Peter D. Rochford

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.

Changes in brain morphology in patients with obstructive sleep apnoea

Background Obstructive sleep apnoea (OSA) is a common disease that leads to daytime sleepiness and cognitive impairment. Attempts to investigate changes in brain morphology that may underlie these impairments have led to conflicting conclusions. This study was undertaken to aim to resolve this confusion, and determine whether OSA is associated with changes in brain morphology in a large group of patients with OSA, using improved voxel-based morphometry analysis, an automated unbiased method of detecting local changes in brain structure. Methods 60 patients with OSA (mean apnoea hypopnoea index 55 (95% CI 48 to 62) events/h, 3 women) and 60 non-apnoeic controls (mean apnoea hypopnoea index 4 (95% CI 3 to 5) events/h, 5 women) were studied. Subjects were imaged using T1-weighted 3-D structural MRI (69 subjects at 1.5 T, 51 subjects at 3 T). Differences in grey matter were investigated in the two groups, controlling for age, sex, site and intracranial volume. Dedicated cerebellar analysis was performed on a subset of 108 scans using a spatially unbiased infratentorial template. Results Patients with OSA had a reduction in grey matter volume in the right middle temporal gyrus compared with non-apnoeic controls (p<0.05, corrected for topological false discovery rate across the entire brain). A reduction in grey matter was also seen within the cerebellum, maximal in the left lobe VIIIb close to XI, extending across the midline into the right lobe. Conclusion These data show that OSA is associated with focal loss of grey matter that could contribute to cognitive decline. Specifically, lesions in the cerebellum may result in both motor dysfunction and working memory deficits, with downstream negative consequences on tasks such as driving.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN Observational, before and after CPAP treatment. SETTING Two tertiary hospital research institutes. PARTICIPANTS 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

Pilot Study of Remote Telemonitoring in COPD

BACKGROUND Remote in-home monitoring (RM) of symptoms and physiological variables may allow early detection and treatment of exacerbations of chronic obstructive pulmonary disease (COPD). It is unclear whether RM improves patient outcomes or healthcare resource utilization. This study determined whether RM is feasible in patients with COPD and if RM reduces hospital admissions or length of stay (LOS) or improves health-related quality of life (HRQOL). SUBJECTS AND METHODS Forty-four patients were randomized to standard best practice care (SBP) (n=22) or SBP+RM (n=22). RM involved daily recording of physiological variables, symptoms, and medication usage. RESULTS There were no differences (mean±SD, SBP versus SBP+RM) in age (68±8 versus 70±9 years), gender (male:female 10:12 in both groups), or previous computer familiarity (59% versus 50%) between groups. The SBP group had a lower forced expiratory volume in 1 s (0.66±0.24 versus 0.91±0.34 L, p<0.01) and more current smokers (six versus none, p<0.05). There were no differences in number of COPD-related admissions/year (1.5±1.8 versus 1.3±1.7, p=0.76), COPD-related LOS days/year (15.6±19.4 versus 11.4±19.6, p=0.66), total admissions/year (2.2±2.1 versus 2.0±2.3, p=0.86), total LOS days/year (22.1±29.9 versus 21.6±30.4, p=0.88), or HRQOL between the two groups. CONCLUSIONS The addition of RM to SBP was feasible but did not reduce healthcare utilization or improve quality of life in this group of patients already receiving comprehensive respiratory care.

Sleep disordered breathing in chronic stroke survivors. A study of the long term follow-up of the SCOPES cohort using home based polysomnography.

Prevalence of sleep-disordered breathing (SDB) (apnea-hypopnea index [AHI] > or = 5) in acute stroke patients ranges between 44% and 95%, compared to the community prevalence, 9 to 35% for women and 8 to 57% for men [age range 30-60 years]. Limited data exists beyond 3 months following stroke. We assessed the prevalence of SDB amongst stroke survivors at 3 years and compared results to data reported in normal and elderly populations. 90/143 eligible stroke survivors from an existing cohort underwent a home based sleep study. Mean age of the 78 subjects with a valid sleep study was 64 years (SD 15). Prevalence of SDB (AHI > or = 5) was 81% (95% CI 72% to 90%) and sleep apnoea syndrome (AHI > or = 5 plus ESS score > or =11) was 20% (95% CI 11% to 29%). Important predictors for AHI > or = 15 were haemorrhagic stroke (aOR12.06 [1.42-102.74]) and stroke severity at 1 month (aOR4.15 [1.05-16.38]). Large case-control studies are needed.

AASM criteria for scoring respiratory events: interaction between apnea sensor and hypopnea definition.

STUDY OBJECTIVES To examine the impact of using a nasal pressure sensor only vs the American Academy of Sleep Medicine (AASM) recommended combination of thermal and nasal pressure sensors on (1) the apnea index (AI), (2) the apnea-hypopnea index (AHI), where the AHI is calculated using both AASM definitions of hypopnea, and (3) the accuracy of a diagnosis of obstructive sleep apnea (OSA). DESIGN Retrospective review of previously scored in-laboratory polysomnography. SETTING A tertiary-hospital clinical sleep laboratory. PATIENTS OR PARTICIPANTS One hundred sixty-four consecutive adult patients with a potential diagnosis of OSA, who were examined during a 3-month period. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Studies were scored with and without the use of the oronasal thermal sensor. AIs and AHIs, using the nasal pressure sensor alone (AI(np) and AHI(np)), were compared with those using both a thermal sensor for the detection of apnea and a nasal pressure transducer for the detection of hypopnea (AI(th) and AHI(th)). Comparisons were repeated using the AASM recommended (AASM(rec)) and alternative (AASM(alt)) hypopnea definitions. AI was significantly different when measured from the different sensors, with AI(np) being 51% higher on average. Using the AASM(rec) hypopnea definition, the mean AHI(np) was 15% larger than the AHI(th); with large interindividual differences and an estimated 9.8% of patients having a false-positive OSA diagnosis at a cutpoint of 15 events and 4.3% at 30 events per hour. Using AASM(alt) hypopnea definition, the mean AHI(np) was 3% larger than the AHI(th), with estimated false-positive rates of 4.6% and 2.4%, respectively. The false-negative rate was negligible at 0.1% for both hypopnea definitions. CONCLUSIONS This study demonstrates that using only a nasal pressure sensor for the detection of apnea resulted in higher values of AI and AHI than when the AASM recommended thermal sensor was added to detect apnea. When the AASM(alt) hypopnea definition was used, the differences in AHI and subsequent OSA diagnosis were small and less than when the AASM(rec) hypopnea definition was used. In situations in which a thermal sensor cannot be used, for example, in limited-channel diagnostic devices, the AHI obtained with a nasal pressure sensor alone differs less from the AHI obtained from a polysomnogram that includes a thermal sensor when the AASM(alt) definition rather than the AASM(rec) definition of hypopnea is used. Thus, diagnostic accuracy is impacted both by the absence of the thermal sensor and by the rules used to analyze the polysomnography. Furthermore, where the thermal sensor is unreliable for sections of a study, it is likely that use of the nasal pressure signal to detect apnea will have modest impact.

Transcutaneous Measurement of Carbon Dioxide Tension During Extended Monitoring: Evaluation of Accuracy and Stability, and an Algorithm for Correcting Calibration Drift

BACKGROUND: When polysomnography is indicated in a patient with a presumed sleep disorder, continuous monitoring of arterial carbon dioxide tension (PaCO2) is desirable, especially if nocturnal hypoventilation is suspected. Transcutaneous CO2 monitors (PtcCO2) provide a noninvasive correlate of PaCO2, but their accuracy and stability over extended monitoring have been considered inadequate for the diagnosis of hypoventilation. We examined the stability and accuracy of PtcCO2 measurements and the performance of a previously described linear interpolation technique designed to correct for calibration drift. METHODS: We compared the PtcCO2 values from 2 TINA TCM-3 monitors to PaCO2 values from arterial blood samples obtained at the beginning, every 15 min of the first hour, and then hourly over 8 hours of monitoring in 6 hemodynamically stable, male, intensive care patients (mean age 46 ± 17 y). RESULTS: Time had a significant (P = .002) linear effect on the PtcCO2-PaCO2 difference, suggesting calibration drift over the monitoring period. We found no differences between monitor type or interaction between time and monitor type. For the 2 monitors the uncorrected bias was 3.6 mm Hg and the limits of agreement were −5.1 to 12.3 mm Hg. Our linear interpolation algorithm improved the bias and limits of agreement to 0.4 and −5.5 to 6.4 mm Hg, respectively. CONCLUSIONS: Following stabilization and correction for both offset and drift, PtcCO2 tracks PaCO2 with minimal residual bias over 8 hours of monitoring. Should future research confirm these findings, then interpolated PtcCO2 may have an increased role in detecting sleep hypoventilation and assessing the efficacy of treatment.

Night-to-night repeatability of supine-related obstructive sleep apnea.

RATIONALE Patients with obstructive sleep apnea (OSA) experience respiratory events with greater frequency and severity while in the supine sleeping position. Postural modification devices (PMDs) prevent supine sleep, although there is a paucity of guidance to help clinicians decide when to use PMDs for their patients. In order for PMDs to treat OSA effectively, patients must experience respiratory events in the supine sleeping position consistently from night to night and must have a low nonsupine apnea and hypopnea index (AHINS). OBJECTIVES To document the repeatability of traditionally defined supine predominant OSA on consecutive polysomnography, to determine whether the consistency of the supine-predominant phenotype can be improved by altering the definition of it, and to determine whether a low AHINS is repeatable from night to night. METHODS We recruited 75 patients for polysomnography on two separate nights. Patients were classified as having supine OSA on each night on the basis of traditional and novel definitions, and the classification systems used were compared on the basis of agreement from night to night. MEASUREMENTS AND MAIN RESULTS The definition of supine OSA with the highest level of agreement from night to night incorporates a supine AHI (AHIS) to AHINS ratio ≥4:1. In addition, agreement exists for males, but there is poor agreement for female patients, regardless of the definition applied. An AHINS <10 events/hour is highly repeatable from night to night. CONCLUSIONS Males with an AHIS:AHINS ratio ≥4:1 and an AHINS <10 events/hour represent a consistent supine-predominant OSA phenotype from night to night. This patient group is likely to benefit from treatment with PMD.

Cardiopulmonary response to oxygen therapy in hypoxaemic chronic airflow obstruction.

The acute change in pulmonary artery pressure in response to oxygen may have prognostic value for patients with chronic obstructive pulmonary disease treated with long term domiciliary oxygen. A study was carried out to elucidate the mechanism of the acute cardio-respiratory response to oxygen in such patients and to determine whether it can be quantified non-invasively. The effects of acute oxygen administration (100% for 20 minutes and 28% oxygen for 24 hours) were assessed by non-invasive means and right heart catheterisation in 17 patients with severe stable hypoxaemic chronic obstructive pulmonary disease. Measurements included change in the ratio of dead space to tidal volume (VD/VT), effective pulmonary capillary blood flow (by rebreathing and single breath soluble gas uptake: QRB, QSB), left ventricular ejection fraction (radionuclide ventriculography), and M mode echocardiographic estimates of ventricular diameters and fractional shortening. These values were compared with those obtained from right heart catheter measurements of pulmonary artery pressure, cardiac index (thermodilution and direct carbon dioxide Fick: QTD, QFICK), and pulmonary vascular resistance. Oxygen administration resulted in a significant fall in pulmonary artery pressure, QTD, and QRB and a significant increase in VD/VT. The fall in QRB after 100% oxygen breathing for 20 minutes correlated strongly with the fall in pulmonary artery pressure (r = 0.86). There was no correlation between the fall in pulmonary artery pressure and the fall in QSB or the risen in VD/VT. Left ventricular ejection fraction did not change significantly. Echocardiography was technically unsatisfactory because of lung hyperinflation. Apart from a possible relation between VO2max and fall in pulmonary artery pressure after 24 hours of 28% oxygen breathing (r = 0.49, p less than 0.1) none of the baseline respiratory function measurements predicted the fall in pulmonary artery pressure or QRB. It is concluded that the cardiopulmonary response to acute oxygen breathing in patients with hypoxic chronic obstructive pulmonary disease includes a reduction in pulmonary artery pressure and cardiac output and a redistribution of pulmonary blood flow, and that rebreathing measurements of effective pulmonary blood flow can be used to quantify this response non-invasively.

Flow–volume curve changes in patients with obstructive sleep apnoea and brief upper airway dysfunction

Patients with obstructive sleep apnoea (OSA) and those with brief upper airway dysfunction (BUAD) have been reported to have abnormalities of maximal flow–volume curves. This study was designed to assess the ability of flow–volume curves to predict the presence of OSA or BUAD.