Low-load blood flow restriction strength training in patients with COPD: a randomised single-blind pilot study.

OBJECTIVE: The objective of this study is to compare the effectiveness of lower limb low-load blood flow restriction training (LL-BFRT) with high-load strength training (HL-ST) as part of an outpatient pulmonary rehabilitation programme on leg strength in patients with chronic obstructive pulmonary disease (COPD). METHODS: Participants were randomised to LL-BFRT or HL-ST (24 sessions). LL-BFRT was done at 30% 1-repetition maximum (1-RM) with 70% arterial occlusion pressure. HL-ST was done at 70% 1-RM. Primary outcome was isometric strength of knee extensors and flexors. Secondary outcomes were 1-RM, functional exercise capacity, physical activity, symptom burden and health-related quality of life. Perceptions of dyspnoea and leg fatigue were recorded after every exercise. We compared groups with t-tests. RESULTS: We included 30 participants (13 women, 17 men, 64 (9) years, forced expiratory volume in 1 s 47 (18)% pred.), 24 completed the study. Isometric knee extensor strength improved to a clinically relevant degree in both legs in both groups (LL-BFRT: right leg 9 (20) Nm, left leg 10 (18) Nm; HL-ST: right leg 15 (26) Nm, left leg 16 (30) Nm, data are mean (SD)), without statistically significant or clinically relevant between-group differences (right leg mean difference= -6.4, 95% CI= -13.20 to 25.92 Nm, left leg mean difference= -5.6, 95% CI= -15.44 to 26.55 Nm). 1 min sit-to-stand test performance improved to a clinically relevant degree only in the LL-BFRT group (4 (4) vs 1 (5) repetitions). Interestingly, physical activity improved to a clinically relevant degree only in the LL-BFRT group (1506 (2441) vs -182 (1971) steps/day). LL-BFRT lowered perceived in-exercise dyspnoea and increased leg fatigue compared with HL-ST in the initial 12 trainings. CONCLUSION: In patients with stable COPD undergoing outpatient pulmonary rehabilitation, LL-BFRT was not superior to HL-ST in improving leg strength. LL-BFRT led to similar strength gains as HL-ST while reducing perceptions of dyspnoea in the initial training phase. TRIAL REGISTRATION NUMBER: NCT04151771.

The effect of longitudinal sleep monitoring on clinician agreement in obstructive sleep apnea diagnosis: The ELSA study.

There is strong evidence for clinically relevant night-to-night variability of respiratory events in patients with suspected obstructive sleep apnea. Sleep experts retrospectively evaluated diagnostic data in 56 patients with suspected obstructive sleep apnea. Experts were blinded to the fact that they were diagnosing the same case twice, once based on a short report of a single in-laboratory respiratory polygraphy and once with the additional information of 14 nights of pulse oximetry at home. All experts (n = 22) were highly qualified, 13 experts (59.1%) treated > 100 patients with suspected obstructive sleep apnea per year. In 12 patients, the apnea-hypopnea index in the respiratory polygraphy was < 5 per hr, but the mean oxygen desaturation index of 14 nights of pulse oximetry was ≥ 5 per hr. The additional information of 14 nights of pulse oximetry helped to diagnose obstructive sleep apnea with a 70% consensus in two of those patients (16.7% [95% confidence interval: 4.7/44.8]). In eight patients, experts could not agree to a 70% consensus regarding continuous positive airway pressure therapy recommendation after respiratory polygraphy. The additional information of multiple-night testing led to a consensus in three of those cases (37.5% [95% confidence interval: 14/69]). Change of obstructive sleep apnea diagnosis and continuous positive airway pressure recommendation was significantly negatively associated with the number of treated obstructive sleep apnea patients > 100 per year compared with 0-29 patients per year (Coef. [95% confidence interval] -0.63 [-1.22/-0.04] and -0.61 [-1.07/-0.15], respectively). Experts found already a high level of consensus regarding obstructive sleep apnea diagnosis, severity and continuous positive airway pressure recommendation after a single respiratory polygraphy. However, longitudinal sleep monitoring could help increase consensus in selected patients with diagnostic uncertainty.

Augmentation Therapy for Severe Alpha-1 Antitrypsin Deficiency Improves Survival and Is Decoupled from Spirometric Decline-A Multinational Registry Analysis.

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.

Increasing Daily Physical Activity and Its Effects on QTc Time in Severe to Very Severe COPD: A Secondary Analysis of a Randomised Controlled Trial.

Approximately, half of COPD patients die from cardiovascular diseases. A prolongation of cardiac repolarization (measured as QTc interval) is associated with cardiovascular events or cardiovascular deaths in populations of older adults and COPD. One way to reduce the QTc could be to increase physical activity (PA). We investigated whether QTc can be reduced by an increase in PA in patients with severe COPD. This is a secondary outcome analysis from a randomized controlled trial investigating the effects of a 3 months pedometer based program to improve PA. 12-lead ECG was assessed at baseline and after 3 months. We measured PA using a validated triaxial accelerometer. Data were analyzed from 59 participants. Multiple regression modeling, including adjustment for baseline QTc, sex, QT prolonging medications, BMI, smoking status and FEV1%, showed no evidence for an association between an improvement of ≥15% PA and QTc reduction. A 15% improvement in PA according to step counts over 3 months seems not to reduce QTc interval by its MCID of 20 ms in patients with severe to very severe COPD.

Severe Obstructive Sleep Apnea Disrupts Vigilance-State-Dependent Metabolism.

The direct pathophysiological effects of obstructive sleep apnea (OSA) have been well described. However, the systemic and metabolic consequences of OSA are less well understood. The aim of this secondary analysis was to translate recent findings in healthy subjects on vigilance-state-dependent metabolism into the context of OSA patients and answer the question of how symptomatic OSA influences metabolism and whether these changes might explain metabolic and cardiovascular consequences of OSA. Patients with suspected OSA were assigned according to their oxygen desaturation index (ODI) and Epworth Sleepiness Scale (ESS) score into symptomatic OSA and controls. Vigilance-state-dependent breath metabolites assessed by high-resolution mass spectrometry were used to test for a difference in both groups. In total, 44 patients were eligible, of whom 18 (40.9%) were assigned to the symptomatic OSA group. Symptomatic OSA patients with a median [25%, 75% quartiles] ODI of 40.5 [35.0, 58.8] events/h and an ESS of 14.0 [11.2, 15.8] showed moderate to strong evidence for differences in 18 vigilance-state-dependent breath compounds compared to controls. These identified metabolites are part of major metabolic pathways in carbohydrate, amino acid, and lipid metabolism. Thus, beyond hypoxia per se, we hypothesize that disturbed sleep in OSA patients persists as disturbed sleep-dependent metabolite levels during daytime.

Obstructive sleep apnoea and the progression of thoracic aortic aneurysm: a prospective cohort study.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with an increased prevalence of aortic aneurysms and it has also been suggested that severe OSA furthers aneurysm expansion in the abdomen. We evaluated whether OSA is a risk factor for the progression of ascending thoracic aortic aneurysm (TAA). METHODS: Patients with TAA underwent yearly standardised echocardiographic measurements of the ascending aorta over 3 years and two level III sleep studies. The primary outcome was the expansion rate of TAA in relation to the apnoea-hypopnoea index (AHI). Secondary outcomes included surveillance for aortic events (composite end-points of rupture/dissection, elective surgery or death). RESULTS: Between July 2014 and March 2020, 230 patients (median age 70 years, 83.5% male) participated in the cohort. At baseline, 34.8% of patients had AHI ≥15 events·h-1. There was no association between TAA diameter and AHI at baseline. After 3 years, mean±sd expansion rates were 0.55±1.25 mm at the aortic sinus and 0.60±1.12 mm at the ascending aorta. In the regression analysis, after controlling for baseline diameter and cardiovascular risk factors, there was strong evidence for a positive association of TAA expansion with AHI (aortic sinus estimate 0.025 mm, 95% CI 0.009-0.040 mm; p<0.001 and ascending aorta estimate 0.026 mm, 95% CI 0.011-0.041 mm; p=0.001). 20 participants (8%) experienced an aortic event; however, there was no association with OSA severity. CONCLUSION: OSA may be a modest but independent risk factor for faster TAA expansion and thus potentially contributes to life-threatening complications in aortic disease.

Predictors of changes in subjective daytime sleepiness in response to CPAP therapy withdrawal in OSA: A post-hoc analysis.

Subjective sleepiness is the hallmark symptom of untreated obstructive sleep apnea (OSA) and leads to an increased risk of motor vehicle accidents and impaired quality of life. Continuous positive airway pressure (CPAP) is the standard therapy for OSA and improves sleepiness. The aim was to identify factors that might predict recurrence of sleepiness in times off CPAP and to define OSA patient types with a likely effect of CPAP on sleepiness. A post-hoc analysis of six clinical trials, including 132 patients with OSA effectively treated with CPAP prior to study inclusion, who were allocated to 2 weeks of CPAP withdrawal, was conducted to assess predictors of a change in subjective sleepiness. A multivariate regression model was used to assess predictors of a change in the Epworth Sleepiness Scale (ESS) score. In response to CPAP withdrawal, the median apnea-hypopnea index (AHI) and the ESS score significantly increased compared to baseline on CPAP by 32.6/hr (95% CI, 28.8, 36.4)/hr and 2.5 (95% CI, 1.8,3.2), respectively (p < .001), in the included 132 patients. There was an independent positive association of AHI (Coef. [95% CI] 0.04 [0.01, 0.08]) with an increase in ESS score upon CPAP withdrawal, and an independent negative association of age (coef. [95% CI], -0.10 [-0.18, -0.2]), ESS on CPAP (coef. [95% CI], -0.21 [-0.40, -0.015]) and active smoking status (coef. [95% CI], -1.22 [-2.26, -0.17]). These findings suggest that younger patients with a low residual sleepiness on CPAP and a recurrence of more severe OSA during CPAP withdrawal are at highest risk of suffering from a clinically relevant return of daytime sleepiness in times off CPAP.

Effect of counselling during pulmonary rehabilitation on self-determined motivation to be physically active for people with chronic obstructive pulmonary disease: a pragmatic RCT.

BACKGROUND: Counselling is considered to be a promising approach to increasing physical activity (PA) in people with chronic obstructive pulmonary disease (COPD). The aim of the current study was to investigate whether a PA counselling program for people with COPD, when embedded in a comprehensive outpatient pulmonary rehabilitation (PR) program, increased their daily PA. METHODS: A two-armed, single blind randomized controlled trial was conducted as a component of a 12-week outpatient pulmonary rehabilitation program. The participants randomized into the intervention group received five counselling sessions, based on the principles of motivational interviewing (MI), with a physiotherapist. The participants' steps per day and other proxies of PA were measured using an accelerometer (SenseWear Pro®) at baseline, at the end of the PR program, and three months later. The group-by-time interaction effect was analyzed. RESULTS: Of the 43 participants,17 were allocated to the intervention group and 26 to the usual-care control group (mean age 67.9 ± 7.9; 21 (49%) males; mean FEV1 predicted 47.1 ± 18.6). No difference between groups was found for any measure of PA at any point in time. CONCLUSIONS: In this study, counselling, based on MI, when embedded in a comprehensive PR program for people with COPD, showed no short-term or long-term effects on PA behavior. To investigate this potentially effective counselling intervention and to analyze the best method, timing and tailoring of an intervention embedded in a comprehensive outpatient PR program, further adequately powered research is needed. TRIAL REGISTRATION: Clinical Trials.gov NCT02455206 (05/21/2015), Swiss National Trails Portal SNCTP000001426 (05/21/2015).

"Can do, don't do" are not the lazy ones: a longitudinal study on physical functioning in patients with COPD.

BACKGROUND AND OBJECTIVE: Reduced physical capacity (PC) and physical activity (PA) are common in COPD patients and associated with poor outcome. However, they represent different aspects of physical functioning and interventions do not affect them in the same manner. To address this, a new PC-PA quadrant concept was recently generated to identify clinical characteristics of sub-groups of physical functioning. The objective of this study was to I) proof the new concept and to verify their differentiating clinical characteristics, II) evaluate the consistency of the concept over time, III) assess whether patients changed their quadrant affiliation over time, IV) and to test if changes in quadrant affiliations are associated with changes in clinical characteristics. METHODS: In a longitudinal, prospective, non-interventional cohort with mild to very severe COPD patients, PC and PA as well as respiratory variables, COPD-specific health status, comorbidities, survival, and exacerbations were yearly assessed. RESULTS: Data from 283 patients were analysed at baseline. Mean (min/max) follow-up time was 2.4 (0.5/6.8) years. The PC-PA quadrants could be characterized as follows: I) "can't do, don't do": most severe and symptomatic, several comorbidities II) "can do, don't do": severe but less symptomatic, several comorbidities III) "can't do, do do": few patients, severe and symptomatic, less comorbidities IV) "can do, do do": mildest and less symptomatic, less comorbidities, lowest exacerbation frequency. Of the 172 patients with at least one follow-up, 58% patients never changed their quadrant affiliation, while 17% declined either PC, PA or both, 11% improved their PC, PA or both, and 14% showed improvement and decline in PC, PA or both during study period. None of the clinical characteristics or their annual changes showed consistent significant and relevant differences between all individual sub-groups. CONCLUSION: Our findings suggest that there are no clinical characteristics allowing to distinguish between the PC-PA quadrants and the concept seems not able to illustrate disease process. However, the already low PA but preserved PC in the "can do, don't do" quadrant raises the question if regularly assessment of PA in clinical practice would be more sensitive to detect progressive deterioration of COPD compared to the commonly used PC. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01527773.

Increased augmentation index in patients with Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos Syndrome (EDS) comprises a heterogeneous group of diseases characterized by joint hypermobility, connective tissue friability, and vascular fragility. Reliable prognostic factors predicting vascular disease progression (e.g. arterial aneurysms, dissections, and ruptures) in EDS patients are still missing. Recently, applanation tonometry derived augmentation index (AIx), an indirect marker of arterial stiffness, has shown to be positively associated with progression of aortic disease in Marfan syndrome. In this study, we assessed aortic AIx in patients with EDS and matched healthy controls. METHODS: We performed noninvasive applanation tonometry in 61 adults with EDS (43 women and 18 men aged 39.3 ± 14.6 years) and 61 age-, gender-, height-, and weight-matched healthy controls. Radial artery pulse waveforms were recorded and analyzed using the SphygmoCor System (AtCor Medical, Sydney, NSW, Australia). Calculated AIx was adjusted to a heart rate of 75/min. Groups were compared and association between AIx and EDS was determined by univariate and multivariate regression analysis. RESULTS: EDS patients were categorized in classical type EDS (34%), hypermobile type EDS (43%), vascular type EDS (5%), or remained unassignable (18%) due to overlapping features. EDS patients showed a significantly increased aortic AIx compared to healthy controls (22.8% ± 10.1 vs 14.8% ± 14.0, p < 0.001). EDS showed a positive association with AIx; independent of age, sex, height, blood pressure, medication, and pack years of smoking. CONCLUSIONS: Patients with EDS showed elevated AIx, indicating increased arterial stiffness when compared to healthy controls. Further investigations are needed in order to assess the prognostic value of increased AIx for cardiovascular outcomes in patients with EDS.

Obstructive sleep apnea and quality of life in Fabry disease: a prospective parallel cohort study.

STUDY OBJECTIVES: Patients with Fabry disease (FD) report impaired quality of life and excessive daytime sleepiness. Obstructive sleep apnea (OSA) is frequently reported among patients with FD; however, its prevalence and its influence on quality of life and daytime sleepiness in this population are unclear. METHODS: Patients with FD in a cohort from the University Hospital Zurich (n = 52) were one-to-two matched to healthy adult controls (n = 104) according to age, sex, and body mass index. Participants underwent structured interviews (including Short Form-36) and level-3 respiratory polygraphy. An apnea-hypopnea index of ≥ 5/h was defined as OSA and the severity of FD was quantified with the Mainz Severity Score Index (MSSI). Conditional logistic regression was used to compare the outcomes. RESULTS: In patients with FD the mean MSSI was 13.3 ± 10.5 points and OSA prevalence was 19.2% vs. 9.0% in the matched control group (p = 0.09). The apnea-hypopnea index was significantly higher in patients with FD than in the control group (0.5/h [0.2-3.0] vs. 0.2/h [0.1-1.8], p = 0.026). OSA severity was associated with impaired quality of life in four dimensions for the whole study population. Furthermore, patients with FD did report significantly higher daytime sleepiness (Epworth Sleepiness Scale 7.6 points vs. 6.3 points; p = 0.01) than healthy controls. CONCLUSION: Patients with mild FD do not have a higher OSA prevalence than matched control subjects. Differences in OSA severity did not reach clinical significance. Further studies are warranted to determine the impact of OSA in patients with moderate-to-severe FD.

Handgrip Strength Seems Not to Be Affected by COPD Disease Progression: A Longitudinal Cohort Study.

Skeletal muscle dysfunction, functional exercise capacity impairment and reduced physical activity are characteristic features in patients with chronic obstructive pulmonary disease (COPD). Assessments addressing muscle strength of the upper limb, such as measurement of handgrip strength (HGS), are rarely performed and reported. We aimed to analyze the course of HGS and possible predictors of changes in HGS over time in COPD. Yearly assessments of various disease markers were performed for a follow-up of up to seven years in a cohort of COPD patients to assess the longitudinal disease process. Data of 194 patients with at least one follow-up measurement were analyzed. HGS decreased significantly by B = -0.86 (95% CI -1.09/-0.62, p < 0.001) over time. The multivariate mixed effects model showed an independent association between greater annual declines in HGS and lower numbers of steps per day by B = 0.11 (95% CI 0.03/0.18, p = 0.006) and an enhanced change in COPD Assessment Test scores by B = -0.01 (95% CI -0.01/-0.00, p = 0.034). No evidence for an independent association between annual decline in HGS and FEV1% pred. by B = -0.01 (95% CI -0.03/0.01, p = 0.297) was shown. Patients who died during follow-up did not exhibit greater declines in HGS compared to survivors (p = 0.884). Although HGS significantly decreased over time, no pathophysiological link with COPD disease progression could be demonstrated. Previous cross-sectional associations between HGS and mortality could not be confirmed in this longitudinal setting. Our data suggests that repeated monitoring of HGS in clinical settings seems not to be helpful to predict COPD specific disease progression.

Endocrine responses during CPAP withdrawal in obstructive sleep apnoea: data from two randomised controlled trials.

The aim of this investigation was to elucidate the effect of CPAP withdrawal on neurometabolic and cardiometabolic markers in patients with obstructive sleep apnoea. We evaluated 70 patients (mean age 61±10 years, 82% men) treated with CPAP in two 2-week, parallel, randomised controlled trials. CPAP withdrawal resulted in elevated 3,4-dihydroxyphenylglycol, norepinephrine and cortisol after 2 weeks of CPAP withdrawal; however, no statistically significant changes of the renin-angiotensin-aldosterone system (RAAS) determinants were documented. In summary, CPAP withdrawal may be more prominently linked to short-term increases in sympathetic activation than hypothalamic-pituitary-adrenal axis or RAAS activation. ClinicalTrials.gov Identifier: NCT02493673 and NCT02050425.

Minimum important difference of the Epworth Sleepiness Scale in obstructive sleep apnoea: estimation from three randomised controlled trials.

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).

Effects of short-term continuous positive airway pressure withdrawal on cerebral vascular reactivity measured by blood oxygen level-dependent magnetic resonance imaging in obstructive sleep apnoea: a randomised controlled trial.

Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR.41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli.OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea-hypopnoea index +38.0 events·h-1, 95% CI 24.2-52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37 mmHg, 95% CI 1.36-17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessed via BOLD MRI under either hyperoxic or hypercapnic conditions.Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal.

Obstructive Sleep Apnoea in Children and Adolescents with Ehlers-Danlos Syndrome.

BACKGROUND: In Ehlers-Danlos syndrome (EDS), a group of monogenic disorders affecting connective tissues, obstructive sleep apnoea (OSA) is highly prevalent in adults. The prevalence of OSA in children with EDS is unknown. OBJECTIVES: This prospective cross-sectional study aimed at determining the prevalence of OSA in paediatric EDS patients. METHODS: Children with EDS (n = 24) were recruited from the Children's Hospital Zurich and matched to healthy controls. Participants completed home respiratory polygraphy and questionnaires (Sleep-Related Breathing Disorder Scale [SRBD], Epworth Sleepiness Scale [ESS], and Child Health Questionnaire [CHQ]). The American Academy of Sleep Medicine criteria were applied for OSA diagnosis (obstructive apnoea-hypopnoea index [oAHI] ≥1/h). Conditional logistic regression was used to compare the prevalence of OSA and to adjust for possible confounding. RESULTS: OSA was found in 42% of paediatric EDS patients and in 13% of matched controls (OR = 4.5, 95% CI = 0.97-20.83, p = 0.054). The median oAHI was higher in EDS patients than in controls (0.77/h, IQR = 0.19-1.76, vs. 0.24/h, IQR = 0.0-0.60, p < 0.001 adjusted for age, sex, and BMI z-score). EDS patients had lower scores in most CHQ scales and higher SRBD and ESS scores than controls (0.26, IQR = 0.1-0.35, vs. 0.07, IQR = 0-0.19, p = 0.004); 7 ± 4 vs. 5 ± 4, p = 0.033, respectively). CONCLUSION: OSA is a previously underestimated EDS-related complication increasing disease burden.

Guiding Ketogenic Diet with Breath Acetone Sensors.

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 ß-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.

Determinants of annual change in physical activity in COPD.

BACKGROUND AND OBJECTIVE: Daily physical activity (PA) is reduced in patients with COPD. Previous cross-sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co-morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co-morbidities is scant. METHODS: In a heterogeneous cohort of COPD patients, we annually assessed the number of steps per day over 1 week and potential determinants including lung function, exacerbations and co-morbidities. Univariable and multivariable mixed effect models were used to investigate associations between the change in steps per day (dependent variable) and possible predictors and their annual changes. RESULTS: A total of 177 COPD patients (46% GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 1/2, 38% stage 3 and 16% stage 4) with a mean (min/max) follow-up time of 2.7 (1/5) years were annually assessed. The number of steps per day decreased significantly over time (P < 0.001) with a mean annual change of -508 steps. The decrease in activity was significantly associated with forced expiratory volume in 1 s (FEV1 ) % predicted (P = 0.020) but not with annual changes in FEV1 . Hyperinflation, exacerbations, co-morbidities and their annual changes, and survival did not significantly affect change in PA. CONCLUSION: COPD patients have a substantial decrease of PA over time. This decrease seems to be determined by the degree of airflow limitation. However, patients with a greater annual decline in lung function did not show a greater decrease in PA. The rate of decline in PA did not differ between survivors and non-survivors in this cohort.

Intrathoracic pressure swings induced by simulated obstructive sleep apnoea promote arrhythmias in paroxysmal atrial fibrillation.

AIMS: There is preliminary evidence for a link between obstructive sleep apnoea (OSA) and arrhythmias such as paroxysmal atrial fibrillation (PAF) and sudden cardiac death but underlying mechanisms remain largely unknown. METHODS AND RESULTS: In this interventional crossover study, we evaluated whether intrathoracic pressure changes, induced by simulated OSA, trigger premature cardiac beats, and alter measures of ventricular repolarization [QTc and Tpeak-to-Tend (TpTec) intervals] in patients with PAF. 12-Lead-electrocardiograms were recorded continuously in 44 patients, while simulating obstructive apnoea (Mueller manoeuvre, MM), obstructive hypopnoea (inspiration through a threshold load, ITH), end-expiratory central apnoea (AP), and during normal breathing (NB) in randomized order. The prevalence of OSA in these 44 patients was assessed by a sleep study. Atrial premature beats (APBs) occurred more frequently during MM (55% of patients) and ITH (32%), but not during AP (14%), compared with NB (9%) (P < 0.001, P = 0.006 and P = 0.688, respectively). Mueller manoeuvre led to a significant prolongation of QTc and TpTec intervals (+17.3 ms, P < 0.001 and +4.3 ms, P = 0.005). Inspiration through a threshold load significantly increased QTc (+9.6 ms, P < 0.001) but not TpTec. End-expiratory central apnoea did not alter QTc and TpTec intervals. According to the sleep study, 56% of patients had OSA (apnoea hypopnoea index ≥5). CONCLUSION: Simulated OSA induces APBs which may be important in patients with PAF, because the majority of episodes of PAF has been shown to be triggered by APBs. Simulated OSA leads to a significant prolongation of ventricular repolarization.

Chronic Obstructive Pulmonary Disease and Cardiac Repolarization: Data from a Randomized Controlled Trial.

BACKGROUND: Altered cardiac repolarization is a risk factor for sudden cardiac death and seems to be increased in chronic obstructive pulmonary disease (COPD) patients. OBJECTIVE: Lung volume reduction surgery (LVRS) has been shown to improve breathing mechanics and lung function in patients with severe COPD and emphysema and possibly also improve altered cardiac repolarization. METHODS: Thirty patients scheduled for LVRS were randomized to LVRS or to the control group. We investigated the treatment effect 3 months after LVRS on measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) derived from electrocardiography. Univariable and multivariable analyses were used to identify possible confounders influencing the treatment effect. RESULTS: LVRS was associated with an improvement in lung function (mean ± SD residual volume/total lung capacity of -9 ± 11% and forced expiratory volume in 1 s of +30 ± 29%). LVRS did not significantly reduce QTc (median -5.3 ms, 95% confidence interval, CI -15.5 to 3.7, p = 0.214) and QT dispersion (median -3.0 ms, 95% CI -13.0 to 7.0, p = 0.536) compared to the control group. No significant association between change in QTc and change in QT dispersion, respectively, and change in possible confounders was found. CONCLUSION: LVRS seems to have no effect on cardiac repolarization in patients with COPD. Thus, lung hyperinflation seems not to be a causal mechanism for altered cardiac repolarization in COPD patients.