Pharmacotherapy for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials.

Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.

Palatal hybrid surgery for obstructive sleep apnea-state-of-the-art annotation of uvulopalatopharyngoplasty.

BACKGROUND: Surgery for obstructive sleep apnea (OSA) has changed in concept and technique that transformed from radical excision to functional reconstruction. The aim of this study was to investigate the safety and effectiveness of palatal hybrid surgery in OSA patients. METHODS: Palatal hybrid surgery is a tissue-specific technique (mucosa-preservation, tonsil-excision, fat-ablation, muscle-relocation/suspension) used in treating OSA patients with velopharyngeal obstruction. The study included 46 consecutive adults OSA patients. The palatal hybrid surgery annotates uvulopalatopharyngoplasty in stereoscopic reconstruction of tonsillar fossa (pharyngoplasty), omni-suspension of the soft palate (palatoplasty) and advancement of uvula (uvuloplasty). RESULTS: No patient experienced airway compromise, voice change or persistent nasal regurgitation following palatal hybrid surgery. One patient existed postoperative tonsillar fossa bleeding received conservative treatment. Postoperative pain in visual analogue scale (VAS) showed average score of 3, 3, 2, 0 at the 1st, 3rd, 7th, 14th day, respectively. Perioperative snoring severity (VAS) (8.7 vs 2.6) and daytime sleepiness (Epworth Sleepiness Scale) (11.3 vs 5.5) all improved significantly (p < 0.001). Posterior air space in retropalatal area increased from 8.4 to 11.1 mm (p < 0.001). Home sleep test showed that apnea-hypopnea index significantly reduced from 41.8 to 18.2 event/h and minimal oxygen saturation increased from 72.4 to 81.5% (p < 0.001). The success rate in individual Friedman stage was 100% (stage I), 63% (stage II) and 58% (stage III) with a total success rate of 63%. CONCLUSION: Palatal hybrid surgery using tissue-specific maneuver annotates UPPP in concept and technique. The results show that palatal hybrid surgery is mini-invasive with low morbid and is effective in improving subjective clinic symptoms, objective sleep parameters and success rate of OSA.

Combined Airway and Bariatric Surgery (CABS) for Obstructive Sleep Apnea Patients with Morbid Obesity: A Comprehensive Alternative Preliminary Study.

Although continuous positive airway pressure is the gold standard for obstructive sleep apnea (OSA), it does not improve obesity. By contrast, bariatric surgery significantly improves obesity but with sustained OSA in the majority of patients. This study proposes a comprehensive technique­combined airway and bariatric surgery (CABS)­to improve both obesity and OSA. The aims of the study are to evaluate the feasibility, safety and efficacy of CABS in morbidly obese OSA patients. The retrospective study enrolled 20 morbidly obese OSA patients (13 males; median age, 44 years; median apnea−hypopnea index (AHI), 63.2 event/h; median body mass index (BMI), 41.4 kg/m2). The study population was divided into two groups based on patients' volition after shared decision making. The bariatric surgery (BS) group included laparoscopic sleeve gastrectomy (LSG, n = 8) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 2). CABS involved bariatric surgery­LSG (n = 8) and LRYGB (n = 2) in conjunction with airway surgery (concurrent nasal/palatal/lingual surgery [n = 8], concurrent palatal/lingual surgery [n = 2]). Patients received a home sleep apnea test at baseline and one year after surgery. The two patient groups were not different in age, sex, preoperative AHI or preoperative BMI. There was no airway compromise, wound bleeding or infection throughout the postoperative period. One year after surgery, patients in both groups achieved significant improvement in AHI and BMI. Furthermore, the improvement in AHI was significantly higher (p = 0.04) in the CABS group than in the BS group despite the insignificant change in BMI reduction (p = 0.63) between the two groups. In the CABS group, the BMI dropped from 40.4 to 28.4 kg/m2 (p < 0.0001) and the AHI decreased from 75.1 to 4.5 event/h (p = 0.0004). The classic success rate for OSA was 90% and the cure rate was 60% in the CABS group. A perioperative assessment of CABS group patients also revealed a significant improvement in the Epworth sleepiness scale, minimal O2 saturation, snoring index and heart rate. CABS is feasible and safe in treating OSA with morbid obesity. CABS achieves more reduction in AHI than BS alone with high success and cure rates for OSA. CABS can also significantly improve quality of life and general health and offers a comprehensive alternative for morbidly obese OSA patients.

Transoral Tongue Suspension for Obstructive Sleep Apnea-A Preliminary Study.

Objectives: To evaluate the safety and efficacy of a novel technique for transoral tongue suspension (TOTS) in obstructive sleep apnea (OSA) patients. Material and Methods: The retrospective study enrolled 24 consecutive OSA patients (21 males; average age, 43 years; average apnea−hypopnea index (AHI), 42.2 event/h; average body mass index (BMI), 25.7 kg/m2) with tongue obstruction confirmed by drug-induced sleep endoscopy. All patients received TOTS as the main procedure in conjunction with uvulopalatopharyngoplasty (UPPP). Key procedures of TOTS included a transoral sublabial approach, drilling two holes on the mandible, passing the polypropylene through the hole to the tongue base using a suture passer and returning the polypropylene through loop traction, and tying the polypropylene to the mandible. Lingual tonsil ablation (n = 8) was also implemented in hypertrophic lingual tonsils (grades III and IV). Results: The operation time for TOTS was around 30 min. No wound bleeding or airway compromise occurred throughout the postoperative period. Minor complications were temporary and included swelling of the tongue, numbness of the lower incisor, and sublabial wound dehiscence (n = 2). The quality of life improved significantly in the patients' subjective daytime sleepiness according to the Epworth Sleepiness Scale (11.4 ± 3.2 vs. 5.7 ± 1.6, p < 0.001). The objective parameters of OSA also improved significantly in the apnea/hypopnea index (42.2 ± 21.8 vs. 19.5 ± 16.2, p < 0.001), minimal oxygen saturation (77.1 ± 12.2 vs. 81.7 ± 8.1, p = 0.026), and snoring index (207 ± 141 vs. 101 ± 91, p = 0.03). Conclusions: The demonstrated TOTS showed its advantage in low morbidity with a scarless exterior and easy performance with free availability in treating adult OSA patients with tongue obstruction. TOTS combined with UPPP significantly improved AHI and daytime sleepiness. TOTS can be implemented with lingual tonsillectomy to achieve both stabilization of the tongue and widening of hypopharyngeal airway.

The Impact of Mouth-Taping in Mouth-Breathers with Mild Obstructive Sleep Apnea: A Preliminary Study.

BACKGROUND: Many patients with obstructive sleep apnea (OSA) are mouth-breathers. Mouth-breathing not only narrows the upper airway, consequently worsening the severity of OSA, but also it affects compliance with nasal continuous positive airway pressure (CPAP) treatment. This study aimed to investigate changes in OSA by the use of mouth tape in mouth-breathers with mild OSA. METHOD: Mouth-breathers with mild OSA who met inclusion criteria and tolerated the sealing of the mouth were enrolled in the study. We used 3M silicone hypoallergenic tape was used to seal the mouths of the participants during sleep. The home sleep test (HST) used in this study was ApneaLink®. Subjects received both a baseline HST and an outcome HST to be used 1 week later while their mouths were taped. The changes between the baseline and the outcome HSTs were compared, and the factors that influenced the differences in the sleep-test parameters after the shift of the breathing route were analyzed. A "responder" was defined as a patient who experienced a reduction from the baseline snoring index of at least 50% under mouth-taping in the HST; otherwise, patients were considered as having a poor response. RESULTS: A total of 20 patients with mild OSA were included. Following the taping of the mouth, a good response was found in 13 patients (65%). The median apnea/hypopnea index (AHI) decreased significantly, from 8.3 to 4.7 event/h (by 47%, p = 0.0002), especially in supine AHI (9.4 vs. 5.5 event/h, p = 0.0001). The median snoring index (SI) was also improved (by 47%, 303.8 vs. 121.1 event/h, p = 0.0002). Despite no significant difference in the mean saturation, improvements in the oxygen desaturation index (8.7 vs. 5.8, p = 0.0003) and the lowest saturation (82.5% vs. 87%, p = 0.049) were noted. The change in AHI was associated with baseline AHI (r = -0.52, p = 0.02), oxygen desaturation index (ODI) (r = -0.54, p = 0.01), and SI (r = -0.47, p = 0.04). The change in SI was strongly associated with baseline SI (r = -0.77, p = 0.001). CONCLUSIONS: Mouth-taping during sleep improved snoring and the severity of sleep apnea in mouth-breathers with mild OSA, with AHI and SI being reduced by about half. The higher the level of baseline AHI and SI, the greater the improvement was shown after mouth-taping. Mouth-taping could be an alternative treatment in patients with mild OSA before turning to CPAP therapy or surgical intervention.

How to manage continuous positive airway pressure (CPAP) failure -hybrid surgery and integrated treatment.

Obstructive sleep apnea (OSA) is a prevalent disease, which influences social relations and quality of life with major health impact. The etiology of OSA is multi-factorial involving both anatomical obstruction and physiological collapse of the upper airway during sleep with different proportion in individual patients. Continuous positive airway pressure (CPAP) is the gold standard and first-line treatment for OSA patients. The mechanism of CPAP is acting as air splint to avoid principal pharyngeal collapse during sleep. Consequently, extrapharyngeal collapse and significant pharyngeal obstructions can lower its compliance and lead to its failure. Adequate mask and pressure with thorough survey to eliminate side effects of CPAP from nasal, mask and flow-related problems are the prerequisite to improve CPAP compliance. For CPAP failure patients, multi-dimensional surgery is an alternative and salvage treatment that involves soft tissue surgery, skeletal surgery, and bariatric surgery. OSA patients with craniofacial anomaly are suggested to skeletal surgery. By contrast, OSA patients with pathological obesity are referred to bariatric surgery. Soft tissue surgery targets at the nose, soft palate, lateral pharyngeal wall, tongue and epiglottis that can be implemented by multi-level surgery with hybrid technique (mucosa-preservation, fat-ablation, muscle-suspension, tonsil-excision, cartilage-reconstruction) to maximize surgical outcomes and minimize complications. Some evolution in surgical concept and technique are noteworthy that include mini-invasive septoturbinoplasty, palatal suspension instead of excision, whole tongue treatment, and two-dimensional supraglottoplasty. Postoperative integrated treatment including myofunctional, positional therapy and body weight control reduces relapse of OSA and improves long-term treatment outcomes.

Risk of Alzheimer's Disease in Obstructive Sleep Apnea Patients With or Without Treatment: Real-World Evidence.

OBJECTIVE: To assess the risk of Alzheimer's disease (AD) in patients with obstructive sleep apnea (OSA) with or without treatment based on real-world evidence. STUDY DESIGN: Retrospective cohort study. METHODS: Patients newly diagnosed with OSA during 1997-2012 were identified using the National Health Insurance Research Database of Taiwan. Patients without OSA were randomly selected and matched in a 1:4 ratio by age, sex, urbanization level, and income. All patients were followed up until death or the end of 2013. The primary outcome was AD occurrence. RESULTS: This study included 3,978 OSA patients and 15,912 non-OSA patients. OSA was independently and significantly associated with a higher incidence of AD in an adjusted Cox proportional hazard model (adjusted hazard ratio: 2.12; 95% confidence interval [CI], 1.27-3.56). The average period of AD detection from the time of OSA occurrence was 5.44 years (standard deviation: 2.96). Subgroup analyses revealed that the effect of OSA remained significant in patients aged ≥60 years, male subgroups, patients without CPAP or surgical treatment, and patients without pharmacological therapies. Patients with OSA who received treatment (continuous positive airway pressure or surgery) exhibited a significantly reduced risk of AD compared with those without treatment (incidence rate ratio 0.23, 95% CI, 0.06-0.98). CONCLUSION: OSA is independently associated with an increased risk of AD. Treatment for OSA reduces the AD risk in OSA patients. AD irreversibility renders OSA as a potential modifiable target for slowing or preventing the process of AD development. LEVEL OF EVIDENCE: IV Laryngoscope, 130:2292-2298, 2020.

Alterations in Alzheimer's Disease-Associated Gene Expression in Severe Obstructive Sleep Apnea Patients.

BACKGROUND: Obstructive sleep apnea (OSA) increases the risk of Alzheimer's disease (AD), and inflammation may be involved in the early pathogenesis of AD in patients with OSA. However, the potential pathways between OSA and AD have yet to be established. In this study, we aimed to investigate differential expressions of AD-associated genes in OSA patients without evident AD or dementia. METHODS: This prospective case-control study included five patients with severe OSA and five age and sex-matched patients with non-severe OSA without evident dementia who underwent uvulopalatopharyngoplasty between 1 January 2013 and 31 December 2015. The expressions of genes associated with AD were analyzed using whole-exome sequencing. Unsupervised two-dimensional hierarchical clustering was performed on these genes. Pearson's correlation was used as the distance metric to simultaneously cluster subjects and genes. RESULTS: The expressions of CCL2, IL6, CXCL8, HLA-A, and IL1RN in the patients with severe OSA were significantly different from those in the patients with non-severe OSA and contributed to changes in the immune response, cytokine-cytokine receptor interactions, and nucleotide-binding oligomerization domain-like receptor signaling pathways. CONCLUSIONS: Inflammation may contribute to the onset of AD and physicians need to be aware of the potential occurrence of AD in patients with severe OSA.

Snoring Sounds Predict Obstruction Sites and Surgical Response in Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Snoring sounds generated by different vibrators of the upper airway may be useful indicators of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study aimed to investigate associations between snoring sounds, obstruction sites, and surgical responses (≥50% reduction in the apnea-hypopnea index [AHI] and <10 events/hour) in patients with OSAHS. This prospective cohort study recruited 36 OSAHS patients for 6-hour snoring sound recordings during in-lab full-night polysomnography, drug-induced sleep endoscopy (DISE), and relocation pharyngoplasty. All patients received follow-up polysomnography after 6 months. Fifteen (42%) patients with at least two complete obstruction sites defined by DISE were significantly, positively associated with maximal snoring sound intensity (40-300 Hz; odds ratio [OR], 1.25, 95% confidence interval [CI] 1.05-1.49) and body mass index (OR, 1.48, 95% CI 1.02-2.15) after logistic regression analysis. Tonsil obstruction was significantly, inversely correlated with mean snoring sound intensity (301-850 Hz; OR, 0.84, 95% CI 0.74-0.96). Moreover, baseline tonsil obstruction detected by either DISE or mean snoring sound intensity (301-850 Hz), and AHI could significantly predict the surgical response. Our findings suggest that snoring sound detection may be helpful in determining obstruction sites and predict surgical responses.

The Frequency and Energy of Snoring Sounds Are Associated with Common Carotid Artery Intima-Media Thickness in Obstructive Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is a known risk factor for atherosclerosis. We investigated the association of common carotid artery intima-media thickness (CCA-IMT) with snoring sounds in OSA patients. A total of 30 newly diagnosed OSA patients with no history of cardiovascular diseases were prospectively enrolled for measuring mean CCA-IMT with B-mode ultrasonography, body mass index, metabolic syndrome, 10-year cardiovascular disease risk score, high-sensitivity C-reactive protein, and homocysteine. Good-quality signals of full-night snoring sounds in an ordinary sleep condition obtained from 15 participants were further acoustically analyzed (Included group). All variables of interest were not significantly different (all p > 0.05) between the included and non-included groups except for diastolic blood pressure (p = 0.037). In the included group, CCA-IMT was significantly correlated with snoring sound energies of 0-20 Hz (r = 0.608, p = 0.036) and 652-1500 Hz (r = 0.632, p = 0.027) and was not significantly associated with that of 20-652 Hz (r = 0.366, p = 0.242) after adjustment for age and sex. Our findings suggest that underlying snoring sounds may cause carotid wall thickening and support the large-scale evaluation of snoring sound characters as markers of surveillance and for risk stratification at diagnosis.

Treatment of snoring with positional therapy in patients with positional obstructive sleep apnea syndrome.

Position therapy plays a role in treating snoring and obstructive sleep apnea syndrome (OSAS). The purpose of this study was to investigate whether position therapy using a head-positioning pillow (HPP) could reduce snoring sounds in patients with mild-to-moderate positional OSAS, taking into account the potential confounding effects of body weight. A total of 25 adults with positional OSAS (apnea-hypopnea index [AHI]supine:AHInon-supine ≥ 2) were prospectively enrolled. Patients were asked to use their own pillows at home during the first night (N0), and the HPP during the second (N1) and third (N2) nights. The primary outcome measures included the subjective snoring severity (SS, measured on a visual analogue scale ranging from 0 to 10) and the objective snoring index (SI, expressed as the number of snoring events per hour measured on an acoustic analytical program). Both endpoints were recorded over three consecutive nights. From N0 to N2, the median SS and SI values in the entire study cohort decreased significantly from 5.0 to 4.0 and from 218.0 events/h to 115.0 events/h, respectively. In the subgroup of overweight patients, SS showed a significant improvement, whereas SI did not. Both SS and SI were found to be significantly improved in normal-weight patients.

Comparative effects of snoring sound between two minimally invasive surgeries in the treatment of snoring: a randomized controlled trial.

BACKGROUND: Minimally invasive surgeries of the soft palate have emerged as a less-invasive treatment for habitual snoring. To date, there is only limited information available comparing the effects of snoring sound between different minimally invasive surgeries in the treatment of habitual snoring. OBJECTIVE: To compare the efficacy of palatal implant and radiofrequency surgery, in the reduction of snoring through subjective evaluation of snoring and objective snoring sound analysis. PATIENTS AND METHOD: Thirty patients with habitual snoring due to palatal obstruction (apnea-hypopnea index ≤15, body max index ≤30) were prospectively enrolled and randomized to undergo a single session of palatal implant or temperature-controlled radiofrequency surgery of the soft palate under local anesthesia. Snoring was primarily evaluated by the patient with a 10 cm visual analogue scale (VAS) at baseline and at a 3-month follow-up visit and the change in VAS was the primary outcome. Moreover, life qualities, measured by snore outcomes survey, and full-night snoring sounds, analyzed by a sound analytic program (Snore Map), were also investigated at the same time. RESULTS: Twenty-eight patients completed the study; 14 received palatal implant surgery and 14 underwent radiofrequency surgery. The VAS and snore outcomes survey scores were significantly improved in both groups. However, the good response (postoperative VAS ≤3 or postoperative VAS ≤5 plus snore outcomes survey score ≥60) rate of the palatal implant group was significantly higher than that of the radiofrequency group (79% vs. 29%, P = 0.021). The maximal loudness of low-frequency (40-300 Hz) snores was reduced significantly in the palatal implant group. In addition, the snoring index was significantly reduced in the radiofrequency group. CONCLUSIONS: Both palatal implants and a single-stage radiofrequency surgery improve subjective snoring outcomes, but palatal implants have a greater effect on most measures of subjective and objective snoring. Multi-stage radiofrequency surgery was not tested. TRIAL REGISTRATION: ClinicalTrials.gov NCT01955083.

Positional dependency and surgical success of relocation pharyngoplasty among patients with severe obstructive sleep apnea.

OBJECTIVE: To examine the effect of positional dependency on surgical success among patients with severe obstructive sleep apnea (OSA) following modified uvulopalatopharyngoplasty, known as relocation pharyngoplasty. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referred center. SUBJECTS AND METHODS: Standard nocturnal polysomnography was used to compare the apnea-hypopnea index (AHI) in different sleep positions before and after relocation pharyngoplasty in 47 consecutive patients with severe OSA (AHI, 59.5 ± 18.2 events/hour; Epworth Sleepiness Scale [ESS] scores, 12.2 ± 4.4) who failed continuous positive airway pressure therapy. Positional (dependency) OSA was defined when the supine:non-supine AHI ratio was >2, otherwise it was defined as nonpositional OSA. Surgical success was defined as a ≥50% reduction in AHI and a postoperative AHI of ≤20 events/hour. Polysomnographic parameters, ESS, and surgical success following surgery were recorded. RESULTS: Of the 47 patients, 27 (57%) had positional OSA and 20 (43%) nonpositional OSA. The nonpositional OSA patients had higher AHI and ESS scores than the positional OSA patients (P = .002 and .104, respectively). Relocation pharyngoplasty significantly improved AHI and ESS scores in both positional and nonpositional OSA groups 6 months postoperatively (P < .05). The overall surgical success rate was 49%; however, positional OSA patients had a significantly higher success rate than nonpositional OSA patients (67% vs 25%, P = .008). CONCLUSION: The presence of positional dependency at baseline was a favorable outcome predictor of surgical success among severe OSA patients undergoing relocation pharyngoplasty.

Predictive validity of a three-dimensional model of performance anxiety in the context of tae-kwon-do.

We tested the predictive validity of the recently validated three-dimensional model of performance anxiety (Chang, Hardy, & Markland, 2009) with elite tae-kwon-do competitors (N = 99). This conceptual framework emphasized the adaptive potential of anxiety by including a regulatory dimension (reflected by perceived control) along with the intensity-oriented dimensions of cognitive and physiological anxiety. Anxiety was assessed 30 min before a competitive contest using the Three-Factor Anxiety Inventory. Competitors rated their performance on a tae-kwon-do-specific performance scale within 30 min after completion of their contest. Moderated hierarchical regression analyses revealed initial support for the predictive validity of the three-dimensional performance anxiety model. The regulatory dimension of anxiety (perceived control) revealed significant main and interactive effects on performance. This dimension appeared to be adaptive, as performance was better under high than low perceived control, and best vs. worst performance was associated with highest vs. lowest perceived control, respectively. Results are discussed in terms of the importance of the regulatory dimension of anxiety.

Survey of short-term patient satisfaction after surgery for obstructive sleep apnea.

BACKGROUND: To investigate the level of satisfaction of patients who received surgery for obstructive sleep apnea (OSA). METHODS: A patient satisfaction survey (PSS) was administered three months after surgery to 76 patients who received either a uvulopalatopharyngoplasty (UPPP) alone, or in combination with a septomeatoplasty (SMP), or a midline laser glossectomy (MLG). Patient satisfaction determinants were also explored. RESULTS: In general, 93.4% of patients rated their overall satisfaction as "excellent" or "very good". High satisfaction levels (excellent + very good >/= 90%) were observed in the dimensions of "professional skill", "personal manner", and "explanation of condition". By contrast, lower satisfaction levels (excellent + very good< 90 %) were observed for "perioperative discomfort". There were no significant differences among the UPPP alone, UPPP + SMP, and UPPP +MLG groups for any dimension of satisfaction (p> 0.05). Older patients had decreased overall levels of satisfaction (adjust R (2) = 0.1, p = 0.02). CONCLUSIONS: The preliminary results reveal a high overall level of satisfaction after surgery for OSA in this short-term survey. However, modest satisfaction with perioperative discomfort was also noted. Combined nasal or tongue base surgeries can be performed with patient satisfaction comparative to that of UPPP alone. Age may confound satisfaction levels in patients receiving OSA surgery.