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BackgroundThe SERVE-HF trial investigated the effect of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with heart failure with reduced ejection fraction (HFrEF).ObjectiveThe aim of the present ancillary analysis of the SERVE-HF major substudy (NCT01164592) was to assess the effects of ASV on the burden of nocturnal ventricular arrhythmias as one possible mechanism for sudden cardiac death in ASV-treated patients with HFrEF and CSA.MethodsThree hundred twelve patients were randomized in the SERVE-HF major substudy [no treatment of CSA (control) vs. ASV]. Polysomnography including nocturnal ECG fulfilling technical requirements was performed at baseline, and at 3 and 12 months. Premature ventricular complexes (events/h of total recording time) and non-sustained ventricular tachycardia were assessed. Linear mixed models and generalized linear mixed models were used to analyse differences between the control and ASV groups, and changes over time.ResultsFrom baseline to 3- and 12-month follow-up, respectively, the number of premature ventricular complexes (control: median 19.7, 19.0 and 19.0; ASV: 29.1, 29.0 and 26.0 events/h; p = 0.800) and the occurrence of ≥1 non-sustained ventricular tachycardia/night (control: 18, 25, and 18% of patients; ASV: 24, 16, and 24% of patients; p = 0.095) were similar in the control and ASV groups.ConclusionAddition of ASV to guideline-based medical management had no significant effect on nocturnal ventricular ectopy or tachyarrhythmia over a period of 12 months in alive patients with HFrEF and CSA. Findings do not further support the hypothesis that ASV may lead to sudden cardiac death by triggering ventricular tachyarrhythmia.

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.

The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items against a panel of comorbidities, lung function, or CT characteristics (qualitative score, 15th percentile of mean lung density), with age, BMI and gender as covariates. This was supported by exploratory factor analysis. Regarding the relationship to comorbidities and emphysema, there were marked differences between CAT items, especially items 1 and 2 versus 3 to 8. This grouping was basically confirmed by factor analysis. Items 4 and 5, and to a lower degree 1, 2 and 6, appeared to be informative regarding the presence of emphysema, whereas the total score was not or less informative. Regarding comorbidities, similar findings as for the total CAT score were obtained for the modified Medical Research Council scale (mMRC) which was also informative regarding emphysema. Our findings suggest that the usefulness of the CAT can be increased if evaluated on the basis of single items which may be indicating the presence of comorbidities and emphysema.

Rationale Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. Methods We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. Results 1506 patients with stable COPD (GOLD grade 1–4; mean age 64.5 ± 8.1 y; mean FEV1 54 ± 18 %predicted, mean eGFR 82.3 ± 16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. Conclusion Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

Analysis of lung density by CT (available for 379 patients). (f) n = 3 missings, (g) n = 89 missings, *panlobular emphysema, PLE; centrilobular emphysema, CLE. Table E2. Multivariate linear regression model with TLCO %pred. as dependent variable. AATD refers to the presence of AATD versus COPD. Figure S1. Patients with AATD revealed a reduced TLCO %pred at similar levels of ITGV %pred. (A, B) or BMI (B, D) for both female and male patients after adjustment for FEV1, sex, BMI, packyears, and age (AATD - dotted line, COPD - straight line). Table S3. Results (Odds Ratio [95% confidence interval] and p-value) of multivariable logistic regression analyses for different comorbidities as dependent variable. (DOCX 265 kb)

Early-onset lung cancer diagnosed up to the age of 50 is a very rare disease, with an increasing incidence rate. Differences in aetiology, characteristics and epidemiology of early and older onset lung cancer have been described previously, suggesting the importance of genetic factors in early-onset lung cancer aetiology. A case-control study was conducted to investigate the effects of genetic polymorphisms in the MPO, EPHX1, GSTT1, GSTM1, GSTP1 and NQO1 genes on the risk of early-onset lung cancer development. Six hundred thirty-eight Caucasian patients under the age of 51 with confirmed primary lung cancer and 1,300 cancer free control individuals, matched by age and sex, were included in this analysis. Seventeen single nucleotide polymorphisms and two deletion polymorphisms were genotyped. No significant association was found for any of the analyzed polymorphisms and overall lung cancer risk. Nonsignificantly decreased risk of lung cancer was observed for carriers of 1 or 2 copies of GSTM1. Subgroup analysis revealed gender- and/or smoking-specific effects of EPHX1 rs2854455 (IV-1464C > T) and rs2234922 (His139Arg), GSTT1 deletion, GSTP1 rs1695 (Ile105Val), rs947895 (+991C > A) and rs4891 (Ser185Ser) and NQO1 rs1800566 (Pro187Ser) polymorphisms. However, none of the observed effects were confirmed by interaction tests nor were they significant after Bonferroni correction for multiple testing. In summary, our study suggested a modifying effect of polymorphisms in EPHX1, GSTP1, GSTT1, GSTM1 and NQO1 genes on the risk of early-onset lung cancer. To confirm these observations and to eliminate possible bias in our analyses, larger studies are warranted.

Duisburg, Essen, Univ., Diss., 2014 Inhalt Ziel unserer prospektiven Querschnittsstudie war, die Prävalenz und Symptomschwere einer möglichen Harninkontinenz und die medizinische Versorgungslage bei Männern und Frauen mit chronisch obstruktiver Lungenerkrankung (COPD) zu erfassen. Die Hypothese war, dass der durch chronischen Husten erhöhte intraabominale Druck möglicher Weise zu einer höheren Prävalenz von HI bei COPD führen könnte. Methodik Es wurden 114 Teilnehmende mit COPD in einer Briefumfrage und 856 Teilnehmende mit COPD in einer Online-Umfrage erfasst. 110 Teilnehmende mit einer Tumorresektion bei Lungentumor Stadium1 wurden mit einer Briefumfrage als Kontrollgruppe eingeschlossen. Prävalenz und Symptomatik von Harninkontinenz wurden mit dem Inkontinenzfragebogen ICIQ-UI SF und die Probleme der Lungenfunktion mit Hilfe des COPD Assessement Test (CAT) erfasst und gegenübergestellt. Zudem wurde die subjektiven Wahrnehmung von Inkontinenzproblemen und die medizinische Versorgung bezüglich Harninkontinenz erfragt. Resultate Von den 114 eingeschlossenen Probanden mit COPD mittels Briefumfrage und den 859 mittels Online-Befragung gaben 58,8%, bzw. 85,3% gegenüber 39,1% der 110 Probanden der Kontrollgruppe Symptome von Harninkontinenz an. Bereits im mittleren Alter (41-60 Jahre) war die Prävalenz von Harninkontinenz in beiden COPD-Gruppen signifikant erhöht. Belastungsinkontinenz war mit 67,2%, bzw. 67,4% bei den inkontinenten Probanden der beiden COPD-Gruppen der dominante Inkontinenztypus, überraschender Weise auch bei den männlichen Probanden (53,5%, bzw. 57,0%). Die Häufigkeit und das Volumen des Harnverlustes lagen bei den Männern der COPD-Gruppen signifikant bis hoch signifikant höher als in der Kontrollgruppe. Mit hoch signifikanten Werten wurden „Husten“, „körperliche Aktivität“ und „Exazerbationen“ als Auslöser für Harnverlust in den COPD-Gruppen identifiziert. In beiden COPD-Gruppen wurde eine starke Korrelation der Harninkontinenz mit der subjektiven Belastung durch Husten, durch Sekret, der Aktivitäten außer Haus, des Schlafs und der Energie ermittelt (r2 = 0,3 und höher) im Vergleich zur Kontrollgruppe (r2 = 0,2 und tiefer). Von allen Befragten bezeichneten sich selbst 13,5% bis 39,4% als kontinent, obwohl sie Inkontinenzsymptome angegeben hatten. 74,2% bis 77,6% der inkontinenten Probanden gaben an, noch nie einen Arzt wegen Harninkontinenz konsultiert zu haben. 48,8% bis 74,6% der inkontinenten Teilnehmenden war Beckenbodentraining als Therapieoption unbekannt und lediglich 1,4% bis 16,6% gaben an, regelmäßig Beckenbodentraining durch zu führen. Schlussfolgerung Aus diesen Daten schlussfolgern wir, dass alle an der medizinischen Versorgung von Menschen mit COPD beteiligten Berufsgruppen dem Thema Harninkontinenz Aufmerksamkeit schenken sollten. Die von Harninkontinenz betroffenen Personen sollten über Behandlungsmöglichkeiten aufgeklärt und einer Einrichtung mit entsprechender Expertise zugewiesen werden.

In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p Clinical Trial Registration: ClinicalTrials.gov NCT01245933.

Duisburg-Essen, Univ., Diss., 2009 In der vorliegenden retrospektiven Studie wurden verschiedene Parameter daraufhin untersucht, ob sie für die Überlebenszeit bei Patienten mit nichtkleinzelligen Bronchial­karzinomen (NSCLC) von prognostischer Bedeutung sind. Hierzu wurden von insge­samt ca. 500 operierten Patienten die Akten von 296 Patienten ausgewertet, die im Zeitraum von 1995 bis 2003 in der Ruhrlandklinik in Essen-Heidhausen in Zusammen­arbeit der Universitätsklinik Essen behandelt wurden. Bei allen in die Studie aufgenommenen Patienten wurde initial ein NSCLC im Stadium IIb, IIIa und IIIb gesichert, somit war formal eine Kuration möglich und anzustreben. Alle ausgewählten Patienten erhielten im Rahmen eines neoadjuvanten Konzepts eine präoperative Polychemotherapie in Kombination mit einer Radiatio. Das beobachtete Patientenkollektiv setzte sich aus 211 Männern (71,3 %) und 85 Frauen (28,7 %) zusammen. Das mittlere Alter betrug 58,2 Jahre. Insgesamt sind 194 von 296 Patienten (65,5 %) dieser Studie bis zum Ende des Beob­achtungszeitraumes verstorben. Ausschlaggebend für die Prognose und damit für die Überlebenszeit der Patienten scheint das Downstagen unter Radiochemotherapie zu sein, insbesondere die Verbesse­rung des N-Status unter der präoperativen Therapie. So lebten Patienten, die nach der Vortherapie ein N0-Status aufweisen konnten, deutlich länger als Patienten mit einer N1- und N2- Situation. Auch das initiale N-Stadium hat eine statistisch signifikante Bedeutung bezogen auf den Verlauf und die Prognose des Patienten. Ferner war die Überlebens­wahrscheinlichkeit signifikant abhängig vom Alter, dem präoperativen sowie dem post­operativen N‑Stadium, einem postoperativen Residualtumor (R1), dem postoperativen Stadium und vom Downstaging. Eine Tendenz bestand hinsichtlich Histologie (Über­leben nach 8 Jahren: Plattenepithel­karzinom 29 %, großzelliges Karzinom 25 %, Adenokarzinom 15 %) und Resektionsort und –ausmaß. Kein signifikanter Zusammen­hang bestand hinsichtlich Geschlecht, postoperativem T-Stadium, postoperativen Sta­dium M1, initialem Stadium und Lokalisation.

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