sleep apnea/hypopnea syndrome (SAHS) treated by nasal continuous positive airway pressure (CPAP) need to use CPAP long-term to prevent recurrence of symptoms. It is thus important to clarify the level of long-term CPAP use and the factors influencing long-term use. We examined determinants of objective CPAP use in 1, 211 consecutive patients with SAHS who were prescribed a CPAP trial between 1986 and 1997. Prospective CPAP use data were available in 1, 155 (95.4%), with a median follow-up of 22 mo (interquartile range [IQR], 12 to 36 mo). Fifty-two (4.5%) patients refused CPAP treatment (these were more often female and current smokers); 1,103 patients took CPAP home, and during follow-up 20% stopped treatment, primarily because of a lack of benefit. Methods of survival analysis showed that 68% of patients continued treatment at 5 yr. Independent predictors of long-term CPAP use were snoring history, apnea/hypopnea index (AHI), and Epworth score; 86% of patients with Epworth > 10 and an AHI >/= 30 were still using CPAP at 3 yr. Average nightly CPAP use within the first 3 mo was strongly predictive of long-term use. We conclude that long-term CPAP use is related to disease severity and subjective sleepiness and can be predicted within 3 mo.

Am J Respir Crit care Med 1999; 159(4 Pt 1): 1108-1114.

Can Intensive Support Improve Continuous Positive Pressure Use in Patients With the Sleep Apnea / Hypopnea Sysndrome?
Hoy CJ; Vennelle M; Kingshett RN; Engleman HM; Douglas NJ.

Continuous positive airway pressure (CPAP) therapy is widely prescribed for patients with the sleep apnea/hypopnea syndrome (SAHS), but the use of CPAP for such patients is disappointingly low. We postulated that providing intensive educational programs and nursing support to SAHS patients might improve CPAP use and outcomes. We also examined the hypothesis that CPAP use would be greater among patients who had initiated their own referral than among those asked to seek help by a partner. We randomized 80 consecutive, new patients with SAHS to receive either usual support or additional nursing input including CPAP education at home and involving their partners, a 3- night trial of CPAP in our institution's sleep center, and additional home visits once they had begun CPAP. The primary outcome variable was objective CPAP use; symptoms, mood, and cognitive function were also assessed after 6 mo. CPAP use over 6 mo was greater (p = 0.003) among patients receiving intensive than among those receiving standard support (5.4 +/- 0.3 versus 3.9 +/- 0. 4 h/night [mean +/- SEM]), with greater improvements (p < 0.05) in SAHS symptoms, mood, and reaction time in the intensively supported group. CPAP use was greater (p = 0.002) among patients who initiated their own referrals. CPAP use and outcomes of therapy can be improved by provision of a nurse-led intensive CPAP education and support program. CPAP use is lower among patients whose partners ask them to seek treatment.

Am J Respir Crit Care Med 1999; 159(4 Pt 1): 1096-1100.

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An Instrument to Measure Functional Status Outcomes for Disorders of Excessive Sleepiness.
Weaver TE, Laizner AM, Evans LK, Maislin G, Chugh DK, Lyon K, Smith PL,Schwartz AR, Redline S, Pack AI and Dinges DF.

This article reports the development of the functional outcomes of sleep questionnaire (FOSQ). This is the first self-report measure designed to assess the impact of disorders of excessive sleepiness (DOES) on multiple activities of everyday living. Three samples were used in the development and psychometric analyses of the FOSQ: Sample 1 (n = 153) consisted of individuals seeking medical attention for a sleep problem and persons of similar age and gender having no sleep disorder; samples 2 (n = 24) and 3 (n = 51) were composed of patients from two medical centers diagnosed with obstructive sleep apnea (OSA). Factor analysis of the FOSQ yielded five factors: activity level, vigilance, intimacy and sexual relationships, general productivity, and social outcome. Internal reliability was excellent for both the subscales (alpha = 0.86 to alpha = 0.91) and the total scale (alpha = 0.95). Test-retest reliability of the FOSQ yielded coefficients ranging from r = 0.81 to r = 0.90 for the five subscales and r = 0.90 for the total measure. The FOSQ successfully discriminated between normal subjects and those seeking medical attention for a sleep problem (T157 = -5.88, p = 0.0001). This psychometric evaluation of the FOSQ demonstrated parameters acceptable for its application in research and in clinical practice to measure functional status outcomes for persons with DOES. Thus, the FOSQ can be used to determine how disorders of excessive sleepiness affect patients' abilities to conduct normal activities and the extent to which these abilities are improved by effective treatment of DOES.

Sleep 1997; 20 (10): 835-843.

Quality of Life Consequences of Sleep-disordered Breathing.
Flemons WW and Tsai W.

Sleep-disordered breathing occurs in approximately 2% to 4% of the adult population and includes conditions in which patients stop breathing completely (apnea) or have marked reductions in airflow (hypopnea) during sleep. Typical symptoms of sleep apnea include snoring, restless sleep, excessive daytime somnolence, nocturnal enuresis, irritability, depression, memory deficits, inability to concentrate, and decreased alertness. The clinically relevant outcomes of these symptoms include impairment in work efficiency, increased automobile accident rates, and decrements in quality of life. Treatment of sleep apnea, primarily with continuous positive airway pressure, reduces sleepiness and improves mood disturbances, neurocognition, and performance. Traditional measurements of sleep apnea severity do not correlate well with current tests and scales that are used to quantify alterations in alertness, performance, quality of life, or sleepiness. A disease-specific quality of life scale has been developed following patient and physician interviews and literature reviews. The Calgary Sleep Apnea Quality of Life Index is expected to capture aspects of quality of life important to sleep apnea patients, such as cognitive function, performance, and mood, that could be improved with appropriate treatment of sleep-disordered breathing.

J Allergy Clin Immunol 1997; 99: S750-S756.

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Health Care Utilization in Males With Obstructive Sleep Apnea Syndrome Two Years After Diagnosis and Treatment.
Bahamman A; Delaive K; Ronald J; Manfreda J; Roos L; Kryger MH.

OBJECTIVE: To document changes in health care utilization (physician claims and hospitalizations) two years after diagnosis and treatment of patients with OSAS. DESIGN: Prospective observational cohort study. SETTING: The study was done in the Canadian Province of Manitoba. OSAS patients were selected from a University-based sleep disorders center. Control subjects were selected from the general population. PATIENTS AND CONTROLS: There were 344 OSAS patients on whom there was utilization data for the period of the study. They were matched to controls from the general population by gender, age, and geographic location. MEASUREMENTS AND RESULTS: The difference in physician claims between the patients and their matched controls two years after diagnosis and treatment ($174+/-32.4 (SE) per year in Canadian dollars) was significantly less than the difference in the year before diagnosis ($260+/-35.7 (SE), p=0.038). Examining the subgroups of patients adhering (PAT) or not adhering (PNAT) to treatment revealed that the changes were only significant in the patients adhering to treatment. Hospital stays for the entire OSAS group decreased from 1.27 days+0.25(SE) per patient per year one year before diagnosis to 0.54+0.13 per patient per year (p=0.01). The changes in the PAT group (1.25+0.28 per patient per year one year before diagnosis to 0.53+0.14 per patient per year (p=0.034) were significant while in the PNAT group they were not. CONCLUSIONS: Adherence to treatment in patients with OSAS results in a significant reduction in physician claims and hospital stays.

Sleep 1999; 22(6): 740-747.

Health Care Utilization in the 10 Years Prior to Diagnosis in Obstructive Sleep Apnea Syndrome Patients.
Ronald J, Delaive K, Roos L, Manfreda J, Bahammam A, Kryger M.

Obstructive sleep apnea syndrome (OSAS) patients may have symptoms for years prior to recognition of their disorder, or they may be treated for the associated comorbidities. We hypothesized that such patients would be heavy consumers of health care resources for several years prior to diagnosis. We therefore compared health service utilization for a 10-year interval prior to diagnosis of 181 OSA patients to those of randomly selected age-, gender-, and geographically matched controls from the general population. OSAS patients used approximately twice as many health care services (as defined by physician claims and overnight stays in hospital) in the 10 years prior to their initial diagnostic evaluation for apnea. Physician claims for the OSA patients totaled $686,365 ($3972 per patient), compared to $356,376 ($1969 per patient) for the controls for the 10-year period examined in this study. Use of health services was significantly higher in 7 of 10 years prior to diagnosis. The OSAS patients also had more overnight hospitalizations: they spent 1118 nights (6.2 per patient) in hospital vs 676 nights (3.7 per patient) for controls in the decade prior to diagnosis. We conclude that by the time patients are finally diagnosed for sleep apnea, they have already been heavy users of health services for several years. It is possible that our findings reflect not OSAS per se, but the presence of some of the risk factors that predispose to OSAS, such as obesity, alcohol usage and perhaps tobacco consumption.

Sleep 1999; 22 (2): 225-229.

Comparison of Therapeutic and Subtherapeutic Nasal Continuous Positive Airway Pressure for Obstructive Sleep Apnea: A Randomised Prospective Parallel Trial.
Jenkinson C; Davies R; Mullins R; Stradling JR.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is widely used as a treatment for obstructive sleep apnoea. However, to date there are no randomised controlled trials of this therapy against a well-matched control. We undertook a randomised prospective parallel trial of therapeutic NCPAP for obstructive sleep apnoea compared with a control group on subtherapeutic NCPAP. METHODS: Men with obstructive sleep apnoea, defined as an Epworth sleepiness score of 10 or more and ten or more dips per h of more than 4% SaO2 caused by obstructive sleep apnoea on overnight sleep study, were randomly assigned therapeutic NCPAP or subtherapeutic NCPAP (about 1 cm H2O) for 1 month. Primary outcomes were subjective sleepiness (Epworth sleepiness score), objective sleepiness (maintenance of wakefulness test), and SF-36 questionnaire measurements of self-reported functioning and well-being. FINDINGS: 107 men entered the study: 53 received subtherapeutic NCPAP and 54 therapeutic NCPAP. Use of NCPAP by the two treatment groups was similar: 5.4 h (therapeutic) and 4.6 h (subtherapeutic) per night. Subtherapeutic NCPAP did not alter the overnight number of SaO2 dips per h compared with baseline, and thus acted as a control. Therapeutic NCPAP was superior to subtherapeutic NCPAP in all primary outcome measures. The Epworth score was decreased from a median of 15.5 to 7.0 on therapeutic NCPAP, and from 15.0 to 13.0 on subtherapeutic NCPAP (between treatments, p<0.0001). Mean maintenance-of-wakefulness time increased from 22.5 to 32.9 min on therapeutic NCPAP and, not significantly, from 20.0 to 23.5 min on subtherapeutic NCPAP (between treatments p<0.005). Effect sizes for SF-36 measures of energy and vitality were 1.68 (therapeutic) and 0.97 (subtherapeutic) NCPAP (between treatments p<0.0001). For mental summary score, the corresponding values were 1.02 and 0.4 (between treatments p=0.002). INTERPRETATION: Therapeutic NCPAP reduces excessive daytime sleepiness and improves self-reported health status compared with a subtherapeutic control. Compared with controls, the effects of therapeutic NCPAP are large and confirm previous uncontrolled clinical observations and the results of controlled trials that used an oral placebo.

Lancet 1999; 353(9170): 2100-2105.

Objective Measurement of Patterns of Nasal CPAP Use by Patients with Obstructive Sleep Apnea.
Kribbs NB, Pack AI, Kline LR, Smith PL, Schwartz AR, Schubert NM, Redline S,Henry JN, Getsy JE and Dinges DF.

Obstruction of the upper airway during sleep (OSAS) is widely treated by having patients self-administer nasal continuous positive airway pressure (CPAP). To obtain objective evidence of the patterns of CPAP use, information was gathered from two urban sites on 35 OSAS patients who were prescribed CPAP for a total of 3,743 days. Patients were given CPAP machines that contained a microprocessor and monitor that measured actual pressure at the mask for every minute of each 24- h day for an average of 106 days per patient. They were not aware of the monitor inside the CPAP machines. Monitor output was compared with patients' diagnostic status, pretreatment clinical and demographic characteristics, and follow-up self-reports of CPAP use, problems, side effects, and aspects of daytime fatigue and sleepiness. Patients attempted to use CPAP an average of 66 +/- 37% of the days monitored. When CPAP was used, the mean duration of use was 4.88 +/- 1.97 h. However, patients' reports of the duration of CPAP use overestimated actual use by 69 +/- 110 min (p < 0.002). Both frequency and duration of CPAP use in the first month reliably predicted use in the third month (p < 0.0001). Although the majority (60%) of patients claimed to use CPAP nightly, only 16 of 35 (46%) met criteria for regular use, defined by at least 4 h of CPAP administered on 70% of the days monitored. Relative to less regular users, these 16 patients had more years of education (p = 0.05), and were more likely to work in professional occupations.(ABSTRACT TRUNCATED AT 250 WORDS)

Am Rev Respir Dis 1993; 147:887-895.

Nasal CPAP: An Objective Evaluation of Patient Compliance.
Reeves-Hocke MK, Meck R and Zwillich CW.

Nasal continuous positive airway pressure (NCPAP) improves sleepiness and prognosis in obstructive sleep apnea (OSA). Our objective was to document NCPAP compliance and the percentage of time that the effective pressure shown to eliminate 95% of the obstructive apneas and hypopneas was maintained. We built and covertly installed an elapsed timer and mask pressure transducer recorder in NCPAP units of 47 OSA patients. Subjects were seen at 2- to 8-wk intervals over 6 months. Group mean age was 51 yr; 38 males, with mean body mass index of 42; all complained of daytime sleepiness. Initial full night polysomnography demonstrated a mean apnea-hypopnea index (AHI) of 58 +/- 2.6 SEM (range, 10 to 115). Nine subjects discontinued therapy within 3 months for various reasons. In the remaining subjects (n = 38) the actual mean nightly hours of use was 4.7 which represents 68% of the stated total sleep time (compliance). However, effective mean hours of use was 4.3 which represents 91% of the time that prescribed effective pressure was maintained at the mask. The AHI did not correlate with compliance, but did correlate with effective use (R = 0.27048, p = 0.0006). Subjective initial complaints of daytime sleepiness correlated with compliance only during the first visit (R = 0.38590, p = 0.05). No predictors for compliance were found.

Am J Resp Crit Care Med 1994; 149: 149-154.

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Three-dimensional CT reconstructions of tongue and airway in adult subjects with obstructive sleep apnea.
Lowe AA, Gionhaku N, Takeuchi K, Fleetham JA

The interaction between airway and tongue structures in a sample of 25 adult men with obstructive sleep apnea was quantified on the basis of a series of preoperative CT slices obtained for each subject. Tracings were completed for tongue, and right and left nasal, nasopharynx, oropharynx, and hypopharynx structures; computer graphics were used to obtain superior and lateral three-dimensional reconstructions of all structures for each subject. In addition, cross-sectional areas of specific sites of airway constriction, surface area, volume, and ratio calculations were completed. The majority of the constrictions occurred in the oropharynx (0.52 +/- 0.18 cm2), but six subjects had two constrictions--one in the oropharynx and one in the hypopharynx. The airway had a mean volume of 13.89 +/- 5.33 cm3, whereas tongue volume ranged from 44.03 to 99.56 cm3 with a mean of 71.96 +/- 13.41 cm3. Subjects with more severe obstructive sleep apnea tended to have larger tongue and smaller airway volumes. The more obese subjects showed larger tongue surface areas and smaller airway surface areas. To determine the structural relationships between airway and tongue variables, a series of logarithmic plots was determined. An isometric relationship characterized tongue surface area and tongue volume. A logarithmic plot of oropharyngeal airway vs. tongue volume showed a negative allometric relationship. Tongue volume increased more rapidly than airway volume in subjects with obstructive sleep apnea. Subjects with large tongue volumes were observed to experience significant complications at the time of surgical treatment. Quantification of the volume of the oropharynx and its relationship to tongue volume provide an overview of the interaction between these structures.

In: Am J Orthod Dentofacial Orthop (1986 Nov) 90(5):364-74

The effect of the tongue retaining device on awake genioglossus muscle activity in patients with obstructive sleep apnea.
Ono T, Lowe AA, Ferguson KA, Pae EK, Fleetham JA

Knowledge of how dental appliances alter upper airway muscle activity when they are used for the treatment of snoring and/or obstructive sleep apnea (OSA) is very limited. The purpose of this study was to define the effect of a tongue retaining device (TRD) on awake genioglossus (GG) muscle activity in 10 adult subjects with OSA and in 6 age and body mass index (BMI) matched symptom-free control subjects. The TRD is a custom-made appliance designed to allow the tongue to remain in a forward position between the anterior teeth by holding the tongue in an anterior bulb with negative pressure, during sleep. This pulls the tongue forward to enlarge the volume of the upper airway and to reduce upper airway resistance. In this study, two customized TRDs were used for each subject. The TRD-A did not have an anterior bulb but incorporated lingual surface electrodes to record the GG electromyographic (EMG) activity. The TRD-B contained an anterior bulb and two similar electrodes. The GG EMG activity was also recorded while patients used the TRD-B but were instructed to keep their tongue at rest outside the anterior bulb; this condition is hereafter referred to as TRD-X. The GG EMG activity and nasal airflow were simultaneously recorded while subjects used these customized TRDs during spontaneous awake breathing in both the upright and supine position. The following results were obtained and were consistent whether subjects were in the upright or the supine position. The GG EMG activity was greater with the TRD-B than with the TRD-A in control subjects (p < 0.05), whereas the GG EMG activity was less with the TRD-B than with the TRD-A in subjects with OSA (p < 0.01). Furthermore, there was no significant difference between the GG EMG activity of the TRD-A and the TRD-X in control subjects, whereas there was less activity with the TRD-X than with the TRD-A in subjects with OSA (p < 0.05). On the basis of these findings, it was concluded that the TRD has different effects on the awake GG muscle activity in control subjects and patients with OSA. The resultant change in the anatomic configuration of the upper airway caused by the TRD may be important in the treatment of OSA because such a change may alleviate the impaired upper airway function.

In: Am J Orthod Dentofacial Orthop (1996 Jul) 110(1):28-35

A tongue retaining device and sleep-state genioglossus muscle activity in patients with obstructive sleep apnea.
Ono T, Lowe AA, Ferguson KA, Fleetham JA

To define the effect of a tongue retaining device (TRD) on genioglossus (GG) muscle activity in seven obstructive sleep apnea subjects, two overnight sleep studies were carried out with two TRDs. TRD-A had no anterior bulb and incorporated two electrodes to record GG electromyographic (EMG) activity. TRD-B had a bulb and it had electrodes similar to those in TRD-A. Episodes of apnea/hypopnea (AH) were analyzed during both rapid eye movement (REM) and non-REM (NREM) sleep. The peak GG muscle activity was measured for the breath immediately before the AH (pre-AH), for the first (first-E) and last (last-E) inspiratory efforts during the AH, and for the first breath after the AH (post-AH). The time lag between the peak GG EMG activity and the maximum inspiratory effort was calculated. The AH index decreased with both TRDs. The peak GG EMG activity preceded the maximum inspiratory effort throughout the periods, however the time lag changed considerably with TRD-A. The time lags with TRD-A and TRD- B differed significantly for the first-E and the last-E during NREM sleep and for the first-E during REM sleep. The TRD reduces AH severity, normalizes the time lag, and counteracts fluctuating GG EMG activity observed when no bulb is present.

In: Angle Orthod (1996) 66(4):273-80

Predicting response to the tongue retaining device for sleep apnea syndrome.
Cartwright RD

Factors associated with increased severity of sleep apnea; obesity, the supine sleep posture, and age, were tested for their association with the effectiveness of the Tongue Retaining Device (TRD) for the control of the apneic events in a group of 16 male patients. Sixty- nine percent of the patients (11 of 16) were successful with this treatment. The strongest predictor of this success was the presence of an increased severity associated with the supine sleep posture. Patients with substantial worsening of apnea index while in the supine sleep position were more responsive to the TRD than those who were equally affected in both sleep positions. A discriminant function analysis that entered age, obesity, and the ratio of apneas per hour in side v back sleep posture correctly classified the success of patients' response to this treatment.

In: Arch Otolaryngol (1985 Jun) 111(6):385-8

A randomized crossover study of an oral appliance vs nasal-continuous positive airway pressure in the treatment of mild-moderate obstructive sleep apnea [see comments]
Ferguson KA, Ono T, Lowe AA, Keenan SP, Fleetham JA

STUDY OBJECTIVE: To compare efficacy, side effects, patient compliance, and preference between oral appliance (OA) therapy and nasal-continuous positive airway pressure (N-CPAP) therapy. DESIGN: Randomized, prospective, crossover study. SETTING: University hospital and tertiary sleep referral center. PATIENTS: Twenty-seven unselected patients with mild-moderate obstructive sleep apnea (OSA). INTERVENTIONS: There was a 2-week wash-in and a 2-week wash-out period, and 2 x 4-month treatment periods (OA and N-CPAP). Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. MEASUREMENTS AND RESULTS: Two patients dropped out early in the study and treatment results are presented on the remaining 25 patients. The apnea/hypopnea index was lower with N-CPAP (3.5 +/- 1.6) (mean +/- SD) than with the OA (9.7 +/- 7.3) (p < 0.05). Twelve of the 25 patients who used the OA (48%) were treatment successes (reduction of apnea/hypopnea to <10/h and relief of symptoms), 6 (24%) were compliance failures (unable or unwilling to use the treatment), and 7 (28%) were treatment failures (failure to reduce apnea/hypopnea index to <10/h and/or failure to relieve symptoms). Four people refused to use N-CPAP after using the OA. Thirteen of the 21 patients who used N-CPAP were overall treatment successes (62%), 8 were compliance failures (38%), and there were no treatment failures. Side effects were more common and the patients were less satisfied with N-CPAP (p < 0.005). Seven patients were treatment successes with both treatments, six of these patients preferred OA, and one preferred N-CPAP as a long-term treatment. CONCLUSIONS: We conclude that OA is an effective treatment in some patients with mild-moderate OSA and is associated with fewer side effects and greater patient satisfaction than N-CPAP. Comment in: Chest 1996 May;109(5):1140-1

In: Chest (1996 May) 109(5):1269-75

Evaluation of variable mandibular advancement appliance for treatment of snoring and sleep apnea [see comments]
Pancer J, Al-Faifi S, Al-Faifi M, Hoffstein V

OBJECTIVE: To evaluate an adjustable mandibular positioning appliance for treatment of snoring and sleep apnea. METHODS: One hundred thirty- four patients with baseline apnea/hypopnea index (AHI) of 37 +/- 28 events/h (mean +/- SD) received the appliance. The efficacy of the appliance was assessed by the following investigations, performed at baseline and with the appliance: polysomnography, Epworth sleepiness scale, bedpartners' assessment of snoring severity, patients' assessment of side effects, and overall satisfaction. RESULTS: Thirteen patients were lost to follow-up. An additional 46 patients had no follow-up polysomnography, but answered the questionnaires. A total of 75 patients had polysomnography at baseline and with the appliance. We found a significant reduction in AHI from 44 +/- 28 events/h to 12 +/- 15 events/h (p < 0.0005) and a reduction in the arousal index from 37 +/- 27 events/h to 16 +/- 13 events/h (p < 0.05). Epworth scores fell from 11 +/- 5 to 7 +/- 3 (p < 0.0005). Bedpartners' assessment revealed marked improvement in snoring. For example, at baseline 96% of patients were judged to snore loudly "often" or "always" by their bedpartners, whereas only 2% were judged so while using dental appliance. The most frequent side effect was teeth discomfort, present "sometimes" or "often" in up to 32% of patients. Follow-up clinical assessment in 121 patients conducted on the average 350 days after the insertion of the appliance revealed that 86% of patients continued to use the appliance nightly; 60% were very satisfied with the appliance, 27% were moderately satisfied, 11% were moderately dissatisfied, and 2% were very dissatisfied. CONCLUSION: We conclude that the adjustable mandibular positioning appliance is an effective treatment alternative for some patients with snoring and sleep apnea. Comment in: Chest 1999 Dec;116(6):1501-3

In: Chest (1999 Dec) 116(6):1511-8

Responsibilities of the dental profession in recognizing and treating sleep breathing disorders.
Barsh LI

The recognition and treatment of snoring and obstructive sleep apnea are two medical areas where dentistry can play a valuable role. Oral appliance therapy has been accepted by the American Sleep Disorders Association as an appropriate treatment modality for some patients. It is essential, however, that dentists work as part of the treatment team and not assume responsibility for diagnosis and treatment without the involvement of a physician or sleep specialist. There are currently more than 35 different oral appliances on the commercial market designed to ameliorate the symptoms and/or treat snoring and obstructive sleep apnea. Dentists interested in pursuing this area should receive sufficient training and education and commit to the study of oral appliance therapy for sleep disordered breathing with the same intensity and integrity applied to the rest of their clinical practice.

In: Chest (1999 Dec) 116(6):1511-8

Dentistry's role in the recognition and treatment of sleep-breathing disorders: the need for cooperation with the medical community.
Barsh LI

While oral appliance therapy for the treatment of sleep-disordered breathing can be an exciting and rewarding adjunct to the practice of dentistry, it is essential that dentists realize that snoring and obstructive sleep apnea are medical and not dental problems. Sleep- disordered breathing and its sequelae are diseases that should remain in the purview of the medical community. While the dentist can identify patients with sleep-breathing disorders and participate in their treatment, it is essential to emphasize that sleep-breathing disorders are potentially life-threatening diseases whose diagnosis and treatment are the domain of the medical profession. Accepting dentistry's position as part of a treatment team, ongoing review of scientific literature, cooperation with medical colleagues, and attendance at educational meetings dedicated to the study of sleep- related disorders are essential to proper and ethical dental participation in the treatment of sleep-disordered breathing.

In: J Calif Dent Assoc (1998 Aug) 26(8):591-8

Oral appliance therapy for the treatment of obstructive sleep apnea.
Fleetham JA, Ferguson KA, Lowe AA, Ryan CF

A variety of oral appliances (OA) are now available for the treatment of obstructive sleep apnea (OSA), OA therapy is effective in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nasal CPAP. Adjustable OA are associated with improved treatment success and fewer compliance failures compared to non-adjustable OA. Large randomized clinical trials are necessary to further determine the precise indications, benefits, and risks of each OA in the treatment of OSA.

In: Sleep (1996 Dec) 19(10 Suppl):S288-90

Sleep Disordered Breathing, Part II: Oral Appliance Therapy
Rogers RR

In: Clark's Clinical Dentistry, Vol. 1, Mosby-Year Book, Inc., Chap. 37A, 1996

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