Effectiveness of Tonsillectomy vs Modified Uvulopalatopharyngoplasty in Patients With Tonsillar Hypertrophy and Obstructive Sleep Apnea: The TEAMUP Randomized Clinical Trial.

Importance: Modified uvulopalatopharyngoplasty (mUPPP) is a surgical treatment for selected adults with obstructive sleep apnea (OSA). Tonsillectomy (TE) alone is a less extensive alternative treatment. Objective: To investigate whether mUPPP is more effective than TE alone in treating adult patients with tonsillar hypertrophy and moderate to severe OSA. Design, Setting, and Participants: This blinded randomized clinical trial compared the effectiveness of mUPPP with TE alone before surgery and 6 months postsurgery in adults with tonsillar hypertrophy (sizes 2, 3, or 4 according to the Friedman staging) and moderate to severe OSA in a university hospital in Stockholm, Sweden. Participants underwent surgery from January 2016 to February 2021; the last postsurgery follow-up was completed in September 2021. Data analyses were performed from January to September 2022. Interventions: mUPPP vs TE alone. Main Outcomes and Measures: Between-group differences on the apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS). Results: The study cohort comprised 93 patients (mean [SD] age, 41.6 [9.4] years; 80 [86%] men; race/ethnicity were not considered) with a mean (SD) body mass index of 29.0 (2.8), calculated as weight in kg divided by height in m2. Of these, 90 participants (97%) completed the protocol (mUPPP, n = 45; TE, n = 45). The mean (SD) AHI score (number of events per hour [events/h]) for the mUPPP group decreased by 43%, from 51.0 (22.6) to 28.0 (20.0) events/h; and for the TE group, 56%, from 56.9 (25.1) to 24.7 (22.6) events/h. The mean between-group difference in AHI score was 9.2 events/h (95% CI, 0.5 to 17.9), with a small effect size (Cohen d = 0.44) in favor of TE. For ESS scores, the between-group difference was also small, only 1.1 (95% CI, -1.3 to 3.4; Cohen d = 0.21). Neither difference was considered to be clinically relevant. Conclusions and Relevance: This randomized clinical trial demonstrated that mUPPP was not more effective than TE alone in treating patients with tonsillar hypertrophy and moderate to severe OSA. However, there was a small difference in favor of TE. Because TE alone is less extensive, it could be considered as an alternative to mUPPP in this selected group of patients with OSA. Trial Registration: ClinicalTrials.gov Identifier: NCT02523248.

Eight-Year Follow-up of Modified Uvulopalatopharyngoplasty in Patients With Obstructive Sleep Apnea.

OBJECTIVE: To investigate whether modified uvulopalatopharyngoplasty (UPPP) for treatment of obstructive sleep apnea (OSA) remained effective after 8 years. METHODS: Prospective intervention study. Sixty-five patients with OSA were offered re-evaluation with polysomnography and the Epworth Sleepiness Scale (ESS) 8 years after UPPP. Results were compared with baseline and with a previous 2-year follow-up. Baseline predictors were analyzed with regression analyses. RESULTS: The dropout rate at the 8-year follow-up was 28%. The mean decrease in apnea-hypopnea index (AHI) between baseline and the 8-year follow-up was significant, 14.0 events/hour (from 52.9 to 38.9), 27% (P < .001). The mean increase in AHI between the 2-year and the 8-year follow-up was significant, 14.7 events/hour (from 24.2 to 38.9), 61% (P < .0001). Overweight at baseline predicted an AHI at the 8-year follow-up that was 22.9 events higher compared to patients with normal weight (P = .015). An increase in body mass index (BMI) of 1 kg/m2 between baseline and the 8-year follow-up predicted a mean AHI increase of 3.8 events/hour (P = .015). The median decrease in ESS between baseline and the 8-year follow-up was significant, 7 (from 13.0 to 6.0), 54% (P < .0001). The median increase in ESS between the 2-year and the 8-year follow-up was not significant, 1.0 (from 5.0 to 6.0), 20%. CONCLUSION: Modified UPPP was effective as a long-term treatment for OSA in selected patients, although the effect on AHI decreased over time. Daytime sleepiness remained improved even in the long term. High BMI at baseline and an increase in BMI predicted a reduced long-term respiratory outcome. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E307-E313, 2021.

Effectiveness of Adenotonsillectomy vs Watchful Waiting in Young Children With Mild to Moderate Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Adenotonsillectomy (ATE) is one of the most common surgical procedures to treat children with obstructive sleep apnea (OSA), but to our knowledge there are no randomized clinical trials confirming the benefit of surgery compared with watchful waiting in children between 2 and 4 years of age. Objective: To determine whether ATE is more effective than watchful waiting for treating otherwise healthy children with mild to moderate OSA. Design, Setting, and Participants: This randomized clinical trial was conducted from December 2014 to December 2017 at the Otorhinolaryngology Department of the Karolinska University Hospital, Stockholm, Sweden. A total of 60 children, 2 to 4 years of age, with an obstructive apnea-hypopnea index (OAHI) score of 2 or greater and less than 10, were randomized to ATE (n = 29) or watchful waiting (n = 31). A total of 53 participants (88%; ATE, n = 25; watchful waiting, n = 28) completed the study. Data were analyzed from August 2018 to December 2018. Interventions: Adenotonsillectomy. Main Outcomes and Measures: The primary outcome was the difference between the groups in mean OAHI score change. Secondary outcomes were other polysomnography parameters, score on the Obstructive Sleep Apnea-18 (OSA-18) questionnaire, and subgroup analyses. Polysomnography and the OSA-18 questionnaire were completed at baseline and after 6 months. Results: Of the 60 included children, 34 (57%) were boys and the mean (SD) age at first polysomnography was 38 (9) months. Both groups had a decrease in mean OAHI score, and the difference in mean OAHI score change between the groups was small (-1.0; 95% CI, -2.4 to 0.5), in favor of ATE. However, there were large differences between the groups in favor of ATE regarding the OSA-18 questionnaire (eg, total OSA-18 score: -17; 95% CI, -24 to -10). Also, a subgroup analysis of 24 children with moderate OSA (OAHI ≥5 and <10) showed a meaningful difference in mean OAHI score change between the groups in favor of ATE (-3.1; 95% CI, -5.7 to -0.5). Of 28 children, 10 (36%) in the watchful waiting group received ATE after the follow-up, and 7 of these had moderate OSA at baseline. Conclusions and Relevance: This randomized clinical trial found only small differences between the groups regarding changes in OAHI, but further studies are needed. However, there were large improvements in quality of life after ATE. These results suggest that otherwise healthy children with mild OSA and mild effect on quality of life may benefit from watchful waiting, while children with moderate OSA should be considered for ATE. Trial Registration: ClinicalTrials.gov Identifier: NCT02315911.

Long-term evaluation of satisfaction and side effects after modified uvulopalatopharyngoplasty.

OBJECTIVES/HYPOTHESIS: We have previously shown that modified uvulopalatopharyngoplasty (UPPP) is effective to treat obstructive sleep apnea (OSA) and that the effect is stable after 24 months. This continuous report includes questionnaires and phone interviews. STUDY DESIGN: Prospective intervention study. METHODS: Sixty-five patients with apnea-hypopnea index (AHI) score ≥ 15, body mass index <36 kg/m2 , and Epworth Sleepiness Scale (ESS) score ≥ 8 underwent modified UPPP after failing nonsurgical treatment. The results from a patient questionnaire at 6 and 24 months after surgery were correlated with age, body mass index, and ESS and AHI scores. Patients reporting side effects and/or regretting the surgery after 24 months were selected for phone interviews 9 years after surgery. RESULTS: The response rate was 80% and 74% at the 6- and 24-month follow-ups, respectively. Of those who responded to the questionnaire, 96% and 83% were satisfied after 6 and 24 months, respectively; 98% and 92% recommended the surgery. Side effects (globus, mucus, and voice and swallowing disorders) occurred in 38% and 31%, respectively. Dissatisfaction correlated significantly with high postoperative AHI and ESS scores, but not with occurrence of side effects. Younger subjects had a higher rate of recommendation and lower rate of side effects than did older subjects. Phone interviews after 9 years were responded to by 14 of 16 selected patients, and the responders reported minor or no side effects. CONCLUSIONS: The vast majority of the OSA patients were satisfied 24 months after surgery, even though a third of them were experiencing side effects. Younger patients had fewer side effects than did older patients. Patients with better OSA outcomes were also more satisfied. After 9 years the side effects were no longer problematic. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:263-268, 2020.

SKUP3 : 6 and 24 months follow-up of changes in respiration and sleepiness after modified UPPP.

OBJECTIVE: Our previous randomized controlled trial of patients with obstructive sleep apnea syndrome (OSAS) showed that modified uvulopalatopharyngoplasty (UPPP), including tonsillectomy, significantly improved nocturnal respiration, daytime sleepiness, and quality of life in the intervention group compared to controls who had delayed surgery after 6 months. This is the continuous report with the 6- and 24-month postoperative results. STUDY DESIGN: Single-center prospective cohort study. METHODS: Sixty-five patients with apnea-hypopnea index (AHI) ≥ 15, body mass index (BMI) < 36, Epworth Sleepiness Scale (ESS) ≥ 8, and Friedman stage I or II underwent UPPP after failing nonsurgical treatment. The results from polysomnography and ESS at 6 and 24 months were compared to baseline. RESULTS: Eight percent and 20% dropped out from the 6- and 24-month follow-ups, respectively. The AHI value decreased significantly from mean (standard deviation) 52.9 (20.5) at baseline to 23.6 (20.2) after 6 months, and to 24.1 (20.9) after 24 months (P < 0.001). Patients with tonsil size 2, and 3 to 4, had significant reductions in the AHI after both follow-ups. The median ESS score decreased significantly from 13 (range 8-21) to 6.5 (1-18) after 6 months, and to 5 (2-17) after 24 months (P < 0.001). The BMI remained unchanged. There were significant modest correlations for the reductions in AHI and ESS after 24 months. CONCLUSION: Modified UPPP was effective in improving nocturnal respiration and daytime sleepiness in OSAS patients at both 6- and 24-month follow-up. Patients with tonsil size 2, and 3 to 4, benefitted similarly from surgery with improved respiration. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1238-1244, 2018.

Blood pressure after modified uvulopalatopharyngoplasty: results from the SKUP3 randomized controlled trial.

OBJECTIVE: Obstructive sleep apnea (OSA) is a risk factor for hypertension. The SKUP3 study showed that modified uvulopalatopharyngoplasty (UPPP) significantly improved nocturnal respiration, sleepiness, and quality of life. The aim of this study was to evaluate the impact of surgery on blood pressure in patients with OSA. METHODS: We used a single-center randomized controlled trial to compare modified UPPP with controls at baseline and after six months. The controls received delayed surgery with an additional six-month follow-up. All operated patients also had a follow-up after 24 months. Polysomnography was performed at each follow-up, with systolic and diastolic blood pressure (SBP, DBP) measured the morning after. RESULTS: A total of 65 patients were randomized to intervention (n = 32) or control (n = 33). At follow-up (n = 61/65, 94%), there were significant differences between the groups in both mean SBP (-9.4 mmHg [95% CI: -17.9, -0.83], p < 0.05) and mean DBP (-6.4 mmHg [95% CI: -12.8, -0.04], p < 0.05), in favor of UPPP. Blood pressure and respiratory parameters at follow-up correlated. The analyses of all operated patients showed a significant decrease in mean (SD) blood pressure after six months (n = 49/65, 75%; SBP: -4.5 [9.0], p = 0.001; DBP: -2.2 [6.6], p = 0.030) as well as after 24 months (n = 35/65, 54%; SBP: -8.9 [11.5], p < 0.0001; DBP: -4.2 [9.4], p = 0.012). CONCLUSIONS: Blood pressure was significantly decreased after surgery, indicating that modified UPPP decreases the blood pressure, in a selected group of patients with moderate to severe OSA. The long-term effect was also significant, but these results are uncertain due to a high proportion of missing values. TRIAL REGISTRATION NUMBER: NCT01659671.

SKUP(3) RCT; continuous study: Changes in sleepiness and quality of life after modified UPPP.

OBJECTIVES/HYPOTHESIS: Our previous study showed that modified uvulopalatopharyngoplasty (UPPP), including tonsillectomy, significantly improved nocturnal respiration in obstructive sleep apnea syndrome (OSAS) patients. This is a continuous study of changes in daytime sleepiness and quality of life. STUDY DESIGN: Prospective randomized controlled trial (RCT), two parallel arms. METHODS: Sixty-five patients with apnea-hypopnea index ≥ 15, body mass index < 36, Epworth Sleepiness Scale (ESS) ≥ 8, Friedman stage I or II, failing nonsurgical treatment. The intervention group (n = 32) underwent surgery, and the controls (n = 33) had no treatment. At baseline and the 7-month follow-up, polysomnography, questionnaires, and vigilance tests were implemented. RESULTS: All patients answered the questionnaires, and 48 took the vigilance test. Epworth Sleepiness Scale decreased significantly in the intervention group, from a mean (standard deviation) of 12.5(3.2) to 6.8(3.9), but nonsignificantly in the control group, from 12.9(3.1) to 12.5(3.9), a significant group difference (P < 0.001). The physical and mental component score on the Short Form-36 questionnaire increased significantly in the intervention group, from a mean 47.8(8.3) to 51.2(8.8) and from 42.1(10.6) to 48.1(9.7), respectively, but with nonsignificant changes in the controls: 49.0(9.0) to 48.3(9.1) and 41.0(10.2) to 42.7(11.5), significant group differences (P = 0.007, P = 0.031), respectively. The sleep latency/vigilance test showed a significant mean increase in the intervention group of 7(12.4) minutes and a decrease in the controls of 2.2(10.6), a significant group difference (P = 0.011). There were significant correlations between changes in subjective outcomes and nocturnal respiration. CONCLUSION: This RCT shows that modified UPPP was effective in improving daytime sleepiness and quality of life in OSAS patients. It strengthens the body of evidence on the potential effect of surgery offered to selected patients. LEVEL OF EVIDENCE: 1b. Laryngoscope, 126:1484-1491, 2016.

The Kölliker-Fuse nucleus: a review of animal studies and the implications for cranial nerve function in humans.

To review the scientific literature on the relationship between Kölliker-Fuse nucleus (KF) and cranial nerve function in animal models, with view to evaluating the potential role of KF maturation in explaining age-related normal physiologic parameters and developmental and acquired impairment of cranial nerve function in humans. Medical databases (Medline and PubMed). Studies investigating evidence of KF activity responsible for a specific cranial nerve function that were based on manipulation of KF activity or the use of neural markers were included. Twenty studies were identified that involved the trigeminal (6 studies), vagus (9), and hypoglossal nerves (5). These pertained specifically to a role of the KF in mediating the dive reflex, laryngeal adductor control, swallowing function and upper airway tone. The KF acts as a mediator of a number of important functions that relate primarily to laryngeal closure, upper airway tone and swallowing. These areas are characterized by a variety of disorders that may present to the otolaryngologist, and hence the importance of understanding the role played by the KF in maintaining normal function.

MicroRNA expression patterns related to merkel cell polyomavirus infection in human merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive and lethal type of neuroendocrine skin cancer. Mutated Merkel cell polyomavirus (MCV) is commonly found in MCC, and leads to upregulation of the survivin oncogene. However, ∼20% of MCC tumors do not have detectable MCV, suggesting alternative etiologies for this tumor type. In this study, our aim was to evaluate microRNA (miRNA) expression profiles and their associations with MCV status and clinical outcomes in MCC. We showed that miRNA expression profiles were distinct between MCV-positive (MCV+) and MCV-negative (MCV-) MCCs and further validated that miR-203, miR-30a-3p, miR-769-5p, miR-34a, miR-30a-5p, and miR-375 were significantly different. We also identified a subset of miRNAs associated with tumor metastasis and MCC-specific survival. Functionally, overexpression of miR-203 was found to inhibit cell growth, induce cell cycle arrest, and regulate survivin expression in MCV- MCC cells, but not in MCV+ MCC cells. Our findings reveal a mechanism of survivin expression regulation in MCC cells, and provide insights into the role of miRNAs in MCC tumorigenesis.

SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea.

OBJECTIVE: To assess the 6-month efficacy of uvulopalatopharyngoplasty (UPPP) compared with expectancy in selected patients with obstructive sleep apnoea syndrome (OSAS). DESIGN: A prospective single-centre randomised controlled trial with two parallel arms stratified by Friedman stage and body mass index (BMI). PARTICIPANTS: 65 consecutive patients with moderate to severe OSAS (apnoea-hypopnoea index (AHI) ≥15 events/h sleep), BMI <36 kg/m(2), Epworth sleepiness scale ≥8, Friedman stage I or II. INTERVENTION: Surgical treatment with UPPP. The control group underwent UPPP after a delay of 6 months. OUTCOMES: Changes in AHI and other polysomnography parameters at baseline compared with the 6-month follow-up. RESULTS: All patients (32 in the intervention group and 33 in the control group) completed the trial. The mean (SD) AHI in the intervention group decreased significantly (p<0.001) by 60% from 53.3 (19.7) events/h to 21.1 (16.7) events/h . In the control group the mean AHI decreased by 11% from 52.6 (21.7) events/h to 46.8 (22.8) events/h, with a significant difference between the groups (p<0.001). The mean time in the supine position and the BMI were unchanged in both groups. Subgroup analyses for Friedman stage, BMI group and tonsil size all showed significant reductions in AHI in the intervention group compared with controls. There were no severe complications after surgery. CONCLUSIONS: This trial demonstrates the efficacy of UPPP in treating selected patients with OSAS with a mean reduction in AHI of 60% compared with 11% in controls, a highly significant and clinically relevant difference between the groups. TRIAL REGISTRATION NUMBER: NCT01659671.

15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data.

CONCLUSIONS: This follow-up showed a stable and significant decrease in median oxygen desaturation index 4% (ODI(4)) values over the years. Approximately two-thirds of the patients fulfilled the success criteria (ODI(4) reduction of 50% and <20) after 15 years. A majority had improved/cured excessive daytime sleepiness (EDS) and were satisfied. No increased mortality rate was seen. OBJECTIVES: To evaluate sleep apnoea recordings and symptoms in patients with obstructive sleep apnoea syndrome 15 years after uvulopalatopharyngoplasty (UPPP) compared to baseline and previous follow-ups. METHODS: This was a non-randomized, prospective intervention study on 50 patients who underwent UPPP during 1985-88. Their initial median age was 49 years (range 38-71) and ODI(4) was 26.5 (4-82). RESULTS: In all, 13 patients had died; 26 patients underwent sleep apnoea recordings. Median ODI(4) had decreased from 26.5 (range 4-82) to 8.5 (0-60), p < 0.01, a mean reduction of 52%; 65% of patients achieved the success criteria. One-third was objectively categorized as non-snorers. Median body mass index was unchanged. The questionnaires were answered by 32 of 37 patients; 88% reported improved or cured EDS and 78% were satisfied. Pharyngeal disturbances ratings were low. The standardized mortality rate did not differ from the general Swedish population.

Elective tracheostomy is an alternative treatment in patients with severe obstructive sleep apnoea syndrome and CPAP failure.

CONCLUSIONS: Elective tracheostomy with custom-made tubes was tolerated in a majority of patients with severe obstructive sleep apnoea syndrome (OSAS), as it reduced daytime symptoms and served as a link to other treatments. OBJECTIVES: To evaluate the tolerability of elective tracheostomy and changes in excessive daytime sleepiness and nocturnal oxygen desaturations (ODI) in patients with severe OSAS and obesity. PATIENTS AND METHODS: The medical records of 10 patients, median age 53.5 years (range 31-77), BMI 36 kg/m(2) (31-50), ODI 81 (55-126) during a 5-year period were reviewed. Inclusion criteria were failure of continuous positive airway pressure (CPAP), acceptance of tracheostomy, excessive daytime sleepiness and ODI > 50. All patients received a custom-made tube. Sleep apnoea recordings and questionnaires with Epworth sleepiness scale (ESS) were performed before and after tracheostomy. RESULTS: Eight of 10 patients tolerated the tube for more than 6 months. The ESS score was reduced from median 18 (range 8-23) to 5 (0-7) and the ODI values from 81 (55-126) to 13 (1-87). Two patients insisted on decannulation because they had nocturnal breathing problems, two underwent palatal surgery and were decannulated, and five still have their tubes. Severe cough, sputum infections and stoma granuloma were seen in all patients.