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ZusammenfassungIn Deutschland findet die Lungenrehabilitation (PR) traditionell in Rehabilitationskliniken statt. Nach der aktuellen deutschen Richtlinie „Diagnostik und Beurteilung asbestbedingter Berufskrankheiten“ kann PR auch als ambulantes Programm mit den wesentlichen Elementen der stationären PR (Kompakt-Rehabilitation [KR]) angeboten werden. Unser Projekt untersuchte die Auswirkungen der KR auf Akzeptanz, körperliche Leistungsfähigkeit und Lebensqualität bei Patienten mit berufsbedingten Lungenerkrankungen. KR umfasste 24 Einheiten à 90 Minuten mit Physiotherapie und Atemtherapie sowie gerätegestütztes Kraft- und Ausdauertraining. Ziel unserer Studie war es, die Auswirkungen der KR bei Patienten mit Berufskrankheiten der Atemwege und einem gesetzlich verankerten Recht auf PR zu untersuchen. Eine Randomisierung war daher nicht geplant. 148 versicherte Personen mit einer bestätigten beruflichen Erkrankung der Lunge wurden von den Berufsgenossenschaften zur Teilnahme eingeladen. 126 Patienten (85 %) nahmen die Einladung an, und 78 Teilnehmer (Durchschnittsalter 71 Jahre) schlossen das gesamte Programm ab (53 %). Gutartige asbestbedingte Erkrankungen (Plaques, Pleuraverdickungen, Asbestose) dominierten mit rund 80 %. Gebrechlichkeit, Depression und Demenz sind typische Hindernisse. Unter strikter Einhaltung der gewählten Einschluss- und Ausschlusskriterien und Trainingsbedingungen traten keine unerwünschten Ereignisse auf. Die Messergebnisse am Beginn der KR wurden mit denen bei Beendigung verglichen. KR führte zu einer signifikanten (p

Cheyne–Stokes respiration (CSR) may trigger ventricular arrhythmia in patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). This study determined the prevalence and predictors of a high nocturnal ventricular arrhythmia burden in patients with HFrEF and CSA (with and without CSR) and to evaluate the temporal association between CSR and the ventricular arrhythmia burden. This cross-sectional ancillary analysis included 239 participants from the SERVE-HF major sub-study who had HFrEF and CSA, and nocturnal ECG from polysomnography. CSR was stratified in ≥20% and 30 premature ventricular complexes (PVCs) per hour of TRT. A sub-analysis was performed to evaluate the temporal association between CSR and ventricular arrhythmias in sleep stage N2. High ventricular arrhythmia burden was observed in 44% of patients. In multivariate logistic regression analysis, male sex, lower systolic blood pressure, non-use of antiarrhythmic medication and CSR ≥20% were significantly associated with PVCs >30·h−1 (OR 5.49, 95% CI 1.51–19.91, p=0.010; OR 0.98, 95% CI 0.97–1.00, p=0.017; OR 5.02, 95% CI 1.51–19.91, p=0.001; and OR 2.22, 95% CI 1.22–4.05, p=0.009; respectively). PVCs occurred more frequently during sleep phases with versus without CSR (median (interquartile range): 64.6 (24.8–145.7) versus 34.6 (4.8–75.2)·h−1 N2 sleep; p=0.006). Further mechanistic studies and arrhythmia analysis of major randomised trials evaluating the effect of treating CSR on ventricular arrhythmia burden and arrhythmia-related outcomes are warranted to understand how these data match with the results of the parent SERVE-HF study., High ventricular arrhythmia burden occurs in 44% of heart failure patients with reduced ejection fraction and central sleep apnoea. Arrhythmia burden is higher in sleep phases with versus without Cheyne–Stokes respiration. https://bit.ly/2QBDamC

BackgroundAdaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA.MethodsHFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea–hypopnoea index (AHI) ≥15 events·h−1with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed.Results40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h−1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min−1at baseline to 44.6±11.2 bursts·min−1; ASV group: 43.0±9.0 bursts·min−1at baseline to 42.74±9.45 bursts·min−1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective.ConclusionsSuppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94–103 in the control group, 77–99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk. in press

In Germany, pulmonary rehabilitation (PR) traditionally takes place in rehabilitation clinics. According to the current German guideline "Diagnostics and assessment of asbestos-related occupational diseases", PR can also be offered as outpatient program with the essential elements of inpatient PR (compact rehabilitation [CR]). Our project investigated the effects of CR regarding acceptance, physical performance, and quality of life of patients with occupational lung diseases. CR included 24 units of 90 minutes each with physiotherapy and breathing therapy as well as device-supported strength and endurance training. The aim of our study was to investigate the effects of CR in subjects with occupational diseases of the respiratory system and a legally anchored right to PR. Randomization was therefore not planned. A total of 148 insured persons with a confirmed occupational disease of the respiratory system were invited to participate by the employers' liability insurance association; 126 patients (85 %) accepted the invitation, and 78 participants (mean age: 71 years) completed the entire program (53 %). Benign asbestos-related diseases (plaques, pleural thickening, asbestosis) dominated with around 80 %. Ailments, depression, and dementia were typical obstacles. No adverse events occurred with strict observance of the chosen inclusion and exclusion criteria and training conditions. The measurement results at enrolment were compared with those at completion of the CR. CR led to a significant (p 0.01) improvement in all parameters of physical performance: 6-minute walking test: + 36 m, ergometer test: + 9 watts, hand dynamometry: + 29 N, quadriceps strength test: + 84 MKI. The inspiratory capacity of the respiratory muscles (PiIn Deutschland findet die Lungenrehabilitation (PR) traditionell in Rehabilitationskliniken statt. Nach der aktuellen deutschen Richtlinie „Diagnostik und Beurteilung asbestbedingter Berufskrankheiten“ kann PR auch als ambulantes Programm mit den wesentlichen Elementen der stationären PR (Kompakt-Rehabilitation [KR]) angeboten werden. Unser Projekt untersuchte die Auswirkungen der KR auf Akzeptanz, körperliche Leistungsfähigkeit und Lebensqualität bei Patienten mit berufsbedingten Lungenerkrankungen. KR umfasste 24 Einheiten à 90 Minuten mit Physiotherapie und Atemtherapie sowie gerätegestütztes Kraft- und Ausdauertraining. Ziel unserer Studie war es, die Auswirkungen der KR bei Patienten mit Berufskrankheiten der Atemwege und einem gesetzlich verankerten Recht auf PR zu untersuchen. Eine Randomisierung war daher nicht geplant. 148 versicherte Personen mit einer bestätigten beruflichen Erkrankung der Lunge wurden von den Berufsgenossenschaften zur Teilnahme eingeladen. 126 Patienten (85 %) nahmen die Einladung an, und 78 Teilnehmer (Durchschnittsalter 71 Jahre) schlossen das gesamte Programm ab (53 %). Gutartige asbestbedingte Erkrankungen (Plaques, Pleuraverdickungen, Asbestose) dominierten mit rund 80 %. Gebrechlichkeit, Depression und Demenz sind typische Hindernisse. Unter strikter Einhaltung der gewählten Einschluss- und Ausschlusskriterien und Trainingsbedingungen traten keine unerwünschten Ereignisse auf. Die Messergebnisse am Beginn der KR wurden mit denen bei Beendigung verglichen. KR führte zu einer signifikanten (p 0,01) Verbesserung aller Parameter der körperlichen Leistung: 6-Minuten-Gehtest: + 36 m, Ergometertest: + 9 Watt, Handdynamometrie: + 29 N, Quadriceps-Krafttest: + 84 MKI. Die Inspirationskapazität der Atemmuskulatur (Pi

Aim: Central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) are associated with increased mortality rates in patients with heart failure and reduced ejection fraction (HFrEF) and may trigger ventricular arrhythmias. Therefore, we investigated predictors of ventricular arrhythmias in HFrEF patients with CSA. Methods: 239 patients with HFrEF and CSA (apnea-hypopnea index g15/h with ≥50% central events) of the SERVE-HF major substudy with available polysomnography including nocturnal ECG were analyzed. CSR was quantified in ≥20% and l20% of total recording time. High ventricular arrhythmia burden was defined as g30 premature ventricular contractions (PVCs) per hour of sleep. A subanalysis was performed to evaluate the temporal association of CSR with ventricular arrhythmias in sleep stage N2 (55 hours). Results: High ventricular arrhythmia burden was observed in 44% of the sample. In multivariate regression analysis, male sex, lower systolic blood pressure, antiarrhythmics and CSR≥20% were associated with PVCg30/hour (odds ratio [95%CI]: 5.49 [1.51;19.91], p=0.010; 0.98 [0.97;1.00], p=0.017; 0.20 [0.08;0.52], p=0.001; 2.22 [1.22;4.05]; p=0.009; respectively). PVCs were more frequent in sleep phases with CSR than without CSR (median [IQR]: 64.6 [24.8; 145.7] vs. 34.6 [4.8; 75.2] per hour N2 sleep; p=0.006). Conclusion: High burden of ventricular arrhythmias occurred in 44% of patients with HFrEF and CSA. Risk factors for PVCsg30/hour were male sex, lower systolic blood pressure, antiarrhythmic medication and CSR≥20%. Ventricular arrhythmia burden was higher during sleep with CSR than without CSR.

A commonly used approach to study the association between a time-varying biomarker, such as forced vital capacity (FVC), and a time-to-event outcome, such as new onset of chronic obstructive pulmonary disease (COPD), is to incorporate the biomarker as a time-dependent covariate in a Cox model. This approach, which is known as the time-dependent Cox model (TDCM), requires knowledge of the value of the time-varying biomarker at all time points at which the event of interest occurs [1]. However, in clinical studies, longitudinal biomarker measurements are taken intermittently during scheduled (and sometimes unscheduled) visits, meaning that imputation of missing values is required for those event times at which the biomarker is not observed. In practical application of the TDCM, this is achieved by carrying forward the most recent biomarker measurement. While the use of last observation carried forward (LOCF) is easy to understand and implement, the resulting step function (see fig. 1, panel C for an example) is unlikely to provide a good approximation of the true biomarker trajectory. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Chen has nothing to disclose. Conflict of interest: Dr. Postmus has nothing to disclose. Conflict of interest: Dr. Cowie has nothing to disclose. Conflict of interest: Dr. Woehrle has nothing to disclose. Conflict of interest: Dr. Wegscheider has nothing to disclose. Conflict of interest: Dr. Simonds has nothing to disclose. Conflict of interest: Dr. Boezen has nothing to disclose. Conflict of interest: Dr. Somers reports other from Steering Committee SERV HF, outside the submitted work. Conflict of interest: Dr. Teschler has nothing to disclose. Conflict of interest: Dr. Eulenburg has nothing to disclose.

CA - Schöbel

International audience; Aims: The Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients with Heart Failure trial investigated the effects of adaptive servo-ventilation (ASV) (vs. control) on outcomes of 1325 patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). The primary outcome (a composite of all-cause death or unplanned HF hospitalization) did not differ between the two groups. However, all-cause and cardiovascular (CV) mortality were higher in the ASV group. Circulating biomarkers may help in better ascertain patients’ risk, and this is the first study applying a large set of circulating biomarkers in patients with both HFrEF and CSA.Methods and results: Circulating protein-biomarkers (n = 276) ontologically involved in CV pathways, were studied in 749 (57% of the trial population) patients (biomarker substudy), to investigate their association with the study outcomes (primary outcome, CV death and all-cause death). The mean age was 69 ± 10 years, and > 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The “best” clinical prognostic model included male sex, systolic blood pressure < 120 mmHg, diabetes, loop diuretic, cardiac device, 6-min walking test distance, and N-terminal pro BNP as the strongest prognosticators. On top of the “best” clinical prognostic model, the biomarkers that significantly improved both the discrimination (c-index) and the net reclassification index (NRI) of the model were soluble suppression of tumorigenicity 2 for the primary outcome; neurogenic locus notch homolog protein 3 (Notch-3) for CV-death and all-cause death; and growth differentiation factor 15 (GDF-15) for all-cause death only.Conclusions: We studied 276 circulating biomarkers in patients with HFrEF and central sleep apnoea; of these biomarkers, three added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch-3 (CV and all-cause death), and GDF-15 (all-cause death).

Summary Background As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs. Methods We did a multicentre, open-label, comparative, randomised trial in 49 centres in Austria, France, Germany, and Italy. Eligible patients had cystic fibrosis, were older than 10 years, and had newly diagnosed diabetes. We used a central randomisation schedule derived from a Geigy random number table to assign patients 1:1 to receive insulin or repaglinide, stratified by sex and age (10–15 years or >15 years). The primary outcome was glycaemic control assessed by mean change in HbA 1c concentration from baseline after 24 months of treatment. Differences between groups were assessed by linear models. The primary and safety analyses were done in the modified intention-to-treat population (including patients who stopped treatment early because of lack of efficacy). This trial is registered with ClinicalTrials.gov, number NCT00662714. Findings We enrolled 34 patients in the repaglinide group and 41 in the insulin group, of whom 30 and 37, respectively, were included in the analyses. At 24 months, glycaemic control was similar in the repaglinide and insulin groups (mean change in HbA 1c concentration from baseline 0·2% [SD 0·7%], 1·7 mmol/mol [8·1 mmol/mol] with repaglinide vs −0·2% [1·3%], −2·7 mmol/mol, [14·5 mmol/mol] with insulin; mean difference between groups −0·4%, (95% CI −1·1 to 0·2 [−4·4 mmol/mol, −11·5 to 2·7], p=0·15). The most frequent adverse events were pulmonary events (43 [40%] of 107 in the repaglinide group and 60 [45%] of 133 in the insulin group), and the most frequent serious adverse events were pulmonary events leading to hospital admission (five [50%] of ten and seven [54%] of 13, respectively). Interpretation Repaglinide for glycaemic control in patients with cystic-fibrosis-related diabetes is as efficacious and safe as insulin. Funding Mukoviszidose eV, Vaincre la Mucoviscidose, ABCF Association, and Novo Nordisk.

Aims The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. Methods and results In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. Conclusion In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure.

In den vergangenen 1,5 Jahren erfolgte die Aktualisierung der Silikose-Leitlinie durch eine interdisziplinar besetzte Arbeitsgruppe. Neue medizinisch-wissenschaftliche Erkenntnisse sowie die zwischenzeitlich in der Begutachtungspraxis gewonnenen Erfahrungen wurden berucksichtigt. Stand bei der Entwicklung der Erstfassung noch die Standardisierung der Diagnostik sowie die Uberarbeitung der nicht dem medizinisch-wissenschaftlichen Erkenntnisstand entsprechenden Masgaben der „Moerser Konvention“ im Vordergrund, ging es beim Update um Feinkorrekturen und Erganzungen, insbesondere der MdE-Kriterien (mit Angleichung an die MdE-Tabelle der Reichenhaller Empfehlung [DGUV 2012]). Die Diagnose Silikose basiert – neben einer eingehenden Arbeitsanamnese – auch weiterhin ganz uberwiegend auf dem typischen radiologischen Befund. Allerdings kommt bei der Erstdiagnose auch der standardisierten LD-HRCT-Aufnahme wegen der im Vergleich mit der konventionellen Rontgenaufnahme hohen Sensitivitat und Spezifitat eine zentrale Rolle zu. Ausnahmen stellen charakteristische, im Langsschnitt dokumentierte Befunde in der Rontgen-Thoraxaufnahme dar. Entsprechend heist es im Leitlinien-Update: „Fur die standardisierte Befundung der Low-Dose-Volumen-HRCT ist die Anwendung der CT-Klassifikation (ICOERD = International Classification of Occupational and Environmental Respiratory Diseases) zwingend erforderlich. Um die Diagnose einer Silikose in der CT-Untersuchung zu stellen, ist der Nachweis scharf berandeter Verdichtungen in beiden Oberlappen, die im Lungenkern und Lungenmantel lokalisiert sein konnen, erforderlich. Beim Vergleich mit dem Referenzfilm muss mindestens die Streuungskategorie 1 im rechten wie auch im linken Oberfeld erreicht sein (Gesamtstreuung mindestens 2).“ Neu sind die bislang kontrovers diskutierten Mindestanforderungen fur eine in tabula erstmals festgestellte Silikose. Hierzu wird in Anlehnung an Hnizdo et al. ausgefuhrt: „Als insignifikant sind Befunde anzusehen, wenn weniger als 5 Silikoseknotchen pro Lungenflugel palpatorisch erfasst und histologisch bestatigt werden konnen.“ Hierbei handelt es sich um eine Konvention und nicht um eine durch eingehende medizinisch-wissenschaftliche Untersuchungen und statistische Auswertungen belegte Grenzziehung; diese basiert allerdings auf den umfangreichen Erfahrungen, die im untertagigen sudafrikanischen Goldbergbau gewonnen werden konnten. In der aktualisierten Fassung wird auch auf den Befall der Hilus- und gelegentlich der Mediastinallymphknoten bei der Silikose eingegangen, wobei aus Sicht der LL keine enge Korrelation mit der Schwere des Lungenbefalls besteht. Ausgedehntere konglomerierende und indurierende Lymphknotenprozesse konnen zu Dislokationen der Hili mit Ruckwirkungen auf die grosen Bronchien und Gefasstamme fuhren. Vorwiegend randstandige schalenformige Verkalkungen stellen sich radiologisch als „Eierschalenhilus“ dar. Die Ausfuhrungen zur Belastungsuntersuchung wurden erganzt: Wenn weder Ergometrie noch Spiroergometrie durchfuhrbar sind, soll ein 6-Minuten-Gehtest mit Pulsoxymetrie erfolgen. Auserdem kann bei der Silikose-Begutachtung eine (nicht mitwirkungspflichtige) Rechtsherzkatheter-Untersuchung in Einzelfallen empfohlen werden, wenn die Echokardiografie Hinweise auf erhohte Druckwerte ergibt oder eine Differenzierung zwischen rechts- und linkskardialer Insuffizienz Schwierigkeiten bereitet. Eine pulmonale Hypertonie ist bei der Beurteilung der MdE zu berucksichtigen und auch prognostisch relevant. Bei der Spirometrie-Beurteilung sind die neuen GLI-Referenzwerte masgeblich. Bei der Graduierung der Einschrankungen folgt die Silikose-LL der Leitlinie Spirometrie der DGP. Nach dem aktuellen medizinisch-wissenschaftlichen Erkenntnisstand bleibt offen, ob bestimmte Krankheitsbilder des rheumatischen Formenkreises wie die Sklerodermie und das Caplan-Syndrom, die bei Silikose-Patienten in Einzelfallen gefunden werden, in toto als BK-Nr. 4101 (Silikose) anzusehen sind. Es braucht weiterer Studien, die die Rolle der beruflichen Quarz-Exposition im Kontext anderer Risikofaktoren untersuchen. Die Mitglieder der Leitliniengruppe hoffen, mit dem Update der Silikose-LL und diesem Beitrag weiterhin zur optimierten Diagnostik und Begutachtung der Silikose-Erkrankungsfalle beizutragen.

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and it is predicted to be third leading cause in 2030. In general, gender differences have not been adequately investigated in COPD, as most studies included small sample sizes of women. Since prevalence is increasing in women there is a rising need to study gender-related predictors of survival. Methods: Between 2011 and 2017 we analyzed retrospectively a total of 550 patients. We studied age, gender, body mass index (BMI), FEV1, 6-min walk distance (6MWD), heart rate before and after 6-min walk test (6MWT) (as determined by ΔHR), SpO₂ before and after 6MWT (as determined by ΔSpO₂). Survival was calculated by Kaplan-Meier analysis and Cox regression. Results: We included 264 women 286 men (48 and 52%). The study population was 58.6 ±10 years old, FEV1 was 30.4±17.8% predicted and BMI 23.9±5.4 kg/m2 while male study population was aged 62.9 ±10.6 years, FEV1 was 34±19% predicted and BMI 25.5±5.5 kg/m2 Five-year survival rate was 57.2% for women and 55.3% for men. 6MWD turned out to be a highly significant predictor for survival in univariate and multivariate analysis for men and women (p Conclusions: This study strengthens the evidence for 6MWD as predictor of mortality in male and female patients with COPD. FEV1, BMI and ΔSpO₂ were good predictors only in men.

International audience; INTRODUCTION:The SERVE-HF trial included patients with heart failure and reduced ejection fraction (HFrEF) with sleep-disordered breathing, randomly assigned to treatment with Adaptive-Servo Ventilation (ASV) or control. The primary outcome was the first event of death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening heart failure. A subgroup analysis of the SERVE-HF trial suggested that patients with Cheyne-Stokes respiration (CSR) 90% were male. Patients with CSR

Introduction: Recent data suggested that different ASV devices are associated with different outcomes based on a physiological experiment in complex sleep apnoea patients with preserved ejection fraction (n=14). Due to changes in technology over time, two different ASV devices were used in the SERVE-HF study of heart failure patients with reduced ejection fraction (Cowie et al. NEJM 2015;373:1095–105). Aim: To compare outcomes by ASV device used in SERVE-HF (n=1325). Methods: Outcome data from the SERVE-HF study were retrospectively analysed based on stratification by ASV device used (AutoSet CS2 at trial start [2009], moving to AutoSet S9SC from 2011; trial end 2013). CS2 was the only device used in 2009 and 2010, and S9SC was the only device used in 2013; in 2011 and 2012 the number of patients using CS2 and S9SC was 65 and 54, and 5 and 145, respectively. Control group patients who started ASV were also included in the analysis. Results: There was no effect of ASV device type on the primary endpoint (left figure), the rate of cardiovascular death (right figure), or on the rate of non-cardiovascular death. No significant interactions were found between device type and the primary endpoint (p=0.572), cardiovascular death (p=0.674) or non-cardiovascular death (p=0.071). Conclusion: Data from the large, randomised, SERVE-HF trial did not show any differential effects of ASV on outcome based on device type.

BACKGROUND AND OBJECTIVE Increases in Cheyne-Stokes respiration (CSR) cycle length (CL), lung-to-periphery circulation time (LPCT) and time to peak flow (TTPF) may reflect impaired cardiac function. This retrospective analysis used an automatic algorithm to evaluate baseline CSR-related features and then determined whether these could be used to identify patients with systolic heart failure (HF) who experienced serious adverse events in the Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE-HF) substudy. METHODS A total of 280 patients had overnight diagnostic polysomnography data available; an automated algorithm was applied to quantify CSR-related features. RESULTS Median baseline CL, LPCT and TTPF were similar in the control (n = 152) and adaptive servo-ventilation (ASV, n = 156) groups. In both groups, CSR-related features were significantly longer in patients who did (n = 129) versus did not (n = 140) experience a primary endpoint event (all-cause death, life-saving cardiovascular intervention or unplanned hospitalization for worsening HF): CL, 61.1 versus 55.1 s (P = 0.002); LPCT, 36.5 versus 31.5 s (P

Die obstruktive Schlafapnoe (OSA) ist charakterisiert durch wiederkehrende Episoden mit pharyngealem Kollaps, die auf eine Verminderung des Tonus der dilatierenden pharyngealen Muskulatur zuruckzufuhren sind. Die elektrische Hypoglossusnervenstimulation (HNS) ist eine neue Methode fur Patienten mit mittelschwerer bis schwerer OSA, die die Standardtherapie mit kontinuierlichem (CPAP) oder automatisch adjustierendem (APAP) positivem Atemwegsdruck und mit einstellbarer Unterkieferprotrusionsschiene nicht tolerieren. Nach Jahrzehnten der umfangreichen Uberprufung der HNS im Tierversuch und beim Menschen zeigen die kurzlich veroffentlichten Ergebnisse der multizentrischen, prospektiven STAR-Studie mit dem Inspire™-Gerat, dass die HNS den pharyngealen Kollaps verhindert, ohne die Patienten aus dem Schlaf zu wecken. Die HNS mit diesem Gerat verbessert die objektiven und subjektiven Parameter des OSA-Schweregrads signifikant. Nachteile der verfugbaren HNS bleiben die relative Invasivitat und die damit verbundenen Kosten. In weiteren Untersuchungen mussen Selektionskriterien und Gerateperformance optimiert und die langfristige Wirksamkeit belegt werden. Das Fehlen eines vollstandigen zirkularen Kollapses der oberen Atemwege auf der Ebene des Weichgaumens im Rahmen einer medikamenteninduzierten Schlafendoskopie ist ein Pradiktor fur den Erfolg der implantierten HNS-Therapie mit dem Inspire™-Gerat. Die medikamenteninduzierte Schlafendoskopie ist daher eine Voraussetzung bei geplanter Implantation des Inspire™-Gerats, die bei vollstandigem zirkularem Kollaps auf Weichgaumenebene selten effektiv ist. HNS-Gerate sollten nur in erfahrenen Zentren mit multidisziplinarem HNO- und Schlaflaborteam implantiert werden. Die Patientenrekrutierung in klinischen Studien und die Einschreibung in klinische Register konnten helfen, Qualitat und Kosten zu kontrollieren.

Bilateral lung transplantation results in complete denervation of the lung and might impair hypercapnic ventilatory response (HCVR). However, experimental and clinical findings are scarce and conflicting. Therefore, this study investigated the relationship between HCVR and exercise capacity after long-term bilateral lung transplantation.This cross-sectional analysis enrolled 46 bilateral lung transplant recipients between October 2011 and July 2012 who underwent cardiopulmonary exercise testing to evaluate maximum workload, and carbon dioxide (CO2) rebreathing. CO2 rebreathing was also evaluated in 35 control subjects.In lung transplant recipients age was 54 ± 11 years, body mass index (BMI) 25.4 ± 4.1 kg/m(2), and time after transplantation 4.5 ± 2.5 years (range 9 months to 10 years). Controls were aged 41 ± 12 years and had a BMI of 24.9 ± 4.0 kg/m(2). There were significant differences between lung transplant recipients and controls in forced expiratory volume in 1 s (76 ± 22 vs. 94 ± 12 % predicted, p 0.001) and inspiratory vital capacity (91 ± 20 vs. 105 ± 14 % predicted, p = 0.001). Blood gases did not differ significantly in patients versus controls. HCVR in lung transplant recipients was 1.44 ± 1.07 L/min/mmHg compared with 2.09 ± 1.14 L/min/mmHg in controls (p = 0.001). Exercise capacity in lung transplant recipients (73 ± 24 W) was 49 % predicted. Linear regression analysis showed that exercise capacity was significantly associated with HCVR. A 1 L/min/mmHg decrease in HCVR decreased exercise capacity by 50 W.HCVR is reduced in long-term bilateral lung transplant recipients and this might explain the observed impairment of exercise capacity.

Objectives This prospective study investigated the prevalence of sleep-disordered breathing (SDB) and its predictors in patients with stable chronic heart failure (HF). Background SDB is increasingly recognized as being important in patients with HF. Methods The multicenter SchlaHF (Sleep-Disordered Breathing in Heart Failure) registry provides demographic and clinical data on chronic, stable, symptomatic patients with HF (New York Heart Association functional class ≥II; left ventricular rejection fraction ≤45%). Moderate-to-severe SDB (apnea-hypopnea index ≥15/h) was determined by a 2-channel screening device (ApneaLink, ResMed, Sydney, Australia). Results Data from 6,876 patients were analyzed. The prevalence of moderate-to-severe SDB was 46%, with a significant sex difference: 36% in women (n = 1,448) versus 49% in men (n = 5,428). Prevalence of SDB rose with increasing age (31%, 39%, 45%, 52%, and 59% in those age ≤50, >50 to 60, >60 to 70, >70 to 80, and >80 years, respectively). Risk factors for SDB were body mass index (per 5 units; odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.22 to 1.36), left ventricular rejection fraction (per 5% decrement from 45%; OR: 1.10; 95% CI: 1.06 to 1.14), age (per 10-year difference to 60 years; OR: 1.41; 95% CI: 1.34 to 1.49), atrial fibrillation (OR: 1.19; 95% CI: 1.06 to 1.34), and male sex (OR: 1.90; 95% CI: 1.67 to 2.17). Conclusions SchlaHF registry data demonstrate a high prevalence of SDB in a representative population of stable patients with chronic HF receiving contemporary medical management. Male sex, age, body mass index, and the severity of both symptoms and left ventricular dysfunction were clinical predictors for prevalent SDB. (Prevalence, Clinical Characteristics and Type of Sleep-disordered Breathing in Patients With Chronic, Symptomatic, Systolic Heart Failure; NCT01500759)

Polysomnography (PSG) is the gold standard for sleep analysis and the diagnosis of sleep-disordered breathing (SDB). As PSG is time-consuming and labor-intensive, it is the last step in a stepwise diagnostic workup. An early preliminary diagnosis can be obtained by a novel single-channel minimal-contact device which is placed under the patient’s mattress topper. This study assessed the diagnostic accuracy of the novel minimal-contact device VitaLog (SWG Sportwerk GmbH & Co. KG, Dortmund, Germany) for sleep–wake classification and measurement of heart rate (HR). The results were compared to PSG. VitaLog is a minimal-contact sensor that does not restrict sleep. The diagnostic accuracy of VitaLog was studied in 49 patients referred to our sleep research unit due to suspected SBD. Results obtained by VitaLog were compared to those of a simultaneous PSG to assess the diagnostic accuracy of VitaLog for sleep–wake classification and measurement of HR. Compared to PSG, the accuracy of HR determined by VitaLog was excellent (r = 0.99) with a bias of 0.15 beats per min (bpm). Regarding total sleep time (TST), we found a good correlation of r = 0.8 and a bias of 14 min. For sleep efficiency (SE) estimated by VitaLog, the correlation was moderate with r = 0.6 with a bias of 4.0%. Sleep latency (SL) and wake after sleep onset (WASO) were underestimated by 1 and 12 min, respectively. VitaLog is a promising approach for the estimation of the sleep-related parameters TST, SE, SL, and WASO based on a minimal-contact sensor. In addition, it measures HR with excellent accuracy. However, algorithm modifications are desired to provide appropriate diagnostic accuracy in all sleep disorder cohorts.

Background Aim of this study was to investigate the association of the time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT). Material and Methods 169 Patients after SOT (lung, liver or kidney) were included and divided into subgroups according their time under (0-1, 1-3, 3-6, 6-10 and >10 years) and form of immunosuppression (Tacrolimus, Cyclosporine, Mycophenolate, Glucocorticoids, Sirolimus and monotherapy vs. combination). Periodontal probing depth (PPD) and clinical attachment loss (CAL) were assessed. Periodontal disease severity was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were investigated for eleven selected potentially periodontal pathogenic bacteria using polymerasechainreaction. Results The mean PPD and CAL as well as prevalence of Treponema denticola and Capnocytophaga species was shown to be different but heterogeneous depending on time under immunosuppression (p

BACKGROUND: Dental status has been implicated in several systemic inflammatory diseases and is a potential focus for systemic infections. Therefore, most lung-transplant centers have recommendations regarding pre-transplant dental care and follow-up, but there are no official clinical guidelines. To date there is little information on oral health status in lung transplant (LTx) recipients. The aim of this study was to systematically assess oral health status in LTx recipients. OBJECTIVES: The aim of this study was to assess oral health status, including periodontal disease, oral health behavior, and awareness of the need for good oral health after LTx. METHODS: LTx recipients were recruited during follow-up outpatient visits at a university clinic transplant unit. Oral health status was quantified using the count of Decayed, Missing and Filled Teeth (DMF-T) and the grade of periodontal disease was measured by probing depth. Patients' oral health behavior was assessed using a questionnaire. RESULTS: Seventy-three patients were included at 5.8±3.4 years after lung transplantation. The mean DMF-T was 21.9±5.5. Patients with cystic fibrosis as the indication for transplantation had a significantly lower DMF-T than patients with chronic obstructive pulmonary disease as the transplant indication. Of the 66 patients with teeth, 97% had moderate or severe periodontal disease. The prevalence of moderate or severe periodontal disease was significantly higher in LTx recipients (mean age 55.9 years) compared with older individuals (age 65-74 years) from the German general population (p

BACKGROUND:There is a lack of robust data about factors predicting continuation (or termination) of positive airway pressure therapy (PAP) for sleep apnea. This analysis of big data from a German homecare provider describes patients treated with PAP, analyzes the therapy termination rate over the first year, and investigates predictive factors for therapy termination. METHODS:Data from a German homecare service provider were analyzed retrospectively. Patients who had started their first PAP therapy between September 2009 and April 2014 were eligible. Patient demographics, therapy start date, and the date of and reason for therapy termination were obtained. At 1 year, patients were classified as having compliance-related therapy termination or remaining on therapy. These groups were compared, and significant predictors of therapy termination determined. RESULTS:Of 98,329 patients included in the analysis, 11,702 (12%) terminated PAP therapy within the first year (after mean 171 ± 91 days). There was a U-shaped relationship between therapy termination and age; therapy termination was higher in the youngest (

Fragestellung Die kardiorespiratorische Polysomnographie (PSG) stellt den Goldstandard in der Diagnostik schlafbezogener Atemstorungen (SBAS) dar. Aufgrund des hohen Arbeits- und Kostenaufwands ist die PSG der letzte Schritt in einer Stufendiagnostik, an deren Anfang ein Screeningtest steht. SleepMinder® ist ein neues Screeninggerat zur Erkennung von respiratorischen Ereignissen. Das Ziel dieser Studie war die Bestimmung der diagnostischen Genauigkeit von SleepMinder®.

Die Lungentransplantation (LuTX) ist eine Therapiemoglichkeit fur Patienten mit terminalen Lungenerkrankungen. Primares Organversagen, Infektionen, zellulare und humorale Abstosungsreaktionen, lymphozytische Bronchiolitis sowie die chronische Abstosungsreaktion mit ihren Phanotypen Bronchiolitis-obliterans-Syndrom und restriktivem Allograft-Syndrom (RAS) sind inzwischen gut charakterisierte Komplikationen nach LuTX und Ursache fur Erkrankungen und Mortalitat.

Introduction: Compliance with PAP therapy is important for maximising the benefits of therapy. To date, the impact of a changing from a nasal mask (NM) to a full face mask (FFM) has not been investigated in large numbers of patients. Aim: This analysis investigated device usage and control of respiratory disturbances before and after a change in mask during the first year of PAP therapy. Methods: Data were retrospectively obtained from a German homecare provider database (ResMed Germany Healthcare). Eligible patients had started PAP therapy for the first time between Jan and Dec 2015, and switched from a nasal mask (NM) or nasal pillows (NP) to a full face mask (FFM) in the first year of treatment. Results: Of 8738 patients, 261 met all the inclusion criteria and were included in the analysis (age 60±13 years, 77% male, 88% with public insurance); first device was automatic or continuous PAP in 98% of patients. Mask change occurred after a mean of 102±95 days. Device usage and the majority of respiratory parameters improved significantly after the switch to a FFM. Pressures were similar before and after mask switch, and leak tended to be lower after the switch. Conclusion: Switch to a FFM significantly improved device usage and sleep apnoea parameters without significantly affecting PAP pressure.

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial. Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias). The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased. On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies., SERVE-HF on-treatment results showed increased cardiovascular risk similar to the intention-to-treat analysis http://ow.ly/hoO130dx4s9

Objective/background: This study investigated the addition of a real-time feedback patient engagement tool on positive airway pressure (PAP) adherence when added to a proactive telemedicine strategy. Patients/methods: Data from a German healthcare provider (ResMed Healthcare Germany) were retrospectively analyzed. Patients who first started PAP therapy between 1 September 2009 and 30 April 2014, and were managed using telemedicine (AirView™; proactive care) or telemedicine + patient engagement tool (AirView™ + myAir™; patient engagement) were eligible. Patient demographics, therapy start date, sleep- disordered breathing indices, device usage hours, and therapy termination rate were obtained and compared between the two groups. Results: The first 500 patients managed by telemedicine-guided care and a patient engagement tool were matched with 500 patients managed by telemedicine-guided care only. The proportion of nights with device usage ≥4 h was 77 ± 25% in the patient engagement group versus 63 ± 32% in the proactive care group (p < 0.001). Therapy termination occurred less often in the patient engagement group (p < 0.001). The apnea-hypopnea index was similar in the two groups, but leak was significantly lower in the patient engagement versus proactive care group (2.7 ± 4.0 vs 4.1 ± 5.3 L/min; p < 0.001). Conclusions: Addition of a patient engagement tool to telemonitoring-guided proactive care was associated with higher device usage and lower leak. This suggests that addition of an engagement tool may help improve PAP therapy adherence and reduce mask leak.

The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers.In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers.In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure.

Recent studies found that the non-contact screening device SleepMinder (ResMed Sensor Technologies, Dublin, Ireland) detects sleep-disordered breathing (SDB) with high diagnostic accuracy in cohorts suspected of this disorder. However, it was reported that in patients with periodic limb movement in sleep (PLMS), this non-contact device overestimates the apnea-hypopnea index (AHI). We aimed to overcome this limitation by introducing the novel sleep disorder index (SDI) which is sum of the AHI and the period limb movement index (PLMI). Between January 2011 and December 2013, we studied a mixed cohort of 57 patients (31 OSA, 19 PLMS). The easy-to-use non-contact device emits a very weak electromagnetic radiation and detects body movement by measuring the Doppler effect. We interpreted the device-generated movement index as the SDI and validated the diagnostic accuracy against simultaneous application of the gold-standard polysomnography (PSG). We found that the SDI of the non-contact device correlated well with the sum of AHI and PLMI derived from PSG (r = 0.79, p = 0.01). For PSG-derived SDI cutoff ≥ 15/h, we obtained a sensitivity of 92.2% and a specificity of 95.8%. Positive likelihood ratio was 23.3 and negative likelihood ratio 0.03. The studied non-contact screening device detects accurately the combination of the sleep disorders SDB and/or PLM. However, further testing is required in order to specify the nature of the underlying sleep disorder. At the current stage of algorithm development, the clinical strength is that the studied non-contact device can be used as a rule-out screening device for SDB and PLM.

Summary Background Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Methods Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. Findings Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (−1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; −1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and −1·60 g/L per year [0·26] at FRC) than in the delayed-start group (−2·26 g/L per year [0·27] at TLC; −2·16 g/L per year [0·26] at TLC plus FRC, and −2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from −2·26 g/L per year to −1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (−1·51 g/L per year to −1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. Interpretation RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment. Funding CSL Behring.