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Importance: Drug-induced sleep endoscopy (DISE) is used to guide therapeutic management of obstructive sleep apnea (OSA), depending on the levels and patterns of pharyngeal collapse. However, the collapsibility of specific pharyngeal sites remains unknown., Objective: To assess collapse sites in patients with OSA undergoing DISE and whether number and location are associated with differences in airway collapsibility; and to quantify differences in collapsibility between primary and secondary sites in multilevel collapse., Design, Setting, and Participants: This cohort study assessed adult patients (≥18 years) with OSA undergoing DISE with manometry and positive airway pressure (PAP) titration at a tertiary care center from November 2021 to November 2023. Patients with an AHI score greater than 5 were included; those with less than 1 apnea event during DISE or incorrect catheter placement were excluded. Data were analyzed from September 28, 2022, to March 31, 2024., Exposure: DISE with manometry and PAP titration., Main Outcomes and Measures: Active pharyngeal critical pressure (Pcrit-A) and pharyngeal opening pressure (PhOP) were used to quantify airway collapsibility, adjusted for covariates (age, sex, race, and body mass index [BMI])., Results: Of 94 screened, 66 patients (mean [SD] age, 57.4 [14.3] years; BMI, 29.2 [3.9]; 51 [77.3%] males) with a mean (SD) apnea-hypopnea index (AHI) of 31.6 (19.0) were included in the analysis. Forty-seven patients (71.2%) had multilevel collapse, 10 (15.2%) had single-level nasopalatal collapse, and 9 (13.6%) had single-level infrapalatal collapse. Groups did not differ in demographic characteristics or established measures of OSA severity. The single-level nasopalatal group had substantially elevated levels of airway collapsibility (Pcrit-A and PhOP covariate adjusted mean, 2.4; 95% CI, 1.1 to 3.8; and 8.2; 95% CI, 6.4 to 9.9 cmH2O) compared to the single-level infrapalatal group (-0.9; 95% CI, -2.4 to 0.5 cmH2O; and 4.9; 95% CI, 3.0 to 6.8 cmH2O, respectively) and similar to the level among the multilevel group (1.3; 95% CI, 0.7 to 2.0; and 8.5; 95% CI, 7.7 to 9.3 cmH2O). The multilevel group had more negative inspiratory pressure (-24.2; 95% CI, -28.1 to -20.2 cmH2O) compared to the single-level nasopalatal group (-9.8; 95% CI, -18.3 to -1.28 cmH2O). In patients with multilevel collapse, airway collapsibility was significantly higher at the primary nasopalatal compared to secondary infrapalatal site (mean difference, 13.7; 95% CI, 11.3 to 16.1 cmH2O)., Conclusions and Relevance: The findings of this cohort study suggest that intervention should target the primary site of pharyngeal collapse, and secondary sites only if they are nearly as collapsible as the primary site. Future work is needed to precisely define the difference in primary and secondary collapsibility that necessitates multilevel treatment.

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, Pcrit A ) 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 Pcrit A 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/m 2 ), 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 Pcrit A , but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive Pcrit A (⍴ = 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., (© 2024 The Authors. Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

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 (P CRIT ) 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/m 2 ). Reduced transverse maxillary dimensions were associated with higher P CRIT (intermolar distance: β [95% confidence interval, CI] = -.25 [-0.14, -0.36] cmH 2 O/mm; p = .03) and PhOP (Interpremolar distance: β = -.25 [-0.14, -0.36] cmH 2 O/mm; p = .02). Longer pharyngeal length was also associated with higher P CRIT (β = .11 [0.08, 0.14] cmH 2 O/mm, p = .04) and PhOP (β [95% CI] = .06 [0.03, 0.09] cmH 2 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., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Hypoglossal nerve stimulation (HNS) is an alternative treatment option for obstructive sleep apnea (OSA) that reduces pharyngeal collapsibility, but HNS nonresponders often demonstrate continued retropalatal and lateral pharyngeal wall collapse. Recent evidence suggests that caudal pharyngeal traction with sternothyroid muscle contraction via ansa cervicalis stimulation (ACS) can also stabilize the pharynx, but the underlying mechanisms have not been elucidated. Our objective was to evaluate the effect of ACS on pharyngeal patency during expiration when the airway is most hypotonic. Eight participants with OSA underwent sustained ultrasound-guided fine-wire stimulation of the medial branch of the right hypoglossal nerve with and without transient stimulation of the branch of the ansa cervicalis nerve plexus innervating the right sternothyroid muscle during drug-induced sleep endoscopy. Airway cross-sectional area and expiratory airflow (V̇e) were measured from endoscopy video with ImageJ and pneumotachometry, respectively. ACS significantly increased retropalatal cross-sectional area (CSA RP ) to 211% [159-263] of unstimulated CSA RP ( P < 0.05). Adding ACS to HNS increased CSA RP from baseline by 341% [244-439] ( P < 0.05), a 180% [133-227] increase over isolated HNS ( P < 0.05). ACS increased V̇e from baseline by 177% [138-217] P < 0.05). Adding ACS to HNS increased V̇e by 254% [207-301], reflecting decreases in pharyngeal collapsibility. Combining ACS with HNS increased retropalatal cross-sectional area and increased expiratory airflow, suggesting decreases in pharyngeal collapsibility. Our findings suggest that ACS exerts caudal traction on the upper airway through sternothyroid muscle contraction and that it may augment HNS efficacy in patients with OSA. NEW & NOTEWORTHY Ansa cervicalis stimulation (ACS) is a recently proposed neurostimulation mechanism for generating caudal pharyngeal traction that may benefit patients with obstructive sleep apnea. Here, we document endoscopic findings with ACS during drug-induced sleep endoscopy and additionally detail the effects of ACS on expiratory airflow, when the pharynx is known to be most hypotonic.

Background: Hypoglossal nerve stimulation (HNS) is an alternative treatment option for patients with OSA unable to tolerate positive airway pressure but implant criteria limit treatment candidacy. Previous research indicates that caudal tracheal traction plays an important role in stabilizing upper airway patency., Research Question: Does contraction of the sternothyroid muscle with ansa cervicalis stimulation (ACS), which pulls the pharynx caudally via thyroid cartilage insertions, increase maximum inspiratory airflow (V I max)?, Study Design and Methods: Hook-wire percutaneous electrodes were used to stimulate the medial branch of the right hypoglossal nerve and right branch of the ansa cervicalis innervating the sternothyroid muscle during propofol sedation. V I max was assessed during flow-limited inspiration with a pneumotachometer., Results: Eight participants with OSA were studied using ACS with and without HNS. Compared with baseline, the mean V I max increase with isolated ACS was 298%, or 473 mL/s (95% CI, 407-539). Isolated HNS increased mean V I max from baseline by 285%, or 260 mL/s (95% CI, 216-303). Adding ACS to HNS during flow-limited inspiration increased mean V I max by 151%, or 205 mL/s (95% CI, 174-236) over isolated HNS. Stimulation was significantly associated with increase in V I max in both experiments (P < .001)., Interpretation: ACS independently increased V I max during propofol sedation and drove further increases in V I max when combined with HNS. The branch of the ansa cervicalis innervating the sternothyroid muscle is easily accessed. Confirmation of the ansa cervicalis as a viable neurostimulation target may enable caudal pharyngeal traction as a novel respiratory neurostimulation strategy for treating OSA., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6-8 weeks genioglossus EMG and dynamic MRI of the upper airway were performed before and after administration of the DREADD ligand clozapine-N-oxide (CNO) or vehicle (saline). In DREADD-treated mice, CNO activated the genioglossus muscle and markedly dilated the pharynx, whereas saline had no effect. Control virus treated mice showed no effect of CNO. Our results suggest that chemogenetic approach can be considered as a treatment option for OSA and other motorneuron disorders.

Respiratory stimulation (RS) during sleep often fails to discontinue flow limitation, whereas electrical stimulation (ES) of the hypoglossus (HG) nerve frequently prevents obstruction. The present work compares the effects of RS and HG-ES on pharyngeal mechanics and the relative contribution of tongue muscles and thoracic forces to pharyngeal patency. We determined the pressure-area relationship of the collapsible segment of the pharynx in anesthetized pigs under the following three conditions: baseline (BL), RS induced by partial obstruction of the tracheostomy tube, and HG-ES. Parameters were obtained also after transection of the neck muscles and the trachea (NMT) and after additional bilateral HG transection (HGT). In addition, we measured the force produced by in situ isolated geniohyoid (GH) during RS and HG-ES. Intense RS was recognized by large negative intrathoracic pressures and triggered high phasic genioglossus and GH EMG activity. GH contraction produced during maximal RS less than a quarter of the force obtained during HG-ES. The major finding of the study was that RS and ES differed in the mechanism by which they stabilized the pharynx: RS lowered the pressure-area slope, i.e., reduced pharyngeal compliance (14.1 ± 2.9 to 9.2 ± 1.9 mm(2)/cmH2O, P < 0.01). HG-ES shifted the slope toward lower pressures, i.e., lowered the calculated extraluminal pressure (17.4 ± 5.8 to 9.2 ± 7.4 cmH2O, P < 0.01). Changes during RS and HG-ES were not affected by NMT, but the effect of RS decreased significantly after HGT. In conclusion, HG-ES and RS affect the pharyngeal site of collapse differently. Tongue muscle contraction contributes to pharyngeal stiffening during RS., (Copyright © 2016 the American Physiological Society.)

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h(-1), diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp ) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104-0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196-0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility., (Copyright ©ERS 2016.)

Objectives: Obstructive sleep apnea (OSA) is the result of pharyngeal obstruction that occurs predominantly during REM in children. Pathophysiologic mechanisms responsible for upper airway obstruction, however, are poorly understood. Thus, we sought to characterize upper airway obstruction in apneic compared to snoring children during sleep. We hypothesized that apneic compared to snoring children would exhibit an increased prevalence and severity of upper airway obstruction, that would be greater in REM compared to non-REM, and would improve following adenotonsillectomy., Study Design: Apneic children were assessed with routine polysomnography before and after adenotonsillectomy, and compared to snoring children matched for gender, age, and BMI z-score. In addition to traditional scoring metrics, the following were used to characterize upper airway obstruction: maximal inspiratory airflow (%VI max) and percent of time with inspiratory flow-limited breathing (%IFL)., Results: OSA compared to snoring children had similar degrees of upper airway obstruction in non-REM; however, during REM, children with sleep apnea exhibited a higher %IFL (98 ± 2% vs.73 ± 8%, P < 0.01) and lower %VI max (56 ± 6 vs.93 ± 10%, P < 0.01). In children with OSA, CO2 levels were elevated during both wake and sleep. Following adenotonsillectomy, upper airway obstruction improved during REM manifest by decreased %IFL (98 ± 2 to 63 ± 9%, P = 0.04), increased %VI max (56 ± 6 to 95 ± 5%, P = 0.01) and decreased CO2 levels., Conclusions: Differences in the prevalence and severity upper airway obstruction suggest impaired compensatory responses during REM in children with OSA, which improved following adenotonsillectomy., Competing Interests: None., (© 2015 Wiley Periodicals, Inc.)

Rationale: Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep., Methods: An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions., Results: Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth., Conclusion: Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility., (Copyright © 2014 the American Physiological Society.)

Defects in pharyngeal mechanical and neuromuscular control are required for the development of obstructive sleep apnea. Obesity and age are known sleep apnea risk factors, leading us to hypothesize that specific defects in upper airway neuromechanical control are associated with weight and age in a mouse model. In anesthetized, spontaneously breathing young and old wild-type C57BL/6J mice, genioglossus electromyographic activity (EMG(GG)) was monitored and upper airway pressure-flow dynamics were characterized during ramp decreases in nasal pressure (Pn, cmH₂O). Specific body weights were targeted by controlling caloric intake. The passive critical pressure (Pcrit) was derived from pressure-flow relationships during expiration. The Pn threshold at which inspiratory flow limitation (IFL) developed and tonic and phasic EMG(GG) activity during IFL were quantified to assess the phasic modulation of pharyngeal patency. The passive Pcrit increased progressively with increasing body weight and increased more in the old than young mice. Tonic EMG(GG) decreased and phasic EMG(GG) increased significantly with obesity. During ramp decreases in Pn, IFL developed at a higher (less negative) Pn threshold in the obese than lean mice, although the frequency of IFL decreased with age and weight. The findings suggest that weight imposes mechanical loads on the upper airway that are greater in the old than young mice. The susceptibility to upper airway obstruction increases with age and weight as tonic neuromuscular activity falls. IFL can elicit phasic responses in normal mice that mitigate or eliminate the obstruction altogether.

The relative impact of mechanical factors on pharyngeal patency in patients with obstructive sleep apnea is poorly understood. The present study was designed to evaluate parameters of the "tube law" on pharyngeal pressure-flow relationships and collapsibility in patients with obstructive sleep apnea. We developed a mathematical model that considered the collapsible segment of the pharynx to represent an orifice of varying diameter. The model enabled us to assess the effects of pharyngeal compliance (C), neutral cross-sectional area (A(o)), external peripharyngeal pressure (P(ex)), and the resistance proximal to the site of collapse on flow mechanics and pharyngeal collapsibility [critical pressure (P(crit))]. All parameters were measured in 15 patients with obstructive sleep apnea under propofol anesthesia, both at rest and during mandibular advancement and electrical stimulation of the genioglossus. The data was used both to confirm the validity of the model and to compare expected and actual relationships between the tube-law parameters and the pharyngeal pressure-flow relationship and collapsibility. We found a close correlation between predicted and measured P(crit) (R = 0.98), including changes observed during pharyngeal manipulations. C and A(o) were closely and directly interrelated (R = 0.93) and did not correlate with P(crit). A significant correlation was found between P(ex) and P(crit) (R = 0.77; P < 0.01). We conclude that the pharynx of patients with obstructive sleep apnea can be modeled as an orifice with varying diameter. Pharyngeal compliance and A(o) are closely interrelated. Pharyngeal collapsibility depends primarily on the surrounding pressure.

The relationship between changes in absolute end-expiratory lung volume (EELV) and collapsibility has not been rigorously quantified. We hypothesized that pharyngeal collapsibility varies inversely with absolute lung volume in sleeping humans during 1) conventional and 2) isovolume measurements of passive critical pressure (Pcrit). Eighteen healthy subjects (11 male, 7 female) slept in a negative pressure ventilator for measurements of pharyngeal collapsibility (Pcrit) during non-rapid eye movement sleep. EELV was 1) allowed to vary with changes in nasal pressure for conventional Pcrit measurements and 2) controlled by maintaining a fixed pressure difference across the respiratory system (P(RS)) from the nose to the body surface for isovolume Pcrit measurements at elevated EELV (P(RS) = +10 cmH(2)O), reduced EELV (P(RS) = -5 cmH(2)O), and functional residual capacity (FRC; P(RS) = 0 cmH(2)O). In each condition, the absolute EELV was determined and the corresponding Pcrit was derived from upper airway pressure-flow relationships. In the entire group, Pcrit varied inversely with EELV (P < 0.001). Pcrit decreased as EELV increased from the conventional to the FRC isovolume condition by -3.5 ± 1.0 cmH(2)O/l (P < 0.003). Subjects with a conventional Pcrit below -2 cmH(2)O exhibited greater reductions in EELV and correspondingly greater decreases in the FRC isovolume compared with the conventional Pcrit (P < 0.001). The overall response, ΔPcrit/ΔEELV, was -2.0 ± 0.2 cmH(2)O/l (P < 0.001) and did not differ between men and women (P = 0.16). Nevertheless, men and women differed significantly in FRC (2.63 ± 0.16 vs. 1.88 ± 0.13 liters, P <0.05) and FRC isovolume Pcrit (-2.3 ± 0.8 vs. -7.2 ± 1.2 cmH(2)O, P < 0.05), implying that the men had larger lungs and more collapsible airways than the women. The ΔPcrit/ΔEELV response was independent of sex, conventional Pcrit, body mass index, and neck, waist, and hip circumferences. We conclude that Pcrit varies inversely with absolute EELV, which may lead to 1) an underestimation of the magnitude of quantitative differences in Pcrit across the spectrum from health (negative Pcrit) to disease (positive Pcrit) and 2) increases in sleep apnea susceptibility in obesity.

We characterized the passive structural and active neuromuscular control of pharyngeal collapsibility in mice and hypothesized that pharyngeal collapsibility, which is elevated by anatomic loads, is reduced by active neuromuscular responses to airflow obstruction. To address this hypothesis, we examined the dynamic control of upper airway function in the isolated upper airway of anesthetized C57BL/6J mice. Pressures were lowered downstream and upstream to the upper airway to induce inspiratory airflow limitation and critical closure of the upper airway, respectively. After hyperventilating the mice to central apnea, we demonstrated a critical closing pressure (Pcrit) of -6.2 +/- 1.1 cmH(2)O under passive conditions that was unaltered by the state of lung inflation. After a period of central apnea, lower airway occlusion led to progressive increases in phasic genioglossal electromyographic activity (EMG(GG)), and in maximal inspiratory airflow (Vi(max)) through the isolated upper airway, particularly as the nasal pressure was lowered toward the passive Pcrit level. Moreover, the active Pcrit fell during inspiration by 8.2 +/- 1.4 cmH(2)O relative to the passive condition (P < 0.0005). We conclude that upper airway collapsibility (passive Pcrit) in the C57BL/6J mouse is similar to that in the anesthetized canine, feline, and sleeping human upper airway, and that collapsibility falls markedly under active conditions. Active EMG(GG) and Vi(max) responses dissociated at higher upstream pressure levels, suggesting a decrease in the mechanical efficiency of upper airway dilators. Our findings in mice imply that anatomic and neuromuscular factors interact dynamically to modulate upper airway function, and provide a novel approach to modeling the impact of genetic and environmental factors in inbred murine strains.

Male sex, obesity, and age are risk factors for obstructive sleep apnea, although the mechanisms by which these factors increase sleep apnea susceptibility are not entirely understood. This study examined the interrelationships between sleep apnea risk factors, upper airway mechanics, and sleep apnea susceptibility. In 164 (86 men, 78 women) participants with and without sleep apnea, upper airway pressure-flow relationships were characterized to determine their mechanical properties [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] during non-rapid eye movement sleep. In multiple linear regression analyses, the effects of body mass index and age on passive Pcrit were determined in each sex. A subset of men and women matched by body mass index, age, and disease severity was used to determine the sex effect on passive Pcrit. The passive Pcrit was 1.9 cmH(2)O [95% confidence interval (CI): 0.1-3.6 cmH(2)O] lower in women than men after matching for body mass index, age, and disease severity. The relationship between passive Pcrit and sleep apnea status and severity was examined. Sleep apnea was largely absent in those individuals with a passive Pcrit less than -5 cmH(2)O and increased markedly in severity when passive Pcrit rose above -5 cmH(2)O. Passive Pcrit had a predictive power of 0.73 (95% CI: 0.65-0.82) in predicting sleep apnea status. Upper airway mechanics are differentially controlled by sex, obesity, and age, and partly mediate the relationship between these sleep apnea risk factors and obstructive sleep apnea.

The present study evaluated the effect of coactivation of tongue protrusors and retractors on pharyngeal patency in patients with obstructive sleep apnea. The effect of genioglossus (GG), hyoglossus (HG), and coactivation of both on nasal pressure (Pn):flow relationships was evaluated in a sleep study (SlS, n = 7) and during a propofol anesthesia study (AnS, n = 7). GG was stimulated with sublingual surface electrodes in SlS and with intramuscular electrodes in AnS, while HG was stimulated with surface electrodes in both groups. In the AnS, the cross-sectional area (CSA):Pn relationships was measured with a pharyngoscope to estimate velopharyngeal compliance . In the SlS, surface stimulation of GG had no effect on the critical pressure (Pcrit), HG increased Pcrit from 2.8 +/- 1.7 to 3.7 +/- 1.6 cmH(2)O, but coactivation lowered Pcrit to 0.2 +/- 1.9 cmH(2)O (P < 0.01 for both). In the AnS, intramuscular stimulation of GG lowered Pcrit from 2.6 +/- 1.3 to 1.0 +/- 2.8 cmH(2)O, HG increased Pcrit to 6.2 +/- 2.5 cmH(2)O (P < 0.01), and coactivation had a similar effect to that of GG (Pcrit = 1.2 +/- 2.4 cmH(2)O, P < 0.05). None of the interventions affected significantly velopharyngeal compliance. We conclude that the beneficial effect of coactivation depends on the pattern of GG fiber recruitment: although surface stimulation of GG failed to protrude the tongue, it prevented the occlusive effect of the retractor, thereby improving pharyngeal patency during coactivation. Stimulation of deeper GG fibers with intramuscular electrodes enlarged the pharynx, and coactivation had no additive effect.

The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion. The pressure/flow and pressure/cross-sectional area relationships of the velo- and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation. Genioglossus contraction decreased the critical pressure significantly from 1.2+/-3.3 to -0.7+/-3.8 cmH(2)O, with individual decreases ranging -0.6-5.9 cmH(2)O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx. Genioglossus contraction enlarges both the velo- and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.

To examine the dynamic modulation of upper airway (UA) function during sleep, we devised a novel approach to measuring the critical pressure (Pcrit) within a single breath in tracheostomized sleep apnea patients. We hypothesized that the UA continuously modulates airflow dynamics during transtracheal insufflation. In this study, we examine tidal pressure-flow relationships throughout the respiratory cycle to compare phasic differences in UA collapsibility between closure and reopening. Five apneic subjects (with tracheostomy) were recruited (2 men, 3 women; 18-50 yr; 20-35 kg/m2; apnea-hypopnea index >20) for this polysomnographic study. Outgoing airflow through the UA (face mask pneumotachograph) and tracheal pressure were recorded during brief transtracheal administration of insufflated airflow via a catheter. Pressure-flow relationships were generated from deflation (approaching Pcrit) and inflation (after Pcrit) of the UA during non-rapid eye movement sleep. During each breath, UA function was described by a pressure-flow relationship that defined the collapsibility (Pcrit) and upstream resistance (Rus). UA characteristics were examined in the presence and absence of complete UA occlusion. We demonstrated that Pcrit and Rus changed dynamically throughout the respiratory cycle. The UA closing pressure (4.4 +/- 2.0 cm H2O) was significantly lower than the opening pressure (10.8 +/- 2.4 cm H2O). Rus was higher for deflation (18.1 +/- 2.4 cm H2O x l(-1) x s) than during inflation (7.5 +/- 1.9 cm H2O x l(-1) x s) of the UA. Preventing occlusion decreases UA pressure-flow loop hysteresis by approximately 4 cm H2O. These findings indicate that UA collapsibility varies dynamically throughout the respiratory cycle and that both local mechanical and neuromuscular factors may be responsible for this dynamic modulation of UA function during sleep.

We sought to establish the feasibility of measuring upper airway narrowing in spontaneously breathing, anesthetized children using dynamic application of negative airway pressure. A secondary aim was to compare differences in upper airway collapsibility after the administration of sevoflurane or halothane. Subjects were randomized to either drug for inhaled anesthetic induction. Each was adjusted to their 1 MAC value (0.9% for halothane and 2.5% for sevoflurane) and a blinded anesthesia provider held the facemask without performing manual airway opening maneuvers but with inclusion of an oral airway device. Inspiratory flows were measured during partial upper airway obstruction created by an adjustable negative pressure-generating vacuum motor inserted into the anesthesia circuit. Critical closing pressure of the pharynx (Pcrit) was obtained by plotting the peak inspiratory flow of the obstructed breaths against the corresponding negative pressure in the facemask and extrapolating to zero airflow using linear correlation. Fourteen children were enrolled, seven in each anesthetic group. Two children in the halothane group did not develop flow-limited airway obstruction despite negative pressures as low as -9 cm H2O. Pcrit for sevoflurane ranged from -6.7 to -11.6 (mean +/- sd, -9.8 +/- 1.9) cm H2O. Pcrit for halothane ranged from -8.1 to -33 (mean +/- sd, -19.4 +/- 9.3) cm H2O (sevoflurane versus halothane, P = 0.048). We conclude that when using dynamic application of negative airway pressure, halothane appears to cause less upper airway obstruction than sevoflurane at equipotent concentrations.

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

We determined whether upper airway obstruction in normal individuals with intact reflexes could produce the syndrome of obstructive sleep apnea. Upper airway obstruction was produced in 12 normal individuals by lowering nasal pressure to -10 cm H(2)O during sleep. Full night polysomnography was performed during two consecutive nights of sleep with subatmospheric nasal pressure and compared with control nights before and after the negative pressure nights. We found that the application of negative pressure was associated with the development of recurrent obstructive apneas (non-REM-disordered breathing rate, 32.6 +/- 34.8 and 37.8 +/- 29.1 events/h during each of two negative pressure nights; p < 0.001) that were associated with oxyhemoglobin desaturation, arousals from sleep, and alterations in sleep stage distribution. Moreover, the median daytime sleep latency after two nights of sleep with subatmospheric pressure fell from 6.9 +/- 1.1 to 3.4 +/- 0.6 min, and rose significantly again to 8.1 +/- 1.5 min (p < 0.03) after the control night following subatmospheric pressure nights. Our findings suggest that a decrease in the pharyngeal transmural pressure alone is a sufficient condition for the production of the sleep apnea syndrome in normal individuals.

The structural properties of the upper airway determine its collapsibility during periods of muscle hypotonia. Both rapid-eye-movement (REM) sleep and increases in nasal pressure (PN) produce hypotonia, which persists even after nasal pressure is abruptly reduced. To determine the factors that influence the collapsibility of the hypotonic airway, the critical pressure (Pcrit) and nasal resistance upstream to the site of pharyngeal collapse (RN) were measured in the first three breaths after abrupt reductions in PN during non-REM and REM sleep. PN was reduced abruptly from 15.2+/-3.2 cm H2O (mean +/- SD) for three breaths in 19 apneic patients. Upper-airway pressure-flow relationships were analyzed to determine Pcrit for each breath in non-REM and REM sleep. We found that Pcrit rose (collapsibility increased, p < 0.001) and RN fell (p = 0.02) between the first and third breath after the decrease in PN, whereas no difference in Pcrit was detected between sleep stages. In six patients, genioglossus-muscle electromyograms (EMGs) were recorded. Peak phasic activity rose between the first and third breath (p = 0.03), but tonic and peak phasic EMG activity fell in REM as compared with non-REM sleep (p < 0.001). We conclude that the hypotonic upper airway becomes most collapsible by the third breath after an abrupt decrease in PN, regardless of sleep stage and despite an increase in genioglossus-muscle activity. Our findings suggest that predominantly mechanical rather than neuromuscular factors modulate the properties of the pharynx after abrupt reductions in nasal pressure.

Previous investigators have demonstrated variable responses to uvulopalatopharyngoplasty (UPP) in patients with obstructive sleep apnea. We hypothesized that this variability is due to either (1) differences in baseline pharyngeal collapsibility preoperatively or (2) differences in magnitude of the decrease in pharyngeal collapsibility resulting from surgery. To determine the relationship between changes in collapsibility and the response to UPP surgery, we measured the upper airway critical pressure (Pcrit) before and after UPP in 13 patients with obstructive sleep apnea. During non-REM sleep, maximal inspiratory airflow (VImax) was quantitated by varying the level of nasal pressure (PN), and Pcrit was determined by the level of PN below which VImax ceased. A positive response to UPP was defined by a greater than or equal to 50% fall in non-REM disordered breathing rate (DBR). In the entire group, UPP resulted in significant decreases in DBR from 71.1 +/- 22.4 to 44.7 +/- 38.4 episodes/h (p = 0.025) and in Pcrit from 0.2 +/- 2.4 to -3.1 +/- 5.4 cm H2O (p = 0.016). Moreover, the percent change in DBR was correlated significantly with the change in Pcrit (p = 0.001). Subgroup analysis of responders and nonresponders demonstrated that significant differences in Pcrit were confined to the responders. Specifically, responders demonstrated a significant fall in Pcrit from -0.8 +/- 3.0 to -7.3 +/- 4.9 cm H2O (p = 0.01), whereas no significant change in Pcrit was detected in the nonresponders (1.1 +/- 1.6 versus 0.6 +/- 2.0 cm H2O. No clinical, polysomnographic, or physiologic predictors of a favorable response were found preoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)