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RATIONALE: Prior work suggests that Black patients have more severe obstructive sleep apnea (OSA) upon clinical presentation. However, the extent to which this may reflect differences in symptoms or other standard measures of OSA risk is unclear. OBJECTIVES: We assessed for racial disparities in OSA characteristics at time of initial clinical diagnosis. METHODS: Data from 890 newly diagnosed patients with OSA at an urban academic sleep center were included in this analysis. All patients completed a standardized questionnaire on demographics and sleep-related symptoms and underwent laboratory polysomnography. Symptom severity at the time of evaluation was compared across race and sex. RESULTS: Black men were underrepresented in the sleep lab, making up only 15.8% of the cohort and 31.3% of Black participants (P

The overlap syndrome, defined by concurrent existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), is associated with poor outcomes. From a large outpatient cohort we aimed to define better the risk factors for increased mortality in the overlap syndrome and hypothesized that CPAP adherence would be associated with improved survival in patients with overlap syndrome.A post hoc analysis from an outpatient database of 10,272 patients from 2007-2010, identified 3,396 patients which were classified in 6 groups; patients both alive or deceased, with the known diagnosis of COPD, OSA, and the overlap of COPD plus OSA. Information regarding their gender, age, pulmonary function, obstructive sleep apnea parameters, and CPAP compliance was collected. A multivariate Cox proportional hazards model was generated for the determinants of mortality.1,112 COPD patients and 2,284 OSA patients were identified by diagnostic coding and then comprehensive chart review. Of these, 227 patients were identified with the overlap syndrome. From this group, 17 patients (7.4%) died. Multivariate analysis revealed hours of CPAP use and age as independent predictors of mortality (HR 0.71 and 1.14, p0.001, 0.002). Greater time on CPAP was associated with reduced mortality; although age did not correlate with CPAP use (p = 0.2), mean age of those with CPAP use2 hours per night was significantly higher than those using CPAP2 hours per night.From this observational cohort, mortality in the overlap syndrome is impacted by CPAP use. Age is also an independent factor which has a negative association with survival and CPAP usage.

Increased circulating endothelial cells (CECs) have been observed in patients with vascular injury associated with acute myocardial infarction, pulmonary hypertension, and congestive heart failure. Decreased circulating endothelial progenitor cells (EPCs) have been observed in patients with risk factors for cardiovascular disease. Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular disease and endothelial dysfunction. Subjects were recruited from patients referred for overnight polysomnograms; 17 subjects had OSA and 10 control subjects did not have OSA. All subjects lacked vascular disease and risk factors for vascular disease. Peripheral blood was obtained from fasting subjects in the morning, following sleep studies. CECs and EPCs were quantified using magnetic bead separation with UV epifluorescence microscopy and flow cytometry immunophenotyping, respectively. Cell counts and demographic variables were compared using unpaired t tests. Regression analysis was performed comparing cell counts with the apnea-hypopnea index (AHI) and nadir SaO2. Subjects with OSA and controls did not differ significantly in terms of age and body mass index. Subjects with OSA had higher AHI, lower nadir SaO2, and greater sleepiness (Epworth Sleepiness Scale scores). There were no significant differences in CEC (7.0 ± 1.5 vs. 4.9 ± 0.9, p > 0.05) or EPC (1077 ± 318 vs. 853 ± 176, p > 0.05) between controls and OSA cases, respectively. In this small study, we found no differences in CECs or circulating EPCs between patients with OSA and controls. OSA may not be associated with these markers of vascular endothelial cell injury in patients with no concomitant vascular disease.

Obstructive sleep apnea (OSA) is a serious disorder with significant daytime consequences. Treatment for OSA most commonly takes the form of positive airway pressure (PAP). Although effective, PAP adherence is often below expectations. Previous studies have suggested that early PAP use can predict long-term adherence, but these studies have not been replicated, nor has follow up been longer than 3 months. This article presents a replication study enhanced by a longer follow up and additional data to suggest that 6-month adherence can be predicted within the first days of PAP use. This article also discusses how this might relate to the experience of significant side effects of treatment.

Background Cardiac resynchronization therapy (CRT) has been shown to improve cardiac function and reduce Cheyne-Stokes respiration but has not been evaluated in patients with obstructive sleep apnea (OSA). In this pilot study, we investigated the impact of both CRT and CRT plus increased rate pacing in heart failure ( ie , congestive heart failure [CHF]) patients with OSA. We hypothesized that through increased cardiac output CRT/pacing would reduce obstructive events and daytime symptoms of sleepiness. Methods Full polysomnograms were performed on CHF patients who were scheduled for CRT, and those patients with an apnea-hypopnea index (AHI) of > 5 events per hour were approached about study enrollment. Patients had a pre-CRT implant baseline echocardiogram and an echocardiogram a mean (± SEM) duration of 6.6 ± 1.4 months post-CRT implant; polysomnography; and responded to the Minnesota Living with Heart Failure questionnaire, the Epworth sleepiness scale, and the Functional Outcomes of Sleep Questionnaire. An additional third polysomnography was performed combining CRT with a pacing rate of 15 beats/min above the baseline sleeping heart rate within 1 week of the second polysomnography. Assessments for the change in cardiac output during the polysomnography were performed using circulation time to pulse oximeter as a surrogate. Results Twenty-four patients were screened, and 13 patients (mean age, 68.6 years; body mass index, 28.7 kg/m 2 ) had evidence of OSA. The mean AHI decreased from 40.9 ± 6.4 to 29.5 ± 5.9 events per hour with CRT (p = 0.04). The mean baseline ejection fraction was 22 ± 1.7% and increased post-CRT to 33.6 ± 2.0% (p r = 0.89; p Conclusions CRT improved cardiac function and reduced the AHI. Reduced circulatory delay likely stabilized ventilatory control systems and may represent a new therapeutic target in OSA.

Sleep apnea syndrome (SAS) is a serious disorder with significant daytime consequences. Treatment for SAS most commonly takes the form of positive airway pressure (PAP). Although effective, PAP adherence is often below expectations. Previous studies have suggested that the provision of information on the importance of PAP use can enhance adherence. In this study, we compare 2 brief behavioral approaches-traditional education (ED) and a motivational enhancement therapy (MET)-designed from theories of behavior change to standard clinical care. PAP discontinuation and adherence are the primary outcome measures. Both brief therapies decreased PAP discontinuation compared to standard care. The MET therapy performed best under the condition of flexible delivery of PAP, although differences were not statistically significant. Implications are discussed.

Copyright © 2015 by the American Thoracic Society. Rationale: Measures of unstable ventilatory control (loop gain) can be obtained directly from the periodic breathing duty ratio on polysomnography in patients with Cheyne-Stokes respiration/ central sleep apnea and can predict the efficacy of continuous positive airway pressure (CPAP) therapy. Objectives: In this pilot study, we aimed to determine if this measure could also be applied to patients with complex sleep apnea (predominant obstructive sleep apnea, with worsening or emergent central apneas on CPAP). We hypothesized that loop gain was higher in patients whose central events persisted 1 month later despite CPAP treatment versus those whose events resolved over time. Methods: We calculated the duty ratio of the periodic central apneas remaining on the CPAP titration (or second half of the split night) while patients were on optimal CPAP with the airway open (obstructive apnea index

EDITORIALS Treatment of Central Sleep Apnea with Adaptive Servoventilation in Chronic Heart Failure Patients with chronic heart failure and systolic dysfunction are at increased risk of having central sleep apnea (CSA) and Cheyne- Stokes respiration, which are associated with hypoxemia, sleep fragmentation, and mortality (1). Positive pressure devices (adaptive servoventilation or autoservoventilation [ASV]) have been designed to treat CSA and are often used in this patient population. These devices provide ventilatory support during periods of central apneas and hypopneas. ASV has been shown to be effective in improving sleep apnea severity, sleep quality, and cardiac function in short-term clinical trials (2). Given these short- term benefits, long-term treatment was hypothesized to result in improvements in robust clinical endpoints in patients with CHF . The SERVE-HF study was designed to address this hypothesis. The rationale and design of this study are described elsewhere (3, ClinicalTrials.gov NCT00733343). In brief, patients with chronic (.12 wk) symptomatic heart failure (New York Heart Association Class III or IV at enrollment, or II with at least one hospitalization for CHF in the last 24 mo) due to systolic dysfunction (left ventricular ejection fraction 10/h, apnea–hypopnea index > 15/h, and .50% central events) were enrolled. Participants were randomized to either standard medical therapy without treatment of CSA, or standard medical therapy with the addition of ASV. The trial completed enrollment with over 1,300 patients recruited and with preliminary results reported (4). No significant difference in the primary composite outcome of all-cause mortality or unplanned hospitalizations was identified (hazard ratio = 1.14, 0.97–1.33 ; P = 0.10); however, cardiovascular mortality was increased in patients in the ASV arm compared with participants in the control arm with an absolute annual mortality rate of 10% versus 7.5% (HR = 1.34, 1.07–1.67; P = 0.010). Although final and more in-depth analyses are still pending, the excess risk appears to be driven by outpatient deaths (likely sudden cardiac deaths). The increased risk of death seemed to be independent of perceived benefit from the device, with no worsening of clinical symptoms or need for hospitalization prior to the event. The results of SERVE-HF are surprising and contrary to the preliminary data showing short-term benefits in symptoms and physiology. More insight into the potential mechanisms for the increased mortality in the ASV arm will hopefully be available once the final results of the study are published; though open for speculation, potential explanations could include imbalances in randomization, hemodynamic effects of positive pressure, potential benefits of CSA (5), or a proarrhythmogenic effect through metabolic/electrolyte abnormalities. At this point, it is unknown whether certain subgroups might be at greater risk (e.g., lower ejection fraction, patients without an implantable defibrillator), but more insight into these issues will likely be available once the final results are published. Field Safety Notice Because of the results, a field safety notice was issued by ResMed, Inc., on May 13, 2015, that provided a number of recommendations (4). Specifically, they recommended that ASV should not be started in patients with symptomatic CHF and left ventricular ejection fraction < 45%, that is, heart failure with reduced ejection fraction (HFrEF), who have predominantly central sleep apnea. Similarly, before considering placing patients on ASV to treat central sleep apnea, a clinical evaluation for the presence of CHF should be done. Patients with suggestive signs and symptoms should be sent for further evaluation for HFrEF, and patients with HFrEF should not be initiated on ASV. Patients with symptomatic HFrEF currently using an ASV machine should be identified and contacted urgently to discuss discontinuation of the device. Ultimately, the decision on whether to continue ASV should be a joint one between the patient and physician balancing risks and benefits, but stopping ASV should be strongly considered given the increased cardiovascular mortality observed in this group. There are, however, a number of additional questions related to clinical management that should be considered in the context of these trial results. How Should ASV Be Discontinued? Given that positive airway pressure reduces ventricular preload and afterload, abrupt discontinuation may result in an exacerbation of heart failure. We would recommend careful assessment of volume status at the time of discontinuation, as this information may help with the timing of positive airway pressure discontinuation and optimization of medical therapy. How Should CSA Be Managed in Patients in Whom ASV Is Discontinued? Certainly, therapies such as supplemental oxygen, acetazolamide, or continuous positive airway pressure (CPAP) can be useful to correct hypoxemia and improve sleep apnea (6). However, the long-term effects of these therapies are unknown and may not be beneficial; for example, in a recent trial, oxygen was found to be potentially detrimental in nonhypoxemic patients with myocardial infarction (7). Clearly, the priority is to ensure that patients have their heart failure medical management optimized. Am J Respir Crit Care Med Vol jj, Iss jj, pp 1–2, jj jj, 2015 Copyright © 2015 by the American Thoracic Society DOI: 10.1164/rccm.201506-1131ED Internet address: www.atsjournals.org Editorials

Although the treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) has been shown to be effective, nightly adherence to treatment remains poor. The objective of this study was to examine the degree to which various levels of PAP therapy adherence normalized verbal memory function after 3 months of therapy in patients with OSA who were memory-impaired prior to the initiation of PAP therapy.Participants were administered neuropsychological testing prior to the initiation of PAP treatment and at a 3-month follow-up visit. Fifty-eight memory-impaired participants were categorized into the following three groups based on 3 months of adherence to PAP therapy: (1) poor users (n = 14), participants who averaged2 h of PAP use per night; (2) moderate users (n = 25), participants who averaged 2 to 6 h of PAP use per night; and (3) optimal users (n = 19), participants who averaged6 h of PAP use per night.Logistic regression analyses revealed that the odds of optimal users exhibiting normalization of memory function following 3 months of PAP therapy were 7.9 times (p = 0.01) the odds of poor users exhibiting normalization of memory abilities. Overall, 21% of poor users, 44% of moderate users, and 68% of optimal users exhibited memory performance in the clinically normal range following 3 months of PAP use (chi(2) = 7.27; p = 0.03).These preliminary findings indicate that impaired verbal memory performance in patients with OSA may be reversible with optimal levels of PAP treatment. OSA patients exhibiting verbal memory impairments may experience a clinically meaningful benefit in their memory abilities when they use PAP for at least 6 h per night.

Background: Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep. Methods: Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at “CPAP lung volume”, with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2). Results: The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001). Conclusion: An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.

There is disagreement in the literature about the importance of sleep disruption from intensive care unit (ICU) environmental noise. Previous reports have assumed that sleep disruption is produced by high-peak noise. This study aimed to determine whether peak noise or the change in noise level from baseline is more important in inducing sleep disruption. We hypothesized that white noise added to the environment would reduce arousals by reducing the magnitude of changing noise levels.Four subjects underwent polysomnography under three conditions: (1) baseline, (2) exposure to recorded ICU noise and (3) exposure to ICU noise and mixed-frequency white noise, while one additional subject completed the first two conditions. Baseline and peak noise levels were recorded for each arousal from sleep.A total of 1178 arousals were recorded during these studies. Compared to the baseline night (13.3+/-1.8 arousals/h) the arousal index increased during the noise (48.4+/-7.6) but not the white noise/ICU noise night (15.7+/-4.5) (P0.004). The change in sound from baseline to peak, rather than the peak sound level, determined whether an arousal occurred and was the same for the ICU noise and white noise/ICU noise condition (17.7+/-0.4 versus 17.5+/-0.3 DB, P=0.65).Peak noise was not the main determinant of sleep disruption from ICU noise. Mixed frequency white noise increases arousal thresholds in normal individuals exposed to recorded ICU noise by reducing the difference between background noise and peak noise.

To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]).A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center.Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months.The groups were similar demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/- 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment.Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.

Background and purpose Depression is commonly reported by patients suffering from Obstructive Sleep Apnea Hypopnea Syndrome (OSAS). We used the factor structure of the Beck Depression Inventory–2nd edition (BDI-II) to examine the unique contributions of OSAS severity and obesity to depressive symptoms in OSAS. We predicted that the Somatic and Cognitive dimensions of the BDI-II would be more strongly associated with apnea severity and obesity, respectively. Patients and methods Ninety-three moderate to severe OSAS patients (61 men, 32 women) were seen for psychological testing prior to initiating CPAP treatment. They completed the BDI-II and Epworth Sleepiness Scale (ESS). Measures of apnea severity (RDI, percent of sleep time below 90% oxygen saturation) and BMI were also collected. Results RDI was significantly related to BMI and BDI-II total score, but not to ESS score. BMI was related to BDI-II total score and ESS score. Partial correlations indicated that RDI was independently related to the Somatic dimension on the BDI-II. By contrast, BMI was uniquely associated with the Cognitive dimension. Although there was no difference in depression scores between men and women, the relationship between the Somatic factor and apnea severity was significant in men, whereas obesity and the Cognitive factor were significantly associated in women. Conclusions OSAS severity and obesity contribute differentially to symptoms of depression in OSAS. In addition, symptoms of depression in OSAS manifest differently in men than in women.

Sepsis accounts for more than 210,000 deaths per year. Despite adequate fluid resuscitation the associated maldistribution of blood flow may cause an imbalance between oxygen delivery and demand, leading to global tissue hypoxia, shock, and, if not reversed, death. Vasoactive therapies including catecholamine and noncatecholamine vasopressors, ionotropes, and vasodilating agents aimed at restoring perfusion and normalizing oxygen consumption have improved outcomes in patients with persistent shock despite crystalloid resuscitation. In this review we discuss the mechanisms, clinical use, and commonly observed pitfalls of the most common and a few uncommon vasodilator agents used in the management of sepsis and septic shock.

STUDY OBJECTIVES Previous studies in both awake and sleeping humans have demonstrated that lung-volume changes substantially affect upper-airway size and pharyngeal resistance and, thus, may influence pharyngeal patency. We sought to systematically investigate the isolated effects of lung-volume changes on pharyngeal collapsibility and mechanics and genioglossus muscle activation during stable non-rapid eye movement sleep. We hypothesized that lower lung volumes would lead to increased pharyngeal collapsibility, airflow resistance, and, in compensation, augmented genioglossus muscle activation. DESIGN Nineteen normal individuals (age, 30.4 +/- 0.5 years; body mass index: 24.5 +/- 0.4 kg/m2) were studied during stable non-rapid eye movement sleep in a rigid head-out shell equipped with a variable positive/negative pressure attachment for manipulations of extrathoracic pressure and, thus, lung volume. SETTING Sleep physiology laboratory. PARTICIPANTS Normal healthy volunteers. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS We measured change in end-expiratory lung volume (EELV) (magnetometers), genioglossus electromyogram (GGEMG) (intramuscular electrodes), pharyngeal pressure, and collapsibility of the pharynx in response to a brief pulse of negative pressure (-8 to -15 cm H2O) under the following conditions: (1) baseline, (2) increased EELV (+1 liter), and (3) decreased EELV (-0.6 liter). Reduced lung volumes led to increased inspiratory airflow resistance (7.54 +/- 2.80 cm H2O x L(-1) x s(-1) vs 4.53 +/- 1.05 cm H2O x L(-1) x s(-1), mean +/- SEM, P = 0.02) and increased genioglossus muscle activation (GGEMG peak 14.6% +/- 1.5% of maximum vs 8.6% +/- 1.5% of maximum, maximum P = 0.001) compared to baseline. The pharynx was also more collapsible at low lung volumes (4.3 +/- 0.5 cm H2O vs 5.4 +/- 0.6 cm H2O, P = 0.04). CONCLUSIONS We conclude that upper-airway muscles respond to changes in lung volumes but not adequately to prevent increased collapsibility. These results suggest that lung volume has an important influence on pharyngeal patency during non-rapid eye movement sleep in normal individuals.

The risk of death for patients with end-stage cystic fibrosis awaiting lung transplantation remains high and most patients succumb to respiratory failure. This study was conducted to evaluate the usefulness of ventilation-perfusion scintillation scans, obtained during the pre-transplant period, to identify patterns that predict prognosis while on the waiting list. These patterns were compared with other pulmonary physiologic markers of ventilation and perfusion obtained from pulmonary function and cardiopulmonary exercise tests.From November 1990 to January 1999, 46 patients with cystic fibrosis were listed for bilateral lung transplantation. Fourteen (30.4%) died while waiting for a transplant (Group 1), whereas 32 were transplanted successfully or remain alive and waiting (Group 2). Mean arterial blood gas values, Brasfield radiograph scores, cardiopulmonary exercise data and the degree of scintillation scan abnormalities between lungs were compared for each group.Mean survival for Group 1 was 10.2 +/- 1.7 months, and for Group 2 was 23.5 +/- 3.0 months (p0.001). The right upper lung zone was the most severely affected segment. The Cox proportional hazards model revealed an increased perfusion disparity and resting hypercapnia as the main predictors of death while on the transplant list. The Kaplan-Meier analysis indicated greater survival for the groups with30% disparity between lungs on the pre-transplant scintillation scans.The results suggest that severe, unilateral perfusion abnormalities seen on scintillation scans in patients with cystic fibrosis are associated with an increased risk of dying while on the lung transplant waiting list and may be helpful in identifying patients who should be considered for early or living-donor transplantation.

Cardiac resynchronization therapy (CRT) has been shown to improve cardiac function and reduce Cheyne-Stokes respiration but has not been evaluated in patients with obstructive sleep apnea (OSA). In this pilot study, we investigated the impact of both CRT and CRT plus increased rate pacing in heart failure (ie, congestive heart failure [CHF]) patients with OSA. We hypothesized that through increased cardiac output CRT/pacing would reduce obstructive events and daytime symptoms of sleepiness.Full polysomnograms were performed on CHF patients who were scheduled for CRT, and those patients with an apnea-hypopnea index (AHI) of5 events per hour were approached about study enrollment. Patients had a pre-CRT implant baseline echocardiogram and an echocardiogram a mean (+/- SEM) duration of 6.6 +/- 1.4 months post-CRT implant; polysomnography; and responded to the Minnesota Living with Heart Failure questionnaire, the Epworth sleepiness scale, and the Functional Outcomes of Sleep Questionnaire. An additional third polysomnography was performed combining CRT with a pacing rate of 15 beats/min above the baseline sleeping heart rate within 1 week of the second polysomnography. Assessments for the change in cardiac output during the polysomnography were performed using circulation time to pulse oximeter as a surrogate.Twenty-four patients were screened, and 13 patients (mean age, 68.6 years; body mass index, 28.7 kg/m(2)) had evidence of OSA. The mean AHI decreased from 40.9 +/- 6.4 to 29.5 +/- 5.9 events per hour with CRT (p = 0.04). The mean baseline ejection fraction was 22 +/- 1.7% and increased post-CRT to 33.6 +/- 2.0% (p0.05). The reduction in AHI with CRT closely correlated with a decrease in circulation time (r = 0.89; p0.001) with CRT. Increased rate pacing made no additional impact on the AHI or circulation time. CRT had a limited impact on sleep architecture or daytime symptom scores.CRT improved cardiac function and reduced the AHI. Reduced circulatory delay likely stabilized ventilatory control systems and may represent a new therapeutic target in OSA.

Weaning covers the entire process of liberating the patient from mechanical support and from the endotracheal tube. Many controversial questions remain concerning the best methods for conducting this process. An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process. An 11-member international jury answered five pre-defined questions. 1) What is known about the epidemiology of weaning problems? 2) What is the pathophysiology of weaning failure? 3) What is the usual process of initial weaning from the ventilator? 4) Is there a role for different ventilator modes in more difficult weaning? 5) How should patients with prolonged weaning failure be managed? The main recommendations were as follows. 1) Patients should be categorised into three groups based on the difficulty and duration of the weaning process. 2) Weaning should be considered as early as possible. 3) A spontaneous breathing trial is the major diagnostic test to determine whether patients can be successfully extubated. 4) The initial trial should last 30 min and consist of either T-tube breathing or low levels of pressure support. 5) Pressure support or assist-control ventilation modes should be favoured in patients failing an initial trial/trials. 6) Noninvasive ventilation techniques should be considered in selected patients to shorten the duration of intubation but should not be routinely used as a tool for extubation failure.

Previous studies have demonstrated that lung volume during wakefulness influences upper airway size and resistance, particularly in patients with sleep apnea. We sought to determine the influence of lung volume on the level of continuous positive airway pressure (CPAP) required to prevent flow limitation during non-REM sleep in subjects with sleep apnea. Seventeen subjects (apnea-hypopnea index, 42.6 +/- 6.2 [SEM]) were studied during stable non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. An epiglottic pressure catheter plus a mask/pneumotachometer were used to assess flow limitation. When lung volume was increased by 1,035 +/- 22 ml, the CPAP level could be decreased from 11.9 +/- 0.7 to 4.8 +/- 0.7 cm H(2)O (p0.001) without flow limitation. The decreased CPAP at the same negative extrathoracic pressure yielded a final lung volume increase of 421 +/- 36 ml above the initial value. Conversely, when lung volume was reduced by 732 +/- 74 ml (n = 8), the CPAP level had to be increased from 11.9 +/- 0.7 to 17.1 +/- 1.0 cm H(2)O (p0.001) to prevent flow limitation, with a final lung volume decrease of 567 +/- 78 ml. These results demonstrate that relatively small changes in lung volume have an important effect on the upper airway in subjects with sleep apnea during non-REM sleep.

Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion.We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses.Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital.17 normal subjects.We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum [%max] +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness.We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep.

We hypothesized that the response of the genioglossus to negative pressure during wakefulness should be intact in obstructive sleep apnea (OSA) patients despite published evidence showing impairment of the response of palatal muscles (Mortimore IL and Douglas NJ. Am J Respir Crit Care Med156: 867–873, 1997). Thus the response of the genioglossus to brief nasal negative pressure applications (NPAs) in early inspiration was compared between OSA patients and an age-matched group of normal subjects at two study sites ( n = 11 per group in Long Beach, n = 14 per group in Boston). Subjects were studied in the sitting (Long Beach) or supine (Boston) posture, and the genioglossus electromyogram (EMGgg) was measured with an intraoral surface electrode (Long Beach) or intramuscular electrode (Boston). The response of the EMGgg was expressed as the percent change from baseline where the baseline EMGgg was the value at the onset of the NPA. In Long Beach, the EMGgg response was significantly higher in the OSA patients at a lower suction pressure of ∼10 cmH2O (75.2 ± 8.4 vs. 37.4 ± 4.0% increase; P < 0.001) but not at a higher suction pressure of ∼20 cmH2O. In Boston, the response in the OSA patients was also greater (107.2 ± 25.9 vs. 46.3 ± 8.3%; P < 0.05) at a suction pressure of ∼13 cmH2O. We conclude that the response of the genioglossus to NPA during wakefulness is not impaired in OSA patients compared with normal subjects and is greater at low suction pressures.

Previous studies have suggested that during non-rapid eye movement (NREM) sleep, neither large short-duration resistive loads nor sustained normoxic hypercapnia alone leads to increased genioglossus muscle activation. However, in normal individuals during stable NREM sleep, genioglossus activity rises above baseline as PCO2 rises and airway resistance increases. We therefore hypothesized that combinations of chemical (PCO2, PO2) and mechanical stimuli during NREM sleep would lead to increased genioglossal activation. We studied 15 normal subjects (9 males, 6 females) during stable NREM sleep, measuring genioglossus electromyogram, epiglottic/choanal pressure, and airflow under six conditions: (1) baseline, (2) inspiratory resistive loading (-5 to -15 cm H2O/ L/second), (3) increased PCO2 (5-10 mm Hg above baseline), (4) combined resistive loading and increased PCO2, (5 ) hypoxia (SaO2 80-85%), and (6 ) combined hypoxia/inspiratory resistive loading. Only the combined condition of hypercapnia and resistive loading led to significantly increased genioglossal activation, 3.91 +/- 0.77% to 9.64 +/- 1.96% of maximum. These data suggest that the genioglossus muscle is less responsive to either chemical stimuli (hypercapnia, hypoxia) or inspiratory resistive loading alone during NREM sleep at the degrees tested. When hypercapnia is combined with resistive loading, the muscle does respond. However, the possibility that higher levels of PCO2 or greater resistive loading alone could activate the muscle cannot be excluded.

Although continuous positive airway pressure (CPAP) has become the standard of care in the treatment of obstructive sleep apnea (OSA), 2 systematic reviews have questioned its utility. Since the publication of these reviews, several randomized controlled trials have been reported. We, therefore, performed a meta-analysis to assess the effect of CPAP on subjective and objective sleepiness.We conducted a thorough literature search to identify all published randomized controlled trials of CPAP in patients with OSA. Meta-analyses were performed using a random-effects model. Statistical heterogeneity was assessed using the Q statistic.Twelve trials of CPAP in patients with OSA meeting our inclusion criteria were found. The Epworth Sleepiness Scale score was reported in 11 studies (706 patients). A meta-analysis found that CPAP reduced the Epworth Sleepiness Scale score an average of 2.94 points more than placebo (P.001). The heterogeneity (Q10 = 57.7, P.001) between studies could not be explained by differences in sex composition, mean age, mean body mass index, or country of study. Trials recruiting subjects with severe OSA plus sleepiness (mean apnea-hypopnea index,or =30 events per hour; and mean Epworth Sleepiness Scale score,or =11) had a greater decrease in the Epworth Sleepiness Scale score than the other studies (4.75 vs 1.10; P.001). Objective measures of sleepiness were reported in 8 trials (482 subjects). Continuous positive airway pressure increased sleep onset latency by 0.93 minute (P =.04) more than placebo.Continuous positive airway pressure therapy significantly improves subjective and objective measures of sleepiness in patients with OSA across a diverse range of populations. Patients with more severe apnea and sleepiness seem to benefit the most.