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.     

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.     

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.     

Effect of albuterol on maximal exercise capacity in cystic fibrosis

BACKGROUND: Inhaled, short-acting beta-adrenergic agonists (SAbetaAs) are widely prescribed in cystic fibrosis (CF) subjects, despite a lack of convincing data for efficacy and the potential for these agents to result in airway instability. We tested the hypothesis that inhaled albuterol would improve maximal exercise performance in CF subjects with airflow obstruction, as a result of acute bronchodilation. METHODS: Randomized, double-blind, placebo-controlled crossover study of the effect of inhaled albuterol on maximal exercise performance in 20 stable adult CF patients (mean +/- SD age, 23.3 +/- 6.1 years; FEV(1), 57.65 +/- 17.13% of predicted). RESULTS: Ventilatory limitation to exercise was demonstrated in 16 subjects (80%). Significant bronchodilation occurred with exercise alone (end-exercise FEV(1), 2.24 +/- 0.8 L; vs preexercise FEV(1), 2.09 +/- 0.77 L; p < 0.0001), but albuterol resulted in significantly greater exercise-induced bronchodilation than placebo (change in FEV(1), 0.3 +/- 0.15 L vs 0.15 +/- 0.11 L; 95% confidence interval [CI], + 0.07 to + 0.23; p < 0.001). However, there was no difference in maximal workload achieved (albuterol, 158 +/- 46 W; vs placebo, 158 +/- 45 W; 95% CI, - 4.41 to + 4.71; p = 0.95), nor any other measure of exercise performance including maximal oxygen uptake. CONCLUSIONS: Despite causing significant acute bronchodilation, inhaled albuterol did not improve maximal exercise performance in ventilatory-limited CF adults, adding to the body of literature that fails to show any clinical benefit of SAbetaAs in CF subjects. The current results provide further evidence to question the widespread use of these agents, although the potential for adrenergic beta-agonists to instead improve submaximal exercise performance merits further investigation.     

Respiratory patterns during sleep in obesity-hypoventilation patients treated with nocturnal pressure support: a preliminary report

BACKGROUND: The obesity-hypoventilation syndrome (OHS), commonly defined as a combination of obesity and diurnal hypercapnia, is efficiently treated using nasal positive pressure ventilation (NPPV). The present study aimed to determine whether nocturnal polysomnography allows detection of respiratory disturbances occurring in patients with OHS treated with NPPV that may interfere with the quality of sleep and of ventilatory support, and are not detected by nocturnal pulse oximetry and capnography. METHODS: Twenty OHS patients in stable clinical condition treated by NPPV for at least 3 months with a bilevel pressure support ventilator were studied. All patients underwent single-night polysomnography under NPPV including transcutaneous measurement of Pco(2) (TcPco(2)). Four types of respiratory events were defined and quantified: patient/ventilator desynchronization, periodic breathing (PB), autotriggering, and apnea-hypopneas. RESULTS: Eleven patients (55%) exhibited desynchronization occurring mostly in slow-wave sleep and rapid eye movement sleep and associated with arousals but not inducing significant changes in TcPco(2) or oxygen saturation using pulse oximetry (Spo(2)). Eight patients (40%) showed a high index of PB, mostly occurring in light sleep and associated with more severe nocturnal hypoxemia. Autotriggering was sporadic and usually limited to one or two breaths, although prolonged and asymptomatic autotriggering occurred in one patient during 10.6% of total sleep time. CONCLUSIONS: Patient/ventilatory asynchrony and PB are respiratory patterns occurring frequently in OHS patients treated using NPPV. Nocturnal monitoring of Spo(2) and TcPco(2), commonly used to assess the efficacy of ventilatory support, do not adequately explore this aspect of therapy that might influence its efficacy as well as sleep quality.     

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.     

Power spectral analysis of EEG activity during sleep in cigarette smokers

BACKGROUND: Research on the effects of cigarette smoking on sleep architecture is limited. The objective of this investigation was to examine differences in sleep EEG between smokers and nonsmokers. METHODS: Smokers and nonsmokers who were free of all medical comorbidities were matched on different factors, including age, gender, race, body mass index, and anthropometric measures. Home polysomnography was conducted using a standard recording montage. Sleep architecture was assessed using visual sleep-stage scoring. The discrete fast Fourier transform was used to calculate the EEG power spectrum for the entire night within contiguous 30-s epochs of sleep for the following frequency bandwidths: delta (0.8 to 4.0 Hz); theta (4.1 to 8.0 Hz); alpha (8.1 to 13.0 Hz); and beta (13.1 to 20.0 Hz). RESULTS: Conventional sleep stages were similar between the two groups. However, spectral analysis of the sleep EEG showed that, compared to nonsmokers, smokers had a lower percentage of EEG power in the delta-bandwidth (59.7% vs 62.6%, respectively; p < 0.04) and higher percentage of EEG power in alpha-bandwidth (15.6% vs 12.5%, respectively; p < 0.001). Differences in the EEG power spectrum between smokers and nonsmokers were greatest in the early part of the sleep period and decreased toward the end. Subjective complaints of lack of restful sleep were also more prevalent in smokers than in nonsmokers (22.5% vs 5.0%, respectively; p < 0.02) and were explained, in part, by the differences in EEG spectral power. CONCLUSIONS: Cigarette smokers manifest disturbances in the sleep EEG that are not evident in conventional measures of sleep architecture. Nicotine in cigarette smoke and withdrawal from it during sleep may contribute to these changes and the subjective experience of nonrestorative sleep.     

Predictors of heartburn during sleep in a large prospective cohort study

BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study. METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep. CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.     

Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy

BACKGROUND: Sympathetic nerve activity is increased in awake and regularly breathing patients with obstructive sleep apnea (OSA). Over time, repetitive hypoxic stress could alter sympathetic chemoreflex function in OSA. METHODS: We determined the responses to acute hypoxia (fraction of inspired oxygen of 0.1, for 5 min), static handgrip exercise, and the cold pressor test (CPT) in 24 patients with OSA (age, 50 +/- 3 years [mean +/- SEM]; apnea-hypopnea index, 47 +/- 6 events per hour) and in 14 age- and weight-matched nonapneic control subjects. Muscle sympathetic nerve activity (MSNA) [peroneal microneurography], BP, and ventilation were monitored. RESULTS: Basal MSNA was higher in OSA patients compared to control subjects (45 +/- 4 bursts per minute vs 33 +/- 4 bursts per minute, respectively; p < 0.05). Furthermore, compared to control subjects, the MSNA responses to hypoxia were markedly enhanced in OSA (p < 0.001). Whereas the ventilatory responses to hypoxia tended to be increased in OSA (p = 0.06), the BP responses did not differ between the groups (p = 0.45). The neurocirculatory reflex responses to handgrip exercise and to the CPT were similar in the two groups (p = not significant). In OSA patients who were retested after 1 to 24 months of continuous positive airway pressure (CPAP) therapy (n = 11), basal MSNA (p < 0.01) and the responses of MSNA to hypoxia (p < 0.01) decreased significantly, whereas the ventilatory responses remained unchanged (p = 0.82). CONCLUSION: These data suggest that the sympathetic responses to hypoxic chemoreflex stimulation are enhanced in OSA and may normalize in part following CPAP therapy.     

Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome

BACKGROUND: The impact of obstructive sleep apnea syndrome (OSAS) on the arterial baroreflex, and its significance, is still under debate. We investigated the baroreflex sensitivity (BRS) during sleep in well-selected OSAS patient and control subject cohorts METHODS: We performed a prospective study of 10 non-OSAS subjects, 14 subjects with mild-to-moderate OSAS, and 14 male subjects with severe OSAS subjects. Groups were matched for age, body mass index, and other relevant variables. Subjects had no other disease and were not receiving regular medication. BP was monitored beat-by-beat (Portapres; Finapres Medical Systems; Amsterdam, the Netherlands) at night during polysomnography. Spontaneous BRS was assessed by the sequence technique. Heart-rate correction was also applied to calculate BRS at a heart rate (HR) of 60 beats/min (BRS-60) to account for intersubject variability in baseline HR. Eight suitable patients were treated with continuous positive airway pressure (CPAP), and BRS measurements were repeated 6 weeks later. RESULTS: BRS and BRS-60 were significantly lower in patients with severe OSAS than in patients with mild-to-moderate OSAS and in non-OSAS subjects, and a separate sleep-stage analysis revealed this difference to be evident in stage 2 non-rapid eye movement sleep and during nocturnal wakefulness. There was no difference in BRS and BRS-60 between non-OSAS subjects and patients with mild-to-moderate OSAS. In multivariate analysis, the desaturation index was the only independent predictor of depressed BRS. CPAP therapy significantly improved the BRS measures. CONCLUSION: Patients with severe OSAS demonstrate depressed BRS during sleep, which may contribute to the cardiovascular pathophysiology in OSAS patients.     

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.     

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.     

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.     

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.     

Quality, size, and composition of pediatric endobronchial biopsies in cystic fibrosis

BACKGROUND: Studies on airway remodeling in children with cystic fibrosis (CF) may be hampered by difficulty in obtaining evaluable endobronchial biopsy specimens because of large amounts of mucus and inflammation in the CF airway. We prospectively assessed how the quality of biopsy specimens obtained from children with CF compare with those from children with other airway diseases. METHODS: Fiberoptic bronchoscopy with endobronchial biopsy was performed in 67 CF children (age range, 0.2 to 16.8 years), 34 children with wheeze/asthma (W/A), and 64 control children with chronic respiratory symptoms. Up to three biopsy specimens were taken and stained with hematoxylin and eosin. Biopsy specimen size and structural composition were quantified using stereology. RESULTS: At least one evaluable biopsy specimen was obtained in 72% of CF children, in 79% of children with W/A, and in 72% of control subjects (difference was not significant). The use of large biopsy forceps (2.0 mm) rather than small biopsy forceps (1.0 mm) [odds ratio (OR), 5.8; 95% confidence interval (CI), 1.1 to 29.8; p = 0.037] and the number of biopsy specimens taken (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.2; p = 0.006) significantly contributed to the success rate. Biopsy size and composition were similar between groups, except that CF children and those patients with W/A had a higher percentage of the biopsy specimen composed of muscle than did control subjects (median 6.2% and 9.7% vs 0.9%, respectively; p = 0.002). CONCLUSIONS: Biopsy size and quality are adequate for the study of airway remodeling in CF children as young as 2 months of age. Researchers should use large forceps when possible and take at least two biopsy specimens per patient. An increased airway smooth muscle content of the airway mucosa may contribute to the pathophysiology of CF lung disease.     

Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure. DESIGN: We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index. MEASUREMENTS AND RESULTS: Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001). CONCLUSIONS: Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.     

Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study

BACKGROUND: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. Trial registration: ClinicalTrials.gov Identifier: NCT00480870.     

Panton-Valentine Leukocidin-positive methicillin-resistant Staphylococcus aureus lung infection in patients with cystic fibrosis

BACKGROUND: Panton-Valentine Leukocidin-expressing (PVL+) methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen worldwide causing fatal necrotizing pneumonias in otherwise healthy individuals but has not been described in patients with cystic fibrosis (CF). Following two cases of patients with CF admitted with lung abscesses in association with PVL+ MRSA, we examined the incidence and the clinical characteristics of MRSA acquisition in our CF patient population. METHODS: Newly acquired MRSA isolates from patients with CF followed up at St. Louis Children's Hospital were analyzed for the presence of Panton-Valentine leukocidin coding region, clindamycin susceptibility, staphylococcal cassette chromosome (SCC) mec type, and multilocus sequence type. Medical records and pulmonary function studies at the time of MRSA isolation were reviewed. RESULTS: MRSA isolates from 40 CF patients were available for analysis. Six children (15%) had PVL+ MRSA infection. All PVL+ organisms were clindamycin susceptible. Patients who acquired a PVL+ organism were more likely to have a focal pulmonary infiltrate on chest radiograph, including cavitary lung lesions in two patients (p = 0.04), a markedly greater decline in FEV1 at the time of MRSA detection (p = 0.01), and a significantly higher WBC count (p = 0.04) and absolute neutrophil count (p = 0.04). These patients were more likely to be admitted for IV antibiotic therapy for respiratory illnesses (p < 0.01). CONCLUSIONS: We describe the emergence of PVL+ MRSA in our CF population in association with development of invasive lung infections including lung abscesses. Early identification and treatment of CF patients with newly acquired PVL+ MRSA may be crucial.     

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.     

Impact of COPD exacerbations on patient-centered outcomes

BACKGROUND: Frequent exacerbations are associated with a faster decline in FEV(1), impaired health status, and worse survival. Their impact and temporal relationship with other outcomes such as functional status, dyspnea, and the multidimensional body mass index, obstruction, dyspnea, exercise capacity (BODE) index remain unknown. HYPOTHESIS: We reasoned that exacerbations affect the BODE index and its components, and that changes in the BODE index could be used to monitor the effect of exacerbations on the host. STUDY DESIGN: Prospective observational study in a Veterans Affairs medical center. METHODS: We studied 205 patients with COPD (mean [+/- SD] FEV(1), 43 +/- 15% predicted), and recorded the body mass index, FEV(1) percent predicted, modified Medical Research Council dyspnea scale, 6-min walk distance, and the BODE index at baseline, during the exacerbation, and at 6, 12, and 24 months following the first episode, and documented all exacerbations for 2 years after the first acute exacerbation. RESULTS: From the cohort, 130 patients (63%) experienced 352 exacerbations or (0.85 exacerbations per patient per year); 48 patients (23%), experienced one episode, 82 patients (40%) experienced 2 or more exacerbations, and 50 patients required hospitalization. At study entry, exacerbators had a worse mean baseline BODE index score (4.2 +/- 2.1 vs 3.57 +/- 2.3, respectively; p < 0.03). The BODE index score worsened by 1.38 points during the exacerbation, and remained 0.8 and 1.1 points above baseline at 1 and 2 years, respectively. There was little change in BODE index score at 2 years in nonexacerbators. CONCLUSION: COPD exacerbations negatively impact on the BODE index and its components. The BODE index is a sensitive tool used to assess the impact of exacerbations and to monitor COPD disease progression.