High prevalence of severe sleep cycle disruption in de novo acromegaly and underdiagnosis by common clinical screening tools: A prospective, observational, cross-sectional study.

CONTEXT: Although sleep disordered breathing (SDB) is well-recognised in acromegaly, most studies have reported heterogeneous, often heavily treated, groups and few have performed detailed sleep phenotyping at presentation. OBJECTIVE: To study SDB using the gold standard of polysomnography, in the largest group of newly-diagnosed, treatment-naïve patients with acromegaly. SETTING AND PATIENTS: 40 patients [22 males, 18 females; mean age 54 years (range 23-78)], were studied to: (i) establish the prevalence and severity of SDB (ii) assess the reliability of commonly employed screening tools [Epworth Sleepiness Scale (ESS) and overnight oxygen desaturation index (DI)] to detect SDB (iii) determine the extent to which sleep architecture is disrupted. RESULTS: Obstructive sleep apnoea (OSA), defined by the apnoea-hypopnoea index (AHI), was present in 79% of subjects (mild, n = 12; moderate, n = 5; severe, n = 14). However, in these individuals with OSA by AHI criteria, ESS (positive in 35% [n = 11]) and DI (positive in 71%: mild, n = 11; moderate, n = 6; severe, n = 5) markedly underestimated its prevalence/extent. Seventy-eight percent of patients exhibited increased arousal, with marked disruption of the sleep cycle, despite most (82%) having normal total time asleep. Fourteen patients spent longer in stage 1 sleep. Deeper sleep stages were severely attenuated in many subjects (reduced stage 2, n = 18; reduced slow wave sleep, n = 24; reduced rapid eye movement sleep, n = 32). CONCLUSION: Our study provides strong support for clinical guidelines that recommend screening for sleep apnoea syndrome in patients with newly-diagnosed acromegaly. Importantly, however, it highlights shortcomings in commonly recommended screening tools (questionnaires, desaturation index) and demonstrates the added value of polysomnography to allow timely detection of obstructive sleep apnoea and associated sleep cycle disruption.

'Distant socializing,' not 'social distancing' as a public health strategy for COVID-19.

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing. However, socializing in a safe context (i.e. over the phone, video-chat, etc.) is especially important during this time of crisis. Therefore, in this narrative review, we suggest the term 'distant socializing' as more apt expression, to promote physical distancing measures while also highlighting the importance of maintaining social bonds. Further, articles discussing the practice, implementation, measurement, and mental health effects of physical distancing are reviewed. Physical distancing is associated with psychiatric symptoms (such as anxiety and depression), suicidal ideation, and domestic violence. Further, unemployment and job insecurity have significantly increased during COVID-19, which may exacerbate these negative mental health effects. Governments, medical institutions, and public health bodies should therefore consider increasing mental health resources both during and after the pandemic, with a specific focus on frontline workers, COVID-19 survivors, and marginalized communities.

Reassessment of the risk of narcolepsy in children in England 8 years after receipt of the AS03-adjuvanted H1N1 pandemic vaccine: A case-coverage study.

BACKGROUND: Early studies of narcolepsy after AS03-adjuvanted pandemic A/H1N12009 vaccine (Pandemrix) could not define the duration of elevated risk post-vaccination nor the risk in children aged under 5 years who may not present until much older. METHODS/FINDINGS: Clinical information and sleep test results, extracted from hospital notes at 3 large pediatric sleep centers in England between September 2017 and June 2018 for narcolepsy cases aged 4-19 years with symptom onset since January 2009, were reviewed by an expert panel to confirm the diagnosis. Vaccination histories were independently obtained from general practitioners (GPs). The odds of vaccination in narcolepsy cases compared with the age-matched English population was calculated after adjustment for clinical conditions that were indications for vaccination. GP questionnaires were returned for 242 of the 244 children with confirmed narcolepsy. Of these 5 were under 5 years, 118 were 5-11 years, and 119 were 12-19 years old at diagnosis; 39 were vaccinated with Pandemrix before onset. The odds ratio (OR) for onset at any time after vaccination was 1.94 (95% confidence interval [CI] 1.30-2.89), The elevated risk period was restricted to onsets within 12 months of vaccination (OR 6.65 [3.44-12.85]) and was highest within the first 6 months. After one year, ORs were not significantly different from 1 up to 8 years after vaccination. The ORs were similar in under five-year-olds and older ages. The estimated attributable risk was 1 in 34,500 doses. Our study is limited by including cases from only 3 sleep centers, who may differ from cases diagnosed in nonparticipating centers, and by imprecision in defining the centers' catchment population. The potential for biased recall of onset shortly after vaccination in cases aware of the association cannot be excluded. CONCLUSIONS: In this study, we found that vaccine-attributable cases have onset of narcolepsy within 12 months of Pandemrix vaccination. The attributable risk is higher than previously estimated in England because of identification of vaccine-attributable cases with late diagnoses. Absence of a compensatory drop in risk 1-8 years after vaccination suggests that Pandemrix does not trigger onsets in those in whom narcolepsy would have occurred later.

Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England.

STUDY OBJECTIVES: An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England. METHODS: Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design. RESULTS: Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45-12.38) using all cases and 9.06 (1.90-43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses. CONCLUSIONS: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design.

Sleep deficits but no metabolic deficits in premanifest Huntington's disease.

OBJECTIVE: Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage. METHODS: We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x-ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain. RESULTS: Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations. INTERPRETATION: The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology.

Clinical features of narcolepsy in children vaccinated with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in England.

AIM: The aim of this study was to investigate whether children in England with narcolepsy who received the ASO3 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix) differed clinically from unvaccinated patients. METHOD: A retrospective review was conducted in children with narcolepsy diagnosed by sleep centres and paediatric neurologists in 16 English hospitals. The inclusion criteria were patient age 4 to 18 years, onset of narcolepsy after January 2008, and diagnosis by the time of the key data-gathering visit in 2011. Clinical data came from hospital notes and general practitioner questionnaires. An expert panel validated the diagnoses. RESULTS: Seventy-five patients with narcolepsy were identified (43 males, 32 females; mean age at onset 10y 4mo, range 3-18y). Of these patients, 11 received the Pandemrix vaccine before narcolepsy onset. On first presentation, there were more frequent reports of cataplexy, among other features, in vaccinated than in unvaccinated patients (82% vs 55%), but only excessive weight gain (55% vs 20%) was significantly more frequent (p=0.03). Facial hypotonia (p=0.03) and tongue protrusion (p=0.01) were eventually seen more frequently in vaccinated children. When considering patients diagnosed within a year of onset, vaccinated children were not diagnosed more rapidly than unvaccinated children. INTERPRETATION: Some symptoms and signs of narcolepsy were more frequently reported in Pandemrix-vaccinated patients. There was no evidence of the more rapid diagnosis in vaccinated patients that has been reported in Finland and Sweden.

Pre-flight assessment in patients with obesity hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Reduced atmospheric pressure during air travel can cause significant hypoxaemia in some patients with respiratory disease. Our aims were to investigate the degree of hypoxaemia in patients with obesity hypoventilation syndrome (OHS) during hypoxic challenge test (HCT), and to identify any predictors of a positive HCT. METHODS: Thirteen patients underwent assessment, including HCT, lung function and incremental shuttle walk test. All had OHS well controlled with long-term nocturnal non-invasive ventilation (NIV). Patients with chronic obstructive pulmonary disease were excluded. A positive HCT was defined according to the British Thoracic Society (BTS) recommendation as arterial oxygen tension (PaO2) <6.6 kPa and/or oxygen saturation <85%. RESULTS: Mean age was 57 (± 11) years. Mean body mass index was 51.7 (± 12) kg/m(2) . Mean baseline PaO2 and arterial carbon dioxide tension (PaCO2) were 10.2 (9.5-11.3) kPa and 5.2 (3.7-6.8) kPa, respectively. Seven patients (54%) had a positive HCT. The correlation between baseline PaO2 and PaO2 at the end of the HCT was not statistically significant (r = 0.433, P = 0.184). A negative correlation was observed between baseline PaCO2 and PaO2 at the end of the HCT (r = -0.793, P = 0.004). A positive correlation was observed between the distance walked and the PaO2 at the end of the HCT (r = 0.608, P = 0.047). CONCLUSIONS: OHS is a risk factor for severe hypoxaemia during air travel even if the ventilatory failure is well controlled. An HCT before air travel is advisable in all OHS patients. Those with positive HCT may use NIV or have oxygen on-board as per BTS recommendation.

Sleep and circadian rhythm regulation in early Parkinson disease.

IMPORTANCE: Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE: To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS: Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES: Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα). RESULTS: Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE: Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.

Narcolepsy Associated with Duane's Syndrome.

The best characterised disorder of REM sleep, narcolepsy has never previously been associated with Duane's syndrome, in which there is developmental failure of the abducens nerve and its nucleus. The major brain stem nuclei responsible for REM sleep generation are situated in the pons in close proximity to the abducens nerve nucleus. We report the novel combination of Duane's syndrome and narcolepsy, providing new insight into the pathogenesis of narcolepsy.

A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy.

CONTEXT: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management. OBJECTIVE: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort. STUDY DESIGN: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy. RESULTS: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 µg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged. CONCLUSIONS: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.

Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis.

OBJECTIVE: To evaluate the risk of narcolepsy in children and adolescents in England targeted for vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine (Pandemrix) from October 2009. DESIGN: Retrospective analysis. Clinical information and results of sleep tests were extracted from hospital notes between August 2011 and February 2012 and reviewed by an expert panel to confirm the diagnosis. Vaccination and clinical histories were obtained from general practitioners. SETTING: Sleep centres and paediatric neurology centres in England. PARTICIPANTS: Children and young people aged 4-18 with onset of narcolepsy from January 2008. MAIN OUTCOME MEASURES: The odds of vaccination in those with narcolepsy compared with the age matched English population after adjustment for clinical conditions that were indications for vaccination. The incidence of narcolepsy within six months of vaccination compared with the incidence outside this period measured with the self controlled cases series method. RESULTS: Case notes for 245 children and young people were reviewed; 75 had narcolepsy (56 with cataplexy) and onset after 1 January 2008. Eleven had been vaccinated before onset; seven within six months. In those with a diagnosis by July 2011 the odds ratio was 14.4 (95% confidence interval 4.3 to 48.5) for vaccination at any time before onset and 16.2 (3.1 to 84.5) for vaccination within six months before onset. The relative incidence from the self controlled cases series analysis in those with a diagnosis by July 2011 with onset from October 2008 to December 2010 was 9.9 (2.1 to 47.9). The attributable risk was estimated as between 1 in 57,500 and 1 in 52,000 doses. CONCLUSION: The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children.

High pain frequency in narcolepsy with cataplexy.

BACKGROUND: Narcolepsy with cataplexy (NC) is caused by the loss of hypocretin neurons. Recent studies highlighted the roles for hypocretins in the modulation of nociceptive transmission. The aims of the present multicenter case-control study were to look at the frequency of pain in NC and to study the determinants and impact of pain on narcolepsy symptoms and quality of life (QoL). METHODS: Sixty-seven adult patients with NC, together with their physician, partner/friend, and sex- and age-matched normal controls underwent a face-to-face interview and completed questionnaires on the presence and frequency of pain, narcolepsy symptoms and QoL (Short-Form 36-item score, Functional Outcomes of Sleep Questionnaire, Medical Outcomes Study, Fatigue Severity Scale, and Beck Depression Inventory). RESULTS: One-third (32.8%) of NC patients experienced pain at least monthly, with a significantly higher frequency and impact than controls (17.9%) and independent of the patients' narcolepsy medication. The reporting of pain was well matched between patients and partners/friends but significant differences were observed between patients and physicians, with physicians significantly underestimating its frequency and impact. The location of chronic pain varies within subjects with differences between NC and controls. We pinpointed that sleep quantity and depression were determinants for pain, and chronic pain had significant impact on sleep quantity, depression and QoL in NC. CONCLUSION: We report, for the first time, evidence that chronic pain is significantly more common and disabling in NC compared to the general population. The findings call for improved attention to assessment and treatment of pain in the follow-up of NC.

Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia.

ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naïve CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naïve CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naïve CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts.

Hypoxic challenge assessment in individuals with obstructive sleep apnea.

BACKGROUND: The degree of arterial hypoxemia during air travel in individuals with obstructive sleep apnea (OSA) is not known. The Aerospace Medical Association considers a ground level arterial oxygen tension (PaO2) above 9.3 kPa as safe before air travel. METHODS: Fifteen subjects with untreated OSA (mean apnea-hypopnea index [AHI] 43/h) and 14 with treated OSA (mean AHI on CPAP 1.9/h) completed an assessment including hypoxic challenge test (HCT). The groups had similar mean age, mean BMI and pre-treatment OSA severity. RESULTS: Four subjects, all in the untreated group and with resting PaO2 >9.3 kPa and oxygen saturation (SpO2) >95%, had a positive HCT (PaO2 <6.6 kPa and/or SpO2 <85%). The PaO2 at the end of the HCT was significantly correlated with the minimum overnight SpO2 (r=.754, p=.002) but not with the daytime PaO2 and SpO2. Using a cut off value of 65%, the minimum overnight SpO2 had positive and negative predictive values of 57% and 100% respectively. CONCLUSIONS: OSA can be an additional risk factor for developing significant arterial hypoxemia during HCT. Baseline PaO2 and SpO2 did not predict arterial hypoxemia during the HCT. Minimum overnight SpO2 <65% may be used as a cut off to advise further assessment. Effective treatment of OSA seems to be the best option before air travel.

Weaning from prolonged invasive ventilation in motor neuron disease: analysis of outcomes and survival.

INTRODUCTION: Non-invasive ventilation (NIV) improves prognosis in patients with motor neuron disease (MND) in the absence of major bulbar involvement. However, some experience a rapid and unexpected decline in respiratory function and may undergo emergency tracheal intubation. Weaning from invasive ventilation can be difficult, and reported independence from invasive ventilation is uncommon with poor prognosis. The outcomes of patients with MND referred to a specialist weaning service following emergency tracheal intubation were examined and compared with MND patients electively initiating NIV. METHODS: A case note review was performed on all patients with MND invasively ventilated and referred to a specialist weaning service between 1992 and 2007. Outcomes were compared with those electively commenced on NIV during the same period. RESULTS: Thirty patients were referred for weaning from invasive ventilation which was started in 17 before MND was diagnosed. Fourteen patients (47%) were weaned from invasive ventilation but still required NIV, 13 failed to wean, and three died. Seventeen were discharged home from hospital. The median survival from tracheal intubation was 13.7 months (95% CI 0 to 30.8) for those previously diagnosed and 7.2 months (95% CI 5.1 to 9.4) for those not previously known to have MND. Comparison with patients initiated electively on NIV demonstrated similar survival estimates to that from emergency intubation (median 9.4 (95% CI 6.9 to 12.0) vs 7.8 (95% CI 2.6 to 12.9) months respectively). CONCLUSION: The prognosis in MND following acute respiratory failure and intubation is not always complete ventilator dependence if patients are offered a comprehensive weaning programme.

Asymptomatic sleep abnormalities are a common early feature in patients with Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric disturbance. In this article, we used polysomnography, actigraphy and a variety of validated questionnaires to ascertain the extent to which sleep changes are identifiable and measurable in mild stage HD, and importantly, to see whether patients are negatively impacted by the changes in their sleep. We found significant differences in sleep architecture and sleep efficiency in patients compared with controls using polysomnography. However, patient scores on the Functional Outcomes of Sleep Questionnaire, Medical Outcomes of Sleep Scale, and Epworth Sleepiness Scale were not significantly different to controls. These results suggest that although marked changes in sleep architecture are present in early HD and can be detected using polysomnography, patients do not necessarily recognize or report these abnormalities.

A randomised crossover trial comparing volume assured and pressure preset noninvasive ventilation in stable hypercapnic COPD.

Recent randomised controlled trials suggest non-invasive ventilation may offer benefit in the long-term management of ventilatory failure in stable COPD. The best mode of ventilation is unknown and newer volume assured modes may offer advantages by optimising ventilation overnight when treatment is delivered. This study compares volume assured with pressure preset non-invasive ventilation. Randomised crossover trial including twenty five subjects previously established on long-term non-invasive ventilation to manage COPD with chronic ventilatory failure. Two 8-week treatment periods of volume assured and pressure preset non-invasive ventilation. The primary outcomes were daytime arterial blood gas tensions and mean nocturnal oxygen saturation. Secondary outcomes included lung function, exercise capacity, mean nocturnal transcutaneous carbon dioxide, health status and compliance. No significant differences were seen in primary or secondary outcomes following 8 weeks of treatment when comparing volume assured and pressure preset ventilation. Primary outcomes assessed: mean (standard deviation) PaO(2) 7.8 (1.2) vs 8.1(1) kPa, PaCO(2) 6.7 (1.1) vs 6.3 (1.2) kPa and mean nocturnal oxygenation 90 (4) vs 91 (3)% volume assured versus pressure preset, respectively. Volume assured and pressure preset non-invasive ventilation appear equally effective in the long-term management of ventilatory failure associated with stable COPD.