Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome.

Lowering surface tension (gamma) of upper airway lining liquid (UAL) reduces upper airway opening (anesthetized humans) and closing (anesthetized rabbits) pressures. We now hypothesize that in sleeping obstructive sleep apnea hypopnea syndrome (OSAHS) patients lowering gamma of UAL will enhance upper airway stability and decrease the severity of sleep-disordered breathing. Nine OSAHS patients [respiratory disturbance index (RDI): 49 +/- 8 (SE) events/h, diagnostic night] participated in a two-part, one-night, polysomnography study. In the first part, upper airway closing pressures (during non-rapid eye movement sleep, Pcrit) were measured and samples of UAL (awake) were obtained before and after 2.5 ml of surfactant (Exosurf, Glaxo Smith Kline) was instilled into the posterior pharynx. The gamma of UAL was determined with the use of the "pull-off" force technique. In the second part, subjects received a second application of 2.5 ml of surfactant and then slept the remainder of the night (205 +/- 30 min). Instillation of surfactant decreased the gamma of UAL from 60.9 +/- 3.1 mN/m (control) to 45.2 +/- 2.5 mN/m (surfactant group) (n = 9, P < 0.001). Pcrit decreased from 1.19 +/- 1.14 cmH2O (control) to -0.56 +/- 1.15 cmH2O (surfactant group) (n = 7, P < 0.02). Compared with the second half of diagnostic night, surfactant decreased RDI from 51 +/- 8 to 35 +/- 8 events/h (n = 9, P < 0.03). The fall in RDI (deltaRDI) correlated with the fall in gamma of UAL (deltagamma) (deltaRDI = 1.8 x deltagamma, r = 0.68, P = 0.04). Hypopneas decreased approximately 50% from 42 +/- 8 to 20 +/- 5 events/h (n = 9, P < 0.03, paired t-test). The gamma of UAL measured the next morning remained low at 49.5 +/- 2.7 mN/m (n = 9, P < 0.001, ANOVA, compared with control). In conclusion, instillation of surfactant reduced the gamma of UAL in OSAHS patients and decreased Pcrit and the occurrence of hypopneas. Therapeutic manipulation of gamma of UAL may be beneficial in reducing the severity of sleep-disordered breathing in OSAHS patients.     

Swallowing function and upper airway sensation in obstructive sleep apnea.

The objective of this study was to determine whether impaired upper airway (UA) mucosal sensation contributes to altered swallowing function in obstructive sleep apnea (OSA). We determined UA two-point discrimination threshold (2PDT) and vibratory sensation threshold (VST) in 15 men with untreated OSA and 9 nonapneic controls (CL). We then assessed swallowing responses to oropharyngeal fluid boluses delivered via a catheter. The threshold volume required to provoke swallowing and the mean latency to swallowing were determined, as was the phase of the respiratory cycle in which swallowing occurred [expressed as percentage of control cycle duration (%CCD)] and the extent of prolongation of the respiratory cycle after swallowing [inspiratory suppression time (IST)]. 2PDT and VST were significantly impaired in OSA patients compared with CL subjects. 2PDT was positively correlated with swallowing latency and threshold volume in CL subjects, but not in OSA patients. Threshold volume did not differ between the groups [median value = 0.1 ml (95% confidence interval = 0.1-0.2) for OSA and 0.15 ml (95% confidence interval = 0.1-0.16) for CL], whereas swallowing latency was shorter for OSA patients [3.3 (SD 0.7) vs. 3.9 (SD 0.8) s, P = 0.04]. %CCD and IST were similar for OSA patients and CL subjects. However, among OSA patients there was a significant inverse relation between VST and IST. These findings suggest that oropharyngeal sensory impairment in OSA is associated with an attenuation of inhibitory modulating inputs to reflex and central control of UA swallowing function.     

Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow

Computational fluid dynamic (CFD) analysis was used to model the effect of airway geometry on internal pressure in the upper airway of three children with obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was reconstructed from magnetic resonance images obtained during quiet tidal breathing, meshed with an unstructured grid, and solved at normative peak resting flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with steady flow boundary conditions in inspiration and expiration, using a two-equation low-Reynolds number turbulence model. Model results were validated using an in-vitro scale model, unsteady flow simulation, and reported nasal resistance measurements in children. Pharynx pressure drop strongly correlated to airway area restriction. Inspiratory pressure drop was primarily proportional to the square of flow, consistent with pressure losses due to convective acceleration caused by area restriction. On inspiration, in OSAS pressure drop occurred primarily between the choanae and the region where the adenoids overlap the tonsils (overlap region) due to airway narrowing, rather than in the nasal passages; in controls the majority of pressure drop was in the nasal passages. On expiration, in OSAS the majority of pressure drop occurred between the oropharynx (posterior to the tongue) and overlap region, and local minimum pressure in the overlap region was near atmospheric due to pressure recovery in the anterior nasopharynx. The results suggest that pharyngeal airway shape in children with OSAS significantly affects internal pressure distribution compared to nasal resistance. The model may also help explain regional dynamic airway narrowing during expiration.     

Determinants of the changes in positive airway pressure for the retitration in patients with obstructive sleep apnea syndrome

Sleep and Biological Rhythms - During long-term follow-up of the patients with obstructive sleep apnea syndrome (OSAS) under the positive airway pressure (PAP) therapy, it waits to be explored...     

Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea

To determine whether the pharyngeal airway is abnormal in awake patients with obstructive sleep apnea (OSA), we measured the ability of the pharyngeal airway to resist collapse from subatmospheric pressure applied to the nose in awake subjects, 12 with OSA and 12 controls. Subatmospheric pressure was applied to subjects placed in the supine position through a tightly fitting face mask. We measured airflow at the mask as well as mask, pharyngeal, and esophageal pressures. Ten patients developed airway obstruction when subatmospheric pressures between 17 and 40 cmH2O were applied. Obstruction did not occur in two patients with the least OSA. Obstruction did not occur in 10 controls; one obese control subject developed partial airway obstruction when -52 cmH2O was applied as did another with -41 cmH2O. We conclude that patients with significant OSA have an abnormal airway while they are awake and that application of subatmospheric pressure may be a useful screening test to detect OSA.     

Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea

Cala, S. J., P. Sliwinski, M. G. Cosio, and R. J. Kimoff.Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea. J. Appl.Physiol. 81(6): 2618-2626, 1996.It haspreviously been reported that the duration of obstructive apneasincreases from the beginning to the end of the night (M. Charbonneau,J. M. Marin, A. Olha, R. J. Kimoff, R. D. Levy, and M. Cosio.Chest 106: 1695-1701, 1994). The purpose of this study wasto test the hypothesis that stimulation of upper airway (UA) sensoryreceptors during obstructed inspiratory efforts contributes to arousaland apnea termination and that a progressive attenuation of thismechanism through the night contributes to apnea lengthening. Westudied seven patients (six men, one woman) with severe obstructivesleep apnea (apnea-hypopnea index = 93 ± 26 events/h) during twoconsecutive nights of polysomnographic monitoring. On one night (randomorder), we performed topical UA anesthesia with 0.2% tetracaine and onthe control night, sham anesthesia. We measured apnea duration,esophageal pressure (Pes) during apneas, and apneicO₂ desaturation. Consistent withprevious findings, apnea duration, number of efforts per apnea, andpeak Pes at end apnea increased from the beginning to the end of the control nights. UA anesthesia produced a significant increase in apneaduration at the beginning of the night but no change in apnea length atthe end of the night. Peak Pes and the rate of increase in Pes duringthe anesthesia nights were greater than during control nights, but therate of increase in Pes was similar for the beginning and end of thecontrol and anesthesia nights. These findings suggest that UA sensoryreceptors play a role in mediating apnea termination at the beginningof the night but that the contribution of these receptors diminishes asthe night progresses such that greater inspiratory efforts arerequired to trigger arousal, leading to apnea prolongation.

     

Gender differences in the preference for upper airway stimulation therapy among Japanese patients with obstructive sleep apnea already treated with continuous positive airway pressure

Sleep and Biological Rhythms - Although upper airway stimulation (UAS) is becoming an established therapy for obstructive sleep apnea (OSA) in Western countries, it is not available in Japan, where...     

Variable site of airway narrowing among obstructive sleep apnea patients

The purpose of this was to determine whether the site of physiological narrowing within the upper airway was uniform or differed among patients with obstructive sleep apnea. Inspiratory pressures were measured with an esophageal balloon catheter and three catheters located at different sites along the upper airway: supralaryngeal airway, oropharynx, and nasopharynx. Peak inspiratory pressure differences between catheters allowed assessment of pressure gradients across three airway segments: lungs-larynx-retroepiglottal airway (esophageal-supralaryngeal pressure), hypopharynx (supralaryngeal-oropharynx pressure), and transpalatal airway (oropharynx-nasopharynx pressure). In five patients, hypopharyngeal obstruction was present, and in four patients no hypopharyngeal obstruction existed. In these four patients the site of obstruction was located at the level of the palate. In a given subject, the site of obstruction was the same during repeated measurements. The presence or absence of hypopharyngeal narrowing during sleep was not predictable from gradients measured across different segments of the upper airway during wakefulness. We conclude that the site of physiological upper airway obstruction varies among patients with obstructive sleep apnea and is not predictable from pressure measured during wakefulness. We speculate that uvulopalatopharyngoplasty may not relieve obstructive apneas in patients with hypopharyngeal obstruction.     

Upper airway pressure-flow relationships in obstructive sleep apnea

We examined the pressure-flow relationships in patients with obstructive sleep apnea utilizing the concepts of a Starling resistor. In six patients with obstructive sleep apnea, we applied incremental levels of positive pressure through a nasal mask during non-rapid-eye-movement sleep. A positive critical opening pressure (Pcrit) of 3.3 +/- 3.3 (SD) cmH2O was demonstrated. As nasal pressure was raised above Pcrit, inspiratory airflow increased in proportion to the level of positive pressure applied until apneas were abolished (P less than 0.01). However, at pressures greater than Pcrit, esophageal pressures either did not correlate or correlated inversely with inspiratory airflow provided that esophageal pressure was less than Pcrit. When pressure was applied to a full face mask, inspiratory airflow did not occur and Pcrit could not be obtained at pressures well above Pcrit demonstrated with the nasal mask. These results are consistent with the view that the upper airway functions as a Starling resistor with a collapsible segment in the oropharynx. These findings offer a unifying construct for the association of sleep apnea, periodic hypopnea, and snoring.     

Orthodontic treatment for obstructive sleep apnea syndrome

Sleep and Biological Rhythms - We report a case where obstructive sleep apnea syndrome (OSAS) was improved with orthodontic treatment. The lower dental arch was expanded, the distance between the...     

Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is two to three times more common in men as in women. The mechanisms leading to this difference are currently unclear but could include gender differences in respiratory stability [loop gain (LG)] or upper airway collapsibility [pharyngeal critical closing pressure (Pcrit)]. The aim of this study was to compare LG and Pcrit between men and women with OSA to determine whether the factors contributing to apnea are similar between genders. The first group of 11 men and 11 women were matched for OSA severity (mean +/- SE apnea-hypopnea index = 43.8 +/- 6.1 and 44.1 +/- 6.6 events/h). The second group of 12 men and 12 women were matched for body mass index (BMI; 31.6 +/- 1.9 and 31.3 +/- 1.8 kg/m2, respectively). All measurements were made during stable supine non-rapid eye movement sleep. LG was determined using a proportional assist ventilator. Pcrit was measured by progressively dropping the continuous positive airway pressure level for three to five breaths until airway collapse. Apnea-hypopnea index-matched women had a higher BMI than men (38.0 +/- 2.4 vs. 30.0 +/- 1.9 kg/m2; P = 0.03), but LG and Pcrit were similar between men and women (LG: 0.37 +/- 0.02 and 0.37 +/- 0.02, respectively, P = 0.92; Pcrit: 0.35 +/- 0.62 and -0.18 +/- 0.87, respectively, P = 0.63). In the BMI-matched subgroup, women had less severe OSA during non-rapid eye movement sleep (30.9 +/- 7.4 vs. 52.5 +/- 8.1 events/h; P = 0.04) and lower Pcrit (-2.01 +/- 0.62 vs. 1.16 +/- 0.83 cmH2O; P = 0.005). However, LG was not significantly different between genders (0.38 +/- 0.02 vs. 0.33 +/- 0.03; P = 0.14). These results suggest that women may be protected from developing OSA by having a less collapsible upper airway for any given degree of obesity.     

Elevated levels of serum chemerin in patients with obstructive sleep apnea syndrome

Context: Chemerin is implicated to be correlated with obesity and inflammation.

Objective: This study aims to investigate whether serum chemerin is associated with the presence of obstructive sleep apnea syndrome (OSAS).

Methods: A total of 132 patients with OSAS and 108 healthy subjects were enrolled in this study.

Results: Serum chemerin levels were significantly elevated in OSAS patients (120.93 ± 25.84 µg/L vs. 107.51 ± 20.41 µg/L). Multivariable logistic regression analysis revealed that serum chemerin levels were an independent determinant of the presence of OSAS (OR 1.030, 95% CI 1.016–1.045; p < 0.001). Serum chemerin levels in severe OSAS patients were significantly higher compared with those in mild and moderate OSAS patients (p = 0.015 and p = 0.020, respectively). Spearman correlation analysis indicated that serum chemerin levels were correlated with the severity of OSAS (r = 0.210, p = 0.016). Serum chemerin were positively correlated with waist circumference (r = 0.164, p = 0.008), body mass index (r = 0.158, p = 0.014), systolic blood pressure (r = 0.135, p = 0.037), homeostasis model assessment of insulin resistance (r = 0.140, p = 0.031), C-reactive protein (r = 0.202, p = 0.002), and apnea–hypopnea index (r = 0.152, p = 0.022).

Conclusion: Elevated serum chemerin levels could be an independent predicting marker of the presence and severity of OSAS.     

Simulation of upper airway occlusion without and with mandibular advancement in obstructive sleep apnea using fluid-structure interaction

Obstructive Sleep Apnea (OSA) is a common sleep disorder characterized by repetitive collapse of the upper airway (UA). One treatment option is a mandibular advancement splint (MAS) which protrudes the lower jaw, stabilizing the airway. However not all patients respond to MAS therapy and individual effects are not well understood. Simulations of airway behavior may represent a non-invasive means to understand OSA and individual treatment responses. Our aims were (1) to analyze UA occlusion and flow dynamics in OSA using the fluid structure interaction (FSI) method, and (2) to observe changes with MAS. Magnetic resonance imaging (MRI) scans were obtained at baseline and with MAS in a known treatment responder. Computational models of the patients' UA geometry were reconstructed for both conditions. The FSI model demonstrated full collapse of the UA (maximum 5.83 mm) pre-treatment (without MAS). The UA collapse was located at the oropharynx with low oropharyngeal pressure (−51.18 Pa to −39.08 Pa) induced by velopharyngeal jet flow (maximum 10.0 m/s). By comparison, simulation results from the UA with MAS, showed smaller deformation (maximum 2.03 mm), matching the known clinical response. Our FSI modeling method was validated by physical experiment on a 1:1 flexible UA model fabricated using 3D steriolithography. This is the first study of airflow dynamics in a deformable UA structure and inspiratory flow. These results expand on previous UA models using computational fluid dynamics (CFD), and lay a platform for application of computational models to study biomechanical properties of the UA in the pathogenesis and treatment of OSA.