John R. Wheatley

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS®; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty‐one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single‐arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea–hypopnea index, from in‐laboratory polysomnogram) and sleep‐related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea–hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h−1) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device‐related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Equivalence of nasal and oronasal masks during initial CPAP titration for obstructive sleep apnea syndrome.

STUDY OBJECTIVE Continuous positive airway pressure (CPAP) titration studies are commonly performed using a nasal mask but some patients may prefer a full-face or oronasal mask. There is little evidence regarding the equivalence of different mask interfaces used to initiate treatment. We hypothesized that oronasal breathing when using an oronasal mask increases upper airway collapsibility and that a higher pressure may be required to maintain airway patency. We also assessed patient preferences for the 2 mask interfaces. DESIGN Prospective, randomized, cross-over design with 2 consecutive CPAP titration nights. SETTING Accredited laboratory in a university hospital. PATIENTS OR PARTICIPANTS Twenty-four treatment-naive subjects with obstructive sleep apnea syndrome and respiratory disturbance index of greater than 15 events per hour. INTERVENTIONS CPAP titration was performed using an auto-titrating machine with randomization to a nasal or oronasal mask, followed by a second titration night using the alternate mask style. MEASUREMENTS AND RESULTS There was no significant difference in the mean pressures determined between nasal and oronasal masks, although 43% of subjects had nasal-to-oronasal mask-pressure differences of 2 cm H(2)O or more. Residual respiratory events, arousals, and measured leak were all greater with the oronasal mask. Seventy-nine percent of subjects preferred the nasal mask. CONCLUSIONS Patients with obstructive sleep apnea syndrome can generally switch between nasal and oronasal masks without changing machine pressure, although there are individual differences that may be clinically significant. Measured leak is greater with the oronasal mask. Most patients with obstructive sleep apnea syndrome prefer a nasal mask as the interface for initiation of CPAP. CLINICAL TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN: ACTRN12611000243910. URL: http://www.ANZCTR.org.au/ACTRN12611000243910.aspx

Decreased surface tension of upper airway mucosal lining liquid increases upper airway patency in anaesthetised rabbits.

The obstructive sleep apnoea syndrome (OSA) is a disorder characterised by repetitive closure and re‐opening of the upper airway during sleep. Upper airway luminal patency is influenced by a number of factors including: intraluminal air pressure, upper airway dilator muscle activity, surrounding extraluminal tissue pressure, and also surface forces which can potentially act within the liquid layer lining the upper airway. The aim of the present study was to examine the role of upper airway mucosal lining liquid (UAL) surface tension (γ) in the control of upper airway patency. Upper airway opening (PO) and closing pressures (PC) were measured in 25 adult male, supine, tracheostomised, mechanically ventilated, anaesthetised (sodium pentabarbitone), New Zealand White rabbits before (control) and after instillation of 0.5 ml of either 0.9 % saline (n= 9) or an exogenous surfactant (n= 16; Exosurf Neonatal) into the pharyngeal airway. The γ of UAL (0.2 μl) was quantified using the ‘pull‐off’ force technique in which γ is measured as the force required to separate two curved silica discs bridged by the liquid sample. The γ of UAL decreased after instillation of surfactant from 54.1 ± 1.7 mN m−1 (control; mean ±s.e.m.) to 49.2 ± 2.1 mN m−1 (surfactant; P < 0.04). Compared with control, PO increased significantly (P < 0.04; paired t test, n= 9) from 6.2 ± 0.9 to 9.6 ± 1.2 cmH2O with saline, and decreased significantly (P < 0.05, n= 16) from 6.6 ± 0.4 to 5.5 ± 0.6 cmH2O with surfactant instillation. Findings tended to be similar for PC. Change in both PO and PC showed a strong positive correlation with the change in γ of UAL (both r > 0.70, P < 0.001). In conclusion, the patency of the upper airway in rabbits is partially influenced by the γ of UAL. These findings suggest a role for UAL surface properties in the pathophysiology of OSA.

Oral airway flow dynamics in healthy humans.

1 Oral airway resistance (RO) is an important determinant of oro‐nasal partitioning of airflow (e.g. during exercise and sleep); however, little is known of factors influencing its magnitude and measurement. 2 We developed a non‐invasive standardized technique for measuring RO (based on a modification of posterior rhinomanometry) and examined inspiratory RO in 17 healthy male subjects (age, 36 ± 2 years (mean ±s.e.m.); height, 177 ± 2 cm; weight, 83 ± 3 kg). 3 Inspiratory RO (at 0.4 ls−1) was 0.86 ± 0.23 cmH2O l−1 s−1 during resting mouthpiece breathing in the upright posture. RO was unaffected by assumption of the supine posture, tended to decrease with head and neck extension and increased to 1.22 ± 0.19 cmH2O l−1 s−1 (n= 10 subjects, P < 0.01) with 40–45 deg of head and neck flexion. When breathing via a mouth‐mask RO was 2.98 ± 0.42 cmH2O l−1 s−1 (n= 7) and not significantly different from nasal airway resistance. 4 Thus, in awake healthy male subjects with constant jaw position, RO is unaffected by body posture but increases with modest degrees of head and neck flexion. This influence on upper airway patency may be important when oral route breathing is associated with alterations in head and neck position, e.g. during sleep.

Enforced mouth breathing decreases lung function in mild asthmatics.

Background and objective:  Nasal breathing provides a protective influence against exercise‐induced asthma. We hypothesized that enforced oral breathing in resting mild asthmatic subjects may lead to a reduction in lung function.

Mass loading of the upper airway extraluminal tissue space in rabbits: effects on tissue pressure and pharyngeal airway lumen geometry

Lateral pharyngeal fat pad compression of the upper airway (UA) wall is thought to influence UA size in patients with obstructive sleep apnea. We examined interactions between acute mass/volume loading of the UA extra-luminal tissue space and UA patency. We studied 12 supine, anesthetized, spontaneously breathing, head position-controlled (50 degrees ), New Zealand White rabbits. Submucosal extraluminal tissue pressures (ETP) in the anterolateral (ETPlat) and anterior (ETPant) pharyngeal wall were monitored with surgically inserted pressure transducer-tipped catheters (Millar). Tracheal pressure (Ptr) and airflow (V) were measured via a pneumotachograph and pressure transducer inserted in series into the intact trachea, with hypopharyngeal cross-sectional area (CSA) measured via computed tomography, while graded saline inflation (0-1.5ml) of a compliant tissue expander balloon in the anterolateral subcutaneous tissue was performed. Inspiratory UA resistance (Rua) at 20 ml/s was calculated from a power function fitted to Ptr vs. V data. Graded expansion of the anterolateral balloon increased ETPlat from 2.3 +/- 0.5 cmH(2)O (n = 11, mean +/- SEM) to 5.0 +/- 1.1 cmH(2)O at 1.5-ml inflation (P < 0.05; ANOVA). However, ETPant was unchanged from 0.5 +/- 0.5 cmH(2)O (n = 9; P = 0.17). Concurrently, Rua increased to 119 +/- 4.2% of baseline value (n = 12; P < 0.001) associated with a significant reduction in CSA between 10 and 70% of airway length to a minimum of 82.2 +/- 4.4% of baseline CSA at 40% of airway length (P < 0.05). We conclude that anterolateral loading of the upper airway extraluminal tissue space decreases upper airway patency via an increase in ETPlat, but not ETPant. Lateral pharyngeal fat pad size may influence UA patency via increased tissue volume and pressure causing UA wall compression.

Influence of breathing route on upper airway lining liquid surface tension in humans

We have recently demonstrated that the severity of sleep‐disordered breathing in obstructive sleep apnoea hypopnoea syndrome (OSAHS) can be reduced by lowering the surface tension (γ) of the upper airway lining liquid (UAL). Morning xerostomia (related to oral breathing during sleep) is reported by most OSAHS patients. In the present study we examine relationships between breathing route, oral mucosal ‘wetness’ and the γ of UAL. We studied eight healthy subjects (age, 25 ± 5 years [mean ±s.d.]; body‐mass index, 23 ± 2 kg m−2) during a 120 min challenge of both nasal‐only breathing (mouth taped) and oral‐only breathing (nose clip), each on a separate day (randomized). Both oral mucosal ‘wetness’ (5 s contact gravimetric absorbent paper strip method) and the γ (‘pull‐off’ force technique) of 0.2 μl samples of UAL obtained from the posterior pharyngeal wall were measured at 15 min intervals (mouth tape removed and replaced as required). Upper airway mucosal ‘wetness’ increased during 120 min of nasal breathing from 4.0 ± 0.4 (mean ±s.e.m.) to 5.3 ± 0.3 μl (5 s)−1 but decreased from 4.5 ± 0.4 to 0.1 ± 0.2 μl (5 s)−1 with oral breathing (both P < 0.001, repeated‐measures ANOVA, Tukeys multiple comparison test, post hoc test). Concurrently, the γ of UAL decreased from 59.3 ± 2.2 to 51.8 ± 0.98 mN m−1 with nasal breathing but increased from 64.4 ± 2.7 to 77.4 ± 1.1 mN m−1 with oral breathing (P < 0.001). For the group and all conditions studied, γ of UAL values strongly correlated with upper airway mucosal ‘wetness’ (correlation coefficient, r2=−0.34, P < 0.001; linear regression). We conclude that oral breathing increases and nasal breathing decreases the γ of UAL in healthy subjects during wakefulness. We speculate that nasal breathing in OSAHS patients during sleep may promote a low γ of UAL that may contribute to reducing the severity of sleep‐disordered breathing.

Nasal dilator strips increase maximum inspiratory flow via nasal wall stabilization

Objective: Inspiratory flow limitation associated with collapse of the nasal vestibular walls is a feature of nasal breathing at high ventilatory levels. We examined whether an external nasal dilator strip (ENDS) device (Breathe Right, CNS Inc., Chanhassen, MN) influences maximum inspiratory and expiratory flow rates. Study Design: Prospective, randomized. Methods: We studied 20 Caucasian subjects (13 female, 7 male; age range, 16–49 y) performing maximum‐effort nasal flow‐volume loop studies with (ENDS) and without ENDS (control) and following topical nasal decongestant (oxymetazoline hydrochloride, 0.2 mg per nostril). Results: ENDS increased peak inspiratory flow from 2.55 ± 0.24 L/s (mean ± standard error [SE]) to 2.86 ± 0.25 L/s and forced inspiratory flow at 50% of vital capacity from 2.23 ± 0.24 L/s to 2.53 ± 0.24 L/s (both, P < .0001), but had no effect on maximum expiratory flows. Nasal decongestant increased the forced expiratory volume in 1 second from 3.39 ± 0.22 L/s to 3.59 ± 0.22 L/s and the average forced expiratory flow over 25% to 75% of vital capacity from 3.31 ± 0.31 L/s to 3.61 ± 0.28 L/s (both, P ⩽ .008), but had no effect on maximum inspiratory flows. The combination of decongestant and ENDS increased both inspiratory and expiratory maximum flows. Conclusion: Since ENDS selectively increases maximum nasal inspiratory flow rates, we conclude that ENDS increases inspiratory nasal patency during maximum inspiratory efforts through the nose by supporting the lateral nasal vestibular walls and making them more resistant to collapse.

Pharyngeal muscle contraction modifies peri-pharyngeal tissue pressure in rabbits

We examined the influence of pharyngeal dilator muscle activity on upper airway extraluminal tissue pressure (ETP) distribution and upper airway patency. We studied seven anaesthetised, supine, spontaneously breathing NZ white rabbits. ETP was measured via pressure transducer tipped catheters in lateral (ETP(lat)) and anterior (ETP(ant)) pharyngeal wall tissues. Airflow (V) and tracheal pressure (P) were monitored and upper airway resistance (RUA) calculated. Genioglossus (GG) or bilateral sternohyoid (SH) muscles were electrically stimulated. Tongue protrusion (TP) during GG stimulation was measured. With GG stimulation, RUA decreased to 57.8+/-10.9% (mean+/-S.E.M.) of baseline and TP increased to 4.8+/-0.5mm (both p<0.05), but ETP(lat) (2.6+/-1.5 cm H(2)O) and ETP(ant) (1.4+/-0.8 cm H(2)O) were unchanged. SH stimulation reduced RUA to 53.6+/-6.8%, and ETP(lat) fell by 1.0+/-0.4 cm H(2)O (both p<0.05). ETP(ant) was unchanged. GG muscle contraction decreased RUA without altering ETP, whereas SH contraction altered RUA and ETP(lat), but not ETP(ant). Contraction of the upper airway dilator muscles results in improvements in upper airway patency associated with changes in peri-pharyngeal tissue pressure.