Ronald Douglas McEvoy

Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial

Background: Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD. Method: A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (Paco2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood. Results: 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01–5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and Paco2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour. Conclusions: Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life. Trial registration number: ACTRN12605000205639

Sleep hypoventilation in hypercapnic chronic obstructive pulmonary disease: prevalence and associated factors

Sleep hypoventilation (SH) may be important in the development of hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD). The prevalence of SH, associated factors, and overnight changes in waking arterial blood gases (ABG), were assessed in 54 stable hypercapnic COPD patients without concomitant sleep apnoea or morbid obesity. Lung function assessment, anthropomorphic measurements, and polysomnography with ABG measurement before and after sleep were conducted in all patients. Transcutaneous carbon dioxide tension (Pt,CO2) was measured in sleep, using simultaneous arterial carbon dioxide tension (Pa,CO2) for in vivo calibration and to correct for drift in the sensor. Of the patients, 43% spent ≥20% of sleep time with Pt,CO2 >1.33 kPa (10 mmHg) above waking baseline. Severity of SH was best predicted by a combination of baseline Pa,CO2, body mass index and per cent rapid-eye movement (REM) sleep. REM-related hypoventilation correlated significantly with severity of inspiratory flow limitation in REM, and with apnoea/hypopnoea index. Pa,CO2 increased mean±sd 0.70±0.65 kPa (5.29±4.92 mmHg) from night to morning, and this change was highly significant. The change in Pa,CO2 was strongly correlated with severity of SH. Sleep hypoventilation is common in hypercapnic chronic obstructive pulmonary disease, and related to baseline arterial carbon dioxide tension, body mass index and indices of upper airway obstruction. Sleep hypoventilation is associated with significant increases in arterial carbon dioxide tension night-to-morning, and may contribute to long-term elevations in arterial carbon dioxide tension.

Accurate Position Monitoring and Improved Supine-Dependent Obstructive Sleep Apnea with a New Position Recording and Supine Avoidance Device

STUDY OBJECTIVES Approximately 30% of obstructive sleep apnea (OSA) patients have supine-predominant OSA, and simply avoiding supine sleep should normalise respiratory disturbance event rates. However, traditional supine-avoidance therapies are inherently uncomfortable, and treatment adherence is poor and difficult to monitor objectively. This study evaluated the efficacy of a novel, potentially more acceptable position monitor and supine-avoidance device for managing supine-predominant OSA and snoring. DESIGN AND SETTING In-laboratory evaluation of position recording accuracy versus video recordings (validation study), and randomized controlled crossover trial of active versus inactive supine-avoidance therapy in the home setting (efficacy study). PATIENTS 17 patients undergoing in-laboratory sleep studies (validation) and 15 patients with supine-predominant OSA (efficacy). INTERVENTIONS EFFICACY STUDY: 1 week of inactive and 1 week of active treatment in randomized order, separated by 1 week. MEASUREMENTS AND RESULTS Agreement between 30-sec epoch-based posture classifications from device versus video records was high (median κ 0.95, interquartile range: 0.88-1.00), and there was good supine time agreement (bias 0.3%, 95%CI: -4.0% to 4.6%). In the efficacy study, apnea-hypopnea index (AHI) and snoring frequency were measured in-home using a nasal pressure and microphone based system during inactive and active treatment weeks. The position monitoring and supine alarm device markedly inhibited supine time (mean ± SEM 19.3% ± 4.3% to 0.4% ± 0.3%, p < 0.001) and reduced AHI (25.0 ± 1.7 to 13.7 ± 1.1 events/h, p = 0.030) but not snoring frequency. CONCLUSIONS This new position monitoring and supine alarm device records sleep position accurately and improves OSA but not snoring in patients with supine-predominant OSA.

Effect of CPAP on intrinsic PEEP, inspiratory effort, and lung volume in severe stable COPD

Background: Intrinsic positive end expiratory pressure (PEEPi) constitutes an inspiratory threshold load on the respiratory muscles, increasing work of breathing. The role of continuous positive airway pressure (CPAP) in alleviating PEEPi in patients with severe stable chronic obstructive pulmonary disease is uncertain. This study examined the effect of CPAP on the inspiratory threshold load, muscle effort, and lung volume in this patient group. Methods: Nine patients were studied at baseline and with CPAP increasing in increments of 1 cm H2O to a maximum of 10 cm H2O. Breathing pattern and minute ventilation (V̇i), dynamic PEEPi, expiratory muscle activity, diaphragmatic (PTPdi/min) and oesophageal (PTPoes/min) pressure-time product per minute, integrated diaphragmatic (EMGdi) and intercostal EMG (EMGic) and end expiratory lung volume (EELV) were measured. Results: Expiratory muscle activity was present at baseline in one subject. In the remaining eight, PEEPi was reduced from a mean (SE) of 2.9 (0.6) cm H2O to 0.9 (0.1) cm H2O (p<0.05). In two subjects expiratory muscle activity contributed to PEEPi at higher pressures. There were no changes in respiratory pattern but V̇i increased from 9.2 (0.6) l/min to 10.7 (1.1) l/min (p<0.05). EMGdi remained stable while EMGic increased significantly. PTPoes/min decreased, although this did not reach statistical significance. PTPdi/min decreased significantly from 242.1 (32.1) cm H2O.s/min to 112.9 (21.7) cm H2O.s/min). EELV increased by 1.1 (0.3) l (p<0.01). Conclusion: High levels of CPAP reduce PEEPi and indices of muscle effort in patients with severe stable COPD, but only at the expense of substantial increases in lung volume.

Upper airway function and arousability to ventilatory challenge in slow wave versus stage 2 sleep in obstructive sleep apnoea

Patients with obstructive sleep apnoea (OSA) have reduced event rates during slow wave sleep (SWS) compared with stage 2 sleep. To explore this phenomenon, ventilatory and arousal timing responses to partial and complete airflow obstruction during SWS versus stage 2 sleep were examined. Methods Ten patients, mean±SD apnoea–hypopnoea index (AHI) 49.7±16.5 events/h with reduced OSA frequency during SWS (SWS AHI 18.9±14.0 events/h) slept with an epiglottic pressure catheter and nasal mask/pneumotachograph. Patients underwent rapid continuous positive airway pressure (CPAP) dialdowns to three subtherapeutic levels and brief airway occlusions in random order. Results Post-dialdown, there were marked reductions in peak flow and minute ventilation, and progressive increases in inspiratory effort (p<0.001), but with limited ventilatory recovery and no differences between sleep stages. CPAP versus peak flow relationships on the third and second to last breath pre-arousal were not different between sleep stages. Arousals occurred later and post-dialdown arousal probability was lower during SWS compared with stage 2 sleep, Cox hazard ratio (95% CI) 0.65 (0.48 to 0.88), p=0.006. During SWS occlusions, time to arousal (mean±SEM) was prolonged (23.0±2.6 vs 17.1±1.7 s, p=0.02). Inspiratory effort developed more rapidly (−1.0±0.2 vs −0.6±0.1 cm H2O/s, p=0.019) and was more negative (−28.7±2.7 vs −20.3±1.6 cm H2O, p<0.001) on the breath preceding arousal. Conclusions Except for a heightened ventilatory drive response during airway occlusion, airway function and ventilatory compensation to ventilatory challenge appear to be similar, but with consistently and substantially delayed arousal responses, in SWS versus stage 2 sleep.

Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy.

STUDY OBJECTIVES The use of opioid medication for chronic pain has been increasing. The main aim of this study was to assess how many patients on opioids for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The impact of these medications on daytime arterial blood gas (ABG) measurements and psychomotor vigilance was also studied. METHODS Twenty-four patients (aged 18-75 years) on long-term opioids were prospectively recruited. Patients underwent home polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG. Overnight PSG findings were compared to those of patients matched for age, sex, and BMI referred to our sleep service for evaluation of SDB. PVT results in the patient cohort were compared to PVT in healthy controls. RESULTS Forty-six percent of opioid patients had severe SDB as defined by an apnea hypopnea index (AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic patients and sleep clinic patients (mean ± SD AHI: Opioid-treated patients 32.7 ± 25.6; Sleep Study comparator group 28.9 ± 24.6, p = 0.6). Opioid patients had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 ± 8.3 vs. 0.3 ± 0.5 events/h; p = 0.004, AI 8.0 ± 4.1 vs. 20.1 ± 13.8, p < 0.001). Pain clinic patients had impaired gas exchange during sleep and wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising number were in chronic respiratory failure. Morphine equivalent doses correlated with the severity of SDB. PVT was impaired when compared to a healthy PVT comparator group (RT: Opioid-treated patients 0.43 ± 0.27: Healthy PVT comparator group 0.28 ± 0.03 sec; p < 0.001). CONCLUSIONS Patients on long-term opioids frequently have severe SDB, which in part is central in origin. PVT was markedly impaired. Half of the patients studied have evidence of chronic ventilatory failure. COMMENTARY A commentary on this article appears in this issue on page 853

Diagnostic accuracy of a questionnaire and simple home monitoring device in detecting obstructive sleep apnea in a high cardiovascular risk Chinese population

Background and objective:  OSA is a common condition associated with cardiovascular (CV) morbidity. It remains underdiagnosed globally in part due to the limited availability and technical requirements of polysomnography (PSG). The aim of this study was to test the accuracy of two simple methods for diagnosing OSA.

Modified uvulopalatopharyngoplasty and coblation channeling of the tongue for obstructive sleep apnea: a multi-centre Australian trial

STUDY OBJECTIVES To investigate the surgical outcomes and efficacy of modified uvulopalatopharyngoplasty (mod UPPP) and Coblation channelling of the tongue (CCT) as a treatment for obstructive sleep apnea (OSA). METHODS Adult patients with simple snoring or obstructive sleep apnea were treated with combined modified UPPP, bilateral tonsillectomy, and CCT (N = 48). Full polysomnography was performed preoperatively and 3 months postoperatively. Postoperative clinical assessment, sleep questionnaires, and patient demographics including body mass index were compared to preoperative data. All polysomnograms were re-scored to AASM recommended criteria by 2 sleep professionals. RESULTS The preoperative AHI (median and interquartile range) of 23.1 (10.4 to 36.6) was lowered to a postoperative AHI of 5.6 (1.9 to 10.4) (p < 0.05). The Epworth Sleepiness Scale score fell from 10.5 (5.5 to 13.5) to 5.0 (3.09 to 9.5) (p < 0.05). Morbidity of the surgery was low, with no long-term complications recorded. CONCLUSIONS Modified UPPP combined with CCT is a highly efficacious intervention for OSA with minimal morbidity. It should be considered for individuals who fail or are intolerant of CPAP or other medical devices.

The Sleep Apnea cardioVascular Endpoints (SAVE) trial: Rationale, Ethics, Design, and Progress

ABSTRACT The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. CLINICAL TRIALS REGISTRATION NUMBER NCT00738179. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY NUMBER ACTRN12608000409370.

The Relationship between Functional Health Literacy and Obstructive Sleep Apnea and its Related Risk Factors and Comorbidities in a Population Cohort of Men

STUDY OBJECTIVES To examine the relationship between functional health literacy (FHL) and obstructive sleep apnea (OSA), its diagnosis, related risk factors, and comorbidities. DESIGN Population cohort study. SETTING Adelaide, South Australia, 2011-12. PARTICIPANTS 1,021 Men Androgen Inflammation Lifestyle Environment and Stress Study participants aged ≥ 40 years, of whom 627 were identified with OSA by self-report (n = 184 previously diagnosed) or with in-home polysomnography in 837 randomly selected participants without self-reported OSA (n = 443 previously undiagnosed). INTERVENTIONS The Newest Vital Sign assessed FHL in 88% of participants. Full in-home unattended polysomnography (Embletta X100) was scored by 2007 AASM (alternative) criteria. MEASUREMENTS AND RESULTS FHL was adequate in 75.3% (n = 122) of previously diagnosed and 68.3% (n = 261) of previously undiagnosed OSA. Not having a previous diagnosis was independently associated with inadequate FHL (odds ratio [OR]:2.84, 95% confidence interval [CI]:1.25-6.45) and workforce participation (OR = 2.04, 95% CI = 1.01-4.00), and inversely associated with previous snoring (OR = 0.48, 95% CI = 0.29-0.81), obesity (OR = 0.35, 95% CI = 0.15-0.81), and cardiovascular disease (OR = 0.45, 95% CI = 0.24-0.85). In polysomnography participants, inadequate FHL was independently associated with previously undiagnosed OSA (OR = 2.43, 95% CI = 1.40-4.20). In undiagnosed men, less than adequate FHL was independently associated with sedentary lifestyle (OR = 2.42, 95% CI = 1.36-4.29), and depression (OR = 2.50, 95% CI = 1.23-5.09) and inadequate FHL was associated with current smoking (OR = 2.87, 95% CI = 1.21-6.84). The depression association was attenuated after additional adjustment for comorbidities and general health (OR = 2.04, 95% CI = 0.93-4.49, P = 0.076). In previously diagnosed OSA, less than adequate FHL was independently associated with cardiovascular disease (OR = 2.76, 95% CI = 1.09-7.01). CONCLUSIONS Limited functional health literacy was independently associated with obstructive sleep apnea (OSA), OSA diagnosis, lifestyle factors and comorbidities, highlighting the importance of developing and promoting national disease-specific health literacy policies.