Exploring hypoglossal nerve stimulation therapy for obstructive sleep apnea: A comprehensive review of clinical and physiological upper airway outcomes.

Obstructive sleep apnea (OSA) is a chronic disorder characterized by recurrent episodes of upper airway collapse during sleep, which can lead to serious health issues like cardiovascular disease and neurocognitive impairments. While positive airway pressure serves as the standard treatment, intolerance in some individuals necessitates exploration of alternative therapies. Hypoglossal nerve stimulation (HGNS) promises to mitigate OSA morbidity by stimulating the tongue muscles to maintain airway patency. However, its effectiveness varies, prompting research for optimization. This review summarizes the effects of HGNS on upper airway obstruction from human and animal studies. It examines physiological responses including critical closing pressure, maximal airflow, nasal and upper airway resistance, compliance, stiffness, and geometry. Interactions among these parameters and discrepant findings in animal and human studies are explored. Additionally, the review summarizes the impact of HGNS on established OSA metrics, such as the apnea-hypopnea index, oxygen desaturation index, and sleep arousals. Various therapeutic modalities, including selective unilateral or bilateral HGNS, targeted unilateral HGNS, and whole unilateral or bilateral HGNS, are discussed. This review consolidates our understanding of HGNS mechanisms, fostering exploration of under-investigated outcomes and approaches to drive advancements in HGNS therapy.

Obstructive sleep apnea diagnosis and beyond using portable monitors.

Obstructive sleep apnea (OSA) is a chronic sleep and breathing disorder with significant health complications, including cardiovascular disease and neurocognitive impairments. To ensure timely treatment, there is a need for a portable, accurate and rapid method of diagnosing OSA. This review examines the use of various physiological signals used in the detection of respiratory events and evaluates their effectiveness in portable monitors (PM) relative to gold standard polysomnography. The primary objective is to explore the relationship between these physiological parameters and OSA, their application in calculating the apnea hypopnea index (AHI), the standard metric for OSA diagnosis, and the derivation of non-AHI metrics that offer additional diagnostic value. It is found that increasing the number of parameters in PMs does not necessarily improve OSA detection. Several factors can cause performance variations among different PMs, even if they extract similar signals. The review also highlights the potential of PMs to be used beyond OSA diagnosis. These devices possess parameters that can be utilized to obtain endotypic and other non-AHI metrics, enabling improved characterization of the disorder and personalized treatment strategies. Advancements in PM technology, coupled with thorough evaluation and validation of these devices, have the potential to revolutionize OSA diagnosis, personalized treatment, and ultimately improve health outcomes for patients with OSA. By identifying the key factors influencing performance and exploring the application of PMs beyond OSA diagnosis, this review aims to contribute to the ongoing development and utilization of portable, efficient, and effective diagnostic tools for OSA.

Role of surgical hyoid bone repositioning in modifying upper airway collapsibility.

Background: Surgical hyoid bone repositioning procedures are being performed to treat obstructive sleep apnea (OSA), though outcomes are highly variable. This is likely due to lack of knowledge regarding the precise influence of hyoid bone position on upper airway patency. The aim of this study is to determine the effect of surgical hyoid bone repositioning on upper airway collapsibility. Methods: Seven anaesthetized, male, New Zealand White rabbits were positioned supine with head/neck position controlled. The rabbit's upper airway was surgically isolated and hyoid bone exposed to allow manipulation of its position using a custom-made device. A sealed facemask was fitted over the rabbit's snout, and mask/upper airway pressures were monitored. Collapsibility was quantified using upper airway closing pressure (Pclose). The hyoid bone was repositioned within the mid-sagittal plane from 0 to 5 mm (1 mm increments) in anterior, cranial, caudal, anterior-cranial (45°) and anterior-caudal (45°) directions. Results: Anterior displacement of the hyoid bone resulted in the greatest decrease in Pclose amongst all directions (p = 0.002). Pclose decreased progressively with each increment of anterior hyoid bone displacement, and down by -4.0 ± 1.3 cmH2O at 5 mm. Cranial and caudal hyoid bone displacement did not alter Pclose (p > 0.35). Anterior-cranial and anterior-caudal hyoid bone displacements decreased Pclose significantly (p < 0.004) and at similar magnitudes to the anterior direction (p > 0.68). Conclusion: Changes in upper airway collapsibility following hyoid bone repositioning are both direction and magnitude dependent. Anterior-based repositioning directions have the greatest impact on reducing upper airway collapsibility, with no effect on collapsibility by cranial and caudal directions. Findings may have implications for guiding and improving the outcomes of surgical hyoid interventions for the treatment of OSA.

Finite Element Modeling of Magnitude and Location of Brain Micromotion Induced Strain for Intracortical Implants.

Micromotion-induced stress remains one of the main determinants of life of intracortical implants. This is due to high stress leading to tissue injury, which in turn leads to an immune response coupled with a significant reduction in the nearby neural population and subsequent isolation of the implant. In this work, we develop a finite element model of the intracortical probe-tissue interface to study the effect of implant micromotion, implant thickness, and material properties on the strain levels induced in brain tissue. Our results showed that for stiff implants, the strain magnitude is dependent on the magnitude of the motion, where a micromotion increase from 1 to 10 µm induced an increase in the strain by an order of magnitude. For higher displacement over 10 µm, the change in the strain was relatively smaller. We also showed that displacement magnitude has no impact on the location of maximum strain and addressed the conflicting results in the literature. Further, we explored the effect of different probe materials [i.e., silicon, polyimide (PI), and polyvinyl acetate nanocomposite (PVAc-NC)] on the magnitude, location, and distribution of strain. Finally, we showed that strain distribution across cortical implants was in line with published results on the size of the typical glial response to the neural probe, further reaffirming that strain can be a precursor to the glial response.

CPAP combined with oral appliance therapy reduces CPAP requirements and pharyngeal pressure swings in obstructive sleep apnea.

Oral appliance (OA) therapy is the leading alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). It is well tolerated compared with CPAP. However, ≥50% of patients using OA therapy have incomplete resolution of their OSA. Combination therapy with CPAP and oral appliance (CPAP + OA) is a potential alternative for incomplete responders to OA therapy. This study aimed to determine the extent to which combination therapy reduces therapeutic CPAP requirements using gold-standard physiological methodology in those who have an incomplete response to OA therapy alone. Sixteen incomplete responders [residual apnea/hypopnea index (AHI) > 10 events/h] to a novel OA with a built-in oral airway were recruited (3 women:13 men, aged 31-65 yr, body mass index: 22-38 kg/m2, residual AHI range: 13-63 events/h). Participants were fitted with a nasal mask, pneumotachograph, epiglottic pressure catheter, and standard polysomnography equipment. CPAP titrations were performed during non-rapid eye movement (NREM) supine sleep in each participant during three conditions (order randomized): CPAP only, CPAP + OA (oral airway open), and CPAP + OA (oral airway closed). OSA was resolved at pressures of 4 ± 2 and 5 ± 2 cmH2O during CPAP + OA (oral airway open) and CPAP + OA (oral airway closed) conditions versus 8 ± 2 cmH2O during CPAP only (P < 0.01). Negative epiglottic pressure swings in oral airway open and closed conditions were normalized to CPAP only levels [-2.5(-3.7, -2.6) vs. -2.3(-3.2, -2.4) vs. -2.1(-2.7, -2.3) cmH2O]. Combined CPAP and OA therapy reduces therapeutic CPAP requirements by 35%-45% and minimizes epiglottic pressure swings. This combination may be a therapeutic alternative for patients with incomplete responses to OA therapy alone and those who cannot tolerate high CPAP levels.NEW & NOTEWORTHY Combined CPAP and oral appliance therapy has been suggested as an alternative for incomplete responders to oral appliance therapy. We used a novel oral appliance incorporating an oral airway together with CPAP to show that pharyngeal pressure swings were normalized at reduced CPAP levels. Our findings demonstrate that using CPAP and oral appliance together may be a beneficial alternative for incomplete responders to oral appliance therapy and intolerant CPAP users due to high-pressure requirements.

Efficacy of a novel oral appliance and the role of posture on nasal resistance in obstructive sleep apnea.

STUDY OBJECTIVES: High nasal resistance is associated with oral appliance treatment failure in obstructive sleep apnea (OSA). A novel oral appliance with a built-in oral airway has been shown to reduce pharyngeal pressure swings during sleep and may be efficacious in those with high nasal resistance. The role of posture and mandibular advancement on nasal resistance in OSA remains unclear. This study aimed to determine (1) the effects of posture and mandibular advancement on nasal resistance in OSA and (2) the efficacy of a new oral appliance device including in patients with high nasal resistance. METHODS: A total of 39 people with OSA (7 females, apnea-hypopnea index (AHI) (mean ± standard deviation) = 29 ± 21 events/h) completed split-night polysomnography with and without oral appliance (order randomized). Prior to sleep, participants were instrumented with a nasal mask, pneumotachograph, and a choanal pressure catheter for gold standard nasal resistance quantification seated, supine and lateral (with and without oral appliance, order randomized). RESULTS: Awake nasal resistance increased from seated, to supine, to lateral posture (median [interquartile range] = 1.8 [1.4, 2.7], 2.7 [1.7, 3.5], 3.4 [1.9, 4.6] cm H2O/L/s, P < .001). Corresponding measures of nasal resistance did not change with mandibular advancement (2.3 [1.4, 3.5], 2.5 [1.8, 3.6], 3.5 [1.9, 4.8] cm H2O/L/s, P = .388). The median AHI reduced by 47% with oral appliance therapy (29 ± 21 versus 18 ± 15 events/h, P = .002). Participants with high nasal resistance (> 3 cm H2O/L/s) had similar reductions in AHI versus those with normal nasal resistance (61 [-8, 82] versus 40 [-5, 62] %, P = .244). CONCLUSIONS: Nasal resistance changes with posture in people with OSA. A novel oral appliance with a built-in oral airway reduces OSA severity in people with OSA, including in those with high nasal resistance. CLINICAL TRIAL REGISTRATION: Registry: ANZCTR; Title: Combination therapy for obstructive sleep apnoea; Identifier: ACTRN12617000492358; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372279.

Respiratory-related displacement of the trachea in obstructive sleep apnea.

Tracheal displacement is thought to be the primary mechanism by which changes in lung volume influence upper airway patency. Caudal tracheal displacement during inspiration may help preserve the integrity of the upper airway in response to increasing negative airway pressure by stretching and stiffening pharyngeal tissues. However, tracheal displacement has not been previously quantified in obstructive sleep apnea (OSA). Accordingly, we aimed to measure tracheal displacements in awake individuals with and without OSA. The upper head and neck of 34 participants [apnea-hypopnea index (AHI) = 2-74 events/h] were imaged in the midsagittal plane using dynamic magnetic resonance imaging (MRI) during supine awake quiet breathing. MRI data were analyzed to identify peak tracheal displacement and its timing relative to inspiration. Epiglottic pressure was measured separately for a subset of participants (n = 30) during similar experimental conditions. Nadir epiglottic pressure and its timing relative to inspiration were quantified. Peak tracheal displacement ranged from 1.0-9.6 mm, with a median (25th-75th percentile) of 2.3 (1.7-3.5) mm, and occurred at 89 (78-99)% of inspiratory time. Peak tracheal displacement increased with increasing OSA severity (AHI) (R2 = 0.28, P = 0.013) and increasing negative nadir epiglottic pressure (R2 = 0.47, P = 0.023). Relative inspiratory timing of peak tracheal displacement also correlated with OSA severity, with peak displacement occurring earlier in inspiration with increasing AHI (R2 = 0.36, P = 0.002). Tracheal displacements during quiet breathing are larger in individuals with more severe OSA and tend to reach peak displacement earlier in the inspiratory cycle. Increased tracheal displacement may contribute to maintenance of upper airway patency during wakefulness in OSA, particularly in those with severe disease.NEW & NOTEWORTHY Tracheal displacement is thought to play an important role in stabilizing the upper airway by stretching/stiffening the pharyngeal musculature. Using dynamic magnetic resonance imaging, this study shows that caudal tracheal displacement is more pronounced during inspiration in obstructive sleep apnea (OSA) compared with healthy individuals. Softer pharyngeal muscles and greater inspiratory forces in OSA may underpin greater tracheal excursion. These findings suggest that tracheal displacement may contribute to maintenance of pharyngeal patency during wakefulness in OSA.

New insights into the timing and potential mechanisms of respiratory-induced cortical arousals in obstructive sleep apnea.

Study Objectives: A negative intrathoracic pressure threshold is one commonly proposed mechanism for triggering respiratory-induced arousals in obstructive sleep apnea (OSA). If so, they should occur during inspiration, shortly after maximal negative pressure swings. Alternatively, respiratory-induced arousals may occur throughout the respiratory cycle if other mechanisms also contribute. However, arousal timing has been minimally investigated. This study aimed to (1) determine the temporal relationship between respiratory-induced arousals and breathing phase and (2) characterize neuromuscular and load compensation responses prior to arousal. Methods: Fifty-one CPAP-treated OSA patients underwent a sleep physiology study with genioglossus and tensor palatini EMG, nasal mask/pneumotachograph, and epiglottic pressure. Transient CPAP reductions were delivered to induce respiratory-related arousals. Results: Of 354 arousals, 65(60-70)%[mean(CI)] occurred during inspiration, 35(30-40)% during expiration. Nadir epiglottic pressure occurred 68(66-69)% into inspiration while inspiratory arousals had a uniform distribution throughout inspiration. Expiratory arousals occurred predominantly in early expiration. CPAP reductions initially reduced minute ventilation by ~2.5 liter/min, which was restored immediately prior to expiratory but not inspiratory arousals. Duty cycle just prior to arousal was greater for inspiratory versus expiratory arousals [0.20(0.18-0.21) vs. 0.13(0.11-0.15)Δbaseline, p = 0.001]. Peak tensor palatini EMG was higher for expiratory versus inspiratory arousals during prearousal breaths [7.6(5.8-9.6) vs. 3.7(3.0-4.5)%Δbaseline, p = 0.001], whereas genioglossus and tonic tensor palatini EMG were similar between arousal types. Conclusions: Over one third of respiratory-induced arousals occur during expiration. These findings highlight the importance of nonpressure threshold mechanisms of respiratory-induced arousals in OSA and suggest that expiratory arousals may be a novel marker of enhanced tensor palatini neuromuscular compensation.

Personalized Management Approach for OSA.

OSA is a heterogeneous disorder. If left untreated, it has major health, safety, and economic consequences. In addition to varying levels of impairment in pharyngeal anatomy (narrow/collapsible airway), nonanatomical "phenotypic traits" are also important contributors to OSA for most patients. However, the majority of existing therapies (eg, CPAP, oral appliances, weight loss, positional therapy, upper airway surgery) target only the anatomical cause. These are typically administered as monotherapy according to a trial and error management approach in which the majority of patients are first prescribed CPAP. Despite its high efficacy, CPAP adherence remains unacceptably low, and second-line therapies have variable and unpredictable efficacies. Recent advances in knowledge regarding the multiple causes of OSA using respiratory phenotyping techniques have identified new targets or "treatable traits" to direct therapy. Identification of the traits and development of therapies that selectively target one or more of the treatable traits has the potential to personalize the management of this chronic health condition to optimize patient outcomes according to precision medicine principles. This brief review highlights the latest developments and emerging therapies for personalized management approaches for OSA.

An automated and reliable method for breath detection during variable mask pressures in awake and sleeping humans.

Accurate breath detection is crucial in sleep and respiratory physiology research and in several clinical settings. However, this process is technically challenging due to measurement and physiological artifacts and other factors such as variable leaks in the breathing circuit. Recently developed techniques to quantify the multiple causes of obstructive sleep apnea, require intermittent changes in airway pressure applied to a breathing mask. This presents an additional unique challenge for breath detection. Traditional algorithms often require drift correction. However, this is an empirical operation potentially prone to human error. This paper presents a new algorithm for breath detection during variable mask pressures in awake and sleeping humans based on physiological landmarks detected in the airflow or epiglottic pressure signal (Pepi). The algorithms were validated using simulated data from a mathematical model and against the standard visual detection approach in 4 healthy individuals and 6 patients with sleep apnea during variable mask pressure conditions. Using the flow signal, the algorithm correctly identified 97.6% of breaths with a mean difference±SD in the onsets of respiratory phase compared to expert visual detection of 23±89ms for inspiration and 6±56ms for expiration during wakefulness and 10±74ms for inspiration and 3±28 ms for expiration with variable mask pressures during sleep. Using the Pepi signal, the algorithm correctly identified 89% of the breaths with accuracy of 31±156ms for inspiration and 9±147ms for expiration compared to expert visual detection during variable mask pressures asleep. The algorithm had excellent performance in response to baseline drifts and noise during variable mask pressure conditions. This new algorithm can be used for accurate breath detection including during variable mask pressure conditions which represents a major advance over existing time-consuming manual approaches.

Velopharyngeal mucosal surface topography in healthy subjects and subjects with obstructive sleep apnea.

Macroscopic pharyngeal anatomical abnormalities are thought to contribute to the pathogenesis of upper airway (UA) obstruction in obstructive sleep apnea (OSA). Microscopic changes in the UA mucosal lining of OSA subjects are reported; however, the impact of these changes on UA mucosal surface topography is unknown. This study aimed to 1) develop methodology to measure UA mucosal surface topography, and 2) compare findings from healthy and OSA subjects. Ten healthy and eleven OSA subjects were studied. Awake, gated (end expiration), head and neck position controlled magnetic resonance images (MRIs) of the velopharynx (VP) were obtained. VP mucosal surfaces were segmented from axial images, and three-dimensional VP mucosal surface models were constructed. Curvature analysis of the models was used to study the VP mucosal surface topography. Principal, mean, and Gaussian curvatures were used to define surface shape composition and surface roughness of the VP mucosal surface models. Significant differences were found in the surface shape composition, with more saddle/spherical and less flat/cylindrical shapes in OSA than healthy VP mucosal surface models (P < 0.01). OSA VP mucosal surface models were also found to have more mucosal surface roughness (P < 0.0001) than healthy VP mucosal surface models. Our novel methodology was utilized to model the VP mucosal surface of OSA and healthy subjects. OSA subjects were found to have different VP mucosal surface topography, composed of increased irregular shapes and increased roughness. We speculate increased irregularity in VP mucosal surface may increase pharyngeal collapsibility as a consequence of friction-related pressure loss.NEW & NOTEWORTHY A new methodology was used to model the upper airway mucosal surface topography from magnetic resonance images of patients with obstructive sleep apnea and healthy adults. Curvature analysis was used to analyze the topography of the models, and a new metric was derived to describe the mucosal surface roughness. Increased roughness was found in the obstructive sleep apnea vs. healthy group, but further research is required to determine the functional effects of the measured difference on upper airway airflow mechanics.

Arousal Intensity is a Distinct Pathophysiological Trait in Obstructive Sleep Apnea.

STUDY OBJECTIVES: Arousals from sleep vary in duration and intensity. Accordingly, the physiological consequences of different types of arousals may also vary. Factors that influence arousal intensity are only partly understood. This study aimed to determine if arousal intensity is mediated by the strength of the preceding respiratory stimulus, and investigate other factors mediating arousal intensity and its role on post-arousal ventilatory and pharyngeal muscle responses. METHODS: Data were acquired in 71 adults (17 controls, 54 obstructive sleep apnea patients) instrumented with polysomnography equipment plus genioglossus and tensor palatini electromyography (EMG), a nasal mask and pneumotachograph, and an epiglottic pressure sensor. Transient reductions in CPAP were delivered during sleep to induce respiratory-related arousals. Arousal intensity was measured using a validated 10-point scale. RESULTS: Average arousal intensity was not related to the magnitude of the preceding respiratory stimuli but was positively associated with arousal duration, time to arousal, rate of change in epiglottic pressure and negatively with BMI (R2 > 0.10, P ≤ 0.006). High (> 5) intensity arousals caused greater ventilatory responses than low (≤ 5) intensity arousals (10.9 [6.8-14.5] vs. 7.8 [4.7-12.9] L/min; P = 0.036) and greater increases in tensor palatini EMG (10 [3-17] vs. 6 [2-11]%max; P = 0.031), with less pronounced increases in genioglossus EMG. CONCLUSIONS: Average arousal intensity is independent of the preceding respiratory stimulus. This is consistent with arousal intensity being a distinct trait. Respiratory and pharyngeal muscle responses increase with arousal intensity. Thus, patients with higher arousal intensities may be more prone to respiratory control instability. These findings are important for sleep apnea pathogenesis.

Development and validation of a computational finite element model of the rabbit upper airway: simulations of mandibular advancement and tracheal displacement.

The mechanisms leading to upper airway (UA) collapse during sleep are complex and poorly understood. We previously developed an anesthetized rabbit model for studying UA physiology. On the basis of this body of physiological data, we aimed to develop and validate a two-dimensional (2D) computational finite element model (FEM) of the passive rabbit UA and peripharyngeal tissues. Model geometry was reconstructed from a midsagittal computed tomographic image of a representative New Zealand White rabbit, which included major soft (tongue, soft palate, constrictor muscles), cartilaginous (epiglottis, thyroid cartilage), and bony pharyngeal tissues (mandible, hard palate, hyoid bone). Other UA muscles were modeled as linear elastic connections. Initial boundary and contact definitions were defined from anatomy and material properties derived from the literature. Model parameters were optimized to physiological data sets associated with mandibular advancement (MA) and caudal tracheal displacement (TD), including hyoid displacement, which featured with both applied loads. The model was then validated against independent data sets involving combined MA and TD. Model outputs included UA lumen geometry, peripharyngeal tissue displacement, and stress and strain distributions. Simulated MA and TD resulted in UA enlargement and nonuniform increases in tissue displacement, and stress and strain. Model predictions closely agreed with experimental data for individually applied MA, TD, and their combination. We have developed and validated an FEM of the rabbit UA that predicts UA geometry and peripharyngeal tissue mechanical changes associated with interventions known to improve UA patency. The model has the potential to advance our understanding of UA physiology and peripharyngeal tissue mechanics.

Pharyngeal mucosal wall folds in subjects with obstructive sleep apnea.

Mechanical processes underlying pharyngeal closure have not been examined. We hypothesized that the pharyngeal mucosal surface would fold during closure, and lowering the upper airway lining liquid surface tension would unfold areas of mucosal apposition, i.e., folds. We compared baseline pharyngeal fold numbers and response to reduction in upper airway liquid surface tension in healthy and obstructive sleep apnea (OSA) subjects. Awake, gated magnetic resonance pharyngeal airway images of 10 healthy and 11 OSA subjects were acquired before and after exogenous surfactant administration (beractant). Upper airway liquid surface tension was measured at the beginning and end of image acquisition and averaged. Velopharyngeal and oropharyngeal images were segmented and analyzed separately for average cross-sectional area, circumference, and fold number. Compared with healthy subjects, at baseline, velopharynx for OSA subjects had a smaller cross-sectional area (98.3 ± 32.5 mm(2) healthy, 52.3 ± 23.6 mm(2) OSA) and circumference (46.5 ± 8.1 mm healthy, 30.8 ± 6.1 mm OSA; both P < 0.05, unpaired t-test), and fewer folds (4.9 ± 1.6 healthy, 3.1 ± 1.8 OSA, P < 0.03). There were no differences in oropharynx for cross-sectional area, circumference, or folds. Reduction in upper airway liquid surface tension from 61.3 ± 1.2 to 55.3 ± 1.5 mN/m (P < 0.0001) did not change cross-sectional area or circumference for velopharynx or oropharynx in either group; however, in OSA subjects, oropharyngeal folds fell from 6.8 ± 3.1 to 4.7 ± 1.2 (n = 8, P < 0.05), and velopharyngeal folds from 3.3 ± 1.9 to 2.3 ± 1.2 (P = 0.08), and were unchanged in healthy subjects. Subjects with OSA have fewer velopharyngeal wall folds, which decrease further when surface tension falls. We speculate that reduced pharyngeal wall folds contribute to an increase in pharyngeal collapsibility.

Peripharyngeal tissue deformation, stress distributions, and hyoid bone movement in response to mandibular advancement.

Mandibular advancement (MA) increases upper airway (UA) patency and decreases collapsibility. Furthermore, MA displaces the hyoid bone in a cranial-anterior direction, which may contribute to MA-associated UA improvements via redistribution of peripharyngeal tissue stresses (extraluminal tissue pressure, ETP). In the present study, we examined effects of MA on ETP distributions, deformation of the peripharyngeal tissue surface (UA geometry), and hyoid bone position. We studied 13 supine, anesthetized, tracheostomized, spontaneously breathing adult male New Zealand White rabbits. Graded MA was applied from 0 to ∼4.5 mm. ETP was measured at six locations distributed throughout three UA regions: tongue, hyoid, and epiglottis. Axial computed tomography images of the UA (nasal choanae to glottis) were acquired and used to measure lumen geometry (UA length; regional cross-sectional area) and hyoid displacement. MA resulted in nonuniform decreases in ETP (greatest at tongue region), ranging from -0.11 (-0.15 to -0.06) to -0.82 (-1.09 to -0.54) cmH2O/mm MA [linear mixed-effects model slope (95% confidence interval)], across all sites. UA length decreased by -0.5 (-0.8 to -0.2) %/mm accompanied by nonuniform increases in cross-sectional area (greatest at hyoid region) ranging from 7.5 (3.6-11.4) to 18.7 (14.9-22.5) %/mm. The hyoid bone was displaced in a cranial-anterior direction by 0.42 (0.36-0.44) mm/mm MA. In summary, MA results in nonuniform changes in peripharyngeal tissue pressure distributions and lumen geometry. Displacement of the hyoid bone with MA may play a pivotal role in redistributing applied MA loads, thus modifying tissue stress/deformation distributions and determining resultant UA geometry outcomes.

Sleep and respiratory physiology in adults.

Respiration during sleep is determined by metabolic demand; respiratory drive is determined by a central respiratory generator. Changes in pharyngeal dilator muscle tone resulting in increased upper airway resistance and collapsibility contribute to hypoventilation. Relative hypotonia of respiratory muscles, body posture changes, and altered ventilatory control result in additional physiologic changes contributing to hypoventilation. This article reviews mechanisms of central control of respiration and normal upper and lower airway physiology. Understanding sleep-related changes in respiratory physiology will help in developing new therapies to prevent hypoventilation in susceptible populations.

Peripharyngeal tissue deformation and stress distributions in response to caudal tracheal displacement: pivotal influence of the hyoid bone?

Caudal tracheal displacement (TD) leads to improvements in upper airway (UA) function and decreased collapsibility. To better understand the mechanisms underlying these changes, we examined effects of TD on peripharyngeal tissue stress distributions [i.e., extraluminal tissue pressure (ETP)], deformation of its topographical surface (UA lumen geometry), and hyoid bone position. We studied 13 supine, anesthetized, tracheostomized, spontaneously breathing, adult male New Zealand white rabbits. Graded TD was applied to the cranial tracheal segment from 0 to ∼ 10 mm. ETP was measured at six locations distributed around/along the length of the UA, covering three regions: tongue, hyoid, and epiglottis. Axial images of the UA (nasal choanae to glottis) were acquired with computed tomography and used to measure lumen geometry (UA length; regional cross-sectional area) and hyoid bone displacement. TD resulted in nonuniform decreases in ETP (generally greatest at tongue region), ranging from -0.07 (-0.11 to -0.03) [linear mixed-effects model slope (95% confidence interval)] to -0.27 (-0.31 to -0.23) cmH2O/mm TD, across all sites. UA length increased by 1.6 (1.5-1.8)%/mm, accompanied by nonuniform increases in cross-sectional area (greatest at hyoid region) ranging from 2.8 (1.7-3.9) to 4.9 (3.8-6.0)%/mm. The hyoid bone was displaced caudally by 0.22 (0.18-0.25) mm/mm TD. In summary, TD imposes a load on the UA that results in heterogeneous changes in peripharyngeal tissue stress distributions and resultant lumen geometry. The hyoid bone may play a pivotal role in redistributing applied caudal tracheal loads, thus modifying tissue deformation distributions and determining resultant UA geometry outcomes.

Resetting the baroreflex during snoring: role of resistive loading and intra-thoracic pressure.

Baroreflex sensitivity (BRS) is reduced during snoring in humans and animal models. We utilised our rabbit model to examine the contribution of increased upper airway resistance to baroreflex resetting during snoring, by comparing BRS and baroreflex operating point (OP) values during IS to those obtained during tracheostomised breathing through an external resistive load (RL) titrated to match IS levels of peak inspiratory pleural pressure (Ppl). During both IS and RL, BRS decreased by 45% and 49%. There was a linear relationship between the change in Ppl and the decrease in BRS, which was similar for IS and RL. During both RL and IS, there was a shift in OP driven by ~16% increase in HR and no change in arterial pressure. Snoring related depression of BRS is likely mediated via a HR driven change in OP, which itself may be the outcome of negative intra-thoracic pressure mediated effects on right atrial wall stretch reflex control of heart rate.

A threshold lung volume for optimal mechanical effects on upper airway airflow dynamics: studies in an anesthetized rabbit model.

Increasing lung volume improves upper airway airflow dynamics via passive mechanisms such as reducing upper airway extraluminal tissue pressures (ETP) and increasing longitudinal tension via tracheal displacement. We hypothesized a threshold lung volume for optimal mechanical effects on upper airway airflow dynamics. Seven supine, anesthetized, spontaneously breathing New Zealand White rabbits were studied. Extrathoracic pressure was altered, and lung volume change, airflow, pharyngeal pressure, ETP laterally (ETPlat) and anteriorly (ETPant), tracheal displacement, and sternohyoid muscle activity (EMG%max) monitored. Airflow dynamics were quantified via peak inspiratory airflow, flow limitation upper airway resistance, and conductance. Every 10-ml lung volume increase resulted in caudal tracheal displacement of 2.1 ± 0.4 mm (mean ± SE), decreased ETPlat by 0.7 ± 0.3 cmH(2)O, increased peak inspiratory airflow of 22.8 ± 2.6% baseline (all P < 0.02), and no significant change in ETPant or EMG%max. Flow limitation was present in most rabbits at baseline, and abolished 15.7 ± 10.5 ml above baseline. Every 10-ml lung volume decrease resulted in cranial tracheal displacement of 2.6 ± 0.4 mm, increased ETPant by 0.9 ± 0.2 cmH(2)O, ETPlat was unchanged, increased EMG%max of 11.1 ± 0.3%, and a reduction in peak inspiratory airflow of 10.8 ± 1.0%baseline (all P < 0.01). Lung volume, resistance, and conductance relationships were described by exponential functions. In conclusion, increasing lung volume displaced the trachea caudally, reduced ETP, abolished flow limitation, but had little effect on resistance or conductance, whereas decreasing lung volume resulted in cranial tracheal displacement, increased ETP and increased resistance, and reduced conductance, and flow limitation persisted despite increased muscle activity. We conclude that there is a threshold for lung volume influences on upper airway airflow dynamics.