Nocturnal oxygen therapy in obstructive sleep apnoea: a systematic review and meta-analysis.

Obstructive sleep apnoea is characterised by recurrent reduction of airflow during sleep leading to intermittent hypoxia. Continuous positive airway pressure is the first-line treatment but is limited by poor adherence. Nocturnal oxygen therapy may be an alternative treatment for obstructive sleep apnoea but its effects remain unclear. This meta-analysis evaluates the effects of nocturnal oxygen therapy on both obstructive sleep apnoea severity and blood pressure.A literature search was performed based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Peer-reviewed, randomised studies that compared the effect of nocturnal oxygen therapy to sham in obstructive sleep apnoea patients were included. The main outcomes were the apnoea-hypopnoea index and systolic and diastolic blood pressure.The search strategy yielded 1295 citations. Nine studies with 502 participants were included. When nocturnal oxygen therapy was compared to sham/air, it significantly reduced the apnoea-hypopnoea index (mean difference (MD) -15.17 events·h-1, 95% CI -19.95- -10.38 events·h-1, p<0.00001). Nocturnal oxygen therapy had no significant effect on blood pressure at follow-up without adjustment for baseline values, but did, where available, significantly attenuate the change in blood pressure from baseline to follow-up for both systolic blood pressure (MD -2.79 mmHg, 95% CI -5.45- -0.14 mmHg, p=0.040) and diastolic blood pressure (MD -2.20 mmHg, 95% CI -3.83- -0.57 mmHg, p=0.008).Nocturnal oxygen therapy reduced the apnoea-hypopnoea index severity and the change in (but not absolute) systolic and diastolic blood pressure, compared to sham. This suggests that nocturnal oxygen therapy may be a treatment option for obstructive sleep apnoea. Further studies with longer-term follow-up and standardised measurements are needed.

Mild obstructive sleep apnoea in females: post hoc analysis of the MERGE randomised controlled trial.

Background: A post hoc analysis of the MERGE trial was conducted, to investigate whether sex differences are evident at the mildest end of the disease spectrum, for symptoms associated with obstructive sleep apnoea (OSA) and the response to continuous positive airway pressure (CPAP) treatment. Methods: MERGE participants with mild OSA (apnoea-hypopnoea index 5-15 events·h-1; American Academy of Sleep Medicine 2012 criteria) were randomised to either CPAP plus standard care (sleep hygiene counselling) or standard care alone for 3 months. Quality of life (QoL) was measured by questionnaires completed before and after the 3 months. This post hoc analysis of participants of the MERGE trial compared the symptom presentation, and response to CPAP, between the sexes. Results: 233 patients were included; 71 (30%) were female. Females were more symptomatic at baseline in all QoL questionnaires. Specifically, females had lower 36-item Short-Form Health Survey (SF-36) Vitality scores (mean±sd 39.1±10.1 versus 44.8±10.3) and higher Epworth Sleepiness Scale (ESS) scores (mean±sd 11.0±4.2 versus 9.5±4.4). Both sexes experienced snoring, but more females reported fatigue and more males reported witnessed apnoeas. All symptoms improved with CPAP for both sexes; however, females had larger improvements in SF-36 Vitality scores, which was the primary outcome of the MERGE trial (mean change 9.4 (95% CI 6.8-12.0) versus 6.0 (95% CI 4.3-7.7); p=0.034), and ESS (mean change -4.1 (95% CI -5.1- -3.0) versus -2.5 (95% CI -3.1- -1.8); p=0.015), after adjustment for baseline scores and CPAP usage. Conclusions: Sex differences are apparent in patients with mild OSA. Females experience worse QoL symptoms than males at presentation to the sleep clinic; however, these improve significantly with CPAP treatment.

Right ventricular responses to CPAP therapy in obstructive sleep apnea: CMR analysis of the MOSAIC randomized trial.

Effects of continuous positive airway pressure (CPAP) on right ventricular (RV) function in patients with untreated mild-to-moderate obstructive sleep apnea (OSA) are unclear. In this exploratory analysis of cardiac magnetic resonance (CMR)-derived indices of RV function in patients with minimally symptomatic OSA from the MOSAIC randomized control trial we found no effect of CPAP on RV CMR parameters. In those with lower RV ejection fraction and higher RV end-diastolic volume (EDV) at baseline, CPAP treatment appeared to improve RV function with a significant reduction in both RV EDV and RV end-systolic volume although between-group effects were not observed. These data suggest potential merit in a larger randomized study of CPAP in patients with mild-to-moderate OSA and a greater breadth of RV dysfunction.

Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial.

BACKGROUND: The evidence base for the treatment of mild obstructive sleep apnoea is limited and definitions of disease severity vary. The MERGE trial investigated the clinical effectiveness of continuous positive airway pressure in patients with mild obstructive sleep apnoea. METHODS: MERGE, a multicentre, parallel, randomised controlled trial enrolled patients (≥18 years to ≤80 years) with mild obstructive sleep apnoea (apnoea-hypopnoea index [AHI] ≥5 to ≤15 events per h using either AASM 2007 or AASM 2012 scoring criteria) from 11 UK sleep centres. Participants were assigned (1:1) to either 3 months of continuous positive airway pressure plus standard care (sleep counselling), or standard care alone, by computer-generated randomisation; neither participants nor researchers were blinded. The primary outcome was a change in the score on the Short Form-36 questionnaire vitality scale in the intention-to-treat population of patients with mild obstructive sleep apnoea diagnosed using the American Academy of Sleep Medicine 2012 scoring criteria. The study is registered with ClinicalTrials.gov, NCT02699463. FINDINGS: Between Nov 28, 2016 and Feb 12, 2019, 301 patients were recruited and randomised. 233 had mild obstructive sleep apnoea using AASM 2012 criteria and were included in the intention-to-treat analysis: 115 were allocated to receive continuous positive airway pressure and 118 to receive standard care. 209 (90%) of these participants completed the trial. The vitality score significantly increased with a treatment effect of a mean of 10·0 points (95% CI 7·2-12·8; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (9·2 points [6·8 to 11·6] vs -0·8 points [-3·2 to 1·5]). Using the ANCOVA last-observation-carried-forward analysis, a more conservative estimate, the vitality score also significantly increased with a treatment effect of a mean of 7·5 points (95% CI 5·3 to 9·6; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (7·5 points [6·0 to 9·0] vs 0·0 points [-1·5 to 1·5]). Three serious adverse events occurred (one allocated to the continuous positive airway pressure group) and all were unrelated to the intervention. INTERPRETATION: 3 months of treatment with continuous positive airway pressure improved the quality of life in patients with mild obstructive sleep apnoea. These results highlight the need for health-care professionals and providers to consider treatment for patients with mild obstructive sleep apnoea. FUNDING: ResMed Ltd.

Highlights from the 2018 European Respiratory Society International Congress: sleep and clinical physiology.

The 2018 European Respiratory Society (ERS) International Congress held in Paris, France, served as a platform to discover the latest research on respiratory diseases, the improvement in their treatments and patient care. Specifically, the scientific sessions organised by ERS Assembly 4 provided novel insights into sleep disordered breathing and fresh knowledge in respiratory physiology, stressing its importance to understanding and treating respiratory diseases. This article, divided by session, will summarise the most relevant studies presented at the ERS International Congress. Each session has been written by early career members specialised in the different fields of this interdisciplinary assembly.

Night-to-night variability of obstructive sleep apnea.

One night of a sleep study is the standard for diagnosis and exclusion of obstructive sleep apnea. Single testing requires high sensitivity of the test method and a stable disease of interest to warrant a low rate of false-negative tests. Obstructive sleep apnea is diagnosed and graded by conventional thresholds of apneas and hypopneas per hour of sleep, and treatment is usually initiated in the presence of symptoms. The aim of this study was to assess night-to-night variability of obstructive sleep apnea to reassess the current practice. Seventy-seven patients previously diagnosed with obstructive sleep apnea, randomised to continuous positive airway pressure withdrawal within four trials, performed nightly pulse-oximetry over 2 weeks while off continuous positive airway pressure. The main outcome of interest was the coefficient of variation of the oxygen desaturation index marking night-to-night variability in obstructive sleep apnea. Obstructive sleep apnea was categorised according to conventional thresholds using oxygen desaturation index (no obstructive sleep apnea: <5 per h; mild: 5-15 per h; moderate: 15-30 per h; and severe: >30 per h). High night-to-night variability of obstructive sleep apnea was evidenced by a coefficient of variation of oxygen desaturation index of 31.1% (SD 16.5). Differences in oxygen desaturation index of >10 per h between nights were found in 84.4% and shifts in obstructive sleep apnea severity category in 77.9% of patients. The probability of missing moderate obstructive sleep apnea was up to 60%. Variability was higher in less severe obstructive sleep apnea. Obstructive sleep apnea shows a considerable night-to-night variability. Single-night diagnostic sleep studies are prone to miscategorise obstructive sleep apnea if arbitrary thresholds are used. Thus, treatment decisions should be based less on the conventional derivatives from sleep studies, especially in patients with less severe obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: www.controlled-trials.com (ISRCTN 93153804, ISRCTN 73047833) and www.clinicaltrials.gov (NCT01332175 & NCT02050425).

In patients with minimally symptomatic OSA can baseline characteristics and early patterns of CPAP usage predict those who are likely to be longer-term users of CPAP.

BACKGROUND: Long-term continuous positive airway pressure (CPAP) usage varies between individuals. It would be of value to be able to identify those who are likely to benefit from CPAP (and use it long term), versus those who would not, and might therefore benefit from additional help early on. First, we explored whether baseline characteristics predicted CPAP usage in minimally symptomatic obstructive sleep apnoea (OSA) patients, a group who would be expected to have low usage. Second, we explored if early CPAP usage was predictive of longer-term usage, as has been shown in more symptomatic OSA patients. METHODS: The MOSAIC trial was a multi-centre randomised controlled trial where minimally symptomatic OSA patients were randomised to CPAP, or standard care, for 6 months. Here we have studied only those patients randomised to CPAP treatment. Baseline characteristics including symptoms, questionnaires [including the Epworth sleepiness score (ESS)] and sleep study parameters were recorded. CPAP usage was recorded at 2-4 weeks after initiation and after 6 months. The correlation and association between baseline characteristics and 6 months CPAP usage was assessed, as was the correlation between 2 and 4 weeks CPAP usage and 6 months CPAP usage. RESULTS: One hundred and ninety-five patients randomised to CPAP therapy had median [interquartile range (IQR)] CPAP usage of 2:49 (0:44, 5:13) h:min/night (h/n) at the 2-4 weeks visit, and 2:17 (0:08, 4:54) h/n at the 6 months follow-up visit. Only male gender was associated with increased long-term CPAP use (male usage 2:56 h/n, female 1:57 h/n; P=0.02). There was a moderate correlation between the usage of CPAP at 2-4 weeks and 6 months, with about 50% of the variability in long-term use being predicted by the short-term use. CONCLUSIONS: In patients with minimally symptomatic OSA, our study has shown that male gender (and not OSA severity or symptom burden) is associated with increased long-term use of CPAP at 6 months. Although, in general, early patterns of CPAP usage predicted longer term use, there are patients in whom this is not the case, and patients with low initial usage may need to extend their CPAP trial before a decision about longer-term use is made.

Circadian rest-activity rhythm is altered in Parkinson's disease patients with hallucinations.

The sleep-wake cycle in Parkinson's Disease (PD) is profoundly disrupted, but less is known about circadian rhythm in PD and its relationship to other important clinical features. This study compared rest-activity rhythms in healthy older adults and PD patients with and without hallucinations. Twenty-nine older adults and 50 PD patients (27 with hallucinations, 23 without) were assessed using wrist-worn actigraphy for 5 days. Disease-related and cognitive data were also collected. PD patients demonstrated reduced amplitude of activity (F = 12.719, P < 0.01) and increased intradaily variability (F = 22.005, P < 0.001), compared to healthy older adults, independently of age, and cognitive status. Hallucinators showed lower interdaily stability (F = 7.493, P < 0.01) significantly greater activity during "night-time" (F = 6.080, P < 0.05) and significantly reduced relative amplitude of activity (F = 5.804, P < 0.05) compared to nonhallucinators, independently of clinical factors including motor fluctuations. PD patients with hallucinations display altered rest-activity rhythm characterized by an unpredictable circadian pattern across days, likely arising from damage to brainstem and hypothalamic sleep centers. Treatment of sleep and rest-activity rhythm disturbance is an important target in Parkinson's Disease.

The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas-mediated apoptosis.

The chemopreventive properties of the isothiocyanates have been attributed to their ability to inhibit phase I enzymes that activate procarcinogens, induce phase II protective enzymes and trigger apoptosis in transformed cells. In this study we provide evidence for a new mechanism of chemoprevention, wherein sublethal doses of phenethyl isothiocyanate (PEITC) sensitize cells to Fas-mediated apoptosis. The phenomenon was observed in the Fas-resistant T24 bladder carcinoma cell line and in Jurkat T cells overexpressing the anti-apoptotic protein Bcl-2. Caspase-3-like activity was increased up to 20-fold of that observed with either PEITC or anti-Fas antibody alone. While PEITC activated ERK, JNK and p38, inhibitors of these MAP kinases did not block apoptosis. PEITC transiently depleted cellular glutathione, providing a putative mechanism for sensitizing the cells to apoptosis. However, lowering glutathione with buthionine sulfoximine did not mimic the effect of PEITC. Instead, we propose that PEITC promotes apoptosis by directly modifying intracellular thiol proteins. The ability of PEITC to sensitize cells to receptor-mediated apoptosis provides an additional mechanism to explain its chemopreventive properties.

Assessing caregiving distress: a conceptual analysis and a brief scale.

OBJECTIVES: Although it is well known that informal caregiving can have negative outcomes, and is an important factor in institutionalization, there is currently no common model to assess psychological distress in caregivers. In this study, we considered the conceptualization of caregiving distress, and present a five-dimension, 17-item Caregiving Distress Scale (CDS). DESIGN: The CDS was developed by administering several scales from the caregiving literature to a sample of 80 Parkinson's disease caregivers longitudinally. METHOD: A total of 58 items from published questionnaires were reduced initially by a hierarchical cluster analysis, then by factor analysis. RESULTS: This procedure produced five distinctive subscales - relationship distress, emotional burden, care-receiver demands, social impact, and personal cost - that also had high internal reliability. CONCLUSION: The CDS is quick to administer and score, and has the potential to be used to profile an individual caregiving situation. Of critical importance for the application of findings from the caregiving literature, the scale can be used to target the type of intervention for the amelioration of caregiving distress.