Abstract: GOALS: Determine the feasibility of using power spectrum of the sleep electroencephalogram (EEG) as a more sensitive tool than sleep architecture to evaluate the relationship between gastroesophageal reflux disease (GERD) and sleep. BACKGROUND: GERD has been shown to adversely affect subjective sleep reports but not necessarily objective sleep parameters. STUDY: Data were prospectively collected from symptomatic patients with heartburn. All symptomatic patients underwent upper endoscopy. Patients without erosive esophagitis underwent pH testing. Sleep was polygraphically recorded in the laboratory. Spectral analysis was performed to determine the power spectrum in 4 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: Eleven heartburn patients were included in the GERD group (erosive esophagitis) and 6 heartburn patients in the functional heartburn group (negative endoscopy, pH test, response to proton pump inhibitors). The GERD patients had evidence of lower average delta-power than functional heartburn patients. Patients with GERD had greater overall alpha-power in the latter half of the night (3 hours after sleep onset) than functional heartburn patients. No significant differences were noted in conventional sleep stage summaries between the 2 groups. CONCLUSIONS: Among heartburn patients with GERD, EEG spectral power during sleep is shifted towards higher frequencies compared with heartburn patients without GERD despite similar sleep architecture. This feasibility study demonstrated that EEG spectral power during sleep might be the preferred tool to provide an objective analysis about the effect of GERD on sleep.
Abstract: OBJECTIVE: To characterize the association between sleep-disordered breathing (SDB) and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and occult diabetes in individuals of different body habitus. RESEARCH DESIGN AND METHODS: Cross-sectional analysis of 2,588 participants (aged 52-96 years; 46% men) without known diabetes. SDB was defined as respiratory disturbance index >or=10 events/h. IFG, IGT, occult diabetes, and body weight were classified according to recent accepted guidelines. Participants with and without SDB were compared on prevalence and odds ratios for measures of impaired glucose metabolism (IGM), adjusting for age, sex, race, BMI, and waist circumference. RESULTS: SDB was observed in 209 nonoverweight and 1,036 overweight/obese participants. SDB groups had significantly higher adjusted prevalence and adjusted odds of IFG, IFG plus IGT, and occult diabetes. The adjusted odds ratio for all subjects was 1.3 (95% CI 1.1-1.6) for IFG, 1.2 (1.0-1.4) for IGT, 1.4 (1.1-2.7) for IFG plus IGT, and 1.7 (1.1-2.7) for occult diabetes. CONCLUSIONS: SDB was associated with occult diabetes, IFG, and IFG plus IGT, after adjusting for age, sex, race, BMI, and waist circumference. The magnitude of these associations was similar in nonoverweight and overweight participants. The consistency of associations across all measures of IGM and body habitus groups and the significant association between SDB and IFG plus IGT, a risk factor for rapid progression to diabetes, cardiovascular disease, and mortality, suggests the importance of SDB as a risk factor for clinically important levels of metabolic dysfunction.
Abstract: BACKGROUND: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy. STUDY DESIGN: Cross-sectional matched-group study. SETTING & PARTICIPANTS: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race. PREDICTOR: HD patients compared with community-dwelling non-HD participants. OUTCOMES & MEASUREMENTS: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale. RESULTS: Average age of study samples was 63 years, 72% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population. LIMITATIONS: The study was limited to participants older than 45 years. CONCLUSIONS: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality.
Abstract: STUDY OBJECTIVES: To explore the relationship between specific factors such as sex and early continuous positive airway pressure (CPAP) use, and 30-day adherence to CPAP therapy. DESIGN AND SETTING: Retrospective study conducted at a single center in southeast Michigan. PATIENTS: One hundred patients with obstructive sleep apnea who were recently initiated on CPAP therapy with electronic adherence information relayed from the CPAP device to a laboratory-based computer through telephone modem. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: An empiric threshold value of objective CPAP use of greater than 4 hours per night measured 3 days following CPAP initiation was predictive of level of CPAP adherence measured 30 days later. Furthermore, CPAP adherence was directly proportional to age (R = 0.25, P = .018). There were no sex-related differences in adherence to CPAP therapy. CONCLUSIONS: Long-term adherence to CPAP therapy can be predicted as early as 3 days following CPAP initiation. The study also demonstrates that younger age and African-American race are independently associated with lower CPAP adherence.
Abstract: BACKGROUND: Our understanding of the effect of the Accreditation Council for Graduate Medical Education (ACGME)-mandated work-hour limitation on physicians' quality of life, sleepiness, and sleep-work habits is evolving. In this study, we sought to determine the effect of work-hour reduction on quality of life in residents and fellows (ICU housestaff) when subject to the ACGME-compliant schedule of one institution. To determine the effect of work-hour reduction on subjective and objective measures of sleepiness in ICU housestaff at a center. METHODS: A single-center study of 34 residents and 10 fellows who were studied before and after the ACGME-mandated work-hour limitation went into effect in July 2003. RESULTS: In a single center, after the work-hour reduction, residents reported statistically significant but minor improvements in sleep time, subjective sleepiness, and some aspects of quality of life (p < 0.05). Both before and after work-hour limitations, subjective sleepiness and quality-of-life indexes deteriorated during the course of the ICU rotation. Following work-hour reductions, subjective sleepiness improved (p < 0.05), but objective sleepiness was unchanged (p = 0.6). Moreover, after the implementation of work-hour reductions, 59%, 43%, and 25% of the ICU team had mean sleep latency < 10, 7, and 5 min, respectively, with 14% of the team manifesting sleep-onset rapid eye movement periods (signifying severe sleepiness) before beginning their extended work-hour period. CONCLUSIONS: In ICU housestaff, at a single center, small benefits to quality of life and subjective sleepiness were realized by an ACGME-compliant work-hour schedule. Significant levels of objective sleepiness, however, remained. Further measures may need to be undertaken to address the persistence of sleepiness in ICU housestaff. These findings may not be generalized outside of the scheduling system studied.
Abstract: The American Academy of Sleep Medicine Task Force on Respiratory Scoring reviewed the evidence that addresses: the validity of specific sensors in detecting airflow, tidal volume, oxyhemoglobin saturation, and CO2; the reliability of specific scoring approaches for quantifying sleep related breathing disorders (SRBD); and the validity of using various definitions of the apnea hypopnea index (AHI) as assessed by the strength and consistency of associations with several comorbidities (hypertension, cardiovascular disease, sleepiness, impaired quality of life, and accidents). The evidence was based on a literature search of relevant articles published through December 2004, which resulted in identifying and extracting data from 182 articles, which were graded using standardized approaches. Diverse physiological sensors have been utilized to quantify airflow limitation in patients with suspected SRBD. Although thermistry appears appropriate for identifying apneas, the available evidence did not indicate it provides valid quantification of airflow reduction. The emerging evidence evaluating the accuracy of signal detection against the gold standard measurements (e.g., pneumotachography) suggested the superiority of inductance plethysmography and nasal pressure transducers for detection of hypopneas, with some evidence that recordings from a nasal pressure transducer may better approximate flow/volume than uncalibrated inductance plethysmography. However, since the nasal pressure transducer has only recently been incorporated into large-scale studies, there are as of yet few data that address the predictive value of transducer-identified events relative to clinical or physiological outcomes. Very few studies directly compared the validity of alternative approaches for defining the duration, amplitude change, and use of corroborative data from desaturation or arousal for defining hypopneas. Many observational studies utilizing various designs and approaches for event detection have shown significant associations between measures of SRBD and health outcomes. Data from the 2 largest sleep cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort, both used definitions of hypopneas based on "discernible" reductions of inductance plethysmography signals with associated desaturation and showed that the derived AHIs using these hypopnea definitions correlated with various indices of morbidity. However, it is not clear whether alternative definitions would provide comparable if not better prediction, or whether optimal approaches for event identification would vary for different outcomes. Despite these limitations, forming a consensus on optimal approaches for recording and measuring respiratory events is an important step toward generating data from different clinical or research laboratories that can be compared. However, additional research is needed, including direct comparisons of alternative measuring approaches for predicting clinical outcomes, with a need to address these issues in large samples across the age spectrum and with inclusion of promising new technology.
Abstract: The American Academy of Sleep Medicine Task Force on Respiratory Scoring reviewed the evidence that addresses: the validity of specific sensors in detecting airflow, tidal volume, oxyhemoglobin saturation, and CO2; the reliability of specific scoring approaches for quantifying sleep related breathing disorders (SRBD); and the validity of using various definitions of the apnea hypopnea index (AHI) as assessed by the strength and consistency of associations with several comorbidities (hypertension, cardiovascular disease, sleepiness, impaired quality of life, and accidents). The evidence was based on a literature search of relevant articles published through December 2004, which resulted in identifying and extracting data from 182 articles, which were graded using standardized approaches. Diverse physiological sensors have been utilized to quantify airflow limitation in patients with suspected SRBD. Although thermistry appears appropriate for identifying apneas, the available evidence did not indicate it provides valid quantification of airflow reduction. The emerging evidence evaluating the accuracy of signal detection against the gold standard measurements (e.g., pneumotachography) suggested the superiority of inductance plethysmography and nasal pressure transducers for detection of hypopneas, with some evidence that recordings from a nasal pressure transducer may better approximate flow/volume than uncalibrated inductance plethysmography. However, since the nasal pressure transducer has only recently been incorporated into large-scale studies, there are as of yet few data that address the predictive value of transducer-identified events relative to clinical or physiological outcomes. Very few studies directly compared the validity of alternative approaches for defining the duration, amplitude change, and use of corroborative data from desaturation or arousal for defining hypopneas. Many observational studies utilizing various designs and approaches for event detection have shown significant associations between measures of SRBD and health outcomes. Data from the 2 largest sleep cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort, both used definitions of hypopneas based on "discernible" reductions of inductance plethysmography signals with associated desaturation and showed that the derived AHIs using these hypopnea definitions correlated with various indices of morbidity. However, it is not clear whether alternative definitions would provide comparable if not better prediction, or whether optimal approaches for event identification would vary for different outcomes. Despite these limitations, forming a consensus on optimal approaches for recording and measuring respiratory events is an important step toward generating data from different clinical or research laboratories that can be compared. However, additional research is needed, including direct comparisons of alternative measuring approaches for predicting clinical outcomes, with a need to address these issues in large samples across the age spectrum and with inclusion of promising new technology.
Abstract: Obstructive sleep apnea (OSA) is a common disorder and is associated with adverse cardiovascular consequences, including hypertension and coronary artery disease. While the mechanisms responsible for increased risk of cardiovascular events in OSA have not yet been fully elucidated, hypoxia, inflammation, obesity, metabolic dysregulation, and sympathetic activation, may contribute to these consequences. Endothelial dysfunction may be another link between OSA and cardiovascular disease. Dysfunctional endothelium is characterized by an imbalance in production of vasoactive hormones, increased adherence of inflammatory mediators to endothelial cells and hypercoagulability, and is a known risk factor for cardiovascular events. Studies have directly measured vascular endothelial function in patients with OSA and found a muted response compared to controls. Other studies have evaluated biochemical markers of endothelial function including circulating levels of vasoactive and thrombosis mediators and provide further proof of endothelial dysfunction in this disorder. A better appreciation of the role of the dysfunctional endothelium in OSA will help shed light on the pathogenesis of cardiovascular disease in this disorder and may lead to development of novel therapies aimed at preventing untoward outcomes.
Abstract: STUDY OBJECTIVES: To study the effect of American Academy of Sleep Medicine accreditation of sleep centers and sleep-medicine certification of physicians on the management of patients with obstructive sleep apnea (OSA). DESIGN: Cross-sectional study. SETTING: National web-based survey. PATIENTS: Six hundred thirty-two patients with OSA. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Self-reported data on details of whether patients with OSA were using positive airway pressure (PAP) devices, timeliness of the initiation of PAP therapy, and overall satisfaction of care received from physicians and centers. After adjusting for covariates, lack of accreditation or certification status of providers was independently associated with discontinuation of PAP therapy (odds ratio [OR] 1.9, 95% confidence interval [CI], 1.1-3.2; p = .03). Patient education leading to perception of risk associated with OSA (OR 0.5, 95% CI, 0.2-0.9) and medications for nasal congestion (OR 0.3, 95% CI, 0.1-0.8) "protected" against discontinuation of PAP therapy, whereas nasal congestion (OR 1.6, 95% Cl, 1.0-2.4) increased the likelihood for discontinuation of PAP therapy. Certified physicians and accredited centers were more likely to educate their patients and received greater satisfaction ratings than non-certified physicians and nonaccredited centers (p < .05). Time delays in instituting PAP therapy were not influenced by accreditation or certification status, but such delays diminished patient satisfaction. CONCLUSIONS: In this web-based survey, accreditation or certification status of sleep centers and physicians was associated with better indexes of clinical management in patients with OSA. Better patient education that fostered risk perception may have been partly responsible for such an association. Prospective studies designed to collect objective data regarding the effect of accreditation or certification status on outcomes in patients with OSA are still needed.
Abstract: BACKGROUND: Sedative medications may be inadvertently prescribed to patients with undiagnosed obstructive sleep apnea (OSA) and may worsen daytime sleepiness. STUDY OBJECTIVES: To determine whether patients with undiagnosed OSA were prescribed sedative medications and whether such prescriptions increased the risk for traffic accidents. A secondary objective was to determine physician characteristics associated with such prescription practices. DESIGN: Retrospective chart review. Telephone interviews of patients and physicians. INTERVENTION: None. PATIENTS: One hundred fifty-one consecutive patients at a sleep laboratory. RESULTS: Forty-one of 137 (30%) patients with undiagnosed OSA had received prescriptions for sedating medications. Regression analysis identified self-report of sleepiness while driving (p = .05) and prescription for risperidone as independent risk factors for motor vehicle accidents (p = .005), while prescription of any sedative (excluding risperidone) tended to be associated with accidents (p =.10). In patients with severe OSA, prescription of sedating medications was associated with a greater risk for motor vehicle accidents than those without such prescriptions (relative risk = 2.6; p = .04). In patients with prescription for sedating medications (n = 41), the apnea-hypopnea index was directly proportional to the risk for motor vehicle accidents (r2 = 0.26; p = .001) suggesting a 'dose effect' of severity of sleep-disordered breathing on risk for accidents. Physicians who did not usually treat patients with sleep disorders were more likely to prescribe sedatives to patients with undiagnosed OSA than were physicians with such expertise: neurologist, pulmonologist, or psychiatrist (52% vs 10%; relative risk = 5.2; p = .02) CONCLUSION: Prescription of sedating medications may increase the risk of road accidents in patients with undiagnosed severe OSA, and such prescription practices are less likely to occur in physicians with expertise in sleep medicine.
Abstract: STUDY OBJECTIVES: The results of small studies have suggested that a nasal-cannula pressure transducer has a higher sensitivity than a thermistor in detecting hypopneas and diagnosing sleep-disordered breathing in both adults and children. We compared a thermistor alone, and in conjunction with a pressure transducer, for detection of sleep-disordered breathing in children during in-home polysomnography. DESIGN: Retrospective analysis of a subsample of a prospective cohort study. SETTING: Students attending elementary school in the Tucson Unified School District. PARTICIPANTS: A subsample of the Tucson Children's Assessment of Sleep Apnea study population. MEASUREMENTS AND RESULTS: Polysomnographic recordings of 40 children (24 girls and 16 boys, mean age 9.2 +/- 1.7 years; range 6-11 years) were analyzed to compare the detection of sleep-disordered breathing events by 2 different methods of measuring airflow: thermistor alone and thermistor with nasal-cannula pressure transducer (transducer) used simultaneously. The transducer detected all the respiratory events detected by the thermistor, but the thermistor detected only 84% of the transducer-defined events. Consequently, the transducer-derived mean respiratory disturbance index was higher than that detected by the thermistor (7.0 +/- 3.8 vs 5.9 +/- 3.4, P < .001). The bias error between transducer respiratory disturbance index and thermistor respiratory disturbance index on a Bland-Altman plot was 1.08 (95% confidence interval, 0.8 - 1.4). There was good agreement between the thermistor and the transducer for making the diagnosis of sleep apnea using a cutoff of a respiratory disturbance index greater than 5 (kappa = 0.69). The quality of the tracings with the transducer was comparable to that of the thermistor, but the transducer dislodged more frequently. CONCLUSION: The use of a nasal transducer in conjunction with a thermistor was more sensitive than the thermistor alone in detecting sleep-disordered breathing in children during unattended polysomnography.
Abstract: PURPOSE OF REVIEW: Sleep-disordered breathing is a widely prevalent condition and may have serious medical, social, and economic consequences. This review evaluates the role of sleep-disordered breathing in cardiovascular morbidity and mortality on the basis of recent literature. RECENT FINDINGS: Epidemiologic studies, retrospective reviews, and prospective clinical trials suggest a strong association between sleep-disordered breathing and adverse cardiovascular events. Individuals with sleep-disordered breathing have a higher prevalence of hypertension, which attenuates with treatment. Furthermore, the presence of sleep-disordered breathing augurs an increased risk of coronary artery disease, cardiac arrhythmias, and heart failure. SUMMARY: Recent research provides an emerging evidence of the role of sleep-disordered breathing as a risk factor for diverse cardiovascular disorders.
Abstract: Sleep disordered breathing is frequently associated with repeated arousals and hypoxia resulting from intermittent partial or complete collapse of upper airway during sleep. There is an emerging recognition of the association of this disorder with metabolic abnormalities, coronary artery disease, congestive heart failure and hypertension. Of these conditions, the data associating obstructive sleep apnea and hypertension are the most compelling. This review evaluates the recent literature investigating this association and identifies areas where additional research is needed.
Abstract: Pulmonary involvement is common in patients with portal hypertension and can manifest in diverse manners. Changes in pulmonary arterial resistance, manifesting either as the hepatopulmonary syndrome or portopulmonary hypertension (PPHTN), have been increasingly recognized in these patients in recent years. This review summarizes the clinicopathologic features, diagnostic criteria, as well as the latest concepts in the pathogenesis and management of PPHTN, which is defined as an elevated pulmonary artery pressure in the setting of an increased pulmonary vascular resistance and a normal wedge pressure in a patient with portal hypertension.
Abstract: Hypoxia causes up-regulation and activation of xanthine dehydrogenase/xanthine oxidase (XDH/XO) in vitro and in the lungs in vivo. This up-regulation, and the likely corresponding production of reactive oxygen species, may underlie the pathogenesis of an array of disorders. Thus, compounds that prevent hypoxia-induced increase in XDH/XO activity may provide a therapeutic strategy in such disorders. The antioxidant properties of estrogens have been demonstrated in several studies. However, the effect of these compounds on XDH/XO has not been explored previously. The aim of this study was to investigate the effects of estrogen on hypoxia-induced increase in XDH/XO activity. Rat pulmonary artery microvascular endothelial cells were exposed to normoxia or hypoxia in the presence or absence of 17beta- or 17alpha-estradiol. The XDH/XO enzyme and gene promoter activities were measured in different groups of cells. Hypoxia caused a twofold increase in XDH/XO enzymatic and promoter activity. Either of the estradiol stereoisomers prevented the hypoxia-induced increase in XDH/XO enzymatic activity, but not the promoter activity. ICI 182,780, an antagonist of the estrogen receptor, failed to block the inhibitory effect of estradiol on XDH/XO. In conclusion, 17alpha- and 17beta-estradiol modulate the hypoxia-induced regulation of XDH/XO activity at a posttranscriptional level by a receptor-independent mechanism.
Abstract: Tobacco smoking has been causally linked to the development of chronic obstructive pulmonary disease. It has been reported that the reactive oxygen species (ROS)- generating enzyme xanthine dehydrogenase/oxidase (XO) is increased in smoking-related stomach ulcers and that gastric mucosal damage caused by tobacco smoke can be blocked by the XO inhibitor allopurinol. In order to test the hypothesis that tobacco may cause the upregulation of XO in the lung, cultured rat pulmonary microvascular endothelial cells were exposed to tobacco smoke condensate (TSC). TSC at a concentration of 20 microg/mL significantly upregulated XO activity after 24 h of exposure. Longer exposure (1 week) to a lower concentration of TSC (2 microg/mL) also caused an increase in XO activity. Unlike hypoxia, TSC treatment did not alter the phosphorylation of XO. However, TSC treatment increased XO mRNA expression and the XO gene promoter activity. Furthermore, actinomycin D blocked the activation of XO by TSC. In conclusion, our results indicate that tobacco smoke condensate causes upregulation of XO transcription and activity.
Abstract: The mechanisms by which ligand-stimulated generation of reactive oxygen species in nonphagocytic cells mediate biologic effects are largely unknown. The profibrotic cytokine, transforming growth factor-beta1 (TGF-beta1), generates extracellular hydrogen peroxide (H2O2) in contrast to intracellular reactive oxygen species production by certain mitogenic growth factors in human lung fibroblasts. To determine whether tyrosine residues in fibroblast-derived extracellular matrix (ECM) proteins may be targets of H2O2-mediated dityrosine-dependent cross-linking reactions in response to TGF-beta1, we utilized fluorophore-labeled tyramide, a structurally related phenolic compound that forms dimers with tyrosine, as a probe to detect such reactions under dynamic cell culture conditions. With this approach, a distinct pattern of fluorescent labeling that seems to target ECM proteins preferentially was observed in TGF-beta1-treated cells but not in control cells. This reaction required the presence of a heme peroxidase and was inhibited by catalase or diphenyliodonium (a flavoenzyme inhibitor), similar to the effect on TGF-beta1-induced dityrosine formation. Exogenous addition of H2O2 to control cells that do not release extracellular H2O2 produced a similar fluorescent labeling reaction. These results support the concept that, in the presence of heme peroxidases in vivo, TGF-beta1-induced H2O2 production by fibroblasts may mediate oxidative dityrosine-dependent cross-linking of ECM protein(s). This effect may be important in the pathogenesis of human fibrotic diseases characterized by overexpression/activation of TGF-beta1.
