Update on hypoglossal nerve stimulation in children with down syndrome and obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Hypoglossal nerve (HGN) stimulation is a novel therapy for obstructive sleep apnea (OSA) in adults. Its efficacy and safety in children with Down syndrome (DS) was previously reported in a preliminary case series of six adolescents. STUDY DESIGN: Case series. METHODS: Twenty nonobese children and adolescents (aged 10-21 years) with DS and severe OSA (apnea-hypopnea index [AHI] >10 and <50 events/hr) despite prior adenotonsillectomy were enrolled. Participants had failed a trial of continuous positive airway pressure therapy and underwent sleep endoscopy confirming surgical candidacy. The primary outcome was to assess safety and monitor for adverse events. Secondary outcomes included efficacy in reducing AHI (% reduction in AHI), adherence to therapy, and change in a validated quality-of-life instrument, the OSA-18 survey. RESULTS: All 20 children (median age = 16.0 years [interquartile range = 13-17 years], 13 male) were implanted with no long-term complications. We report two interval adverse events, both of which were corrected with revision surgery. Twenty participants completed the 2-month polysomnogram, with median percent reduction in titration AHI of 85% (interquartile range = 75%-92%). The median nightly usage for these children was 9.21 hours/night. There was a median change in the OSA-18 score of 1.15, indicating a moderate, yet significant, clinical change. CONCLUSIONS: HGN stimulation was safe and effective in the study population. Two minor surgical complications were corrected surgically. Overall, these data suggest that pediatric HGN stimulation appears to be a safe and effective therapy for children with DS and refractory severe OSA. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E263-E267, 2020.

Perceptual Clinical Features in Exercise-Induced Laryngeal Obstruction (EILO): Toward Improved Diagnostic Approaches.

INTRODUCTION: Athletes with exercise-induced laryngeal obstruction (EILO) (previously commonly referred to as paradoxical vocal fold motion disorder, or paradoxical vocal fold motion, among other terms) are often misdiagnosed, resulting in prolonged, and at times inappropriate, clinical management. The high prevalence of misdiagnosis is largely due to a lack of universal consensus of key clinical features indicating EILO and a dearth of validated quantitative approaches to accurately detect episodic laryngeal breathing disorders (ELBD) from other pathologies. Additionally, mechanisms underlying EILO clinical presentation are poorly understood, further confounding identification and management of the condition. Therefore, the objectives of this study were twofold. The first was to identify patient-centered perception of symptoms that could distinguish adolescent athletes with EILO from athletes without the condition, at baseline (rest) and during an exercise challenge (provocation), and to quantify symptom severities for use as preliminary diagnostic benchmarks. The second objective was to investigate the merit of one commonly proposed mechanism in the EILO literature-stress reactivity (temperament)-by comparing personality traits in athletes with and without EILO. METHODS: Twelve (12) athletes diagnosed with EILO and 14 healthy athletic volunteers without the condition were asked to rate the severity of their present symptoms using a 0-100 continuous visual analog scale. Participants then underwent an exercise challenge with simultaneous laryngoscopy and were asked to complete the same set of symptom severity ratings experienced during rigorous exercise. Finally, participants completed the Fear subscale on the early adolescent temperament questionnaire-revised (EATQ-R) to measure self-perceived levels of stress reactivity. RESULTS: There were significant group differences for inspiratory and expiratory dyspnea with exercise (P = 0.01). Symptoms of stridor (EILO: P = .01; control: P = .001) and throat tightness (EILO: P = .01, control: P = .01) were statistically different between rest and exercise in both groups. However, no group differences were found on these two parameters (P > .05). Other symptoms from the list of previously purported symptoms indicative of ELBD (e.g. cough, dysphonia) were infrequently reported in the exercise variant. Additionally, measurements of stress reactivity on the EATQ-R Fear subscale were similar between the two athletic groups. Interestingly, EATQ-R Fear Subscale scores for both groups were significantly higher compared to typical adolescents in the U.S. population (P < .001, respectively). DISCUSSION: Results suggest dyspnea severity, particularly when experienced during an exercise-induced ELBD (EILO) episode, is the most sensitive symptom parameter to distinguish individuals with EILO from those without the condition. These findings confirm previous literature describing episodic laryngeal breathing disorders in clinical cohorts. Results also showed symptoms of throat tightness and stridor is more prevalent during exercise, compared to rest. However, the level of their severity occurred variably across both groups of athletes and may point to a less robust indication of pathology. Finally, similarities to stress reactivity between the two athletic groups imply certain temperaments historically attributed to patients with EILO may instead better reflect temperaments in competitive young athletes, in general. CONCLUSION: Study findings highlight the importance of using normative comparisons in the study of episodic laryngeal breathing disorders to prevent overgeneralization of characteristics to clinical cohorts. Results also speak of the clinical utility of exercise challenge to improve specificity of EILO diagnosis.

The Study of Laryngoscopic and Autonomic Patterns in Exercise-Induced Laryngeal Obstruction.

OBJECTIVES: (1) Identify laryngeal patterns axiomatic to exercise-induced laryngeal obstruction (EILO) and (2) investigate the role of autonomic function in EILO. METHODS: Twenty-seven athletic adolescents (13 EILO, 14 control) underwent laryngoscopy at rest and exercise. Glottal configurations, supraglottic dynamics, systolic blood pressure responses, and heart rate recovery were compared between conditions and groups. RESULTS: Inspiratory glottal angles were smaller in the EILO group than the control group with exercise. However, group differences were not statistically significant ( P > .05), likely due to high variability of laryngeal responses in the EILO group. Expiratory glottal patterns showed statistically greater abductory responses to exercise in the control group ( P = .001) but not the EILO group ( P > .05). Arytenoid prolapse occurred variably in both groups. Systolic blood pressure responses to exercise were higher in the control group, and heart rate recovery was faster in the EILO group. However, no significant differences were seen between the 2 groups on either autonomic parameter ( P > .05). CONCLUSIONS: "Paradoxical" inspiratory and blunted expiratory vocal fold pattern responses to exercise best characterize EILO. Group differences were only seen with exercise challenge, thus highlighting the utility of provocation and control groups to identify EILO.

Indirect vs Direct Voice Therapy for Children With Vocal Nodules: A Randomized Clinical Trial.

Importance: Benign vocal fold nodules affect 12% to 22% of the pediatric population, and 95% of otolaryngologists recommend voice therapy as treatment. However, no randomized clinical trials that we are aware of have shown its benefits. Objective: To determine the impact of voice therapy in children with vocal fold nodules according to pretherapy and posttherapy scores on the Pediatric Voice-Related Quality of Life (PVRQOL) survey; secondary objectives included changes in phonatory parameters. Design, Setting, and Participants: For this multicenter randomized clinical trial, 114 children ages 6 to 10 years with vocal fold nodules, PVRQOL scores less than 87.5, and dysphonia for longer than 12 weeks were recruited from outpatient voice and speech clinics. This age range was identified because these patients have not experienced pubertal changes of the larynx, tolerate stroboscopy, and cooperate with voice therapy. Participants were blinded to treatment arm. Interventions: Participants received either indirect or direct therapy for 8 to 12 weeks. Indirect therapy focused on education and discussion of voice principles, while direct treatment used the stimulus, response, antecedent paradigm. Main Outcomes and Measures: The primary outcome measure was PVRQOL score change before and after treatment. Secondary phonatory measures were also compared. Results: Overall, 114 children were recruited for study (mean [SD] age, 8 [1.4] years; 83 males [73%]); with 57 randomized to receive either indirect or direct therapy. Both direct and indirect therapy approaches showed significant differences in PVRQOL scores pretherapy to posttherapy. The mean increase in PVRQOL score for direct therapy was 19.2, and 14.7 for indirect therapy (difference, 4.5; 95.3% CI, -10.8 to 19.8). Of 44 participants in the direct therapy group, 27 (61%) achieved a clinically meaningful PVRQOL improvement, compared with 26 of 49 (53%) for indirect therapy (difference, 8%; 95% CI, -12 to 28). Post hoc stratification showed robust effects in the direct therapy group for older children (Cohen d = 0.50) and the latter two-thirds of participants (Cohen d = 0.46). Vocal fold nodules reduced in size in 31% (22 of 70) and completely resolved in 11% (8 of 70) of participants who consented to a second set of images after going through the recruitment process. Conclusions and Relevance: Both direct and indirect voice therapy improved voice-related quality of life in children with vocal fold nodules, although there was no significant difference between approaches. Future studies may focus upon which voice therapy approaches are effective in treating age-defined populations. Trial Registration: clinicaltrials.gov Identifier: NCT01255735.

Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea.

IMPORTANCE: Obstructive sleep apnea (OSA) affects up to 60% of children with Down syndrome (DS) and may persist in half of patients after adenotonsillectomy. Children with DS who have persistent OSA often do not tolerate treatment with positive pressure airway support devices or tracheotomy for their residual moderate to severe OSA. The hypoglossal nerve stimulator is an implantable device that delivers an electrical impulse to anterior branches of the hypoglossal nerve in response to respiratory variation, resulting in tongue base protrusion that alleviates upper airway obstruction in adults. OBJECTIVE: To determine whether hypoglossal nerve stimulation is safe and effective in children with DS. DESIGN, SETTING, AND PARTICIPANTS: Case series of the first 6 adolescents with DS to undergo hypoglossal nerve stimulator implantation. Participants were 6 children and adolescents (12-18 years) with DS and severe OSA (apnea hypopnea index [AHI] > 10 events/h) despite prior adenotonsillectomy. INTERVENTION: Inspire hypoglossal nerve stimulator placement. MAIN OUTCOMES AND MEASURES: Patients were monitored for adverse events. Adherence to therapy was measured by hours of use recorded by the device. Efficacy was evaluated by comparing AHI and OSA-18, a validated quality-of-life instrument, scores at baseline and follow-up. RESULTS: In 6 patients (4 male, 2 female; aged 12-18 years), hypoglossal nerve stimulator therapy was well tolerated (mean use, 5.6-10.0 h/night) and effective, resulting in significant improvement in OSA. At 6- to 12-month follow-up, patients demonstrated a 56% to 85% reduction in AHI, with an overall AHI of less than 5 events/h in 4 children and less than 10 events/h in 2 children. Children also demonstrated a clinically significant improvement (mean [SD] overall change score, 1.5 [0.6]; range, 0.9-2.3) on the OSA-18, a validated quality-of-life instrument. CONCLUSIONS AND RELEVANCE: Hypoglossal nerve stimulation was well tolerated and effective in the study population, representing a potential therapeutic option for patients with DS and refractory OSA after adenotonsillectomy who are unable to tolerate positive pressure airway devices. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT2344108.

Validation of the dyspnea index in adolescents with exercise-induced paradoxical vocal fold motion.

IMPORTANCE: Paradoxical vocal fold motion (PVFM) affects almost 1 million adolescents in the United States. However, to date, no disease-specific objective measure exists to assess symptom severity and response to treatment in adolescents with exercise-induced PVFM. OBJECTIVES: To validate the Dyspnea Index (DI) quality-of-life instrument (previously validated for adults with breathing disorders) in children aged 12 to 18 years with exercise-induced PVFM and to determine the minimum significant DI change corresponding to patient-reported or caregiver-reported improvement or worsening of symptoms. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal study of 56 patients (age range, 12-18 years) diagnosed as having exercise-induced PVFM and their caregivers from February 1, 2013, to September 30, 2013, in an outpatient pediatric otolaryngology office practice. INTERVENTIONS: The DI was administered to patients and caregivers, with items modified to reflect the perspective of caregivers. MAIN OUTCOMES AND MEASURES: Appropriate DI change was measured to reflect improvement or worsening of symptoms. Test-retest reliability was accomplished by having a subset of patients and caregivers complete the instrument twice within 2 weeks before therapy. Internal consistency was assessed by calculation of Cronbach α. Discriminant validity and convergent validity were determined by comparing DIs with assessment of global change in symptoms. RESULTS: The patient and caregiver mean (SD) DI changes were -12.9 (9.6) and -14.7 (9.3), respectively (P < .001 for both). Reliability was established by test-retest analysis with an intraclass correlation coefficient of 0.8 and by calculation of Cronbach α = 0.80, demonstrating internal consistency. Discriminant validity was determined by assessing for a significant DI change when patients globally perceived that a change existed after treatment (P < .001). A DI change of 8 or higher (P < .001) correlated with patient-reported significant change. Convergent validity was demonstrated by evaluating for significant DI change when no change was reported following treatment (P < .001). CONCLUSIONS AND RELEVANCE: The DI appears to be a valid and reliable instrument to assess quality of life in exercise-induced pediatric PVFM. A DI change of 8 or higher seems significant. This instrument can serve as an objective tool to assess change in exercise-induced pediatric PVFM following speech therapy.