Background The Epworth Sleepiness Scale (ESS) is a widely used tool for assessing sleepiness in patients with obstructive sleep apnoea (OSA). We aimed to estimate the minimal important difference (MID) in patients with OSA. Methods We used individual data from three randomised controlled trials (RCTs) in patients with OSA where the preintervention to postintervention change in ESS was used as a primary outcome. We used anchor-based linear regression and responder analysis approaches to estimate the MID. For anchors, we used the change in domains of the Functional Outcomes of Sleep Questionnaire and 36-Item Short Form Health Survey. We also used the distribution-based approaches Cohen’s effect size, SE of measurement and empirical rule effect size to support the anchor-based estimates. The final MID was determined by triangulating all estimates to a single MID. Findings A total of 639 patients with OSA were included in our analyses across the three RCTs with a median (IQR) baseline ESS score of 10 (6–13). The median (IQR) ESS change score overall was −2 (−5 to 1). The anchor-based estimates of the MID were between −1.74 and −4.21 points and estimates from the responder analysis were between −1 and −3 points. Distribution-based estimates were smaller, ranging from −1.46 to −2.36. Interpretation We propose an MID for the ESS of 2 points in patients with OSA with a disease severity from mild to severe. This estimate provides the means to plan trials and interpret the clinical relevance of changes in ESS. Trial registration number Provent, NCT01332175; autoCPAP trial, NCT00280800; MOSAIC,ISRCTN (3416388).

Ketogenic diet (KD; high fat, low carb) is a standard treatment for obesity, neurological diseases (e.g., refractory epilepsy) and a promising method for athletes to improve their endurance performance. Therein, the level of ketosis must be regulated tightly to ensure an effective therapy. Here, we introduce a compact and inexpensive breath sensor to monitor ketosis online and non-invasively. The sensor consists of Si-doped WO₃ nanoparticles that detect breath acetone selectively with non-linear response characteristics in the relevant range of 1 to 66 ppm, as identified by mass spectrometry. When tested on eleven subjects (five women and six men) undergoing a 36-h KD based on the Johns Hopkins protocol, this sensor clearly recognizes the onset and progression of ketosis. This is in good agreement to capillary blood β-hydroxybutyrate (BOHB) measurements. Despite similar dieting conditions, strong inter-subject differences in ketosis dynamics were observed and correctly identified by the sensor. These even included breath acetone patterns that could be linked to low tolerance to that diet. As a result, this portable breath sensor represents an easily applicable and reliable technology to monitor KD, possibly during medical treatment of epilepsy and weight loss.

Rationale: Intravenous plasma-purified alpha-1 antitrypsin (IV-AAT) has been used as therapy for alpha-1 antitrypsin deficiency (AATD) since 1987. Previous trials (RAPID and RAPID-OLE) demonstrated efficacy in preserving computed tomography of lung density but no effect on FEV1. This observational study evaluated 615 people with severe AATD from three countries with socialized health care (Ireland, Switzerland, and Austria), where access to standard medical care was equal but access to IV-AAT was not. Objectives: To assess the real-world longitudinal effects of IV-AAT. Methods: Pulmonary function and mortality data were utilized to perform longitudinal analyses on registry participants with severe AATD. Measurements and Main Results: IV-AAT confers a survival benefit in severe AATD (P < 0.001). We uncovered two distinct AATD phenotypes based on an initial respiratory diagnosis: lung index and non–lung index. Lung indexes demonstrated a more rapid FEV1 decline between the ages of 20 and 50 and subsequently entered a plateau phase of minimal decline from 50 onward. Consequentially, IV-AAT had no effect on FEV1 decline, except in patients with a Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 lung index. Conclusions: This real-world study demonstrates a survival advantage from IV-AAT. This improved survival is largely decoupled from FEV1 decline. The observation that patients with severe AATD fall into two major phenotypes has implications for clinical trial design where FEV1 is a primary endpoint. Recruits into trials are typically older lung indexes entering the plateau phase and, therefore, unlikely to show spirometric benefits. IV-AAT attenuates spirometric decline in lung indexes in GOLD stage 2, a spirometric group commonly outside current IV-AAT commencement recommendations.

Resistance training of peripheral muscles has been recommended in order to increase muscle strength in patients with Chronic Obstructive Pulmonary Disease (COPD). However, whether peripheral muscle strength is associated with exercise performance (EP) and physical activity in daily life (PADL) in these patients needs to be investigated.

Obstructive sleep apnoea is a highly prevalent chronic disorder and has been shown to be associated with disturbed glucose metabolism and type 2 diabetes. However, the evidence from individual clinical trials on the effect of continuous positive airway pressure (CPAP) treatment on glycaemic control in patients with co-existing obstructive sleep apnoea and type 2 diabetes remains controversial. A systematic review of randomised controlled trials assessing the effect of CPAP on glycaemic control in patients with obstructive sleep apnoea and type 2 diabetes was conducted using the databases MEDLINE, Embase, Cochrane and Scopus up to December 2022. Meta-analysis using a random-effect model was performed for outcomes that were reported in at least two randomised controlled trials. From 3031 records screened, 11 RCTs with a total of 964 patients were included for analysis. CPAP treatment led to a significant reduction in haemoglobin A1c (HbA1c) (mean difference −0.24%, 95% CI −0.43– −0.06%, p=0.001) compared to inactive control groups. Meta-regression showed a significant association between reduction in HbA1c and hours of nightly CPAP usage. CPAP therapy seems to significantly improve HbA1c and thus long-term glycaemic control in patients with type 2 diabetes and obstructive sleep apnoea. The amount of improvement is dependent on the hours of usage of CPAP and thus optimal adherence to CPAP should be a primary goal in these patients.

Background: Altered cardiac repolarization and increased dispersion of repolarization have been identified as risk factors for sudden cardiac death (SCD). The prevalence of and the mechanisms contributing to altered cardiac repolarization are currently unknown in COPD. Methods: In 91 COPD patients, 32 controls matched for age, cardiovascular risk and medication, and 41 healthy subjects, measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) were derived from 12-lead electrocardiography (ECG). Prevalence rates of heart rate corrected QT (QTc) >450ms and QT dispersion >60ms were determined to assess the number of subjects at risk for SCD. Univariate and multivariate analyses were used to identify possible factors contributing to altered cardiac repolarization. Results: QTc was found to be prolonged in 31.9% and QT dispersion in 24.2% of the COPD patients compared to 12.5% in matched controls and 0% in healthy subjects. The QTc interval was longer in COPD patients compared to matched and healthy controls respectively (437.9 ± 29.5 vs. 420.1 ± 25.3 ms, p = 0.001 and vs. 413.4 ± 18.2 ms, p < 0.001). QT dispersion was significantly increased in COPD patients compared to healthy subjects (45.4 (34.8 , 59.5) vs. 39.7 (29.3 , 54.8) ms, p = 0.049). Only oxygen saturation was independently associated with QTc duration in multivariate analysis (β = -0.29, p = 0.015). Conclusion: One third of a typical COPD population has altered cardiac repolarization and increased dispersion of repolarization, which may be related to hypoxia. Altered cardiac repolarization may expose these patients to an increased risk for malignant ventricular arrhythmias and SCD.