Association Between Soft Tissue Measures From Computed Tomography and Upper Airway Collapsibility on Drug-Induced Sleep Endoscopy.

OBJECTIVE: Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility. STUDY DESIGN: Cross-sectional analysis from a prospective cohort. SETTING: Academic medical center. METHODS: Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, PcritA) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either PcritA or PhOP. RESULTS: One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m2), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or PcritA, but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive PcritA (⍴ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures. CONCLUSION: After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis.

The Effect of Surgical Therapy for Obstructive Sleep Apnea on Blood Pressure and Peripheral Arterial Tonometry.

OBJECTIVE: To determine the effect of upper airway surgery on cardiovascular function in patients with obstructive sleep apnea (OSA). STUDY DESIGN: A prospective, self-controlled study from 2018 to 2023. SETTING: Two academic medical centers. METHODS: Seventy-four patients underwent surgery for OSA, including: tonsillectomy, adenoidectomy, epiglottidectomy, modified uvulopalatopharyngoplasty, maxillary expansion, and maxillomandibular advancement. Twenty-four-hour ambulatory blood pressure (BP), peripheral arterial tonometry (PAT)-based home sleep study, and sleep-related patient-reported outcomes (PROs) were captured preoperatively and at 6 months postoperatively. Paired T-tests evaluated changes in outcomes after surgery. RESULTS: Forty-one patients successfully completed preoperative and postoperative assessments. Patients were generally middle-aged (43.8 ± 12.5 years), obese (BMI 33.0 ± 5.8 kg/m2), male (68%), White (71%), and had severe OSA (apnea-hypopnea index [AHI] 33.9 ± 29.5 events/h). The 4% oxygen desaturation index (ODI) decreased from 30.7 ± 27.1 to 12.2 ± 13.6 events/h (P < .01) after surgery. There was no significant difference in 24-h BP following surgery, though clinically meaningful reductions in nocturnal systolic (-1.95 [-5.34, 1.45] mmHg) and nocturnal diastolic (-2.30 [-5.11, 0.52] mmHg) blood pressure were observed. Stratified analysis showed patients undergoing skeletal surgery (n = 17) demonstrated larger average reductions compared to those undergoing soft tissue surgery in nocturnal systolic (-4.12 [-7.72, -0.51] vs -0.10 [-5.78, 5.58] mmHg) and nocturnal diastolic (-3.94 [-7.90, 0.01] vs -0.90 [-5.11, 3.31] mmHg) pressures. No meaningful changes were observed in PAT Autonomic Index (PAI) measurements. CONCLUSION: Surgical therapy for OSA did not demonstrate statistically significant improvements in 24-h BP. However, clinically meaningful reductions in nocturnal BP were observed, particularly in skeletal surgery patients, supporting the need for larger studies of cardiovascular outcomes following OSA surgery.

Hypoglossal Nerve Stimulation and Cardiovascular Outcomes for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA). Objective: To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function. Design, Setting, and Participants: This double-blind, sham-controlled, randomized crossover therapy trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the trial. Data analysis was performed from January to September 2022. Interventions: Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values. Main Outcomes and Measures: The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points. Results: Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment. Conclusions and Relevance: In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03359096.

Airway Collapsibility during Drug-Induced Sleep Endoscopy Relates with Clinical Features of Obstructive Sleep Apnea.

INTRODUCTION: Increased pharyngeal collapsibility leads to obstructive sleep apnea (OSA). Positive airway pressure titration during drug-induced sleep endoscopy (DISE-PAP) provides objective collapsibility metrics, the pharyngeal opening pressure (PhOP), and active pharyngeal critical pressure (PcritA ). We examined the interrelationships between risk factors of OSA, airway collapsibility measures, and clinical manifestations of the disease. METHODS: This is a cross-sectional analysis of consecutive OSA patients undergoing DISE-PAP. Nasal PAP was increased stepwise until inspiratory flow limitation was abolished, signifying PhOP. PcritA was derived from the resulting titration pressure-flow relationships. Clinical data including demographics, anthropometrics, sleep studies, and patient-symptom questionnaires were obtained from the electronic medical record. Multivariate regression was used to evaluate the relationship between risk factors, airway collapsibility, and clinical data. RESULTS: On average, the 164 patients meeting inclusion criteria were middle-aged (54.2 ± 14.7 years), overweight/obese (BMI 29.9 ± 4.5 kg/m2 ), male (72.6%), White (79.3%) and had severe OSA (AHI 32.0 ± 20.5 events/hour). Mean PhOP was 7.5 ± 3.3 cm H2 O and mean PcritA was 0.80 ± 3.70 cm H2 O. Younger age (Standardized ß = -0.191, p = 0.015) and higher BMI (Standardized ß = 0.176, p = 0.028) were associated with higher PhOP, but not PcritA . PhOP and PcritA were both associated with AHI, supine AHI, and SpO2 nadir. Higher PhOP was associated with higher snoring scores (Standardized ß = 0.246, p = 0.008), but not other patient-reported outcomes. CONCLUSION: Objective assessment of passive and active airway mechanics during DISE relates with clinical risk factors for OSA. Quantitative measures of collapsibility provide accessible and meaningful data, enhancing the standard sleep surgery evaluation. LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.

Transverse Maxillary Deficiency Predicts Increased Upper Airway Collapsibility during Drug-Induced Sleep Endoscopy.

OBJECTIVE: To examine the relationship between craniofacial skeletal anatomy and objective measures of pharyngeal collapse obtained during drug-induced sleep endoscopy. We hypothesized that transverse maxillary deficiency and an increased pharyngeal length will be associated with higher levels of pharyngeal collapsibility. STUDY DESIGN: Cross-sectional analysis in a prospective cohort. SETTING: University Hospital. METHODS: A cross-sectional analysis was conducted in a cohort of consecutive patients from the positive airway pressure (PAP) alternatives clinic who underwent computed tomography (CT) analysis and drug-induced sleep endoscopy for characterization of upper airway collapsibility. PAP titration was used to determine pharyngeal critical pressure (PCRIT ) and pharyngeal opening pressure (PhOP). CT metrics included: Transverse maxillary dimensions (interpremolar and intermolar distances) and pharyngeal length (posterior nasal spine to hyoid distance). RESULTS: The cohort (n = 103) of severe obstructive sleep apnea (Apnea and Hipopnea Index 32.1 ± 21.3 events/h) was predominantly male (71.8%), Caucasian (81.6%), middle-aged (54.4 ± 14.3 years), and obese (body mass index [BMI] = 30.0 ± 4.9 kg/m2 ). Reduced transverse maxillary dimensions were associated with higher PCRIT (intermolar distance: ß [95% confidence interval, CI] = -.25 [-0.14, -0.36] cmH2 O/mm; p = .03) and PhOP (Interpremolar distance: ß = -.25 [-0.14, -0.36] cmH2 O/mm; p = .02). Longer pharyngeal length was also associated with higher PCRIT (ß = .11 [0.08, 0.14] cmH2 O/mm, p = .04) and PhOP (ß [95% CI] = .06 [0.03, 0.09] cmH2 O/mm, p = .04). These associations persisted after adjustments for sex, age, height, and BMI. CONCLUSION: Our results further the concept that skeletal restriction in the transverse dimension and hyoid descent are associated with elevations in pharyngeal collapsibility during sleep, suggesting a role of transverse deficiency in the pathogenesis of airway obstruction.

The Accuracy and Reliability of Visually Assessed Pharyngeal Opening Pressures During Drug-Induced Sleep Endoscopy.

OBJECTIVE: To examine the accuracy and interrater reliability of a visually assessed vs airflow-based measure of pharyngeal collapsibility obtained in patients with obstructive sleep apnea undergoing drug-induced sleep endoscopy (DISE). STUDY DESIGN: Prospective observational study. SETTING: Academic tertiary care practice. METHODS: Patients underwent DISE with airflow monitoring and nasal positive airway pressure titration to determine visual and airflow-based levels of pharyngeal opening pressure (PhOP). Visual DISE-PhOP was assessed by 2 blinded independent raters and defined as the pressure at which visual confirmation of airway collapse, including snoring, was abolished. Airflow-based DISE-PhOP was defined as the minimally effective positive airway pressure that abolished inspiratory flow limitation. Equivalence testing between visual and airflow DISE-PhOP of each rater was performed with the two one sided T-test (TOST) with an a priori equivalence bound of ±1 cm H2 O. Interrater reliability was evaluated with the intraclass correlation coefficient. RESULTS: One hundred patients were enrolled in the study and 77 completed the full evaluation. The population was predominantly male (74%) with an average age of 54.8 years, body mass index of 30.1 kg/m2 , and apnea-hypopnea index of 30.7 events/h. Equivalence testing showed that both raters were within ±1 cm H2 O of airflow-based DISE-PhOP (-0.43 to 0.09 cm H2 O and -0.32 to 0.48 cm H2 O). Interrater reliability of visual DISE-PhOP between the raters was also good to excellent with an intraclass correlation coefficient of 0.895 (95% CI, 0.84-0.932). CONCLUSION: DISE-PhOP, a measure of upper airway collapsibility, was equivalent between airflow-based and visual assessments with strong interrater reliability, supporting its adoption as a standardized objective parameter in clinical DISE.

Enhanced drug-induced sleep endoscopy: Distinguishing central from obstructive apnea.

This case report describes a patient originally diagnosed with obstructive sleep apnea (OSA) who was later found to have central sleep apnea (CSA) during drug-induced sleep endoscopy, which was subsequently confirmed on an in-laboratory sleep study. The revised diagnosis resulted in a change in recommended therapy from hypoglossal nerve stimulation to phrenic nerve stimulation. This case report is a reminder that the sleep surgeon must be cognizant of the possibility of CSA being misclassified as OSA especially as home sleep studies become increasingly routine, and discusses ways to more easily distinguish between CSA and OSA. Laryngoscope, 133:706-708, 2023.

Beyond VOTE: The New Frontier of Drug-Induced Sleep Endoscopy.

Alternatives to positive airway pressure therapy, including surgery, represent an important area of research. Specifically, predictors of response to surgical therapy remain underdeveloped. Drug-induced sleep endoscopy (DISE) holds promise as a diagnostic tool to identify patient-specific causes of airway collapse. Herein, we present a novel, standardized approach which combines anatomic and physiologic measurements during DISE. Our DISE platform measures airflow, airway compliance, airway collapsibility, and structural drivers of collapse. Taken together, these inputs provide a comprehensive framework to further inform the surgeon in providing personalized care of the patient with obstructive sleep apnea.

Influence of apnea vs hypopnea predominance in predicting mean therapeutic positive airway pressures among patients with obstructive sleep apnea.

STUDY OBJECTIVES: Lower therapeutic positive airway pressure (PAP) levels are associated with improved response to non-PAP therapies in the treatment of obstructive sleep apnea. The aim of this study was to evaluate the prevailing notion that patients with apnea-predominant obstructive sleep apnea require higher therapeutic PAP levels compared to patients with hypopnea-predominant obstructive sleep apnea. METHODS: An institutional review board-approved retrospective review was performed using strict inclusion criteria: presence of type I or III sleep study, apnea-hypopnea index > 10 events/h, and adherence to auto-adjusting continuous positive airway pressure. Patients were stratified by apnea (> 50% apneas) or hypopnea (≤ 50% apneas) predominance, and PAP data were compared. Statistical analyses were performed using Student's t test and linear regression modeling. RESULTS: Between January 1, 2018 and January 1, 2020, 500 patients met inclusion criteria. Two hundred twenty-one (44.1%) patients were apnea-predominant and 279 (55.8%) were hypopnea-predominant. Apnea-predominant patients had a slightly greater mean PAP (9.01 vs 8.36, P = .002) than hypopnea-predominant patients. Univariable and multivariable linear regression of 7 variables (obstructive apnea percentage, age, sex, body mass index, apnea-hypopnea index, O2 nadir, mask type) showed obstructive apnea percentage was the weakest predictor of therapeutic PAP levels. CONCLUSIONS: Apnea-predominant individuals demonstrated a clinically insignificant difference in PAP level compared to hypopnea-predominant individuals; moreover, obstructive apnea percentage was not a strong predictor of therapeutic PAP levels. Of the modeled variables, the strongest predictor of PAP level was apnea-hypopnea index. Further studies are needed to explore these relationships as well as additional variables that may contribute to predicting therapeutic PAP levels. CITATION: Yu JL, Liu Y, Tangutur A, et al. Influence of apnea vs hypopnea predominance in predicting mean therapeutic positive airway pressures among patients with obstructive sleep apnea. J Clin Sleep Med. 2021;17(11):2171-2178.

Clinical Radiographic Predictors of Response to Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To determine if clinically acquired cephalometric measurements, specifically soft palate size, can predict hypoglossal nerve stimulation outcomes. STUDY DESIGN: Combined prospective cohort study and retrospective review. SETTING: US sleep otolaryngology training program. METHODS: Adults with obstructive sleep apnea and apneahypopnea index greater than 15 events/h who underwent hypoglossal nerve stimulation. Eligible subjects had diagnostic preoperative sleep studies and full-night efficacy postoperative studies for analysis. Lateral neck x-rays were obtained as part of routine clinical care and measured for key cephalometric variables by trained head and neck radiologists. Continuous variables were compared using the Student t test, while χ2 testing was used for categorical variables. RESULTS: Fifty-one patients met all study criteria. On average, patients were white, middle aged, and overweight. Following hypoglossal nerve stimulation, the overall cohort achieved a significant apnea-hypopnea index reduction from 36.7 events/h to 20.6 events/h (P < .01) and a response rate of 47% (defined as apnea-hypopnea index reduction >50% and apnea-hypopnea index <20 events/h). On average, therapy responders had significantly thinner soft palates than nonresponders (13.4 ± 3.8 mm vs 16.0 ± 3.4 mm, P = .045). CONCLUSIONS: Patient-specific anatomic factors, specifically soft palate thickness, may help identify optimal candidates for hypoglossal nerve stimulation. A larger, prospective study including both anatomic and physiologic variables is required to validate these findings.

Evaluation of Therapeutic Positive Airway Pressure as a Hypoglossal Nerve Stimulation Predictor in Patients With Obstructive Sleep Apnea.

Importance: Recent retrospective hypoglossal nerve stimulation (HGNS) outcomes data suggest that patients with low therapeutic positive airway pressure (PAP) levels achieve greater success than patients with high therapeutic PAP levels. Objective: To examine the use of therapeutic nasal PAP levels at the soft palate in predicting the outcomes of HGNS for patients with obstructive sleep apnea. Design, Setting, and Participants: This prospective cohort study used drug-induced sleep endoscopy (DISE) to evaluate the predictive capacity of therapeutic PAP levels in HGNS outcomes. In an academic sleep surgery center, 27 consecutive patients with obstructive sleep apnea who underwent DISE before implantation of an HGNS device were evaluated. The study was conducted from May 1, 2018, to June 26, 2019. Exposures: Positive airway pressure delivered through a nasal mask during DISE. Main Outcomes and Measures: Improvement in apnea-hypopnea index as measured from full-night preoperative and postoperative efficacy studies. Results: Twenty-seven patients met all inclusion criteria. The mean (SD) age was 62.0 (14.4) years, 14 participants were men (51.9%), and mean body mass index was 28.1 (4.0). Responders to HGNS therapy (n = 18) had significantly lower mean (SD) palatal opening pressure compared with nonresponders (n = 9) (5.0 [2.8] vs 9.2 [3.7] cm H2O, respectively; mean difference, -4.2; 95% CI, -6.8 to -1.6 cm H2O). After adjusting for age, sex, and body mass index, the mean palatal opening pressure value for the responders remained 3.5 cm H2O lower (95% CI, -6.7 to -0.4 cm H2O) than that of nonresponders. A palatal opening pressure cutoff level less than 8 cm H2O demonstrated a positive predictive value of 82.4%; sensitivity, 77.8%; and specificity, 66.7%. Conclusions and Relevance: In this small prospective cohort study, therapeutic nasal PAP levels during DISE differed significantly between responder and nonresponders to HGNS. Because DISE represents a mandatory, relatively standardized diagnostic tool for HGNS candidacy, the use of therapeutic nasal PAP through DISE can be broadly implemented and studied across multiple centers to possibly improve patient selection for HGNS.

Upper airway surgery to rescue the "untitratable" patient with OSA and obesity.

None: This is a case report of an 41-year-old male with obesity (body mass index 90 kg/m²), severe obstructive sleep apnea (OSA), and an apnea-hypopnea index of 90 events/h despite high bilevel positive airway pressure (BPAP). He presented to the PAP Alternatives Clinic and underwent tonsillectomy, expansion sphincter pharyngoplasty, and partial uvulectomy to improve positive airway pressure effectiveness. Postoperative BPAP retitration resolved the patient's OSA. The patient is currently using BPAP therapy at home with improvement in both objective and self-reported OSA outcomes.

Therapeutic Positive Airway Pressure Level Predicts Response to Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

STUDY OBJECTIVES: To determine whether therapeutic positive airway pressure (PAP) level predicts response to hypoglossal nerve stimulation (HGNS) for obstructive sleep apnea using the coprimary outcomes of apnea-hypopnea index (AHI) and 4% oxygen desaturation index. METHODS: Combined cohort study from two US sleep otolaryngology training programs. Subjects were adults with AHI > 15 events/h who underwent HGNS. Eligible subjects had diagnostic preoperative sleep studies, full-night efficacy postoperative studies and therapeutic PAP levels available for analysis. Low and high PAP groups were compared using the t test for continuous variables and chi-square test for categorical variables. RESULTS: Fifty-six patients met all inclusion criteria. On average, patients were male, Caucasian, middle-aged, and overweight. Thirteen patients were in the low PAP group (< 8 cm H2O) and 43 patients in the high PAP group (≥ 8 cm H2O). Although both groups experienced improvement of polysomnographic measures with HGNS, the low PAP group achieved a significantly larger mean AHI reduction (36.7 ± 22.7 versus 18.4 ± 23.4, P = .02). Additionally, the low PAP group had a greater response rate (defined as AHI < 20 events/h and > 50% reduction of AHI) than the high PAP group (92% versus 44%, P < .01). CONCLUSIONS: Therapeutic PAP level may aid in the discernment of candidacy for HGNS, with a strong positive predictive value for PAP levels < 8 cm H2O. A larger prospective study is needed to confirm these findings. CITATION: Lee CH, Seay EG, Walters BK, Scalzitti NJ, Dedhia RC. Therapeutic positive airway pressure level predicts response to hypoglossal nerve stimulation for obstructive sleep apnea. J Clin Sleep Med. 2019;15(8):1165-1172.

IMAGES: Drug-Induced Sleep Endoscopy: An Investigative Tool for Mechanisms of PAP Failure.

ABSTRACT: This is a case report of a 60-year-old female with mild obstructive sleep apnea (OSA) who presented to CPAP Alternatives clinic following multiple failed attempts at positive airway pressure (PAP) therapy. She underwent drug-induced sleep endoscopy (DISE) with the concurrent application of PAP via two different mask types. Application of the oronasal mask at low pressures demonstrated soft palate collapse, while high pressures resulted in posterior tongue collapse. In contrast, application of the nasal mask eliminated palatal and tongue obstruction at low pressures, despite mask leak at higher pressures. She was recommended a trial of nasal autoPAP, which with the use of a chinstrap, resulted in both subjective and objective improvement of her OSA.