Correlations between objective and subjective outcomes after adenotonsillar surgery in children with OSA.

Objectives: To investigate whether the OSA-18 questionnaire and a postoperative patient-reported outcome measure (PROM) question correlated with polysomnography (PSG) data. Methods: A prospective study of otherwise healthy young children with moderate to severe obstructive sleep apnea (OSA) to investigate if the obstructive apnea-hypopnea index (OAHI) before and 6-12 months after adenotonsil surgery correlated with the OSA-18 total symptom score (TSS) and the sleep disturbance subscale (SDS), as well as a PROM question on symptom improvement with responses on a 4-grade Likert scale. Results: Of 201 children, 173 (86%) had complete data of OAHI and OSA-18 pre- and postoperatively. The mean age was 3.2 years (SD 1.0) and the mean OAHI was 15.9 (11.3). Significant correlations between changes in the OAHI and OSA-18 were found, both TSS (r = 0.29, p < .001) and SDS (r = 0.53, p < .001). A total of 136 (68%) patients responded to the PROM question, the majority of whose symptoms had disappeared (n = 102) or almost disappeared (n = 30). Four patients had unchanged symptoms, and none had worsening symptoms. A correlation was found between the PROM question and a change in the OAHI (r = 0.36, p < .001), as well as a change in the OSA-18 TSS (r = 0.24, p = .006) and the SDS (r = 0.34, p < .001). The specificity of the PROM question for prediction of a postoperative OAHI < 2 was 82%, and the sensitivity was 38%. Conclusion: Changes in the OAHI significantly correlated with changes in the OSA-18, especially with the sleep disturbance scale, which could be an alternative for evaluation at follow-ups. Level of Evidence: 3.

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.

The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea.

Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naïve CD27-CD21hi B cells and a relative reduction of ILCs. The enrichment of naïve B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.

Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue.

Cross-reactive CD4+ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2­reactive CD8+ T cells. However, large numbers of memory CD8+ T cells reside in tissues, feasibly harboring localized SARS-CoV-2­specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19 (coronavirus disease 2019). We found that SARS-CoV-2­specific memory CD4+ T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2­specific memory CD8+ T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2­specific memory CD8+ T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus­specific memory CD8+ T cells, but were functionally less potent than other virus-specific memory CD8+ T cell responses. The presence of preexisting tissue-resident memory CD8+ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.

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.

Postoperative morbidity after adenotonsillectomy versus adenopharyngoplasty in young children with obstructive sleep apnea: an RCT.

PURPOSE: In our previous randomized controlled trial (RCT), comparing adenotonsillectomy (ATE) with adenopharyngoplasty (APP) in children with severe obstructive sleep apnea (OSA), there were no differences in respiratory sleep parameters or quality of life. The purpose of the present report was to evaluate postoperative morbidity from this RCT. METHODS: The study was a blinded RCT in 83 children (ATE = 47; APP = 36), 2-4 years of age, with an obstructive apnea-hypopnea index of ≥ 10. Pain was assessed from the first until the tenth day after surgery with a logbook that reported pain by child (FPS-R, Faces Pain Scale-Revised) and caregiver (visual analogue scale), analgesic use, return to normal diet, and weight change. Bleeding, infection, satisfaction with treatment, speech, and swallowing were assessed with a questionnaire and medical records 6 months after surgery. RESULTS: Sixty-four children (77%) returned the logbook and 65 (78%) answered the questionnaire. The median (interquartile range) day the children graded themselves as pain free (FPS-R = 0) was 7 (6-10) after ATE, compared with 9 (7 to > 10) after APP (p = 0.018). There were no other significant differences between the groups regarding any other pain-related outcomes, bleeding, infection, satisfaction, swallowing, or speech, but three children (11%) reported impaired speech after APP compared to none after ATE (p = 0.067). CONCLUSION: The results regarding postoperative morbidity were in favor of ATE and the results from our previous report showed no advantages of APP. Therefore, APP should not be recommended in young, otherwise healthy children with OSA.

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.

Adenopharyngoplasty vs Adenotonsillectomy in Children With Severe Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Adenotonsillectomy (ATE) is the primary surgical method for treating obstructive sleep apnea (OSA) in children. However, children with severe OSA have an increased risk for residual OSA after ATE. Previous studies indicate that adenopharyngoplasty (APP), a modified ATE with closure of the tonsillar pillars, might improve the surgical outcome, but the overall evidence is weak. Objective: To determine whether APP is more effective than ATE for treating severe OSA in otherwise healthy children. Design, Setting, and Participants: A blinded randomized clinical trial was conducted at the otorhinolaryngology department at Karolinska University Hospital, Stockholm, Sweden. Eighty-three children, aged 2 to 4 years, with an obstructive apnea-hypopnea index (OAHI) score of 10 or higher, were randomized to APP (n = 36) or ATE (n = 47). Participants were recruited from December 1, 2014, through November 31, 2016. Interventions: Adenotonsillectomy was performed in all 83 patients in both groups by the cold steel technique. The APP group also underwent closure of the tonsillar pillars with 2 inverted sutures on each side. Main Outcomes and Measures: The primary outcome was the difference between the groups in OAHI score change before and after surgery. A higher score indicates worse problems and a score of 10 or higher is defined as severe OSA. The outcome was evaluated per protocol and with intention-to-treat analysis. Secondary outcomes were other polysomnography variables and the Obstructive Sleep Apnea-18 (OSA-18) questionnaire (possible total symptom score range, 18-126; higher scores indicate worse quality of life). Polysomnography was performed and the OSA-18 questionnaire was completed preoperatively and 6 months postoperatively. Results: A total of 83 children (49 [59%] boys; mean [SD] age, 36.6 [9.2] months) were included in the study. Of these, 74 (89%) (APP, n = 30; ATE, n = 44) completed the study. The mean (SD) preoperative OAHI score was 23.8 (11.8) for APP and 23.8 (11.5) for ATE. Both the APP and ATE groups had a significant decrease in mean OAHI score after surgery (-21.7; 95% CI, -26.3 to -17.2; and -21.1; 95% CI, -24.5 to -17.7, respectively), but there was no significant difference between the groups (0.7; 95% CI, -4.8 to 6.1). Furthermore, no significant differences between the groups were seen regarding other polysomnography variables (eg, respiratory distress index: mean, 0.6; 95% CI, -5.0 to 6.3) or the OSA-18 questionnaire (eg, total symptom score: -0.5; 95% CI, -13 to 12). One patient from each group was readmitted owing to postoperative bleeding, but no other complications were seen. Conclusions and Relevance: This trial did not show that APP was more effective than ATE alone to treat otherwise healthy children with severe OSA. This finding suggests that ATE should continue to be the primary treatment for OSA in children. Trial Registration: ClinicalTrials.gov Identifier: NCT02315911.

Low inter-examiner agreement of the Friedman staging system indicating limited value in patient selection.

PURPOSE: The Friedman staging system is a clinical method for selecting patients with obstructive sleep apnoea who are likely to benefit from uvulopalatopharyngoplasty. The objective of this study was to evaluate the system by determining its inter-examiner agreement. METHODS: Twelve patients with obstructive sleep apnoea were examined by 14 doctors. The Friedman stage was derived from tonsil size and tongue position, and a Cohen's kappa analysis was performed to assess inter-examiner agreement. RESULTS: One hundred and sixty-eight ratings were performed. The median kappa for tongue position was 0.32 (first and third quartiles: 0.21 and 0.44) and was 0.62 (0.50 and 0.63) for tonsil size. The median kappa for the Friedman stage was 0.38 (0.24 and 0.55), which corresponds to only a slight or fair agreement. CONCLUSION: The Friedman staging system demonstrated a low inter-examiner agreement, indicating that the system is an uncertain method for selecting patients for uvulopalatopharyngoplasty. LEVEL OF EVIDENCE: 2B.

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.