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Background: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information. Objective: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD. Methods: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves. Results: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk. Conclusion: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further.

Peter Alter,1 Kathrin Kahnert,2 Franziska C Trudzinski,3 Robert Bals,4 Henrik Watz,5 Tim Speicher,1 Sandra Söhler,1 Stefan Andreas,6 Tobias Welte,7 Klaus F Rabe,8 Emiel FM Wouters,9 Antonia Sassmann-Schweda,10 Hubert Wirtz,11 Joachim H Ficker,12,13 Claus F Vogelmeier,1 Rudolf A Jörres14 1Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR), Germany, Member of the German Center for Lung Research (DZL), Marburg, Germany; 2Department of Internal Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany; 4Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 5Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 6LungClinic Immenhausen and Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany, Member of the German Center for Lung Research (DZL), Göttingen, Germany; 7Clinic for Pneumology, Hannover Medical School, Member of the German Center for Lung Research (DZL), Hannover, Germany; 8LungenClinic Grosshansdorf and Department of Medicine, Christian-Albrechts University, Kiel, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 9Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, Netherlands and Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; 10Center for Clinical Studies, Research Center Borstel, Borstel, Germany; 11Department of Internal Medicine I, Pneumology, University of Leipzig, Leipzig, Germany; 12Department of Respiratory Medicine, Allergology and Sleep Medicine, Klinikum Nuremberg, Nürnberg, Germany; 13Paracelsus Medical University Nuremberg, Nürnberg, Germany; 14Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, GermanyCorrespondence: Peter Alter, Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR), Baldingerstrasse 1, Marburg, Germany, Email Alter@uni-marburg.deBackground: Multimorbidity plays an important role in chronic obstructive pulmonary disease (COPD) but is also a feature of ageing. We estimated to what extent increases in the prevalence of multimorbidity over time are attributable to COPD progression compared to increasing patient age.Methods: Patients with COPD from the long-term COSYCONET (COPD and Systemic Consequences - Comorbidities Network) cohort with four follow-up visits were included in this analysis. At each visit, symptoms, exacerbation history, quality of life and lung function were assessed, along with the comorbidities heart failure (HF), coronary artery disease (CAD), peripheral arterial disease (PAD), hypertension, sleep apnea, diabetes mellitus, hyperlipidemia, hyperuricemia and osteoporosis. Using longitudinal logistic regression analysis, we determined what proportion of the increase in the prevalence of comorbidities could be attributed to patients’ age or to the progression of COPD over visits.Results: Of 2030 patients at baseline, 878 completed four follow-up visits (up to 4.5 years). CAD prevalence increased over time, with similar effects attributable to the 4.5-year follow-up, used as indicator of COPD progression, and to a 5-year increase in patients’ age. The prevalence of HF, diabetes, hyperlipidemia, hyperuricemia, osteoporosis and sleep apnea showed stronger contributions of COPD progression than of age; in contrast, age dominated for hypertension and PAD. There were different relationships to patients’ characteristics including BMI and sex. The results were not critically dependent on the duration of COPD prior to enrolment, or the inclusion of patients with all four follow-up visits vs those attending only at least one of them.Conclusion: Analyzing the increasing prevalence of multimorbidity in COPD over time, we separated age-independent contributions, probably reflecting intrinsic COPD-related disease progression, from age-dependent contributions. This distinction might be useful for the individual assessment of disease progression in COPD.Keywords: chronic obstructive pulmonary disease, comorbidities, multimorbidity, prognosis, disease progression

Introduction: Prolonged mechanical ventilation (PMV) and weaning failure are factors associated with prolonged hospital length of stay and increased morbidity and mortality. In addition to the burden these places on patients and their families, it also imposes high costs on the public health system. The aim of this systematic review was to identify risk factors for PMV and weaning failure. Methods: The study was conducted according to PRISMA guidelines. After a comprehensive search of the COCHRANE Library, CINHAL, Web of Science, MEDLINE, and the LILACS Database a PubMed request was made on June 8, 2020. Studies that examined risk factors for PMV, defined as mechanical ventilation ≥96 h, weaning failure, and prolonged weaning in German and English were considered eligible; reviews, meta-analyses, and studies in very specific patient populations whose results are not necessarily applicable to the majority of ICU patients as well as pediatric studies were excluded from the analysis. This systematic review was registered in the PROSPERO register under the number CRD42021271038. Results: Of 532 articles identified, 23 studies with a total of 23,418 patients met the inclusion criteria. Fourteen studies investigated risk factors of PMV including prolonged weaning, 9 studies analyzed risk factors of weaning failure. The concrete definitions of these outcomes varied considerably between studies. For PMV, a variety of risk factors were identified, including comorbidities, site of intubation, various laboratory or blood gas parameters, ventilator settings, functional parameters, and critical care scoring systems. The risk of weaning failure was mainly related to age, previous home mechanical ventilation (HMV), cause of ventilation, and preexisting underlying diseases. Elevated PaCO2 values during spontaneous breathing trials were indicative of prolonged weaning and weaning failure. Conclusion: A direct comparison of risk factors was not possible because of the heterogeneity of the studies. The large number of different definitions and relevant parameters reflects the heterogeneity of patients undergoing PMV and those discharged to HMV after unsuccessful weaning. Multidimensional scores are more likely to reflect the full spectrum of patients ventilated in different ICUs than single risk factors.

Kathrin Kahnert,1 Rudolf A Jörres,2 Tanja Lucke,2 Franziska C Trudzinski,3 Pontus Mertsch,1 Christiane Bickert,1 Joachim H Ficker,4 Jürgen Behr,1 Robert Bals,5 Henrik Watz,6 Tobias Welte,7 Claus F Vogelmeier,8 Peter Alter8 On behalf of COSYCONET Study Group1Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany; 4Department of Respiratory Medicine, Nürnberg General Hospital, Paracelsus Medical University, Nürnberg, Germany; 5Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 6Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 7Clinic for Pneumology, Hannover Medical School, Member of the German Center for Lung Research (DZL), Hannover, Germany; 8Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg (UMR), Germany, Member of the German Center for Lung Research (DZL), Marburg, GermanyCorrespondence: Kathrin KahnertDepartment of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, GermanyTel +49 89 4400 52590Fax +49 89 4400 54905Email kathrin.kahnert@med.uni-muenchen.deBackground: Patients with chronic obstructive pulmonary disease (COPD) often have osteoporosis and diabetes as comorbid conditions. Anti-diabetic medication, including metformin, has protective effects on osteoporosis in experimental studies. We therefore studied whether patients with COPD receiving anti-diabetic medication had a lower osteoporosis prevalence in a large COPD cohort, COSYCONET.Methods: Assessment of osteoporosis was based on patients’ reports of physician-based diagnoses and the presence of disease-specific medication. The predictive value of physical characteristics, lung function, comorbidities, cardiovascular medication, and the use of anti-inflammatory diabetes medication, including metformin, sulfonylureas, glinides or DPP4I, was evaluated using logistic regression analysis. ClinicalTrials.gov: NCT01245933.Results: In total, 2222 patients were eligible for analysis (863 [39%] female, mean age 65 y), 515 of whom had higher symptoms and exacerbations (Global Initiative for Chronic Obstructive Lung Disease group D). Osteoporosis was present in 15.8% of the overall cohort, and in 24.1% of GOLD D patients. Regression analyses identified the following as associated with osteoporosis (p < 0.05): female sex, higher age, lower body-mass index, asthma, higher air trapping, oral steroids, and cardiovascular medication. Although oral anti-diabetic medication was overall not associated with a lower prevalence of osteoporosis (p = 0.131), anti-inflammatory anti-diabetic medication (p = 0.009) and metformin-containing therapy (p = 0.039) were. This was driven by GOLD D patients.Conclusion: In a large COPD cohort, anti-inflammatory diabetes therapy, including metformin, was associated with a lower prevalence of osteoporosis, especially in patients with higher symptoms and exacerbations. These findings suggest a protective effect of common anti-diabetic medication on osteoporosis, possibly as a result of attenuated systemic inflammation.Keywords: chronic obstructive pulmonary disease, oral corticosteroids, inhaled corticosteroids, anti-inflammatory, metformin, diabetes

Background Lung emphysema is an important phenotype of chronic obstructive pulmonary disease (COPD), and CT scanning is strongly recommended to establish the diagnosis. This study aimed to identify criteria by which physicians with limited technical resources can improve the diagnosis of emphysema. Methods We studied 436 COPD patients with prospective CT scans from the COSYCONET cohort. All items of the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale, as well as data from spirometry and CO diffusing capacity, were used to construct binary decision trees. The importance of parameters was checked by the Random Forest and AdaBoost machine learning algorithms. Results When relying on questionnaires only, items CAT 1 & 7 and SGRQ 8 & 12 sub-item 3 were most important for the emphysema- versus airway-dominated phenotype, and among the spirometric measures FEV1/FVC. The combination of CAT item 1 (≤ 2) with mMRC (> 1) and FEV1/FVC, could raise the odds for emphysema by factor 7.7. About 50% of patients showed combinations of values that did not markedly alter the likelihood for the phenotypes, and these could be easily identified in the trees. Inclusion of CO diffusing capacity revealed the transfer coefficient as dominant measure. The results of machine learning were consistent with those of the single trees. Conclusions Selected items (cough, sleep, breathlessness, chest condition, slow walking) from comprehensive COPD questionnaires in combination with FEV1/FVC could raise or lower the likelihood for lung emphysema in patients with COPD. The simple, parsimonious approach proposed by us might help if diagnostic resources regarding respiratory diseases are limited. Trial registration ClinicalTrials.gov, Identifier: NCT01245933, registered 18 November 2010, https://clinicaltrials.gov/ct2/show/record/NCT01245933. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-021-01837-2.

Johanna I Lutter,1 Rudolf A Jörres,2 Franziska C Trudzinski,3 Peter Alter,4 Christina Kellerer,2,5 Henrik Watz,6 Tobias Welte,7 Robert Bals,8 Diego Kauffmann-Guerrero,9 Jürgen Behr,9 Rolf Holle,10 Claus F Vogelmeier,4 Kathrin Kahnert9 On behalf of the COSYCONET study group1Institute of Health Economics and Health Care Management, Helmholtz Zentrum München GmbH – German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, LMU Hospital, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany; 4Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg (UMR), Germany, Member of the German Center for Lung Research (DZL), Marburg, Germany; 5School of Medicine, Institute of General Practice and Health Services Research, Technical University of Munich (TUM), Munich, Germany; 6Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 7Department of Pneumology, Hannover Medical School, Hannover, Germany; 8Department of Internal Medicine V – Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 9Department of Medicine V, University of Munich (LMU), Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, Germany; 10Institute for Medical Informatics, Biometry and Epidemiology, LMU Hospital, Munich, GermanyCorrespondence: Kathrin KahnertDepartment of Internal Medicine V, University of Munich (LMU), LMU Hospital, Ziemssenstraße 1, Munich, 80336, GermanyEmail Kathrin.Kahnert@med.uni-muenchen.deBackground: In COPD patients of GOLD groups A and B, a high degree of treatment with inhaled corticosteroids (ICS) has been reported, which is regarded as overtreatment according to GOLD recommendations. We investigated which factors predict ICS use and which relationship it has to clinical and functional outcomes, or healthcare costs.Methods: We used pooled data from visits 1 and 3 of the COSYCONET cohort (n=2741, n=2053, interval 1.5 years) including patients categorized as GOLD grades 1– 4 and GOLD group A or B at both visits (n=1080). Comparisons were performed using ANOVA, and regression analyses using propensity matching and inverse probability weighting to adjust for differences between ICS groups. These were defined as having ICS at both visits (always) vs no ICS at both visits (never). Measures were divided into predictors of ICS treatment and outcomes.Results: Among 1080 patients, 608 patients were eligible for ICS groups (n=297 never, n=311 always). Prior to matching, patients with ICS showed significantly (p< 0.05 each) impaired lung function, symptoms and exacerbation history. After matching, the outcomes generic quality of life and CO diffusing capacity were increased in ICS patients (p< 0.05 each). Moreover, costs for respiratory medication, but not total health care costs, were significantly elevated in the ICS group by 780€ per year.Conclusion: ICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach.Keywords: COPD, inhaled corticosteroids, GOLD groups, overtreatment

Chronic obstructive pulmonary disease (COPD) is frequently associated with coronary artery disease (CAD). When considering computed tomography (CT) for COPD phenotyping, coronary vessel wall calcification would be a potential marker of cardiac disease. However, non-ECG gated scans as used in COPD monitoring do not comply with established quantitative approaches using ECG-triggered CT and the Agatston score. We studied the diagnostic potential of Agatston scores from non-triggered scans for cardiac disease. The study population was a sub-group of the COPD cohort COSYCONET that underwent CT scanning in addition to comprehensive clinical assessments, echocardiographic data and physician-based diagnoses of comorbidities. Agatston scores from non-contrast enhanced, non-triggered CT were used to identify a cut-off value for CAD via ROC analysis. 399 patients were included (152 female, mean age 66.0 ± 8.2 y). In terms of CAD, an Agatston score ≥1500 AU performed best (AUC 0.765; 95% CI: 0.700, 0.831) and was superior to the conventional cut-off value (400 AU). Using this value for defining groups, there were differences (p lt; 0.05) in lung function, left atrial diameter and left ventricular end-systolic diameter as well as CT-determined central airway wall thickness pointing towards a bronchitis phenotype. In multivariate analysis, BMI, hyperlipidemia, arterial hypertension, GOLD D (p lt; 0.05) but particularly Agatston score ≥1500 AU (Odds ratio 10.5; 95% CI: 4.8; 22.6)) were predictors of CAD. We conclude that in COPD patients, Agatston scores derived from non-ECG gated CT showed a much higher cut-off value (1500 AU) for actionable coronary artery disease than the score derived from ECG-triggered CT in cardiology patients.

BACKGROUND Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale. RESULTS In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean ± SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 ± 0.22 to 0.87 ± 0.20 and the visual analog scale from 72.9 ± 18.8 to 74.4 ± 19.1. INTERPRETATION In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management. CLINICAL TRIAL REGISTRATION German Clinical Trials Registry (Deutsches Register Klinischer Studien: www.drks.de); No.: DRKS00005939.

High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences—Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00–1.87) compared to baseline RHR ≤ 72 bpm. The time-updated RHR > 72 bpm was markedly superior (HR 1.79, 1.30–2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.

Background: Oxygenated hemoglobin(OxyHem) is a simple-to-measure marker of oxygen content capable of predicting all-cause mortality in stable chronic obstructive pulmonary disease (COPD). Objectives: We aimed to analyze its predictive value during acute exacerbations of COPD (AECOPD). Methods: In this retrospective study, data from 227 patients discharged after severe AECOPD at RoMed Clinical Center Rosenheim, Germany, between January 2012 and March 2018, was analyzed. OxyHem (hemoglobin concentration [Hb] × fractional SpO2, g/dL) was calculated from oxygen saturation measured by pulse oximetry and hemoglobin assessed within 24 h after admission. The follow-up (1.7 ± 1.5 years) covered all-cause mortality, including readmissions for severe AECOPD. Results: During the follow-up period, 127 patients died, 56 due to AECOPD and 71 due to other reasons. Survivors and non-survivors showed differences in age, FVC % predicted, C-reactive protein, hemoglobin, Cr, Charlson Comorbidity Index (CCI), and OxyHem (p < 0.05 each). Significant independent predictors of survival were BMI, Cr or CCI, FEV1 % predicted or FVC % predicted, Hb, or OxyHem. The predictive value of OxyHem (p = 0.006) was superior to that of Hb or SpO2 and independent of oxygen supply during blood gas analysis. OxyHem was also predictive when using a cutoff value of 12.1 g/dL identified via receiver operating characteristic curves in analyses including either the CCI (hazard ratio 1.85; 95% CI 1.20, 2.84; p = 0.005) or Cr (2.04; 95% CI 1.35, 3.10; p = 0.001) as covariates. Conclusion: The concentration of OxyHem provides independent, easy-to-assess information on long-term mortality risk in COPD, even if measured during acute exacerbations. It therefore seems worth to be considered for broader clinical use.

Extracorporeal carbon dioxide removal (ECCO2R) is increasingly considered a viable therapeutic approach in the management of hypercapnic lung failure to avoid intubation or to allow lung-protective ventilator settings. This study aimed to analyze efficacy and safety of a minimal-invasive ECCO2R device, the Homburg lung. The Homburg lung is a pump-driven system for veno-venous ECCO2R with ¼″ tubing and a 0.8 m surface oxygenator. Vascular access is usually established via a 19F/21 cm bilumen cannula in the right internal jugular vein. For this work, we screened patient registries from two German centers for patients who underwent ECCO2R with the Homburg lung because of hypercapnic lung failure since 2013. Patients who underwent extracorporeal membrane oxygenation before ECCO2R were excluded. Patients who underwent ECCO2R more than one time were only included once. In total, 24 patients (aged 53.86 ± 12.49 years; 62.5% male) were included in the retrospective data analysis. Ventilatory failure occurred because of chronic obstructive pulmonary disease (50%), cystic fibrosis (16.7%), acute respiratory distress syndrome (12.5%), and other origins (20.8%). The system generated a blood flow of 1.18 ± 0.23 liters per minute (lpm). Sweep gas flow was 3.87 ± 2.97 lpm. Within 4 hours, paCO2 could be reduced significantly from 82.05 ± 15.57 mm Hg to 59.68 ± 12.27 mm Hg, thereby, increasing pH from 7.23 ± 0.10 to 7.36 ± 0.09. Cannulation-associated complications were transient arrhythmia (1/24 patients) and air embolism (1/24). Fatal complications did not occur. In conclusion, the Homburg lung provides effective carbon dioxide removal in hypercapnic lung failure. The cannulation is a safe procedure, with complication rates comparable to those in central venous catheter implantation.

Introduction Alpha-1 antitrypsin deficiency (AATD, OMIM #613490) is a rare metabolic disorder affecting lungs and liver. The purpose of this study is to assess the impact of the US orphan drug act on AATD by providing a quantitative clinical-regulatory insight into the status of FDA orphan drug approvals and designations for compounds intended to treat AATD.Methods: Cross-sectional analysis of the FDA database for orphan drug designations. Primary endpoint: orphan drug approvals. Secondary endpoint: orphan drug designations by the FDA. Close of database: 16 July 2021. STROBE criteria were respected.Results Primary: one compound, alpha-1-proteinase inhibitor (human) was approved as an orphan drug in 1987 with market exclusivity until 1994.Secondary: sixteen compounds received FDA orphan drug designation including protein, anti-inflammatory, mucolytic, gene, or cell therapy.Conclusion: Drug development activities in the field were comparable to other rare conditions and led to the FDA-approval of one compound, based on a relatively simple technological platform. The current unmet medical need is to fill the gap of missing agents for therapy of extrapulmonary manifestations of AATD. Orphan drug development is actually focusing on (1) diversified recombinant AAT production platforms, and (2) innovative gene therapies, which may, encompass a more holistic therapeutic approach.

Oxygenated hemoglobin (OxyHem) in arterial blood may reflect disease severity in patients with systemic sclerosis (SSc). The aim of this study was to analyze the predictive value of OxyHem in SSc patients screened for pulmonary hypertension (PH). OxyHem (g/dl) was measured by multiplying the concentration of hemoglobin with fractional oxygen saturation in arterialized capillary blood. Prognostic power was compared with known prognostic parameters in SSc using uni- and multivariable analysis. A total of 280 SSc patients were screened, 267 were included in the analysis. No signs of pulmonary vascular disease were found in 126 patients, while 141 patients presented with mean pulmonary arterial pressure ≥ 21 mmHg. Interstitial lung disease (ILD) was identified in 70 patients. Low OxyHem ≤ 12.5 g/dl at baseline was significantly associated with worse survival (P = 0.046). In the multivariable analysis presence of ILD, age ≥ 60 years and diffusion capacity for carbon monoxide (DLCO) ≤ 65% were negatively associated with survival. The combination of low DLCO and low OxyHem at baseline could predict PH at baseline (sensitivity 76.1%). This study detected for the first time OxyHem ≤ 12.5 g/dl as a prognostic predictor in SSc patients. Further studies are needed to confirm these results.

Background Beyond smoking, several risk factors for the development of chronic obstructive pulmonary disease (COPD) have been described, among which socioeconomic status including education is of particular interest. We studied the contribution of education to lung function and symptoms relative to smoking in a group of never-smokers with COPD compared to a group of long-time ex-smokers with COPD. Methods We used baseline data of the COSYCONET cohort, including patients of GOLD grades 1-4 who were either never-smokers (n=150, age 68.5y, 53.3% female) or ex-smokers (≥10 packyears) for at least 10 years (n=616, 68.3y, 29.9% female). Socioeconomic status was analyzed using education level and mortality was assessed over a follow-up period of 4.5 years. Analyses were performed using ANOVA and regression models. Results Spirometric lung function did not differ between groups, whereas CO diffusing capacity and indicators of lung hyperinflation/air-trapping showed better values in the never-smoker group. In both groups, spirometric lung function depended on the education level, with better values for higher education. Quality of life and 6-MWD were significantly different in never-smokers as well as patients with higher education. Asthma, alpha-1-antitrypsin deficiency, and bronchiectasis were more often reported in never-smokers, and asthma was more often reported in patients with higher education. Higher education was also associated with reduced mortality (hazard ratio 0.46; 95% CI 0.22-0.98). Conclusion Overall, in the COSYCONET COPD cohort, differences in functional status between never-smokers and long-time ex-smokers were not large. Compared to that, the dependence on education level was more prominent, with higher education associated with better outcomes, including mortality. These data indicate that non-smoking COPD patients' socioeconomic factors are relevant and should be taken into account by clinicians.

Carolina Fischer,1 Rudolf A Jörres,1 Peter Alter,2 Franziska C Trudzinski,3 Önder Yildirim,4 Robert Bals,5 Claus F Vogelmeier,2 Diego Kauffmann-Guerrero,6 Jürgen Behr,6 Henrik Watz,7 Rolf Holle,8 Kathrin Kahnert6 And members of the COSYCONET study group1Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 2Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg (UMR), Germany, Marburg, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany; 4Institute of Lung Biology and Disease (ILBD), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 5Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 6Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 7Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Grosshansdorf, Germany; 8Institute for Medical Informatics, Biometry and Epidemiology, University Hospital, LMU Munich, Munich, GermanyCorrespondence: Kathrin Kahnert, Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Ziemssenstraße 1, Munich, 80336, Germany, Email Kathrin.Kahnert@med.uni-muenchen.deIntroduction: In many chronic diseases, including COPD, the patients’ basic knowledge of the disorder has been shown to be relevant for the course of the disease. We studied which clinical and functional characteristics were related to this knowledge as well as the patients’ satisfaction with their knowledge about COPD.Methods: The study population comprised 645 patients of GOLD grades 1– 4 who participated in Visit 6 of the COSYCONET cohort (COPD and Systemic Consequences - Comorbidities Network). The assessments covered a broad panel of clinical and functional characteristics, including generic and disease-specific quality of life and the COPD Assessment Test (CAT). The study aim was addressed by two questions, referring to patients’ knowledge of the meaning of FEV1 and the overall satisfaction with their knowledge of COPD.Results: Knowledge of FEV1 was higher in patients of higher spirometric GOLD grades or exacerbation risk, in males, with higher educational level, and after participation in a prior educational training on COPD. Patients with more detailed knowledge showed a higher satisfaction with their knowledge. Satisfaction was associated with higher generic quality of life and a lower CAT score. Furthermore, satisfaction was higher in patients with a treatment plan but lower in patients with cardiac comorbidities. It appeared that females with basic education, high burden from COPD and low quality of life had the greatest knowledge deficits.Discussion: The results suggest room for education programs adapted to the educational level of the participants. They also emphasize the major role of a disease management plan for the patients.Keywords: chronic obstructive pulmonary disease, knowledge, education, satisfaction

Background Two antifibrotic drugs, pirfenidone and nintedanib, are licensed for the treatment of patients with idiopathic pulmonary fibrosis (IPF). However, there is neither evidence from prospective data nor a guideline recommendation, which drug should be preferred over the other. This study aimed to compare pirfenidone and nintedanib-treated patients regarding all-cause mortality, all-cause and respiratory-related hospitalizations, and overall as well as respiratory-related health care costs borne by the Statutory Health Insurance (SHI). Methods A retrospective cohort study with SHI data was performed, including IPF patients treated either with pirfenidone or nintedanib. Stabilized inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for observed covariates. Weighted Cox models were estimated to analyze mortality and hospitalization. Weighted cost differences with bootstrapped 95% confidence intervals (CI) were applied for cost analysis. Results We compared 840 patients treated with pirfenidone and 713 patients treated with nintedanib. Both groups were similar regarding two-year all-cause mortality (HR: 0.90 95% CI: 0.76; 1.07), one-year all cause (HR: 1.09, 95% CI: 0.95; 1.25) and respiratory-related hospitalization (HR: 0.89, 95% CI: 0.72; 1.08). No significant differences were observed regarding total (€− 807, 95% CI: €− 2977; €1220) and respiratory-related (€− 1282, 95% CI: €− 3423; €534) costs. Conclusion Our analyses suggest that the patient-related outcomes mortality, hospitalization, and costs do not differ between the two currently available antifibrotic drugs pirfenidone and nintedanib. Hence, the decision on treatment with pirfenidone versus treatment with nintedanib ought to be made case-by-case taking clinical characteristics, comorbidities, comedications, individual risk of side effects, and patients’ preferences into account.

Background: In daily routine, many COPD patients lament early onset augmented dyspnea following use of NIV (Deventilation Syndrome, DVS) as a negative side-effect. This is the first study to this date to quantify and characterize DVS. MethodsThis monocenter prospective observational study collected demographic, physiologic and symptomatic data from 67 in-patients with severe COPD Gold III-IV and chronic hypercapnic failure before, during and after use of an established NIV.During their inpatient follow-up, we examined patients during the first hour after termination of nocturnal NIV. DVS was defined by the authors as an increase of ≥ 2 points on the Borg scale during the first 30 minutes. We monitored cardiovascular and respiratory data and measured diaphragm excursion. Subjective dyspnea was documented by use of the Borg scale and questionnaires. In addition, respirator and demographic data were collected.ResultsDVS occurred in 58% of our COPD patients. Patients with DVS were more severely ill than non-DVS concerning bronchial obstruction (FEV1 0.6 vs 0.8l, pConclusionsThis is the first trial quantifying and characterizing early onset augmented dyspnea after the use of NIV, referred to as DVS. It is now brought to attention as a frequent side effect of long-term home ventilation and possible pathophysiologic mechanisms are elucidated.

ZusammenfassungDie Erkennung, Diagnosestellung und Behandlung von Infektionen durch atypische Mykobakterien stellen eine besondere klinische Herausforderung dar. Über invasive Erkrankungen durch das zum Mycobacterium avium-intracellulare complex gehörige Mycobacterium chimaera wurde in den letzten Jahren vermehrt berichtet, insbesondere bei Patienten nach kardiochirurgischen Operationen mit Thorakotomie. Es konnte nachgewiesen werden, dass diese Infektionen durch eine intraoperative, Aerosol-gebundene Übertragung des Pathogens über kontaminierte Hypothermiegeräte (Heater-Cooler-Units), die zum Betrieb von Herz-Lungen-Maschinen eingesetzt werden, zu erklären waren. Es handelt sich dabei um ein weltweites Ausbruchsgeschehen mit bisher etwa 120 diagnostizierten Fällen, wobei die Latenz zwischen Exposition und dem Auftreten erster Symptome häufig mehrere Jahre beträgt. Das klinische Bild einer M. chimaera-Infektion ist mannigfaltig und kann neben Endokarditis oder Implantat-assoziierten Prozessen auch mit nicht kardialer Manifestation (z. B. Sarkoidose-ähnliches Krankheitsbild, Spondylodiscitis, Chorioretinitis) einhergehen. Die Diagnosestellung erfolgt über den Erregernachweis aus speziellen Blutkulturen oder intraoperativen Gewebeproben, insofern eine spezifische mikrobiologische Testung auf Mykobakterien angefordert wird. Ein noninvasives Testverfahren steht nicht zur Verfügung, sodass bei entsprechender Exposition bei Patienten mit passender Klinik aktiv an diese Erkrankung gedacht werden sollte. Die Behandlung von M. chimaera-Infektionen erfordert neben der Entfernung infizierter Implantate eine prolongierte antimykobakterielle Kombinationstherapie. Dieser Übersichtsartikel stellt die aktuelle Bedeutung, Epidemiologie, klinische Symptomatik, Diagnostik und Therapie von M. chimaera-Infektionen für Pneumologen zusammenfassend dar.

Der klinische Verlauf einer Lungenembolie kann nur schwer vorhergesagt werden, er reicht vom plotzlichen Tod bis zur vollstandigen Wiederherstellung. Die schwerste Folge ist die chronisch thromboembolische pulmonale Hypertonie, die leider oft ubersehen oder falsch klassifiziert wird. Das kann dazu fuhren, dass Patienten nicht oder erst spat einer der drei zur Verfugung stehenden Therapieoptionen zugefuhrt werden.

BACKGROUND: Lung function impairment in COPD is known to be related to reductions of left heart size, while short-term interventional trials with bronchodilators showed positive effects on cardiac parameters. We investigated whether COPD maintenance therapy has analogous long-term effects. METHODS: Pooled data of GOLD grade 1-4 patients from visits 1 and 3 (1.5y apart) of the COSYCONET cohort were used. Medication was categorized as use of ICS, LABA+ICS, LABA+LAMA and triple therapy (LABA+LAMA+ICS), contrasting "always" versus "never". Echocardiographic parameters comprised left ventricular end-diastolic and -systolic diameter (LVEDD, LVESD), ejection fraction (LVEF) and left atrial diameter (LA). Associations were identified by multiple regression analysis, as well as propensity score analysis. RESULTS: Overall, 846 patients (mean age 64.5y; 41% female) were included, 53% using ICS at both visits, 51% LABA+ICS, 56% LABA+LAMA, 40% LABA+LAMA+ICS (triple) therapy. Conversely, 30%, 32%, 28% and 42% had no ICS, LABA+ICS, LABA+LAMA or triple therapy, respectively, at both visits. Among echocardiographic measures, only LA showed statistically significant associations (increases) with medication, whereby significant effects were linked to ICS, LABA+ICS and LABA+LAMA (p&nbsp