The impact of different CPAP delivery approaches on nightly adherence and discontinuation rate in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The impact of direct mail order sales of positive airway pressure (PAP) devices, accentuated by the coronavirus disease 2019 (COVID-19) pandemic, on PAP adherence in patients with obstructive sleep apnea remains unclear. In this study we compared the impact of different modes of continuous positive airway pressure delivery on adherence and daytime symptoms. We hypothesized that adherence would not be affected by remote PAP setup, aided by telehealth technology. METHODS: Three groups were studied: 1) standard group PAP setup (3-4 people); 2) direct home shipment of PAP, followed by telehealth interactions; 3) direct home shipment of PAP, during the COVID-19 pandemic where delivery choice was removed. Demographics, sleepiness, PAP data, and insurance information were also compared. RESULTS: A total of 666 patients were studied in 3 groups. 1) Standard group PAP setup had 225 patients and adherence with PAP (% of nights used more than 4 hours) was 65.3 ± 2.1%. 2) Direct home shipment of PAP group had 231 patients, and adherence was 54.2 ± 2.4%. 3) Direct mailed PAP units during the COVID-19 pandemic group had 210 patients, and adherence was 55.9 ± 2.5%. Adherence was lower in both groups receiving home shipments compared to those in groups in-center (analysis of variance, Tukey, P = .002). Discontinuation of PAP was less in the in-center group setup patients (χ2 = 10.938 P ≤ .001). CONCLUSIONS: Patients receiving direct home PAP shipments had lower adherence and were more likely to discontinue PAP compared to standard in-person setup. CITATION: Stanchina M, Lincoln J, Prenda S, et al. The impact of different CPAP delivery approaches on nightly adherence and discontinuation rate in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(8):2023-2027.

Clinical Use of Loop Gain Measures to Determine Continuous Positive Airway Pressure Efficacy in Patients with Complex Sleep Apnea. A Pilot Study.

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 < 1/h). Loop gain was calculated by the formula: LG = 2π/[(2πDR - sin(2πDR)]. Patients were followed on CPAP for 1 month. Post-treatment apnea-hypopnea index and compliance data were recorded from smart cards. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients with complex sleep apnea were identified, and 17 patients had full data sets. Eight patients continued to have a total of more than five events per hour (11.8 ± 0.5/h) (nonresponders). The remaining nine patients had an apnea-hypopnea index less than 5/h (2.2 ± 0.4/h) (responders). Loop gain was higher in the nonresponders versus responders (2.0 ± 0.1 vs. 1.7 ± 0.2, P = 0.026). Loop gain and the residual apnea-hypopnea index 1 month after CPAP were associated (r = 0.48, P = 0.02). CPAP compliance was similar between groups. CONCLUSIONS: In this pilot study, loop gain was higher for patients with complex sleep apnea in whom central apneas persisted after 1 month of CPAP therapy (nonresponders). Loop gain measurement may enable an a priori determination of those who need alternative modes of positive airway pressure.

Impact of CPAP use and age on mortality in patients with combined COPD and obstructive sleep apnea: the overlap syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p < 0.001, 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 use < 2 hours per night was significantly higher than those using CPAP > 2 hours per night. CONCLUSIONS: 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.

Circulating endothelial cells and endothelial progenitor cells in obstructive sleep apnea.

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 SaO(2). 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 SaO(2), 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.

How early in treatment is PAP adherence established? Revisiting night-to-night variability.

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.

The impact of cardiac resynchronization therapy on obstructive sleep apnea in heart failure patients: a pilot study.

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 < 0.05). The reduction in AHI with CRT closely correlated with a decrease in circulation time (r = 0.89; p < 0.001) 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. 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.

Brief behavioral therapies reduce early positive airway pressure discontinuation rates in sleep apnea syndrome: preliminary findings.

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.

Normalization of memory performance and positive airway pressure adherence in memory-impaired patients with obstructive sleep apnea.

BACKGROUND: 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. METHODS: 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 averaged < 2 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 averaged > 6 h of PAP use per night. RESULTS: 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). CONCLUSIONS: 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.

The influence of white noise on sleep in subjects exposed to ICU noise.

BACKGROUND AND PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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) (P<0.004). 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). CONCLUSIONS: 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.

Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy.

STUDY OBJECTIVES: 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]). DESIGN AND SETTING: 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. PARTICIPANTS: 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. MEASUREMENTS AND RESULTS: 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. CONCLUSIONS: 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.

Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea.

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 (p < 0.001) 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 (p < 0.001) 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.

Examining the construct of depression in obstructive sleep apnea syndrome.

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.

Postural effects on pharyngeal protective reflex mechanisms.

STUDY OBJECTIVES: 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. DESIGN: 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. SETTING: Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital. SUBJECTS/PARTICIPANTS: 17 normal subjects. MEASUREMENTS AND RESULTS: 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. CONCLUSION: 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.

Vasoactive drug use in septic shock.

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.

The influence of lung volume on pharyngeal mechanics, collapsibility, and genioglossus muscle activation during sleep.

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.

Within-breath control of genioglossal muscle activation in humans: effect of sleep-wake state.

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnoea syndrome. Substantial data support the role of a local negative pressure reflex in modifying genioglossal activation across inspiration during wakefulness. Using a model of passive negative pressure ventilation, we have previously reported a tight relationship between varying intrapharyngeal negative pressures and genioglossal muscle activation (GGEMG) during wakefulness. In this study, we used this model to examine the slope of the relationship between epiglottic pressure (Pepi) and GGEMG, during stable NREM sleep and the transition from wakefulness to sleep. We found that there was a constant relationship between negative epiglottic pressure and GGEMG during both basal breathing (BB) and negative pressure ventilation (NPV) during wakefulness (slope GGEMG/Pepi 1.86+/-0.3 vs. 1.79+/-0.3 arbitrary units (a.u.) cmH2O(-1)). However, while this relationship remained stable during NREM sleep during BB, it was markedly reduced during NPV during sleep (2.27+/-0.4 vs. 0.58+/-0.1 a.u. cmH2O(-1)). This was associated with a markedly higher pharyngeal airflow resistance during sleep during NPV. At the transition from wakefulness to sleep there was also a greater reduction in peak GGEMG seen during NPV than during BB. These data suggest that while the negative pressure reflex is able to maintain GGEMG during passive NPV during wakefulness, this reflex is unable to do so during sleep. The loss of this protective mechanism during sleep suggests that an airway dependent upon such mechanisms (as in the patient with sleep apnoea) will be prone to collapse during sleep.

Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.