Summary of Evidence

Obstructive sleep apnea not only impacts sleep quality, but can have other serious health impacts if untreated. Current care options for moderate to severe OSA include continuous positive airway pressure therapy (CPAP) and other forms of noninvasive positive pressure ventilation. Despite its efficacy and many redesigns by manufacturers aimed at increasing patient comfort, patient adherence to CPAP therapy remains low. Several surgical and non-surgical treatments have been explored for the treatment of OSA and snoring. Current recommendations to reduce snoring include lifestyle modifications such as weight loss, changing sleep position, reducing nasal congestion, and avoidance of alcohol prior to bedtime. 

Rationale

Oral appliances are an alternative for patients who cannot tolerate CPAP. Oral appliance therapies include mandibular advancement devices, which keep the patient's jaw forward to maintain an open airway, and tongue-retaining devices, which splint the tongue in place to keep the airway open.  

Another option is the implantable hypoglossal nerve stimulator, which works by stimulating the genioglossus (upper airway dilator muscle) during apnea, resulting in protrusion of the tongue and relief of the obstruction (Slow (EPAP) has been proposed as an alternative to CPAP. In EPAP, positive pressure is only exerted during exhaling. An EPAP device fits in or over the nostrils and contains a valve that creates pressure as an individual exhales, helping to keep the airway open with later inhalations. Biomimetic oral appliance therapy (BOAT) differs from conventional MAD therapy in that it purportedly corrects the nasal airway through midfacial redevelopment, followed by mandibular correction. 

Evidence on nasal EPAP devices in patients with OSA has been reported in smaller randomized controlled trials (RCTs), an industry-sponsored RCT, and a systematic review that did not include the industry-sponsored RCT. The main finding of the industry-sponsored RCT was a decrease in AHI with a minor impact on oxygenation and ESS scores. An oral EPAP device did not have significant benefit when added to an oral appliance in a small RCT.

A systematic review by Riaz, et al (2015), identified 18 studies (n = 920) that had data on pre-and postnasal EPAP. (4) Study designs included 10 conference papers and 8 publications (case series, cohort studies, RCTs). For patients included in the meta-analysis (n = 345), AHI decreased from 27.32 to 12.78 events per hour (p <.001). For 359 patients, Epworth Sleepiness Scale (ESS) score modestly improved from 9.9 to 7.4 (p <.001). Data from the Berry, et al (2011), RCT (described below) were not included in this meta-analysis because mean data were not reported. Response to the nasal EPAP was variable and inconsistent, and there were no clear characteristics (demographic factors, medical history, and/or physical exam finding) that predicted a favorable response. Authors concluded further studies are needed to evaluate long-term efficacy and delineate clinical and polysomnographic profiles of patients best suited for the therapy. 

Berry et al (2011) reported on an industry-sponsored multicenter, double-blind, randomized sham-controlled trial of EPAP. (5) Two hundred fifty patients with OSA and an AHI of 10 or more events per hour were randomized to nasal EPAP (n = 127) or to a sham device (n = 123) for 3 months. Polysomnography (PSG) was performed on 2 nights (device-on, device-off, in random order) at week 1 (92% follow-up) and after 3 months of treatment (78% follow-up). EPAP reduced median AHI from 13.8 to 5.0 events per hour (-52.7%) at week 1, and from 14.4 to 5.6 events per hour (-42.7%) at 3 months. This reduction in AHI in the treatment group was significantly greater (-7.3% at week 1, -10.1% at 3 months) than in the sham group. Over 3 months, the decrease in ESS score was statistically greater in the EPAP group (from 9.9 to 7.2) than in the sham group (from 9.6 to 8.3), although the clinical significance of a 1-point difference in ESS score is unclear. Treatment success and oxygenation data were presented only for the 58% of per-protocol patients who had an AHI of 5 or more events per hour on the device-off PSG night. The oxygenation results (Oxygenation Desaturation Index and percent of total sleep time with oxygen saturation <90%) showed small but statistically significant decreases at 1 week and 3 months. Treatment success, defined as a 50% or greater reduction in the AHI or an AHI reduction to less than 10 events per hour (if device-off AHI was >10 events per hour), was greater in the EPAP group at 1 week (62% vs. 27.2%) and at 3 months (50.7% vs. 22.4%). Device-related adverse events were reported by 45% of patients in the EPAP group and by 34% of patients in the sham group, with 7% of patients in the EPAP group discontinuing due to adverse events. Overall, the validity of these results was limited by the high dropout rate and uncertainty of the clinical significance of the results. 

Kryger et al (2011), in an open-label extension of the randomized study by Berry et al (2011), evaluated the 12-month safety and durability of the treatment response in patients who had an initially favorable response to EPAP. (6) Included were 41 (32%) of the 127 patients in the EPAP arm of the study who used the device for an average of at least 4 hours per night on at least 5 nights a week during months 1 and 2 and had at least a 50% reduction in AHI, or reduction to less than 10 events per hour, compared with the device-off PSG. Of the 51 (40%) of 127 eligible patients, 41 enrolled in the extension study, and 34 (27%) of 127 were still using the EPAP device at the end of 12 months. Median AHI was reduced from 15.7 to 4.7 events per hour; the percentage of patients who met criteria for success was not reported. The arousal index was modestly decreased (from 23.9 to 19.0). After 12 months of treatment, the ESS score decreased from 11.1 to 6.0. The median percentage of reported nights used (entire night) was 89.3%. Device-related adverse events were reported by 42% of patients, most frequently difficulty exhaling, nasal discomfort, dry mouth, headache, and insomnia. This open-label extension study was limited by its inclusion only of responders and by the potential for a placebo effect on the ESS score. However, the data suggested that some patients might have responded to this device, and the patient compliance data might indicate a positive effect on daytime sleepiness that leads to continued use of the device in about 25% of patients. Additional controlled studies are needed to distinguish between these alternatives. 

Lai et al (2019) reported on a study with 22 patients (ages 29 – 71 years) with OSA who were incomplete responders to an oral appliance (AHI > 5). (7) They were assessed with the oral appliance, plus either an oral or an oronasal EPAP. Both the oral and oral/nasal devices were studied in the same night (split night PSG); the order of the EPAP devices was randomized. Power analysis indicated that 20 participants would be sufficient to detect an AHI difference of 7 between conditions. The trial enrolled 19 males, 3 females. Results demonstrated that 5 patients (23%) had at least a 50% reduction in total AHI with the oral EPAP compared to the oral appliance alone, while 10 patients (45%) had a 50% reduction in AHI with the combined oral and nasal EPAP valves. Neither of these was statistically significant. Only 2 patients (9%) achieved an AHI of less than 5, with the oral EPAP device compared to 9 (41%) with the combined oral and nasal valves. However, sleep efficiency was disrupted with the oronasal EPAP valves.

Kureshi et al (2014) reported on a small (n = 14) double-blind, pilot, crossover RCT of EPAP in children to evaluate efficacy and compliance with this new treatment. (8) PSG with EPAP or a placebo device showed a significant mean improvement in Obstructive Apnea Index with EPAP (0.6 vs. 4.2, p =.01), but responses varied (3 did not improve, 2 worsened). No other measures were statistically significant in this trial. For responders who used the devices at home for 30 days, adherence was 83% of nights. ESS scores improved from 11 to 7 (p =.031) and Obstructive Sleep Apnea-18 questionnaire scores improved from 50 to 39 (p =.028). Other outcome measures did not improve significantly.

The FDA assessed the safety and effectiveness of the eXciteOSA device in 115 patients with snoring, including 48 patients with snoring and mild sleep apnea. All patients used the device for 20 minutes, once a day for 6 weeks, then discontinued use for 2 weeks before they were reassessed. Overall, the percent of time spent snoring at levels louder than 40dB was reduced by more than 20% in 87 out of the 115 patients. In a 48-patient subset with snoring and mild OSA, the average AHI reduced by 48%, from 10.21 to 5.27, in 41 out of 48 patients. The most common adverse events observed were excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging and tight jaw.

In 2016, Singh, et al, reported on a series of 15 consecutive patients with severe sleep apnea who were treated with a DNA Appliance or mRNA Appliance. All patients had failed to comply with CPAP. Pre- and post-treatment AHI was assessed in a home sleep study without the oral appliance. AHI decreased from a mean 45.9 events per hour to 16.5 (p<0.01) after a mean 9.7 months of treatment (15). In a 2017 study, Singh and Cress reported on a series of 19 patients who had mild-to-moderate sleep apnea who were treated with a DNA or mRNA Appliance. Only patients who complied with oral appliance wear were included in the study. The mean AHI was reduced from 12.85 to 6.2 events per hour (p<0.001) without the appliance while the oxygen saturation index improved from 6.3% to 2.6% (p<0.001) (16). Limitations of these studies included the use of a home sleep study rather than the more accurate laboratory PSG, uncertain blinding of the physician evaluating the sleep study, the small number of patients studied, the lack of intention-to-treat analysis, and the lack of long-term follow-up.

The German Society of Otorhinolaryngology, Head and Neck Surgery guideline on diagnosis and treatment of snoring in adults notes that currently, there is "not enough evidence to confirm the effectiveness of muscle stimulation or other forms of muscle training," and as such, these treatments cannot be recommended. A clinical guideline for the treatment of OSA and snoring from the American Academy of Sleep Medicine (AASM) and American Academy of Dental Sleep Medicine (AADSM) recommends the use of oral appliances, rather than no therapy, for adult patients who request treatment of primary snoring (without obstructive sleep apnea). 

An American Academy of Sleep Medicine and American Academy of Dental Sleep Medicine Clinical Practice Guideline included the following recommendations, specific to the use of oral appliances 

1. We recommend that sleep physicians prescribe oral appliances, rather than no therapy, for adult patients who request treatment of primary snoring (without obstructive sleep apnea). (STANDARD) 
2. When oral appliance therapy is prescribed by a sleep physician for an adult patient with obstructive sleep apnea, we suggest that a qualified dentist use a custom, titratable appliance over non-custom oral devices. (GUIDELINE).
3. We recommend that sleep physicians consider prescription of oral appliances, rather than no treatment, for adult patients with obstructive sleep apnea who are intolerant of CPAP therapy or prefer alternate therapy. (STANDARD) 
4. We suggest that qualified dentists provide oversight—rather than no follow-up—of oral appliance therapy in adult patients with obstructive sleep apnea, to survey for dental-related side effects or occlusal changes and reduce their incidence. (GUIDELINE)
5. We suggest that sleep physicians conduct follow-up sleep testing to improve or confirm treatment efficacy, rather than conduct follow-up without sleep testing, for patients fitted with oral appliances. (GUIDELINE) 
6. We suggest that sleep physicians and qualified dentists instruct adult patients treated with oral appliances for obstructive sleep apnea to return for periodic office visits—as opposed to no follow-up—with a qualified dentist and a sleep physician. (GUIDELINE)

American Academy of Sleep Medicine 

Treatment of Adult Obstructive Sleep Apnea with Positive Airway Pressure Clinical Practice Guideline

The following statements are based on expert consensus and recommended within this clinical practice guideline for appropriate and effective management of patients with OSA treated with positive airway pressure: (1) Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing. (2) Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.

Smoking cessation 

In 2022, Chiang et al published results on a retrospective, cohort study of 1,156,002 patients, utilizing files of the American College of Surgeons National Surgical Quality Improvement Program database. Multivariable logistic regression was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative wound complications, pulmonary complications, and in-hospital mortality associated with smokers. Smoking was associated with a significantly increased risk of postoperative wound disruption (OR 1.65, 95% CI 1.56-1.75), surgical site infection (OR 1.31, 95% CI 1.28-1.34), reintubation (OR 1.47, 95% CI 1.40-1.54), and in-hospital mortality (OR 1.13, 95% CI 1.07-1.19) compared with nonsmoking. The length of hospital stay was significantly increased in smokers compared with non-smokers. They found that current smokers who underwent surgery had approximately 30% increased odds of developing surgical site infection (SSI) and 65% increased odds of developing wound disruption. Study conclusions state smoking status is related to increased perioperative risk for wound complications following major surgical procedures. The current literature review has shown that smoking harms wound healing. The study adds to existing evidence and improves understanding of healing complications in smoking surgical cases. Wound complications are associated with other adverse outcomes and have a significant impact on patient quality of life and health care budgets. Therefore, patients who smoke should be informed about the potentially increased risks of complications before surgery. 

In 2022, Liu et al published a meta-analysis on the effect of preoperative smoking and smoking cessation on wound healing and infection in post-surgery subjects. This analysis incorporated 11 trials involving 218,567 patients following surgery; 176,670 were previous or non-smokers, and 41,897 were smokers. Never smokers or those who had ceased smoking had significantly lower postoperative wound healing problems (odds ratio 0.74; 95% CI 0.63-0.87, p < .001) compared with smokers. Non-smokers had significantly lower postoperative wound healing problems and surgical site wound infection compared with smokers.

Sorensen et al (2012) reported on the results of a meta-analysis that sought to clarify the evidence on smoking and postoperative healing complications across surgical specialties and determine the impact of perioperative smoking cessation intervention. Smokers and non-smokers were compared in 140 cohort studies that included 479K patients. Pooled adjusted odds ratios (95% CI) were 3.60 (2.62 - 4.93) for necrosis, 2.07 (1.53-2.81) for healing delay and dehiscence, 1.79 (1.57-2.04) for surgical site infection, 2.27 (1.82-2.84) for wound complications, 2.07 (1.23-3.47) for hernia, and 2.44 (1.66-3.58) for lack of fistula or bone healing. Investigators concluded that postoperative healing complications occur significantly more often in smokers compared with non-smokers and in former smokers compared with those who never smoked. 

Nolan and Warner (2015) authored a narrative review to discuss the current evidence for nicotine replacement therapy’s (NRT)efficacy and safety in patients scheduled for surgical treatment and other invasive procedures. Noting the lack of human trials, the authors stated that although available data are limited, there is no evidence from human studies that NRT increases the risk of healing-related or cardiovascular complications. Clinical trials of tobacco use interventions that include NRT have found either no effect or a reduction in complications. Authors concluded that given the benefits of smoking abstinence to both perioperative outcomes and long-term health and the efficacy of NRT in achieving and maintaining abstinence, any policies that prohibit the use of NRT in surgical patients should be reexamined.

In 2020, Stefan et al reported on a retrospective study (n=147,506). Researchers analyzed the association between nicotine replacement therapy (within 2 days of admission) and inpatient complications and outcomes. In the propensity-matched analysis, there was no association between receipt of NRT and in-hospital complications (OR, 0.99; 95% CI, 0.93-1.05), mortality (OR, 0.84; 95% CI, 0.68-1.04), all-cause 30-day readmissions (OR, 1.02; 95% CI, 0.97-1.07), or 30-day readmission for wound complications (OR, 0.96; 95% CI, 0.86-1.07). Authors concluded that this demonstrates that perioperative NRT is not associated with adverse outcomes after surgery. These results strengthen the evidence that NRT should be prescribed routinely in the perioperative period.

In 2020, The Society for Perioperative Assessment and Quality Improvement (SPAQI) convened a multidisciplinary panel of 17 experts in perioperative smoking cessation. Members of the Task Force were from the fields of anesthesiology, internal medicine, surgery, public health, and pharmacy from both academic and nonacademic settings in Canada, United States, Australia, New Zealand, Asia, and Europe. The panel issued the following consensus statement: Interventions should occur as soon as practicable in relation to surgical scheduling. Evidence from observational studies of spontaneous quitting suggests that longer durations of preoperative abstinence are associated with lower rates of respiratory and wound healing complications. Evidence from RCTs supports an effect of preoperative smoking cessation interventions that are 4–8 weeks long.

In 2024, The National Comprehensive Cancer Network (NCCN) published guidelines on smoking cessation. The guideline states the following: Nicotine replacement therapy (NRT) is not a contraindication to surgery. There is no evidence that NRT degrades the wound-healing benefits of abstinence from smoking in humans. NRT offers benefits over continued smoking. NRT typically provides less nicotine than cigarettes, and nearly doubles the chance of smoking abstinence.

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