Sleep-disordered breathing in severe mental illness: clinical evaluation of oximetry diagnosis and management limitations.

BACKGROUND: To describe the diagnosis and management pathway of sleep-disordered breathing (SDB) in a sample of patients with severe mental illness (SMI), and to assess the feasibility and patient acceptability of overnight oximetry as a first-step screening method for detecting severe SDB in this population. METHODS: The study was a retrospective audit of patients with SMI seen at a Collaborative Centre for Cardiometabolic Health in Psychosis service who were invited for overnight oximetry between November 2015 and May 2018. The adjusted oxygen desaturation index (ODI) was calculated using 4% desaturation criteria. Results were discussed with a sleep specialist and categorized into a 4-level risk probability tool for SDB. RESULTS: Of 91 adults consenting for overnight oximetry, 90 collected some oximetry data, though 11 of these 90 patients collected technically unsatisfactory oximetry. Thus 79/90 patients (88%) collected adequate oximetry data for at least one night. The oximetry traces suggested likely minimal obstructive sleep apnea (OSA) in 41 cases, moderate to severe OSA in 25 patients, severe OSA in 9 patients and possible obesity hypoventilation syndrome (OHS) in 4 cases. Full polysomnography was recommended for 39 patients but only one-third underwent testing. Nineteen patients were reviewed by a sleep specialist. Of the 10 patients who initiated CPAP, four were considered adherent to treatment. CONCLUSION: Home oximetry may be a pragmatic option for SDB screening in patients with SMI but reliable full diagnostic and management pathways need to be developed.

Hours of work and rest in the rail industry.

Currently, the National Transport Commission is considering four options to form the regulatory framework for rail safety within Australia with respect to fatigue. While the National Transport Commission currently recommends no limitations around hours of work or rest, we provide evidence which suggests regulatory frameworks should incorporate a traditional hours of service regulation over more flexible policies. Our review highlights: Shift durations >12 h are associated with a doubling of risk for accident and injury. Fatigue builds cumulatively with each successive shift where rest in between is inadequate (<12 h). A regulatory framework for fatigue management within the rail industry should prescribe limits on hours of work and rest, including maximum shift duration and successive number of shifts. Appropriately, validated biomathematical models and technologies may be used as a part of a fatigue management system, to augment the protection afforded by limits on hours of work and rest. A comprehensive sleep disorder screening and management programme should form an essential component of any regulatory framework.

Sleep, blood pressure and obesity in 22,389 New Zealanders.

AIM: To determine the relationship of sleep disorders with blood pressure and obesity in a large, relatively healthy, community-based cohort. METHODS: A cross-sectional study was undertaken using data from 22,389 volunteer blood donors in New Zealand aged 16-84 years. Height, weight, neck circumference and blood pressure were measured directly, and data on sleep and other factors were ascertained using a validated self-administered questionnaire. RESULTS: Even in a relatively young, non-clinical cohort, lack of sleep (34%), snoring (33%), high blood pressure (20%) and obesity (19%) are common. After adjusting for relevant confounders, participants at high risk of sleep apnoea had double the odds of having high blood pressure but only in participants over 40 years. Very low and high quantities of sleep are also associated with high blood pressure. Even after controlling for neck circumference, self-reported sleep apnoea, sleep dissatisfaction and low amounts of sleep are associated with a higher body mass index. CONCLUSIONS: Obesity and hypertension have significant associations with a variety of sleep disorders, even in those less than 40 years of age and after adjusting for a wide range of potential confounders.

Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study.

Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity. The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgery versus conventional treatment for the treatment of severe obesity and its complications (mean ± SD body mass index 41 ± 5 kg · m(-2)). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs). Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40-2.18)). In a range of multivariate models of mortality risk, controlling for ≤ 16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01-1.65)). Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.

Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea.

This study aimed to explore the effect of mandibular advancement splints (MAS) on upper airway anatomy during wakefulness in obstructive sleep apnoea (OSA). Patients commencing treatment for OSA with MAS were recruited. Response to treatment was defined by a >or=50% reduction in the apnoea/hypopnoea index. Nasopharyngoscopy was performed in the supine position. Nasopharyngoscopy was performed in 18 responders and 17 nonresponders. Mandibular advancement caused an increase in the calibre of the velopharynx (mean+/- sem +40+/-10%), with relatively minor changes occurring in the oropharynx and hypopharynx. An increase in cross-sectional area of the velopharynx with mandibular advancement occurred to a greater extent in responders than nonresponders (+56+/-16% versus +22+/-13%; p<0.05). Upper airway collapse during the Müller manoeuvre, relative to the baseline cross-sectional area, was greater in nonresponders than responders in the velopharynx (-94+/-4% versus -69+/-9%; p<0.01) and oropharynx (-37+/-6% versus -16+/-3%; p<0.01). When the Müller manoeuvre was performed with mandibular advancement, airway collapse was greater in nonresponders than responders in the velopharynx (-80+/-11% versus +9+/-37%; p<0.001), oropharynx (-36+/-6% versus -20+/-5%; p<0.05) and hypopharynx (-64+/-6% versus -42+/-6%; p<0.05). These results indicate that velopharyngeal calibre is modified by MAS treatment and this may be useful for predicting treatment response.

Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial.

BACKGROUND: Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD. METHOD: A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (PaCO2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood. RESULTS: 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour. CONCLUSIONS: Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life. TRIAL REGISTRATION NUMBER: ACTRN12605000205639.

Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation.

BACKGROUND: Untreated, obesity hypoventilation is associated with significant use of health care resources and high mortality. It remains unclear whether continuous positive airway pressure (CPAP) or bilevel ventilatory support (BVS) should be used as initial management. The aim of this study was to determine if one form of positive pressure is superior to the other in improving daytime respiratory failure. METHODS: A prospective randomised study was performed in patients with obesity hypoventilation referred with respiratory failure. After exclusion of patients with persisting severe nocturnal hypoxaemia (Spo(2) < 80% for > 10 min) or carbon dioxide retention (> 10 mm Hg) despite optimal CPAP, the remaining patients were randomly assigned to receive either CPAP or BVS over a 3-month period. The primary outcome was change in daytime carbon dioxide level. Secondary outcome measures included daytime sleepiness, quality of life, compliance with treatment and psychomotor vigilance testing. RESULTS: Thirty-six patients were randomised to either home CPAP (n = 18) or BVS (n = 18). The two groups did not differ significantly at baseline with regard to physiological or clinical characteristics. Following 3 months of treatment, daytime carbon dioxide levels decreased in both groups (CPAP 6 (8) mm Hg; BVS 7 (7) mm Hg) with no between-group differences. There was no difference in compliance between the two treatment groups (5.8 (2.4) h/night CPAP vs 6.1 (2.1) h/night BVS). Although both groups reported an improvement in daytime sleepiness, subjective sleep quality and psychomotor vigilance performance were better with BVS. CONCLUSIONS: Both CPAP and BVS appear to be equally effective in improving daytime hypercapnia in a subgroup of patients with obesity hypoventilation syndrome without severe nocturnal hypoxaemia. TRIAL REGISTRATION NUMBER: Australian Clinical Trials Registry ACTRN01205000096651.

Sleep health New South Wales: chronic sleep restriction and daytime sleepiness.

AIMS: The aim of this study was to provide the first population-based descriptions of typical sleep duration and the prevalence of chronic sleep restriction and chronic sleepiness in community-dwelling Australian adults. METHODS: Ten thousand subjects randomly selected from the New South Wales electoral roll, half aged 18-24 years and the other half aged 25-64 years were posted a questionnaire asking about sleep behaviour, sleepiness and sleep disorders. RESULTS: Responses were received from 3300 subjects (35.6% response rate). The mean +/- standard deviation of sleep duration was 7.25 +/- 1.48 h/night during the week and 7.53 +/- 2.01 h/night in the weekends. Of the working age group, 18.4% reported sleeping less than 6.5 h/night. Chronic daytime sleepiness was present in 11.7%. Logistic modelling indicated that the independent risk factors for excessive daytime sleepiness were being older, sleeping less than 6.5 h per night during the week, getting qualitatively insufficient sleep, having at least one symptom of insomnia and lacking enthusiasm (marker of depression). CONCLUSION: In New South Wales almost one-fifth of the people are chronically sleep restricted and 11.7% are chronically sleepy. Chronic sleepiness was most commonly associated with voluntarily short sleep durations and symptoms of insomnia and depression. If the experimentally observed health effects of sleep restriction also operate at a population level, this prevalence of chronic sleep restriction is likely to have a significant influence on public health in Australia.

Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing.

Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy.

We studied the effects of sleep apnea on neuroendocrine function in a cross-sectional study of 225 consecutive men undergoing sleep studies and in a longitudinal study of 43 men with severe obstructive sleep apnea before and after 3 months of successful treatment with nasal continuous positive airways pressure to eliminate upper airways obstruction. Blood samples were collected at 0600-0630 h on awakening for measurement of plasma insulin-like growth factor I (IGF-I), total and free testosterone, sex hormone-binding globulin (SHBG), LH, FSH, PRL, T4, T4-binding globulin, and cortisol. The plasma hormone levels were analyzed in relation to the severity of sleep apnea, as indicated by the desaturation index (the hourly rate of episodes of arterial oxygen desaturation greater than 4% of the stable baseline) and the mean minimal oxygen saturation during the desaturation episodes. In the cross-sectional study plasma IGF-I, free and total testosterone, and SHBG levels were significantly lower in relation to the severity of sleep apnea, whereas plasma LH, FSH, PRL, T4, T4-binding globulin, and cortisol were not. The decreases in plasma IGF-I and total and free testosterone were independent of the effects of aging and adiposity by covariance analysis. In the longitudinal study plasma IGF-I, total testosterone, and SHBG, but not free testosterone, significantly increased after 3 months of nasal continuous positive airways pressure treatment. We conclude that sleep apnea causes reversible neuroendocrine dysfunction in men, which is manifested by decreased plasma. IGF-I, testosterone, and SHBG levels. This neuroendocrine dysfunction is related to the severity of the sleep apnea, as indicated by the nadir levels of arterial oxygen desaturation and the rate of desaturation episodes. These hormonal measurements may provide biochemical markers for both the severity of sleep apnea and its response to therapeutic intervention. In addition, sleep apnea may be a previously unrecognized confounder of the neuroendocrine correlates of aging.

Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness.

Patients with noninsulin-dependent diabetes mellitus (NIDDM) are often obese and frequently complain of tiredness. These features are also characteristically seen in patients with obstructive sleep apnea (OSA). Therefore, it was the aim of this study to assess the prevalence of OSA among a group of obese NIDDM patients who have some clinical features of OSA. The effect of reversal of OSA by nasal continuous positive airway pressure (CPAP) treatment on insulin responsiveness was also investigated. From a population of 179 NIDDM patients with a body mass index (BMI) greater than 35 kg/m2, we performed ambulatory sleep monitoring on 31 (15 males and 16 females) who admitted to either heavy snoring or excessive sleepiness. Results were reviewed by a sleep physician blinded to the clinical status of the patients, and 22 (70%) were found to have moderate or severe OSA, with mean oxygen desaturation indexes of 10.3 +/- 5.3 and 30.7 +/- 13.2 episodes/h, respectively. A subgroup of 10 patients (seven males and three females) with a mean BMI of 42.7 +/- 4.3 kg/m2 was treated with nightly CPAP for 4 months. These subjects all had significant OSA, with frequent obstructive apneas (mean, 47 +/- 31.6 episodes/h) and oxygen desaturation (mean minimum O2 saturation, 74 +/- 9.5%), as determined by polysomnography. One patient was excluded from analysis because of infrequent use of CPAP. Insulin responsiveness in terms of glucose disposal measured by hyperinsulinemic euglycemic clamps improved from 11.4 +/- 6.2 to 15.1 +/- 4.6 mumol/kg.min (P < 0.05) during CPAP treatment. These results indicate that OSA occurs commonly in obese NIDDM patients with excessive sleepiness or heavy snoring. Treatment of their OSA may improve insulin responsiveness.

Sleep apnea and hypothyroidism: mechanisms and management.

PURPOSE: There is a high incidence of sleep apnea in patients with untreated hypothyroidism. Thyroxine treatment is said to significantly reduce the apnea index and length and sleep apnea symptoms. We undertook a review of 10 consecutive hypothyroid patients with sleep apnea to investigate mechanisms and management of these two disorders. PATIENTS AND METHODS: Polysomnograms were obtained in 10 consecutive hypothyroid patients referred to our sleep disorders unit. All patients were studied while hypothyroid. Eight patients were restudied later when euthyroid. Lung function, blood gas values, and awake supraglottic resistance were also assessed in each patient. RESULTS: All 10 patients had sleep apnea and were treated with thyroxine. In one patient, hypothyroid myopathy involving the upper airway was demonstrated to be a potential mechanism of sleep apnea in hypothyroidism. Nocturnal angina and ventricular arrhythmias developed in two patients, despite the use of low thyroxine doses. Nasal continuous positive airways pressure (CPAP) was begun in eight patients. Initiation of CPAP prevented further angina or arrythmia in the patients with these cardiac complications. Six of the eight patients who were available for follow-up studies had persistent sleep apnea despite an euthyroid status (apnea index before thyroxine, 51 +/- 6; apnea index after thyroxine, 45 +/- 8), and CPAP therapy was continued in these patients. CONCLUSION: Our experience suggests that the apnea index does not decrease significantly in all patients with hypothyroidism and sleep apnea when euthyroidism is achieved. Treatment of hypothyroidism in the presence of sleep apnea is potentially hazardous and may lead to cardiovascular complications. Management by a combination of CPAP and low-dose thyroxine is helpful in this situation.

Treatment options for sleep apnoea.

Sleep apnoea (SA) is a common sleep disorder affecting 4 to 25% of the adult population. The most common form, obstructive SA, is characterised by recurrent upper airway obstruction during sleep associated with sleep disruption and hypoxaemia. There is increasing evidence that SA leads to impaired vigilance, quality of life, driving accidents and probably represents a vascular disease risk factor. Currently, the most effective treatments are aimed at increasing upper airway space by either air pressure [(continuous positive airway pressure (CPAP)], upper airway surgery or oral appliances. CPAP is the main treatment modality for moderate to severe SA but noncompliance approaches 50% in clinic populations. A number of pharmacological agents have been used in SA but at this stage, none are indicated in moderate to severe SA.

Metabolic aspects of sleep apnea.

Sleep apnea is associated with abnormalities in metabolic function. First, there is a strong epidemiological link between central obesity and sleep apnea. Some evidence suggests that sleep apnea may promote weight gain or prevent weight loss by several mechanisms: reduction in anabolic (growth hormone and testosterone) hormone secretion, influences on energy balance and insulin sensitivity, and altered central serotonergic tone.

Impact of self-reported sleep-breathing disturbances on psychosocial performance in the Swedish Obese Subjects (SOS) Study.

Patients with severe obesity commonly have obstructive sleep apnea (OSA). In order to determine the impact of OSA on psychosocial morbidity in severe obesity, subjects enrolled in the Swedish Obese Subjects (SOS) Study were classified into two subgroups based on questionnaire data: one group with a high likelihood and one with a low likelihood of OSA. These groups were contrasted and multivariable analysis was used to examine whether OSA had independent effects on divorce rate, sick leave, work performance, income and self-estimated general health after adjustment for obesity, fat distribution, alcohol, smoking, medications and coexisting medical conditions. A high likelihood of OSA was identified in 338 men and 155 women, compared with 216 men and 481 women who had a low likelihood of OSA. Men with OSA were identical in age to men without OSA and had slightly higher levels of visceral fat (p = 0.01), but were similar in most psychosocial variables except self-perceived general health. Women with OSA were identical in age and visceral fat mass to women without OSA, but were characterized by a higher rate of impaired work performance, sick leave and divorce. When frequent sleepiness was used as an additional discriminator between OSA and non-OSA groups, marked differences in psychosocial morbidity were observed. Multivariable analysis revealed either OSA or frequent sleepiness or both to be independent predictors of amount of sick leave, worse self-rated general health, impaired work performance and divorce rate. Therefore OSA, measured by self report, is an important independent predictor of psychosocial morbidity in subjects with severe obesity.

Acute withdrawal of nasal CPAP in obstructive sleep apnea does not cause a rise in stress hormones.

We hypothesized that withdrawal of nasal continuous positive airway pressure (CPAP) in patients with sleep apnea would produce a measurable stress response. To test this hypothesis, we ceased CPAP in eight patients regularly using nasal CPAP long term and measured the effect on sleep apnea as well as plasma and urinary levels of the stress hormones, noradrenaline, cortisol and adrenocorticotropic hormone (ACTH). CPAP withdrawal led to an immediate recurrence of sleep apnea with increases in apnea index, arousal index and oxygen desaturation (all p < .0001) but no change in levels of noradrenaline, cortisol or ACTH. We conclude that acute withdrawal of CPAP in patients with sleep apnea does not lead to a classic stress response.

Effect of nasal continuous positive airway pressure during sleep on 24-hour blood pressure in obstructive sleep apnea.

Ambulatory blood pressure (BP) was measured noninvasively (Oxford Medilog ABP) at 15-minute intervals for 24 hours before and after 8 weeks of treatment with nasal continuous positive airway pressure (nCPAP) in 19 men with obstructive sleep apnea (OSA). We included both normotensive and hypertensive patients, but hypertensives were studied after withdrawal of antihypertensive drugs. Ambulatory BP before and after treatment was compared using patients as their own controls. Treatment with nCPAP was successfully established in 14 of the 19 patients (74%). Blood pressure fell significantly in patients who were successfully treated: 24-hour mean BP (systolic/diastolic) decreased from 141 +/- 18/89 +/- 11 mm Hg to 134 +/- 19/85 +/- 13 mm Hg (p < 0.05). The reduction in 24-hour mean systolic BP occurred during both day and night, but a significant fall in mean diastolic BP was only observed during the day. The mean blood pressure fell in both normotensive and hypertensive patients. Patients who were inadequately treated with nCPAP had no reduction in mean 24-hour BP. Effective treatment of sleep apnea with nCPAP was associated with a significant fall in both systolic and diastolic BP independent of changes in body weight or alcohol consumption, suggesting that sleep apnea was an independent factor contributing to elevated nighttime and daytime BP in these patients.

Noninvasive ventilatory support during sleep improves respiratory failure in kyphoscoliosis.

We investigated the effect on daytime respiratory function and quality of sleep, of providing adequate ventilation either by intermittent positive pressure ventilation (IPPV) or by continuous positive airways pressure (CPAP) both administered through a nose mask in a group of seven patients with severe thoracic kyphoscoliosis. All night control sleep studies were performed with and without ventilatory assistance. Patients underwent standard polysomnography including all night measurements of transcutaneous CO2 (tcCO2) and arterial oxyhemoglobin saturation (SaO2). Awake arterial blood gas tensions (ABGs), respiratory muscle strength (Pmus), and lung function tests were measured in the sitting position. Follow-up studies after three months of treatment showed normal sleep patterns, improvement in daytime ABGs, lung volumes, and respiratory muscle strength. We concluded that maintenance of nocturnal ventilation by either nasal CPAP or nasal IPPV in patients with nocturnal respiratory failure does significantly improve clinical measurements of respiratory function and quality of sleep.

Predicting sleep-disordered breathing in patients with cystic fibrosis.

STUDY OBJECTIVES: To examine predictors of sleep-disordered breathing in patients with cystic fibrosis (CF) and moderate-to-severe lung disease using a comprehensive evaluation of both sleep and daytime function. DESIGN: Cross-sectional analysis of sleep studies, lung function, respiratory muscle strength, and evening and morning arterial blood gas measurements in patients with stable CF. A questionnaire addressing sleep quality was administered. Forward stepwise regression analysis was used to identify the parameters that best predict sleep-related desaturation, hypercapnia, and respiratory disturbance. SETTING: Sleep investigation unit and lung function laboratory. PATIENTS: Thirty-two patients with CF and FEV(1) < 65% predicted, in stable clinical condition. Patients were aged 27 +/- 8 years (mean +/- 1 SD) with FEV(1) of 36 +/- 10% predicted, evening PaO(2) of 68 +/- 8 mm Hg, and PaCO(2) of 43 +/- 5 mm Hg. RESULTS: Evening PaO(2) (p < 0.0001) and morning PaCO(2) (p < 0.01) were predictive of the average minimum oxyhemoglobin saturation per 30-s epoch of sleep (r(2) = 0.74; p < 0.0001). Evening PaO(2) (p < 0.001) was predictive of the rise in transcutaneous carbon dioxide (TcCO(2)) seen from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep (r(2) = 0.37; p < 0.001). In addition, there was some relationship between expiratory respiratory muscle strength and the REM respiratory disturbance index (r(2) = 0.22; p < 0.01). CONCLUSION: Evening PaO(2) was found to contribute significantly to the ability to predict both sleep-related desaturation and the rise in TcCO(2) from NREM sleep to REM sleep in this subgroup of patients with CF.

Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson disease.

OBJECTIVE: Using salivary dim light melatonin onset (DLMO) and actigraphy, our study sought to determine if Parkinson disease (PD) patients demonstrate circadian disturbance compared to healthy controls. Additionally, our study investigated if circadian disturbances represent a disease-related process or may be attributed to dopaminergic therapy. METHODS: Twenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 healthy controls. All participants underwent neurologic assessment and 14 days of actigraphy to establish habitual sleep-onset time (HSO). DLMO time and area under the melatonin curve (AUC) were calculated from salivary melatonin sampling. The phase angle of entrainment was calculated by subtracting DLMO from HSO. Overnight polysomnography (PSG) was performed to determine sleep architecture. RESULTS: DLMO and HSO were not different across the groups. However, the phase angle of entrainment was more than twice as long in the medicated PD group compared to the unmedicated PD group (U = 35.5; P = .002) and was more than 50% longer than controls (U = 130.0; P = .021). The medicated PD group showed more than double the melatonin AUC compared to the unmedicated group (U = 31; P = 0.001) and controls (U = 87; P = .001). There was no difference in these measures comparing unmedicated PD and controls. CONCLUSIONS: In PD dopaminergic treatment profoundly increases the secretion of melatonin. Our study reported no difference in circadian phase and HSO between groups. However, PD patients treated with dopaminergic therapy unexpectedly showed a delayed sleep onset relative to DLMO, suggesting dopaminergic therapy in PD results in an uncoupling of circadian and sleep regulation.