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Latest Advances in Sleep MedicineLatest Advances in Obstructive Sleep Apnea: Obstructive Sleep Apnea FREE TO VIEW

Sibyl Simon, MD; Nancy Collop, MD, FCCP
Author and Funding Information

From the Division of Sleep Medicine, Emory University, Atlanta, GA.

Correspondence to: Nancy Collop, MD. Sleep Disorders Center, 1841 Clifton Rd NE, Atlanta, GA 30329; e-mail: nancy.collop@emory.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(6):1645-1651. doi:10.1378/chest.12-2391
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This article is a review of the pertinent scientific data regarding obstructive sleep apnea (OSA) as presented in the medical literature. Attention regarding the diagnosis of OSA focused on the debate regarding home testing as compared with in-laboratory polysomnography (PSG), with a surprising result of possibly more cost benefit from PSG. New advances abound in the treatment of OSA, including those directed at preventing pharyngeal collapsibility. Multiple studies reviewed the comparative effects of oral appliances in conjunction with CPAP, with little difference between the two noted, especially for mild OSA. Finally, a number of studies evaluated both risks of OSA and outcomes from the use of CPAP, including functional outcomes, direct cardiac benefits, and overall cardiac mortality.

Much of the emphasis on the diagnosis of obstructive sleep apnea (OSA) sought to compare home sleep testing (HST) as a viable alternative to laboratory polysomnography (PSG). Kuna and colleagues1 and Rosen and colleagues2 examined the difference between those patients tested at home vs those tested in a laboratory. Kuna and colleagues1 randomized 296 Veterans Affairs (VA) patients with suspected OSA to either HST and auto-titrating CPAP (autoPAP) if needed or in-laboratory testing (LABORATORY) with either split-night study or diagnostic PSG followed by CPAP titration. Seventy-five percent (213) were initiated on CPAP, 113 (76.4%) in the HST group and 110 (74.3%) in the LABORATORY group. Over the 3-month treatment period, mean CPAP use was 3.49 ± 2.45 h/d in the HST group and 2.92 ± 2.32 h/d in the LABORATORY group (P = .08). The adjusted group difference (HST − LABORATORY) in mean CPAP daily use was 0.55 ± 0.32 h (SEM) (P = .085), which rejects the null hypothesis that home testing is clinically inferior (P < .05). Patient outcomes were assessed by the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Center for Epidemiologic Studies Depression Scale, Health Outcomes Short Form (SF)-12, Multivariable Apnea Prediction, and performance on the 10-min Psychomotor Vigilance Task (PVT). All scores improved after 3 months of treatment in both groups, although not all results proved significant. Some cautions include a higher pretest probability of OSA in the studied population (VA) than in the general population and an adherence reported in this study that was comparatively lower than other reports. Another key issue preventing direct comparison of LABORATORY vs HST groups was the difference in the definition of hypopneas: The criteria for PSG were a > 30% reduction from baseline in a respiratory signal for ≥ 10 s associated with a ≥ 4% oxygen desaturation and/or an arousal; the criteria for HST were either a 30% reduction in a respiratory signal for ≥ 10 s associated with ≥ 4% oxygen desaturation or > 50% reduction in airflow for ≥ 10 s, due to the lack of arousal data recording in the HST device used.

In the study by Rosen and colleagues,2 373 patients were placed in either HST or PSG arms for suspected OSA based on clinical observation and ESS. Of the 186 tested on PSG, 92 (49%) were confirmed to have an apnea-hypopnea index (AHI) ≥ 15 and moved to CPAP titration, either by split-night or full titration night; 105 of 187 patients in the HST group (56%) were eligible to continue on to treatment with autoPAP. At 3 months, PAP usage was 1 h greater in the home group, 4.7 ± 2.1 h compared with 3.7 ± 2.4 h in the laboratory group (P = .01), and adherence was 12.6% higher in HST vs LABORATORY groups, 62.8% ± 29.2% vs 49.4% ± 36.1% (P = .02). Functional outcome measures as identified by ESS, FOSQ, the Sleep Apnea Quality of Life Instrument (SAQLI), and the vitality subscale of SF-36 were significantly improved within groups at 1 and 3 months (all P < .0001) but did not differ between arms; this was also seen regarding acceptance of PAP therapy, titration pressures needed, and time to treatment. Only 30% of the LABORATORY group and 40% of the HST group met Centers for Medicare & Medicaid Services guidelines for acceptable CPAP use at 1 month with improvement between 1 and 3 months (39% and 50%) in the LABORATORY and HST groups, respectively, likely due to the efforts of the researchers to address PAP adherence. There were several exclusion criteria that could have affected the results seen, including the exclusion of patients with an AHI < 15/h. Twenty-three of 74 of the HST participants (31%) with home-based AHI < 15 had a subsequent AHI ≥ 15 if they underwent a full-night laboratory-based PSG, illustrating the potential underscoring of events during home testing. The authors reported no significant change between the use of either HST or PSG and even noted a significant increase in the adherence of those with home testing at 3 months. An area of future research involves creating possible predictors to more efficiently assign patients to HST vs PSG to avoid repeat PSG studies and potentially reduce cost further.

Masa and colleagues3 sought to define the benefit of therapeutic decision between PSG and HST, specifically considering the underestimation of AHI by home testing. They randomized 366 patients to either HST or PSG to determine the degree of agreement between both in the area of therapeutic decision-making. Site investigators made therapeutic decisions based on study results and a single set of auxiliary clinical values. Therapeutic decisions using HST demonstrated a sensitivity of 73%, specificity of 77% (positive likelihood ratio [LR] of 3.53, 95% CI, 2.45-5.07; negative LR of 0.32, 95% CI, 0.25–0.41), and an agreement level of 76%, which was −16% compared with the reference value they created from two therapeutic decisions based on the “gold standard” PSG results. Patients with an AHI > 30 (41% of the sample) had a sensitivity of 94% and specificity of 44% (negative LR of 0.13, 95% CI, 0.05-0.36; positive LR of 1.69, 95% CI, 0.94-3.04), and the agreement level was 91%. Cautions about this study include the taking of all comers as subjects, incorporating a younger, thinner, and healthier population than is usually seen in OSA research, likely affecting the results obtained. The use of HST seems to have more agreement with PSG in those patients with severe OSA, indicating the possibility of potential cost savings in this population. Additional research is needed to assess efficacy and cost analysis of HST on less severe disease.

Given the chronicity and comorbidities seen with untreated OSA, the value of effective treatment is believed to be significant; however, there is little literature defining the costs of treated against untreated OSA to health-care systems. With the advent of HST, it is assumed that it results in lower cost burden. Pietzsch and colleagues4 used a Markov model to compare the cost-effectiveness of three diagnostic modalities—full-night PSG, split-night PSG, and home testing—over a 10-year interval and the expected patient lifetime. The measure of cost-effectiveness was incremental to quality-adjusted life year (QALY) with analysis on a hypothetical cohort of 50-year-old mens with moderate to severe OSA defined by AHI ≥ 15/h. Data showed that in a patient with moderate to severe OSA, CPAP therapy provides an incremental cost-effectiveness ratio of $15,915 per QALY over their lifetime. By their model, treatment with CPAP reduces the 10-year risk of motor vehicle collisions (fatal and nonfatal) by 52%, the 10-year expected number of myocardial infarctions by 49%, and the 10-year risk of stroke by 31%. In a population with 50% prevalence of OSA, full-night PSG with CPAP therapy is the most economically efficient strategy at any willingness-to-pay > $17,131 per QALY over the lifetime due to its superior diagnostic accuracy resulting in less cost and provision of greater benefits comparatively related to the differences in sensitivity and specificity seen across modalities. Cautions include the following: Because of limited data available on the cost of untreated vs treated OSA, the power of the sample size analyzed was affected; however, it appears that PSG offers intangible benefits that overcome the initial lower cost of home monitoring units. The authors state that more research to identify at-risk patients would contribute to offering quality patient care at relative cost.

Patients with OSA have an associated risk for cardiovascular events, including arterial hypertension, stroke, arrhythmias, and all-cause mortality. Given this association, Randby and colleagues5 examined if any appreciable change or alteration existed in the new, high-sensitive assay of cardiac troponin T (cTnT) in 505 subjects from the general population. Of the group, 205 had mild to moderate OSA (AHI, 5-29.9), and 75 had severe OSA (AHI ≥ 30), whereas of the total sample, 216 (42.8%) had detectable cTnT (≥ 3 ng/L). The proportion of subjects with detectable cTnT in the different categories was 29.8% in subjects without OSA, 46.3% in those with mild to moderate disease, and 72.0% among those with severe OSA (P < .001). Of all patients with OSA, 53.2% had detectable cTnT vs 29.8% of subjects without OSA (P < .001); however, multivariate analyses failed to show an independent association between AHI and detectable cTnT. In examining oxygen desaturation indices, post hoc correlation analyses demonstrated detectable cTnT levels with nadir arterial oxygen saturation (Sao2), average Sao2 during sleep, and percent of total sleep time with Sao2 below 90% (r = −0.26, r = −0.30, r = 0.32, respectively; P < .001 for all). The authors postulate chronic, low-level troponin elevation rather than episodic troponin surges associated with myocardial ischemia as the predominant troponin pattern in patients with OSA. Considerations for this study include lack of imaging or diagnostic cardiac data and higher association of actual cardiac disease in the OSA population, specifically illustrated by the lack of an independent association between AHI and detectable cTNT.

The risk factors potentially associated with sleep apnea include diabetes mellitus; however, short-term data show conflicting results, and no long-term data determining the association exist. Lindberg and colleagues6 used a community-based model to examine the effects of OSA on glucose metabolism on 141 men, initially seen without diabetes and with a mean AHI of 4.7 (as measured by an HST); the subjects were followed over a period of 11 years. At the end of the study period, 23 men had diabetes, and an oxygen desaturation index (ODI) of > 5 was a predictor of developing diabetes (adjusted OR, 4.4; 95% CI, 1.1-18.1; P = .04) after adjusting for age, BMI, hypertension, and use of CPAP. The ODI was inversely related to the insulin sensitivity index at the follow-up (r = −0.27, P = .003), and all the variables of OSA (AHI, AHI > 5, ODI, ODI > 5, and minimum Sao2) were associated with a decrease in homeostatic insulin resistance in those with severe insulin resistance even when adjusting for confounders (all P values < .05). When excluding treatment with CPAP from the multivariate model, all associations weakened, showing that OSA is independently related to the development of insulin resistance and, eventually, diabetes mellitus. Cautions to note include: the study included only male subjects, one-half of the subjects were diagnosed with hypertension prior to the baseline evaluation, the baseline evaluation was HST rather than PSG, and there was lack of significant association between AHI and the insulin sensitivity index. The authors conclude that hypoxia plays a major role in insulin sensitivity and that future studies confirming the role of CPAP treatment to modify this risk should be done in randomized, controlled trials.

Nasal Expiratory Positive Airway Pressure

In the development of novel treatments for OSA, an expiratory positive airway pressure nasal device (EPAP) provides an alternative treatment option, using a mechanical valve with low inspiratory resistance and high expiratory resistance applied over each nostril. The high expiratory pressure creates a positive pressure throughout expiration, splinting the upper airway, hence, preventing collapse on subsequent inspiration. Berry and colleagues7 sought to compare EPAP treatment in a randomized, multicenter, double-blind trial of 250 patients with AHI of at least 10/h against a sham device. Each participant underwent treatment of 1 week with device use of at least three nights, after which they had two sleep studies on nonconsecutive nights, one with the device on and one with the device off. After 3 months of treatment, patients had another clinic evaluation and underwent two repeat sleep studies. In those receiving EPAP, the median AHI reduction was 52.7% (week 1) and 42.7% (month 3) as compared with sham (P < .001). The reductions in the arterial ODI and percent total sleep time with oxygen saturation by pulse oximetry < 90% with the EPAP device were significantly greater than with sham for both week 1 (P < .001, P = .004) and month 3 (P = .025, P = .002). Although the study contained a large number of exclusion criteria, including patients who had tried CPAP, had significant oxygen desaturation, or had undergone upper airway surgery, it appears that EPAP may provide some patients with mild to moderate OSA an alternative treatment to CPAP and dental appliances.

Hypoglossal Nerve, Genioglossal Muscle Stimulation

Hypoglossal nerve stimulation is being re-evaluated as a therapeutic approach for treatment of OSA by recruitment of the lingual musculature leading to decreases in pharyngeal collapsibility during sleep. Schwartz and colleagues8 examined the actual airflow responses to an implantable hypoglossal nerve stimulation system (HGNS) to determine if they could provide incremental improvements in OSA with titration. In an open-label trial, they measured the effects of treatment with HGNS on measurements of airflow in 30 patients with severe OSA (average AHI, 45.4 ± 7.8). The HGNS was implanted on the hypoglossal nerve distal to branches innervating the styloglossus and hypoglossus muscles, with placement verified intraoperatively with fluoroscopic assessment of pharyngeal opening. Stimulation was applied with increasing current to alternative breaths during sleep. Maximal inspiratory airflow increased in all 30 patients with stimulation compared with no stimulation, and the level of stimulated peak flow correlated with the unstimulated flow, suggesting the degree of airway opening depended on the severity of upper airway obstruction at baseline (r = 0.50, P = .005). Stimulation generated progressive increases in airflow from flow capture threshold (216 ± 24 mL/s at 1.05 ± 0.09 mA) to peak flow threshold (538 ± 41 mL/s at 1.46 ± 0.11 mA), resulting in an average 321 ± 36 mL/s increase in airflow (P < .001). Inspiratory airflow limitation (IFL) was abolished in 57% of patients despite a similar increase in airflow in the IFL vs non-IFL groups (256 ± 31 mL/s vs 323 ± 52 mL/s, P = .15). Peak airflow did not differ in the flow-limited compared with non-flow-limited group (438 ± 35 mL/s vs 564 ± 58 mL/s), although the flow-limited group required greater current to achieve peak flow from the threshold (0.57 ± 0.12 mA vs 0.30 ± 0.03 mA, P < .05). There were no arousals noted with the increase in stimulation based on EEG rhythm, increases in heart rate, or increase in maximal inspiratory airflow from baseline levels. Notable issues with this study include it being an open-label trial with patients electing to undergo HGNS implantation; also, the inspiratory flow measurement was assessed not by esophageal manometry but by assessment of flow contour, which is less sensitive. Moreover, flow-response curves were not determined in all body positions or sleep stages. The authors conclude that HGNS reduces pharyngeal closure with systematic titrations of the electrical impulse to the lingual tissue without causing arousals in selected patients with OSA.

Complementing the work of Schwartz and colleagues8, Eastwood and colleagues9 examined the role of stimulation techniques in HGNS and the propensity for arousals, as well as sleep quality, patient satisfaction, and adherence data. They enrolled 21 patients with moderate to severe OSA unable to tolerate CPAP; each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by AHI during in-laboratory PSG at baseline and 3 and 6 months post implant. Therapy compliance was assessed by nightly hours of use, and symptoms were assessed using the ESS, FOSQ, SAQLI, and the Beck Depression Inventory. HGNS was used on 89% ± 15% of nights (n = 21) for 5.8 ± 1.6 h per night. There was significant improvement from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7, P < .001), ESS (12.1 ± 4.7 to 8.1 ± 4.4, P < .001), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2, P < .001), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3, P < .001), Pittsburgh Sleep Quality Index (10.1 ± 2.6 to 8.7 ± 3.9, P = .19), and Beck Depression Inventory (15.8 ± 9.0 to 9.7 ± 7.6, P < .001). Notable issues with this study include two serious device-related adverse events; moreover, this was a single-arm, open-label study of those patients who had already failed CPAP treatment, suggesting possible bias without a control group. Also, at the conclusion of the 6-month trial, Pittsburgh Sleep Quality Index remained > 5, considered to be in the range of poor sleep quality; the decrease seen in the rating of the measure also was not significant. At 6 months, the AHI in those with a BMI < 35 kg/m2 was less than those with a BMI > 35 kg/m2 (14.0 ± 7.7 events/h vs 31.5 ± 24.6 events/h, P = .03) despite both groups having a similar AHI at baseline (43.0 ± 19.5 vs 44.5 ± 13.6 events/h). HGNS can be implanted safely for treatment of OSA in those patients who have failed CPAP; however, it does not appear to perform as well in obese patients with severe sleep apnea, indicating that additional research is needed to define risk stratification, differentiating between groups of responders vs nonresponders prior to implantation.

In addition to these studies examining HGNS, another novel approach examined direct stimulation of the genioglossus muscle, the largest upper airway dilator muscle. Steier and colleagues10 studied the effects of transcutaneous electrical stimulation in healthy subjects and subjects with OSA in this proof-of-concept trial. For the first portion of the study, the effective, tolerable dose of stimulation required to determine effective muscle contraction of the genioglossus in 11 awake, normal subjects was performed using ultrasonography. Ultrasonography measurements showed a significant increase in tongue diameter during stimulation (sagittal, 10.0% [± 2.8%]; coronal, 9.4% [± 3.7%]). For the second portion of the study, 11 patients with OSA were studied during sleep. Findings included a reduction in snoring (P < .001) and an improvement in oxygenation (P = .001) during stimulation. The respiratory disturbance index fell from 28.1 (SD 26.3) to 10.2 (SD 10.2) events/h during stimulation (P = .002) and returned to 26.6 (SD 26.0) events/h after stimulation was stopped. Transdiaphragmatic pressure swings and transesophageal diaphragm electromyogram pressures also decreased (transdiaphragmatic pressure, P = .022; transesophageal diaphragm pressure, P < .001) during stimulation and increased back to baseline after stimulation was withdrawn. Notable concerns with this study include that it was an open-label study without a matching control group, and the technique of electrical stimulation may have led to arousals. Although the authors conclude that transcutaneous stimulation of the genioglossus muscle may provide benefits as an alternative therapy for OSA, no device has yet been created for genioglossal stimulation. The authors suggest that transcutaneous genioglossal stimulation may be helpful in the identification of responders and nonresponders to HGNS prior to implantation of that device.

Focusing on the effectiveness of oral appliance therapy (OAT), two groups sought to compare OAT to CPAP. Holley and colleagues11 provided a retrospective analysis on 497 patients in the VA system who were treated with OAT for any degree of OSA (it was standard practice to prescribe both CPAP and OAT to patients expected to deploy to areas with limited electricity). Patients with mild, moderate, and severe disease achieved mean AHI improvement with OAT by −4.46, −13.5, and −44.5, respectively (P < .001 for all). Success rates defined as AHI < 5 for CPAP vs OAT were 76.2% vs 62.3% (P = .15), 71.0% vs 50.8% (P = .001), and 63.4% vs 39.9% (P < .001) for mild, moderate, and severe disease, respectively, and 70.1% vs 51.6% overall (P < .001). Multivariate analysis examining age, BMI, sex, oxygenation, and AHI found only baseline AHI was a significant predictor of achieving an AHI < 5 on OAT titration. Because this was a retrospective study in a selective, military population bias may have played a role; however, the authors conclude that the use of OAT remains comparable to CPAP in patients with mild OSA, whereas CPAP is superior for patients with moderate to severe disease.

Aarab and colleagues12 noted that since CPAP had been titrated in most studies comparing it to OAT, an unbiased comparison should observe the results of OAT titration alongside CPAP titration. They examined 64 patients with mild to moderate OSA in a randomized, partially blinded, placebo-controlled trial of either OAT, CPAP, or placebo device, reviewing polysomnographic findings before and 6 and 12 months after treatment. Titration examinations for CPAP included one laboratory study and for OAT, four ambulatory recordings at prescribed levels of protrusion. The primary outcome variable was change in AHI, and secondary outcome variables were any changes in excessive daytime sleepiness, other sleep variables, compliance, and side effects. The changes in AHI in the two therapy groups were significantly larger than those in the placebo group (P= .000 and .002, respectively). The AHI improved an average of 4.1 events/h more in the CPAP than in the OAT group, whereas other measures, such as excessive daytime sleepiness, compliance, and snoring, were not shown to be significantly different. Cautions include: although the researchers were careful in blinding the OAT patients to treatment or placebo, there was no such blinding between those groups vs CPAP. The patients assigned to OAT therapy had significantly lower BMI than placebo and CPAP patients (P = .002 and P = .006, respectively). Regardless, OAT is comparable to CPAP in a more select population (ie, those with lower BMIs and with milder OSA as defined by AHI).

Although OAT provides an effective alternative to CPAP in the treatment of OSA, the degree of mandibular advancement is a balance between efficacy, tolerance, and side effects. Fixed OATs offer advantages of lower cost, ease of accessibility, and less time to therapy when compared with adjustable OATs; however, because fixed OATs cannot be titrated, this may lead to inadequate treatment of obstructive events. Lettieri and colleagues13 retrospectively reviewed 805 patients, 602 with an adjustable OAT (OATa) vs 203 with a fixed OAT (OATf). The mean AHI was 30.7 ± 25.6. Compared with baseline PSG, OATa AHI fell 74.4% and OATf fell 64.9% (P = .08); however, the mean change in AHI was −22.6 events/h and −18.8 events/h, respectively (P = .14). Successful therapy, defined as AHI < 5, was achieved in 57.2% of OATa but only 46.9% of OATf (P = .02). The mean AHI reduction between OATa vs OATf based on mild (5.3 ± 5.6 vs 3.8 ± 7.3, P = .11), moderate (13.9 ± 8.6 vs 11.4 ± 9.3, P = .08), and severe (44.4 ± 16.1 vs 39.9 ± 12.6, P = .07) disease show that although adjustable devices provide better treatment in moderate and severe disease, there was no significant difference in mild disease. Thus, although adjustable OATs provide greater reductions in AHI than fixed devices, given the financial and time benefits, fixed OAT devices may be a better initial treatment option than adjustable OATs in mild OSA.

In comparing PSG with home testing, a prime area of concern remains the adherence of patients to treatment and whether the manner of diagnosis actually affects compliance. Although both HST and PSG allow clinician visits, the more formal testing, PSG, allows for greater clinician-patient interaction. An important finding would be what, if any, effect the method of diagnosis has on CPAP adherence. Lettieri and colleagues14 placed a cohort of 210 patients with OSA at the VA system into a three-armed study: Group 1 underwent HST then autoPAP, group 2 underwent PSG then CPAP titration, and group 3 underwent PSG then home autoPAP titration to determine possible difference in PAP usage based on method of diagnosis. Accordingly, PAP usage was 70.7%, 73.2%, and 72.4% of nights in groups 1, 2, and 3, respectively (P = .94). Further, there was no difference in mean duration of nightly PAP use (4.7 ± 2.0 h/night, 4.7 ± 1.1 h/night, and 4.8 ± 1.7 h/night on nights used [P = .98] and 3.8 ± 2.1 h/night, 3.7 ± 1.4 h/night, and 3.9 ± 2.2 h/night during all nights [P = .91]). Only 54.3%, 51.4%, and 50.0% of patients in groups 1, 2, and 3 regularly used PAP (P = .84), and discontinuation rates were 12.9%, 8.6%, and 10.0% (P = .78). Considerations for this study include: it was an observational study of patients diagnosed with OSA without randomization or blinding, and none of the results demonstrated statistical significance. Although there does not seem to be any difference in outcome from the method of diagnosis, given compliance rates, the relative initial cost reduction with HST should be compared with the burden of disease untreated in those with poor adherence. Clinical intervention studies are needed to determine the perfect admixture of clinical support and therapy.

Although CPAP definitively helps those with severe OSA, the literature of efficacy in mild to moderate disease shows variability. Potential improvements in functioning, including sleepiness and mood in patients with less disease may be helped with treatment. Weaver and colleagues15 conducted a multicenter double-blind, randomized, placebo-controlled study involving 239 patients who were placed in either CPAP arm or sham arm for treatment of AHI between 5 to 30 events/h and ESS of > 10 with functional outcomes measured on FOSQ, SF-36, ESS, PVT, and Profile of Mood States (POMS). On the primary measure, FOSQ, the adjusted mean change in score after an 8-week intervention was 0.89 for the treated group (n = 113) and −0.06 for the placebo group (n = 110) (P = .006). The ESS score was −2.6 ± 4.3 for the treated group (P < .00001) and −0.5 ± 3.5 in the sham group (P = .12), whereas the adjusted mean difference between groups was −1.8 (SE, 0.5; P = .001; 95% CI, bounds −2.8 to −0.8). Both the POMS and SF-36 were noted to be significantly improved in the treated vs sham groups (P ≤ .014 and P < .04, respectively), whereas no significant change occurred in the PVT (P = .12). On crossover analysis, sham to CPAP treatment, mean improvement in FOSQ score was 1.73 ± 2.50 (90% CI = 6.59, P < .00001) with an effect size of 0.69, whereas ESS score improved by 2.3 ± 4.0 (P < .001), as did SF-36 (P < .020), several areas of POMS (P < .003), and the PVT (mean change of −3.93 ± 13.46). At study conclusion, the ESS score remained at least 10 in a substantial population of CPAP-treated arm, indicating that many were still sleepy. CPAP helps those with mild to moderate OSA, particularly in the setting of daytime functioning, improving subjective sleepiness, and mood; interestingly, improvements were noted with relatively low adherence, suggesting greater research into CPAP usage may be helpful in identifying outcomes.

Although OSA confers increased risk of cardiovascular events, CPAP treatment has shown short-term improvement in cardiovascular remodeling in patients. Long-term effects of CPAP treatment on systolic and diastolic function remain unknown. Colish and colleagues16 selected 52 patients for a prospective study examining cardiac biomarkers, including C-reactive protein, N-terminal proB-type natriuretic peptide, and troponin T (TnT); transthoracic echocardiography (TTE); and cardiac MRI (CMR) scan at time of OSA diagnosis and 3, 6, and 12 months after initiation of CPAP. All patients had severe OSA (mean AHI, 63 ± 30/h) and were sleepy (ESS 14 ± 3) but otherwise healthy. The biomarkers (C-reactive protein, troponin T, brain natriuretic peptide) were normal at baseline and did not change after CPAP. At 3 months after CPAP, improvements noted included decreased right atrial volume index (RAVI) (P < .05), right ventricular (RV) end-diastolic diameter (P < .05), left atrial volume index (P < .05), and RV systolic pressures (P < .05) on transthoracic echocardiogram; at 12 months, TTE showed further reduction in RAVI, left atrial volume index (LAVI), RV end-diastolic diameter, and RV systolic pressure as well as decreased mean early diastolic filling/early diastolic annular velocity, (substitute marker of left ventricular [LV] filling pressure) (all P < 0 0.05). On CMR scan at 6 months treatment, LV mass index decreased, and RAVI, LAVI, and RV end-diastolic volume index improved significantly, (all P < .05); at 12 months, CMR scan demonstrated LV mass further decreased and RAVI, LAVI, and RV end-diastolic volume index improved significantly (all P < .05). Cautions to interpretation of this study include: there was no control group, and the final cohort in this study was selected without preexisting cardiac disease, likely affecting results seen. Also, there was no significant change seen in LV ejection fraction or RV ejection fraction on either CMR or TTE. The authors conclude CPAP treatment can potentially correct abnormalities in the cardiovascular system of those with severe OSA when used over a period of time and that future studies examining CPAP effects in those with milder OSA and with more cardiovascular disease are needed to define how well CPAP works in those populations.

Finally, Campos-Rodriguez and colleagues17 sought to answer if OSA is a potential risk factor in cardiovascular death in women. In a prospective, controlled cohort examination of 1,116 women referred for OSA in Spain (AHI, 10 to ≥ 30), the authors calculated cardiovascular mortality rates for treated and untreated OSA by dividing the number of cardiovascular deaths by the number of person-years accumulated during follow-up, with rates expressed as per 100 person-years. Untreated groups of mild to moderate and severe OSA had higher mortality rates (0.94 per 100 person-years [95% CI, 0.10-2.40], P = .034; 3.71 per 100 person-years [95% CI, 0.09-7.50], P < .001, respectively) as compared with control subjects (0.28 per 100 person-years [95% CI, 0.10-0.91]), and CPAP treatment showed reduced rates (mild to moderate: 0.10 [95% CI, 0.08-0.59], severe: 0.31 [95% CI, 0.11-0.84]), although P values were not listed. Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 0.19 (95% CI, 0.02-1.67; P = .135) for the CPAP-treated, mild to moderate OSA group, 1.60 (95% CI, 0.52-4.90; P = .40) for the untreated, mild to moderate OSA group, 0.55 (95% CI, 0.17-1.74; P = .31) for the CPAP-treated, severe OSA group, and 3.50 (95% CI, 1.23-9.98; P = .019) for the untreated, severe OSA group. Cautions to note include that control subjects used for this study were patients referred to the sleep units and found to have AHI < 10 and that the untreated group may also be noncompliant with other medical recommendations, all creating possible bias. Moreover, the statistical power was not enough to obtain other cardiovascular cofounders, such as age, hormonal status, and previous cardiac events, which may have contributed to the small number of deaths seen; cardiac confounders may have limited the significance of cardiovascular death seen in mild to moderate OSA as compared with severe OSA, an effect also shown in the male population. Further studies in randomized, controlled populations of women are needed to elucidate whether severe OSA is an independent risk factor for cardiovascular mortality and if mild to moderate disease plays any cardiovascular role.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

AHI

apnea-hypopnea index

autoPAP

auto-titrating CPAP

CMR

cardiac MRI

cTnT

cardiac troponin T

ESS

Epworth Sleepiness Scale

FOSQ

Functional Outcomes of Sleep Questionnaire

HGNS

hypoglossal nerve stimulation system

HST

home sleep testing

IFL

inspiratory airflow limitation

LAVI

left atrial volume index

LR

likelihood ratio

LV

left ventricular

OAT

oral appliance therapy

OATa

adjustable oral appliance therapy

OATf

fixed oral appliance therapy

ODI

oxygen desaturation index

OSA

obstructive sleep apnea

POMS

Profile of Mood States

PSG

polysomnography

PVT

Psychomotor Vigilance Task

QALY

quality-adjusted life year

RAVI

right atrial volume index

RV

right ventricular

Sao2

arterial oxygen saturation

SAQLI

Sleep Apnea Quality of Life Instrument

SF

Short Form

TTE

transthoracic echocardiography

Kuna ST, Gurubhagavatula I, Maislin G, et al. Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea. Am J Respir Crit Care Med. 2011;183(9):1238-1244. [CrossRef] [PubMed]
 
Rosen CL, Auckley D, Benca R, et al. A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: the HomePAP study. Sleep. 2012;35(6):757-767. [PubMed]
 
Masa JF, Corral J, Pereira R, et al;; Spanish Sleep Network Spanish Sleep Network. Therapeutic decision-making for sleep apnea and hypopnea syndrome using home respiratory polygraphy: a large multicentric study. Am J Respir Crit Care Med. 2011;184(8):964-971. [CrossRef] [PubMed]
 
Pietzsch JB, Garner A, Cipriano LE, Linehan JH. An integrated health-economic analysis of diagnostic and therapeutic strategies in the treatment of moderate-to-severe obstructive sleep apnea. Sleep. 2011;34(6):695-709. [PubMed]
 
Randby A, Namtvedt SK, Einvik G, et al. Obstructive sleep apnea is associated with increased high-sensitivity cardiac troponin T levels. Chest. 2012;142(3):639-646. [CrossRef] [PubMed]
 
Lindberg E, Theorell-Haglöw J, Svensson M, Gislason T, Berne C, Janson C. Sleep apnea and glucose metabolism: a long-term follow-up in a community-based sample. Chest 2012;142(4):935-942. [CrossRef]
 
Berry RB, Kryger MH, Massie CA. A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. Sleep. 2011;34(4):479-485. [PubMed]
 
Schwartz AR, Barnes M, Hillman D, et al. Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. Am J Respir Crit Care Med. 2012;185(4):420-426. [CrossRef] [PubMed]
 
Eastwood PR, Barnes M, Walsh JH, et al. Treating obstructive sleep apnea with hypoglossal nerve stimulation. Sleep. 2011;34(11):1479-1486. [PubMed]
 
Steier J, Seymour J, Rafferty GF, et al. Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study. Chest. 2011;140(4):998-1007. [CrossRef] [PubMed]
 
Holley AB, Lettieri CJ, Shah AA. Efficacy of an adjustable oral appliance and comparison with continuous positive airway pressure for the treatment of obstructive sleep apnea syndrome. Chest. 2011;140(6):1511-1516. [CrossRef] [PubMed]
 
Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial. Respiration. 2011;81(5):411-419. [CrossRef] [PubMed]
 
Lettieri CJ, Paolino N, Eliasson AH, Shah AA, Holley AB. Comparison of adjustable and fixed oral appliances for the treatment of obstructive sleep apnea. J Clin Sleep Med. 2011;7(5):439-445. [PubMed]
 
Lettieri CF, Lettieri CJ, Carter K. Does home sleep testing impair continuous positive airway pressure adherence in patients with obstructive sleep apnea?. Chest. 2011;139(4):849-854. [CrossRef] [PubMed]
 
Weaver TE, Mancini C, Maislin G, et al. CPAP treatment of sleepy patients with milder OSA: results of the CATNAP randomized clinical trial. Am J Respir Crit Care Med. 2012;186(7):677-683. [CrossRef] [PubMed]
 
Colish J, Walker JR, Elmayergi N, et al. Obstructive sleep apnea: effects of continuous positive airway pressure on cardiac remodeling as assessed by cardiac biomarkers, echocardiography, and cardiac MRI. Chest. 2012;141(3):674-681. [CrossRef] [PubMed]
 
Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med. 2012;156(2):115-122. [PubMed]
 

Figures

Tables

References

Kuna ST, Gurubhagavatula I, Maislin G, et al. Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea. Am J Respir Crit Care Med. 2011;183(9):1238-1244. [CrossRef] [PubMed]
 
Rosen CL, Auckley D, Benca R, et al. A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: the HomePAP study. Sleep. 2012;35(6):757-767. [PubMed]
 
Masa JF, Corral J, Pereira R, et al;; Spanish Sleep Network Spanish Sleep Network. Therapeutic decision-making for sleep apnea and hypopnea syndrome using home respiratory polygraphy: a large multicentric study. Am J Respir Crit Care Med. 2011;184(8):964-971. [CrossRef] [PubMed]
 
Pietzsch JB, Garner A, Cipriano LE, Linehan JH. An integrated health-economic analysis of diagnostic and therapeutic strategies in the treatment of moderate-to-severe obstructive sleep apnea. Sleep. 2011;34(6):695-709. [PubMed]
 
Randby A, Namtvedt SK, Einvik G, et al. Obstructive sleep apnea is associated with increased high-sensitivity cardiac troponin T levels. Chest. 2012;142(3):639-646. [CrossRef] [PubMed]
 
Lindberg E, Theorell-Haglöw J, Svensson M, Gislason T, Berne C, Janson C. Sleep apnea and glucose metabolism: a long-term follow-up in a community-based sample. Chest 2012;142(4):935-942. [CrossRef]
 
Berry RB, Kryger MH, Massie CA. A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. Sleep. 2011;34(4):479-485. [PubMed]
 
Schwartz AR, Barnes M, Hillman D, et al. Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. Am J Respir Crit Care Med. 2012;185(4):420-426. [CrossRef] [PubMed]
 
Eastwood PR, Barnes M, Walsh JH, et al. Treating obstructive sleep apnea with hypoglossal nerve stimulation. Sleep. 2011;34(11):1479-1486. [PubMed]
 
Steier J, Seymour J, Rafferty GF, et al. Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study. Chest. 2011;140(4):998-1007. [CrossRef] [PubMed]
 
Holley AB, Lettieri CJ, Shah AA. Efficacy of an adjustable oral appliance and comparison with continuous positive airway pressure for the treatment of obstructive sleep apnea syndrome. Chest. 2011;140(6):1511-1516. [CrossRef] [PubMed]
 
Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial. Respiration. 2011;81(5):411-419. [CrossRef] [PubMed]
 
Lettieri CJ, Paolino N, Eliasson AH, Shah AA, Holley AB. Comparison of adjustable and fixed oral appliances for the treatment of obstructive sleep apnea. J Clin Sleep Med. 2011;7(5):439-445. [PubMed]
 
Lettieri CF, Lettieri CJ, Carter K. Does home sleep testing impair continuous positive airway pressure adherence in patients with obstructive sleep apnea?. Chest. 2011;139(4):849-854. [CrossRef] [PubMed]
 
Weaver TE, Mancini C, Maislin G, et al. CPAP treatment of sleepy patients with milder OSA: results of the CATNAP randomized clinical trial. Am J Respir Crit Care Med. 2012;186(7):677-683. [CrossRef] [PubMed]
 
Colish J, Walker JR, Elmayergi N, et al. Obstructive sleep apnea: effects of continuous positive airway pressure on cardiac remodeling as assessed by cardiac biomarkers, echocardiography, and cardiac MRI. Chest. 2012;141(3):674-681. [CrossRef] [PubMed]
 
Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med. 2012;156(2):115-122. [PubMed]
 
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