Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure

BACKGROUND: Polysomnography findings between matched groups with obstructive sleep apnea (OSA) and OSA plus obesity-hypoventilation syndrome (OHS) before and after continuous positive airway pressure (CPAP), particularly in the extremely severe obese (body mass index [BMI] >or= 50 kg/m2), are unclear. DESIGN: Prospective study of subjects (BMI >or= 50 kg/m2) undergoing diagnostic polysomnography. Subjects with an apnea-hypopnea index (AHI) >or= 15/h underwent a second polysomnography with CPAP. The effect of 1 night of CPAP on sleep architecture, AHI, arousal indexes, and nocturnal oxygenation was assessed. OHS was defined as those subjects with obesity, PaCo2 > 45 mm Hg, and PaO2 < 70 mm Hg in the absence of lung disease. RESULTS: Twenty-three subjects with moderate-to-severe OSA and 23 subjects with moderate-to-severe OSA plus OHS underwent a 1-night trial of CPAP. Both groups were matched for spirometry, BMI, and AHI, but oxygen desaturation was worse in the OSA-plus-OHS group. CPAP significantly improved rapid eye movement (REM) duration (p < 0.005), AHI (p < 0.005), arousal indexes (p < 0.005), and percentage of total sleep time (TST) with oxygen saturation (SpO2) < 90% (p < 0.005) in both groups. In subjects with OSA plus OHS, 43% continued to spend > 20% of TST with SpO2 < 90%, compared to 9% of the OSA group, despite the adequate relief of upper airway obstruction. CONCLUSIONS: Extremely severe obese subjects (BMI >or= 50 kg/m2) with moderate-to-severe OSA plus OHS exhibit severe oxygen desaturation but similar severities of AHI, arousal indexes, and sleep architecture abnormalities when compared to matched subjects without OHS. CPAP significantly improves AHI, REM duration, arousal indexes, and nocturnal oxygen desaturation. Some subjects with OHS continued to have nocturnal desaturation despite the control of upper airway obstruction; other mechanisms may contribute. Further long-term studies assessing the comparative role of CPAP and bilevel ventilatory support in such subjects with OHS is warranted.     

Oxidative stress in obstructive sleep apnea

STUDY OBJECTIVES: To investigate the relationship between the severity of obstructive sleep apnea (OSA) and oxidative stress, which plays an important role in the pathogenesis of cardiovascular disease, and to elucidate the factors contributing to this relationship. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 128 consecutive subjects referred to the sleep laboratory of our hospital for screening or treatment of OSA. INTERVENTIONS: Not applicable. MEASUREMENTS: The severity of sleep-disordered breathing was evaluated by polysomnography. We measured urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an in vivo parameter of oxidative stress. Known risk factors for oxidative stress (age, obesity, smoking, hyperlipidemia, hypertension, and diabetes mellitus) were also investigated. RESULTS: Seventy subjects had nonsevere OSA (an apnea-hypopnea index [AHI] < 30), and 58 subjects had severe OSA (AHI >or= 30). Urinary 8-OHdG excretion was significantly higher in the severe OSA group (p = 0.03). Furthermore, urinary 8-OHdG excretion was significantly correlated with parameters of sleep-disordered breathing, including AHI, the apnea index, the oxygen desaturation index (ODI), the duration of oxygen saturation < 90%, and the respiratory arousal index. However, only ODI was significantly correlated with urinary 8-OHdG excretion after adjustment for confounding factors that are considered to be related to oxidative stress. CONCLUSIONS: The severity of OSA is independently associated with oxidative stress. Among various sleep-disordered breathing parameters, ODI is most closely related to oxidative stress.     

A case-control study of obstructive sleep apnea-hypopnea syndrome in obese and nonobese chinese children

BACKGROUND: Obesity is a risk factor for obstructive sleep apnea-hypopnea syndrome (OSAHS) in adults. However, the prevalence of OSAHS in children is not clear, and the relationship between obesity and OSAHS remains controversial. METHODS: Obese children were recruited from the endocrinology, respiratory, and ear, nose, and throat clinics. Weight-matched, age-matched, and sex-matched children were recruited as control subjects. Standard questionnaires were administered, and a standardized physical examination was carried out. Lateral neck roentgenography, sleep polysomnography, full blood count, and arterial blood gas analysis were also performed. Children with body mass index z-scores of > 1.96 were considered to be obese. An adenoidal/nasopharygeal ratio of > 0.67 was considered to constitute adenotonsillar hypertrophy (ATH). OSAHS was defined as an apnea-hypopnea index (AHI) score of > 5 or obstructive apnea index (OAI) score of > 1. RESULTS: Ninety-nine obese children and 99 control subjects were recruited into the study. Obese patients had significantly higher AHI and OAI scores, and lower sleep efficiency and minimum arterial oxygen saturation (MinSao(2)) than control subjects. The prevalence of OSAHS was significantly higher in obese children with or without the ATH groups than their nonobese counterparts (odds ratio, 1.9 vs 108, respectively; 95% confidence interval, 1.21 to 4.7 vs 6.2 to 191, respectively). Obesity, tonsillar hypertrophy, and adenoid hypertrophy were independent risk factors for OSAHS (p < 0.001, p = 0.042, and p = 0.004, respectively). There was a positive correlation between the degree of obesity and AHI (r = 0.535; p < 0.001), and an inverse correlation between obesity and MinSao(2) (r = -0.507; p < 0.001). End-tidal CO(2), Paco(2), and bicarbonate levels were within the normal range. CONCLUSIONS: Obesity is a risk factor for OSAHS, and the degree of obesity is positively correlated with the severity of OSAHS.     

Impaired objective daytime vigilance in obesity-hypoventilation syndrome: impact of noninvasive ventilation

BACKGROUND: Obesity-hypoventilation syndrome (OHS) is efficiently treated by noninvasive ventilation (NIV). Sleep respiratory disturbances, reduced ventilatory drive, and excessive daytime sleepiness (EDS) are commonly reported, but their relationships remain unclear. OBJECTIVES: To characterize sleep breathing disorders encountered in patients with OHS, to compare low and normal CO(2) responders in terms of sleep abnormalities, subjective and objective measures of EDS, and to measure the changes induced by NIV on these parameters. METHODS: At baseline and after 5 nights of NIV, 15 consecutive patients (mean [+/- SD] age, 55 +/- 9 years; mean body mass index, 38.7 +/- 6.1 kg/m(2); Paco(2), 47.3 +/- 2.3 mm Hg) prospectively underwent polysomnography, CO(2) ventilatory response testing, Epworth sleepiness scale scoring, and the Oxford Sleep Resistance (OSLER) test, which is an objective vigilance test. RESULTS: OHS patients exhibited obstructive sleep apnea syndrome (mean apnea-hypopnea index, 62 +/- 32 events per hour) and rapid eye movement (REM) sleep hypoventilation (mean REM sleep time, 35 +/- 33%). Baseline CO(2) sensitivity was significantly related to the proportion of hypoventilation during REM sleep (r = 0.54; p = 0.037). Six patients showed abnormal sleep latencies during the OSLER test (71% of the low CO(2) responders vs 14% of the normal CO(2) responders). Low CO(2) responders exhibited significantly shorter sleep latencies during the OSLER test (23 +/- 14 vs 37 +/- 8 min, respectively; p = 0.05). Using NIV, diurnal blood gas levels were improved and REM sleep hypoventilation were suppressed. Objective sleepiness was improved in low CO(2) responders (p = 0.04). CONCLUSION: In OHS patients, the lower the daytime CO(2) response, the higher the proportion of REM sleep hypoventilation and daytime sleepiness. Short-term therapy with NIV improves all of these parameters.     

Association between polysomnographic measures of disrupted sleep and prothrombotic factors

BACKGROUND: Subjective sleep disturbances have been associated with increased risk of coronary artery disease (CAD). We hypothesized that disrupted sleep as verified by polysomnography is associated with increased levels of prothrombotic hemostasis factors previously shown to predict CAD risk. METHODS: Full-night polysomnography was performed in 135 unmedicated men and women (mean age +/- SD, 36.8 +/- 7.8 years) without a history of sleep disorders. Morning fasting plasma levels of von Willebrand Factor (VWF) antigen, soluble tissue factor (sTF) antigen, d-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were determined. Statistical analyses were adjusted for age, gender, ethnicity, body mass index, BP, and smoking history. RESULTS: Higher total arousal index (ArI) was associated with higher levels of VWF (beta = 0.25, p = 0.011, DeltaR(2) = 0.045), and longer wake after sleep onset was associated with higher levels of sTF (beta = 0.23, p = 0.023, DeltaR(2) = 0.038). More nighttime spent at mean oxygen saturation < 90% (beta = 0.20, p = 0.020, DeltaR(2) = 0.029) and higher apnea-hypopnea index (AHI) [beta = 0.19, p = 0.034, DeltaR(2) = 0.024] were associated with higher PAI-1. There was a trend for a relationship between mean oxygen desaturation < 90% and PAI-1 (p = 0.053), even after controlling for AHI. Total ArI (beta = 0.28, p = 0.005, DeltaR(2) = 0.056) and WASO (beta = 0.25, p = 0.017, DeltaR(2) = 0.042) continued to predict VWF and sTF, respectively, even after controlling for AHI. CONCLUSIONS: Polysomnographically verified sleep disruptions were associated with prothrombotic changes. Measures of sleep fragmentation and sleep efficiency were related to VWF and sTF, respectively. Apnea-related measures were related to PAI-1. Our findings suggest that sleep disruptions, even in a relatively healthy population, are associated with potential markers of prothrombotic cardiovascular risk.     

An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea

BACKGROUND: Oral appliances (OAs) are first-line therapy for mild-to-moderate obstructive sleep apnea (OSA) and are being used with increasing frequency. Additionally, best practice of OA titration is unknown. We describe the experience of patients treated with an OA, identify factors that predict treatment success with an OA, and offer a protocol for OA titration. METHODS: We retrospectively studied patients seen in a dental sleep clinic between 2002 and 2006. Patients selected for OA treatment underwent baseline polysomnography, were individually fit with an OA, and were instructed to titrate it at home until symptom resolution or discomfort. During follow-up polysomnography, additional titration was performed as needed. Primary outcome was successful treatment, defined as apnea-hypopnea index (AHI) <10 events per hour and AHI decrease at least 50% from baseline. Logistic regression models were created to identify associations between patient characteristics and successful treatment. Overall differences in AHI at baseline, after home titration, and after final titration were compared using Kruskal-Wallis test, and post hoc comparisons were performed with sign tests, with Bonferroni corrections. RESULTS: Of 57 subjects treated with an OA, 37 subjects (64.9%) were successfully treated with OA therapy. Of the 49 subjects for whom data were available for AHI after home titration, 27 subjects (55%) achieved successful treatment of OSA by self-titration, without need for further titration during follow-up polysomnography. CONCLUSIONS: A majority of subjects, regardless of OSA severity, are successfully treated with an OA. Men and younger patients were found to be the best responders. The titration protocol for an OA offers a beneficial initial step in the treatment of OSA.     

Independent association between obstructive sleep apnea and subclinical coronary artery disease

BACKGROUND: Obstructive sleep apnea (OSA) is associated with coronary risk factors, but it is unknown if OSA is associated with development of coronary disease. We evaluated the association between OSA and the presence of subclinical coronary disease assessed by coronary artery calcification (CAC). METHODS: Consecutive patients with no history of coronary disease who underwent electron-beam CT within 3 years of polysomnography between March 1991 and December 2003 were included. OSA was defined by an apnea-hypopnea index (AHI) > or = 5 events per hour, and patients were grouped by quartiles of AHI severity. Logistic regression modeled the association between OSA severity and presence of CAC. RESULTS: There were 202 patients (70% male; median age, 50 years; mean body mass index, 32 kg/m(2); 8% diabetic; 9% current smokers; 60% hypercholesterolemic; and 47% hypertensive). OSA was present in 76%. CAC was present in 67% of OSA patients and 31% of non-OSA patients (p < 0.001). Median CAC scores (Agatston units) were 9 in OSA patients and 0 in non-OSA patients (p < 0.001). Median CAC score was higher as OSA severity increased (p for trend by AHI quartile < 0.001). With multivariate adjustment, the odds ratio for CAC increased with OSA severity. Using the first AHI quartile as reference, the adjusted odds ratios for the second, third, and fourth quartiles were 2.1 (p = 0.12), 2.4 (p = 0.06), and 3.3 (p = 0.03), respectively. CONCLUSIONS: In patients without clinical coronary disease, the presence and severity of OSA is independently associated with the presence and extent of CAC. OSA identifies patients at risk for coronary disease and may represent a highly prevalent modifiable risk factor.     

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.     

Relationship between serum substance P levels and daytime sleepiness in obstructive sleep apnea syndrome

OBJECTIVE: We hypothesized that intermittent hypoxia might influence serum substance P levels, and that this effect might in turn contribute in excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Fifty-five patients with newly diagnosed OSAS and 15 age-matched nonapneic control subjects were enrolled in this study. Full polysomnography was performed in all patients. Single blood samples were drawn between 8:00 am and 9:00 am after the sleep study. Substance P levels were analyzed with a competitive enzyme immunoassay (substance P EIA kit; Cayman Chemical; Ann Arbor, MI). RESULTS: There were no significant differences in age, gender, body mass index, smoking habit, and snoring between the two groups. Serum substance P levels in the OSAS group were significantly lower than that in the control group (p < 0.0001). Serum substance P levels were positively correlated with rapid eye movement sleep (r = 0.330, p = 0.049) and slow-wave sleep (r = 0.324, p = 0.049) phases. Serum substance P levels were negatively correlated with Epworth sleepiness scale score (r = - 0.253, p = 0.048), number of total apneas during the night (r = - 0.247, p = 0.036), number of respiratory events during the night (r = - 0.266, p = 0.024), apnea-hypopnea index (r = - 0.287, p = 0.015), respiratory arousal index (r = - 0.267, p = 0.026), time spent in apnea and hypopnea (r = - 0.307, p = 0.01), average oxygen desaturation (r = - 0.265, p = 0.026), and oxygen desaturation index (r = - 0.254, p = 0.031). CONCLUSION: We concluded that EDS seen in some of the OSAS patients might be associated with various pathophysiologic mechanisms including substance P levels.     

Relationship between beta-blocker treatment and the severity of central sleep apnea in chronic heart failure

BACKGROUND: We sought to examine the relationship between use of beta-blockers and the severity of central sleep apnea (CSA) in patients with chronic heart failure. METHODS: We performed polysomnography in 45 patients with chronic heart failure (New York Heart Association functional class II/III and left ventricular ejection fraction < 50%) and examined the relationship between use of beta-blockers and the severity of CSA. Central apnea index (CAI) was used as an indicator of CSA. RESULTS: Patients receiving beta-blockers (ie, carvedilol; n = 27) had lower apnea-hypopnea index (AHI) and CAI than patients not receiving beta-blockers (n = 18) [mean +/- SD, 14 +/- 11 vs 33 +/- 17, p < 0.0001; and 1.9 +/- 3.2 vs 11 +/- 12, p = 0.0004, respectively]. AHI and CAI were negatively correlated with the dose of carvedilol (Spearman rho = - 0.61, p < 0.0001; and Spearman rho = - 0.57, p = 0.0002, respectively). Multiple regression analysis selected no use of beta-blockers as an independent factor of CAI (p = 0.0006). In five patients with CAI > 5 who underwent serial sleep studies, CAI decreased significantly after 6 months of treatment with carvedilol (9.5 +/- 4.9 to 1.3 +/- 2.4, p = 0.03). CONCLUSIONS: In patients with chronic heart failure, CAI was lower according to the dose of beta-blockers, and no use of beta-blockers was independently associated with CAI. In addition, 6 months of treatment with carvedilol decreased CAI. These results suggest that beta-blocker therapy may dose-dependently suppress CSA in patients with chronic heart failure.     

Central sleep apnea induced by acute ingestion of opioids

OBJECTIVES: Three cases are presented in which patients were using opioids as required for nonmalignant pain management and significant central sleep apnea developed. Patients in the first two cases had no evidence of sleep-related breathing disorders on polysomnography until they ingested an opioid for treatment of chronic pain during the night and severe central sleep apnea developed. The patient in our third case had established obstructive sleep apnea but experienced a significant number of central events after the ingestion of an opioid analgesic, leading to worsening severity of his underlying sleep-related breathing disorder. CONCLUSION: The short-term ingestion of opioid analgesics can precipitate central sleep apnea in patients with chronic pain receiving long-term opiate therapy who otherwise show no evidence of central sleep apnea and have no cardiac or neurologic disease that would predispose them to central sleep apnea.     

Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension

OBJECTIVE: Obstructive sleep apnea (OSA) and primary aldosteronism are common in subjects with resistant hypertension; it is unknown, however, if the two disorders are causally related. This study relates plasma aldosterone and renin levels to OSA severity in subjects with resistant hypertension, and in those with equally severe OSA but without resistant hypertension serving as control subjects. METHODS: Seventy-one consecutive subjects referred to the University of Alabama at Birmingham (UAB) for resistant hypertension (BP uncontrolled on three medications) and 29 control subjects referred to UAB Sleep Disorders Center for suspected OSA were prospectively evaluated by an early morning plasma aldosterone concentration (PAC) and renin level, and by overnight, attended polysomnography. RESULTS: OSA (apnea-hypopnea index [AHI] > or = 5/h) was present in 85% of subjects with resistant hypertension. In these subjects, PAC correlated with AHI (rho = 0.44, p = 0.0002) but not renin concentration. Median PAC was significantly lower in control subjects compared to subjects with resistant hypertension (5.5 ng/dL vs 11.0 ng/dL, p < 0.05) and not related to AHI. In male subjects compared to female subjects with resistant hypertension, OSA was more common (90% vs 77%) and more severe (median AHI, 20.8/h vs 10.8/h; p = 0.01), and median PAC was significantly higher (12.0 ng/dL vs 8.8 ng/dL, p = 0.006). CONCLUSION: OSA is extremely common in subjects with resistant hypertension. A significant correlation between PAC and OSA severity is observed in subjects with resistant hypertension but not in control subjects. While cause and effect cannot be inferred, the data suggest that aldosterone excess may contribute to OSA severity.     

Beneficial effect of bilevel positive airway pressure on left ventricular function in ambulatory patients with idiopathic dilated cardiomyopathy and central sleep apnea-hypopnea: a preliminary study

BACKGROUND: Sleep-disordered breathing is common in individuals with left ventricular (LV) dysfunction and has been treated with nocturnal positive airway pressure. We investigated whether treatment of central sleep apnea-hypopnea with bilevel positive airway pressure (BPAP) in ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) might improve LV function. METHODS: Fifty-two consecutive patients with IDCM who underwent both cardiac catheterization and standard polysomnography were enrolled in the study; individuals with obstructive sleep apnea syndrome were excluded. Subjects with an apnea-hypopnea index (AHI) >or= 20 episodes per hour were randomized to receive medical therapy either alone (n = 11) or together with BPAP (n = 10). RESULTS: LV end-diastolic pressure, pulmonary capillary wedge pressure, and plasma concentration of brain natriuretic peptide were significantly greater, and LV ejection fraction (LVEF) was significantly lower in patients with an AHI >or= 20/h (n = 21, 40.4%) than in those with an AHI < 20/h (n = 31, 59.6%). LVEF (30.5 +/- 1.6% vs 50.8 +/- 3.5%, p < 0.001) [mean +/- SE] and plasma concentration of brain natriuretic peptide (162.8 +/- 44.5 pg/mL vs 32.7 +/- 17.6 pg/mL, p = 0.02) were significantly increased and decreased, respectively, after treatment with BPAP (daily use, 4.8 +/- 0.3 h) for 3 months, whereas these parameters remained unchanged in the control subjects. CONCLUSIONS: Our findings suggest that treatment of coexisting central sleep apnea-hypopnea with BPAP improves LV function in ambulatory patients with IDCM. BPAP should thus be considered as a nonpharmacologic adjunct to conventional drug therapy in such patients.     

Prospective evaluation of nocturnal oximetry for detection of sleep-related breathing disturbances in patients with chronic heart failure

BACKGROUND: Because patients with chronic heart failure (CHF) can benefit from specific treatment for coexisting obstructive and central sleep apnea (CSA), there is a need to develop accurate screening tools to identify or exclude these sleep-related breathing disturbances (SRBDs) in patients with CHF. OBJECTIVES: To evaluate, prospectively, the diagnostic value of nocturnal home oximetry in identifying SRBD in CHF patients and in distinguishing central events from obstructive events. DESIGN: Blinded comparison of hospital and home oximetry, and polysomnographic nocturnal recordings SETTING: Cardiac heart failure and sleep clinics in three tertiary referral centers. PATIENTS: Fifty consecutive patients who were investigated for participation in the Canadian Continuous Positive Airway Pressure Trial for Congestive Heart Failure with Central Sleep Apnea and were recruited from three different centers. MEASUREMENTS AND RESULTS: Patients underwent two oximetry recordings, one at home and one during a polysomnographic study. The criterion for an SRBD was the presence of > 15 apneas and hypopneas per hour of sleep during polysomnography or an oxygen desaturation index of > 10 events per hour during oximetry. The pattern of desaturation/resaturation during oximetry was also examined to distinguish obstructive events from central events. Using a 2% fall in pulse oximetric saturation as the criterion for oxygen desaturation, home oximetry had a 85% sensitivity and a 93% specificity (p < 0.001) for detecting an SRBD. However, the desaturation/resaturation pattern did not accurately distinguish between obstructive events and central events (eg, 100% sensitivity, 17% specificity for identifying CSA). The interpretation of the oximetry recording was highly consistent between scorers (p < 0.001). CONCLUSIONS: Overnight home oximetry is a sensitive and specific tool for identifying SRBDs in patients with CHF, but not for distinguishing between obstructive and central events in such patients.     

Brain natriuretic peptide in patients with congestive heart failure and central sleep apnea

STUDY OBJECTIVE: To assess the possible relationship between Cheyne-Stokes respiration (CSR) associated with central sleep apnea (CSA) syndrome and brain natriuretic peptide (BNP) in an outpatient population presenting with stable congestive heart failure (CHF). MEASUREMENTS AND RESULTS: Ninety patients with CHF due to systolic dysfunction (left ventricular ejection fraction 相似文献   

Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea

BACKGROUND: Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. DESIGN: Prospective study. SETTING: Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. PARTICIPANTS: A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. RESULTS: A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). CONCLUSION: Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.     

Cystic fibrosis patients have poor sleep quality despite normal sleep latency and efficiency

STUDY OBJECTIVES: Cystic fibrosis (CF) patients may be predisposed to poor sleep quality due to upper and lower airway abnormalities and impaired gas exchange. Previous sleep investigations of CF patients using single-night polysomnography have reported conflicting results. We hypothesized that sampling sleep for a prolonged period in a patient's normal environment may give a more representative assessment of sleep quality than a single-night polysomnogram, and that impaired sleep quality would correlate with pulmonary disease severity and self-assessed sleep quality. DESIGN: Using wrist actigraphy, we measured sleep quality in clinically stable CF patients and age-matched control subjects. In addition, each CF patient and control subject completed the following three questionnaires: the Epworth sleepiness scale; the Pittsburgh sleep quality index (PSQI); and the Medical Outcomes Study 36-item short form. RESULTS: Twenty CF patients and control subjects were enrolled in the study, and were well-matched for age, sex, and body mass index. The mean (+/- SD) FEV(1) for CF patients was 61.0 +/- 20.1% predicted. CF patients and control subjects had similar sleep duration, sleep latency, and sleep efficiency. However, CF patients had higher PSQI scores (6.45 vs 4.55, respectively; p = .04), a higher fragmentation index (FI) [31.72 vs 18.02, respectively; p < 0.001], and less immobile time (88.87 vs 91.89, respectively; p = 0.02). There was a significant correlation of FI with FEV(1) and PSQI scores. CONCLUSIONS: Stable CF patients have disrupted sleep, and sleep disruption may in part be related to the severity of pulmonary disease. In addition, the PSQI may be useful in detecting CF patients with poor sleep quality.     

Does Endothelin Play a Role in Chemoreception During Acute Hypoxia in Normal Men?

BACKGROUND: The peripheral chemoreceptors are the dominant reflex mechanism responsible for the rise in ventilation and muscle sympathetic nerve activity (MSNA) in response to hypoxia. Animal studies have suggested that endothelin (ET) plays an important role in chemosensitivity. Moreover, several human clinical conditions in which circulating ET levels are increased are accompanied by enhanced chemoreflex sensitivity. Whether ET plays a role in normal human chemosensitivity is unknown. METHODS: We determined whether bosentan, a nonspecific ET receptor antagonist, would decrease chemoreflex sensitivity in 14 healthy subjects. We assessed the effects of bosentan on the response to isocapnic hypoxia, using a randomized, crossover, double-blinded study design. RESULTS: Bosentan increased mean (+/- SEM) plasma ET levels from 1.97 +/- 0.28 to 2.53 +/- 0.23 pg/mL (p = 0.01). Hypoxia increased mean minute ventilation from 6.7 +/- 0.3 to 8+/0.4 L/min (p < 0.01), mean MSNA from 100 to 111 +/- 5% (p < 0.01), mean heart rate from 67 +/- 3 to 86 +/- 3 beats/min (p < 0.01), and mean systolic BP from 116 +/- 3 to 122 +/- 3 mm Hg (p < 0.01). However, none of these responses differed between therapy with bosentan and therapy with placebo (p = 0.26). Bosentan did not affect the mean MSNA responses to the apneas, during normoxia (change from baseline: placebo, 259 +/- 58%; bosentan, 201 +/- 28%; p = 0.17) or during hypoxia (change from baseline: placebo, 469 +/- 139%; bosentan, 329 +/- 46%; p = 0.24). The durations of the voluntary end-expiratory apneas in normoxia and hypoxia, and the subsequent reductions in oxygen saturation, were also similar with therapy using bosentan and placebo (p = 0.42). CONCLUSION: In healthy men, ET does not play an important role in peripheral chemoreceptor activation by acute hypoxia.     

Depressed myocardial contractile reserve in patients with obstructive sleep apnea assessed by tissue Doppler imaging with dobutamine stress echocardiography

BACKGROUND: Hypoxia has been suggested to affect myocardial contractile function in patients with obstructive sleep apnea (OSA). We sought to determine whether myocardial contractile reserve (MCR), as evaluated by echocardiographic tissue Doppler imaging with dobutamine stress (TDDS), might be depressed in OSA patients. METHODS: Thirty patients with suspected OSA (25 men and 5 women; mean age, 51 +/- 11 years [+/- SD]) underwent overnight polysomnography and TDDS. Peak myocardial systolic velocity (Sm) and peak myocardial early diastolic velocity (Em) in the 12 myocardial segments of the left ventricular (LV) walls were averaged, and the mean Sm and Em during TDDS were compared between patients with apnea-hypopnea index (AHI) <15/h (group 1, n = 13) and those with AHI >/= 15/h (group 2, n = 17). MCR was calculated as the difference between the resting and peak Sm during TDDS. RESULTS: In both groups, Sm increased dose dependently during TDDS. However, the relative increase in Sm was significantly lower in group 2, resulting in a lower value of MCR (5.5 +/- 1.2 cm/s vs 7.4 +/- 1.3 cm/s, p < 0.001). The Em was lower in group 2 compared with group 1 throughout TDDS. MCR was correlated significantly with AHI (r = - 0.67, p < 0.0001), resting Em (r = 0.53, p < 0.005), and body mass index (r = - 0.46, p < 0.05) independent of the LV mass index. CONCLUSIONS: OSA can affect MCR, implying an etiologic contribution from repetitive hypoxic events. TDDS could identify subtle abnormalities of OSA-related cardiac involvement.     

Lung aeration during sleep

BACKGROUND: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.