Publications by authors named "Hubert Wirtz"

102 Publications

Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial.

Lancet Respir Med 2021 Mar 30. Epub 2021 Mar 30.

Center for Interstitial and Rare Lung Diseases, Justus-Liebig University Giessen, Giessen, Germany; Member of the German Center for Lung Research and Cardiopulmonary Institute, and Agaplesion Lung Clinic Waldhof-Elgershausen, Greifenstein, Germany.

Background: Pirfenidone has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). However, there are few treatment options for progressive fibrotic interstitial lung diseases (ILDs)) other than IPF. In view of the pathomechanistic and clinical similarities between IPF and other progressive fibrotic ILDs, we aimed to assess the efficacy and safety of pirfenidone in patients with four non-IPF progressive fibrotic ILDs.

Methods: We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18-80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40-90% predicted, a diffusing capacity of the lung for carbon monoxide of 10-90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6-24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebo-controlled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32; DRKS00009822 and is no longer recruiting.

Findings: Between April 5, 2016, and Oct 4, 2018, we randomly assigned 127 patients to treatment: 64 to pirfenidone, 63 to placebo. After 127 patients had been randomised, the study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks and in the overall population of 127 patients, rank ANCOVA with diagnostic group included as a factor showed a significantly lower decline in FVC % predicted in the pirfenidone group compared with placebo (p=0·043); the result was similar when the model was stratified by diagnostic group (p=0·042). A significant treatment effect was also observed when applying the LOCF and multiple imputation methods to analyses of the primary endpoint. The median difference (Hodges-Lehmann estimate) between pirfenidone and placebo groups for the primary endpoint was 1·69 FVC % predicted (95% CI -0·65 to 4·03). In the linear mixed-model repeated measures slope analysis of FVC % predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3·53 FVC % predicted (95% CI 0·21 to 6·86) with imputation of deaths as prespecified, or 2·79 FVC % predicted (95% CI 0·03 to 5·54) without imputation. One death (non-respiratory) occurred in the pirfenidone group (2%) and five deaths (three of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (five [8%] in the pirfenidone group, ten [16%] in the placebo group); general disorders including disease worsening (two [3%] in the pirfenidone group, seven [11%] in the placebo group); and cardiac disorders (one ([2%] in the pirfenidone group, 5 [8%] in the placebo group). Adverse events (grade 3-4) of nausea (two patients on pirfenidone, two on placebo), dyspnoea (one patient on pirfenidone, one on placebo), and diarrhoea (one patient on pirfenidone) were also observed.

Interpretation: In view of the premature study termination, results should be interpreted with care. Nevertheless, our data suggest that in patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment might attenuate disease progression as measured by decline in FVC.

Funding: German Center for Lung Research, Roche Pharma.
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http://dx.doi.org/10.1016/S2213-2600(20)30554-3DOI Listing
March 2021

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry.

Respir Med 2021 Mar 12;178:106220. Epub 2020 Nov 12.

Department of Respiratory Medicine and the German Center for Lung Research, Hannover Medical School, Hannover, Germany.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice.

Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms.

Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]).

Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified.
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http://dx.doi.org/10.1016/j.rmed.2020.106220DOI Listing
March 2021

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry.

Respir Med 2020 Dec 3;177:106241. Epub 2020 Dec 3.

University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Member of the German Center for Lung Research (DZL), Germany.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice.

Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms.

Results: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years.

Conclusion: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH.
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http://dx.doi.org/10.1016/j.rmed.2020.106241DOI Listing
December 2020

Idiopathic Pulmonary Fibrosis in Elderly Patients: Analysis of the INSIGHTS-IPF Observational Study.

Front Med (Lausanne) 2020 16;7:601279. Epub 2020 Nov 16.

Comprehensive Pneumology Center (CPC-M), Asklepios Klinik Gauting and Helmholtz Center Munich, Ludwig-Maximilians University, München, Germany.

An association between idiopathic pulmonary fibrosis (IPF) and advancing age is suspected since IPF occurs primarily in patients over 60 years of age. Though, little is known about the disease in the elderly. The aim of this study was to characterize elderly IPF patients using data from the longitudinal, German-wide INSIGHTS-IPF registry. Patients were grouped into elderly (≥75 years) and nonelderly IPF (<75 years) at the time of enrollment into the study. Baseline clinical characteristics, comorbidities, health related quality of life (HRQoL), medical therapy and survival were compared between age groups. Effects of antifibrotic therapy on forced vital capacity (FVC) were analyzed over 24 months. Of 1,009 patients, 350 (34.7%) were ≥75 years old. Elderly IPF patients compared to younger patients had a higher number of comorbidities (3.6 ± 2.5 vs. 2.8 ± 2.3; < 0.001). The mean ± SD EQ-5D score (0.64 ± 0.21 vs. 0.69 ± 0.21; = 0.005), and the overall WHO-5 score (13.1 ± 5.9 vs. 14.3 ± 6.0; = 0.015) were significantly lower while the UCSD-SOBQ (52.6 ± 31.2 vs. 45.5 ± 31.2; = 0.030) was significantly higher in elderly patients, indicating a more impaired HRQoL and more breathlessness. At baseline, 55.4% of elderly and 56.8% of nonelderly patients with IPF were treated with antifibrotic therapy ( = 0.687). For FVC decline after initiation of antifibrotic therapy, there was neither a significant difference between age groups at the different time points over 24 months (beta: 0.41; 95%-CI: -0.98 to 1.81; = 0.563) nor over the whole course of time (beta: -0.05; 95%-CI: -0.20 to 0.09; = 0.478). All-cause mortality was higher in elderly patients (49.1 vs. 37.9%; HR 1.65; 95%-CI 1.36-2.00; < 0.001). Antifibrotic therapy was associated with improved survival in IPF patients, independent from age (<75 years: beta 0.76; 95%-CI: 0.59-0.99; = 0.049; ≥75 years: beta 0.71; 95%-CI: 0.51-0.98; = 0.043). In real life, a significant proportion of IPF patients are ≥75 years old, characterized by higher number of comorbidities and global reduced HRQoL. However, the effect of an antifibrotic therapy was similar between age groups and associated with a survival benefit emphasizing the importance for an early antifibrotic therapy in IPF, independent from age.
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http://dx.doi.org/10.3389/fmed.2020.601279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703706PMC
November 2020

Returning to work in lung cancer survivors-a multi-center cross-sectional study in Germany.

Support Care Cancer 2020 Nov 19. Epub 2020 Nov 19.

Division of Epidemiology and Health Services Research, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 69, 55131, Mainz, Germany.

Purpose: To investigate the work situation of lung cancer survivors and to identify the factors associated with their returning to work.

Methods: Descriptive analysis and logistic regression were used to evaluate study population characteristics and independent factors of subsequently returning to work. To analyze time to return to work, Cox regression was used.

Results: The study sample included 232 lung cancer survivors of working age from 717 enrolled participants in the multi-center cross-sectional LARIS (Quality of Life and Psychosocial Rehabilitation in Lung Cancer Survivors) study. About 67% of the survivors were not employed during the survey. More than 51% of the survivors who were employed before their illness did not return to their work. The survivors who had returned to their careers were younger, associated with higher household income, lower fatigue score, and stable relationship and vocational training. Patients who received social service counseling showed a higher chance of regaining their career.

Conclusions: Lung cancer survivors were found to be associated with a high risk of unemployment and very low professional reintegration after interruption due to illness. More comprehensive studies are needed to support lung cancer survivors and targeting of patients in need of special attention in rehabilitation that would benefit from the findings in the present study.
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http://dx.doi.org/10.1007/s00520-020-05886-zDOI Listing
November 2020

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

J Heart Lung Transplant 2020 12 30;39(12):1435-1444. Epub 2020 Sep 30.

Clinic for General and Interventional Cardiology and Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.
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http://dx.doi.org/10.1016/j.healun.2020.09.011DOI Listing
December 2020

Increased pulmonary serotonin transporter in patients with chronic obstructive pulmonary disease who developed pulmonary hypertension.

Eur J Nucl Med Mol Imaging 2021 Apr 3;48(4):1081-1092. Epub 2020 Oct 3.

Department of Respiratory Medicine, University Hospital Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.

Purpose: Pulmonary hypertension (PH) is characterized by a progressive remodelling of the pulmonary vasculature resulting in right heart failure and eventually death. The serotonin transporter (SERT) may be involved in the pathogenesis of PH in patients with chronic-obstructive pulmonary disease (COPD). This study investigated for the first time the SERT in vivo availability in the lungs of patients with COPD and PH (COPD+PH).

Methods: SERT availability was assessed using SERT-selective [C]DASB and positron emission tomography/computed tomography (PET/CT) with dynamic acquisition over 30 min in 4 groups of 5 participants each: COPD, COPD+PH, pulmonary arterial hypertension, and a healthy control (HC). Time activity curves were generated based on a volume of interest within the middle lobe. Tissue-to-blood concentration ratios after 25 to 30 min (TTBR) served as receptor parameter for group comparison and were corrected for lung tissue attenuation. Participants underwent comprehensive pulmonary workup. Statistical analysis included group comparisons and correlation analysis.

Results: [C]DASB uptake peak values did not differ among the cohorts after adjusting for lung tissue attenuation, suggesting equal radiotracer delivery. Both the COPD and COPD+PH cohort showed significantly lower TTBR values after correction for lung attenuation than HC. Attenuation corrected TTBR values were significantly higher in the COPD+PH cohort than those in the COPD cohort and higher in non-smokers than in smokers. They positively correlated with invasively measured severity of PH and inversely with airflow limitation and emphysema. Considering all COPD patients ± PH, they positively correlated with right heart strain (NT-proBNP).

Conclusion: By applying [C]DASB and PET/CT, semiquantitative measures of SERT availability are demonstrated in the lung vasculature of patients with COPD and/or PH. COPD patients who developed PH show increased pulmonary [C]DASB uptake compared to COPD patients without PH indicating an implication of pulmonary SERT in the development of PH in COPD patients.
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http://dx.doi.org/10.1007/s00259-020-05056-7DOI Listing
April 2021

Benefits of pulmonary rehabilitation in patients with advanced lymphangioleiomyomatosis (LAM) compared with COPD - a retrospective analysis.

Orphanet J Rare Dis 2020 09 22;15(1):255. Epub 2020 Sep 22.

Department of Pulmonary Rehabilitation, Philipps - University of Marburg, German Center for Lung Research (DZL), Marburg, Germany.

Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung disease with limited therapeutic options. We retrospectively analyzed the effects of a comprehensive 4-week inpatient pulmonary rehabilitation (PR) program in 58 patients with advanced LAM (FEV1: 45 ± 34%predicted, 6-min walk distance (6MWD): 338 ± 167 m). Exercise performance (6MWD: + 49 ± 50 m; p < 0.001) and quality of life (SF-36 physical component: + 2.4 ± 7.8 points; p = 0.049 and mental component: + 5.2 ± 12.1 points; p < 0.001) increased significantly after PR comparable to an COPD cohort. There were no clinical parameters that predicted changes in outcomes following PR. PR seems to be an effective therapeutic option even in patients with advanced LAM. TRIAL REGISTRATION: Clinical-Trials registration number: NCT04184193 ; date of registration: December 3, 2019.
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http://dx.doi.org/10.1186/s13023-020-01540-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507679PMC
September 2020

Nocardiosis mimicking lung cancer in a heart transplant patient with end-stage renal disease.

Respir Med Case Rep 2020 27;30:101101. Epub 2020 May 27.

Department of Pneumology, University Hospital of Leipzig, Germany.

Nocardiosis is a rare bacterial opportunistic infection that most commonly manifests as lung disease. However, disseminated infection and abscess formation can occur. Due to diverse radiographic findings and difficult cultivation it is not an easy diagnosis to make. Antibiotics such as Trimethoprimsulfamethoxazole alone or in combination with imipenem or imipenem in combination with amikacin need to be administered over a period of at least six to twelve weeks. We report a case of a 64-year old female heart transplant recipient requiring dialysis who suffered from dyspnea and a productive cough among other symptoms. Computed tomography revealed a tumor in the left upper lobe suggesting lung cancer. Both transbronchial and transthoracic biopsy could not confirm a malignant disease. Finally, Nocardia nova was isolated from a bronchoalveolar lavage and specific antibiotic treatment was initiated. As a result, the mass in the left upper lobe significantly regressed after a few weeks.
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http://dx.doi.org/10.1016/j.rmcr.2020.101101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283146PMC
May 2020

Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry.

J Clin Med 2020 05 13;9(5). Epub 2020 May 13.

Universitätsklinik Köln- Herzzentrum, Klinik III für Innere Medizin, 50937 Köln, Germany.

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension.

Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data.

Methods And Results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients´ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy ( = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan-Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status.

Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.
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http://dx.doi.org/10.3390/jcm9051456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290703PMC
May 2020

Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry.

Eur Respir J 2020 08 13;56(2). Epub 2020 Aug 13.

German Center for Lung Research (DZL), Germany.

Objective: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions.

Methods: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy.

Results: Among the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity () were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% 46% and 62% 21%, respectively, for patients with without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and was slow and did not differ significantly between patients with or without antifibrotic therapy.

Conclusions: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and .
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http://dx.doi.org/10.1183/13993003.02279-2019DOI Listing
August 2020

Mutually reinforcing effects of genetic variants and interferon-β 1a therapy for pulmonary arterial hypertension development in multiple sclerosis patients.

Pulm Circ 2019 Jul-Sep;9(3):2045894019872192. Epub 2019 Nov 18.

Department of Respiratory Medicine, University Hospital of Leipzig, Leipzig, Germany.

Based on a small number of cases, interferon beta (IFN-β) has been added to the list of drugs that might induce pulmonary arterial hypertension (PAH) in the current European guidelines for the diagnosis and treatment of pulmonary hypertension. Here, we propose that multiple sclerosis patients who are genetically predisposed to PAH may be at higher risk to develop disease when treated with IFN-β. We included two patients with multiple sclerosis who developed a manifest PAH after five amd eight years on IFN-β 1a therapy, respectively (without confirmed right heart catheterization). In both patients, PAH markedly improved after discontinuation of IFN-β 1a and initiation of targeted PAH therapy. For genetic analysis, we used a PAH-gene panel based on next-generation sequencing of 16 PAH and 38 candidate genes. In one of the two patients, we could identify a nonsense variant in the PAH gene . The second patient showed a missense variant of the gene, which might be linked to PAH predisposition. The results of this study support the hypothesis that multiple sclerosis patients who receive IFN-β 1a therapy might be at higher risk for the development of manifest PAH, if they carry a pathogenic variant or sequence variant genetically predisposing to the disease. However, further studies are necessary to systematically investigate the presence of predisposing PAH gene variants in these patients.
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http://dx.doi.org/10.1177/2045894019872192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862775PMC
November 2019

Response to the letter to the editor "Nasal high-flow versus non-invasive ventilation in patients with chronic hypercapnic COPD" [Response to letter].

Int J Chron Obstruct Pulmon Dis 2019 9;14:2119-2120. Epub 2019 Sep 9.

Department of Respiratory Medicine, University of Leipzig AöR, Leipzig, Germany.

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http://dx.doi.org/10.2147/COPD.S228830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748159PMC
November 2019

Nasal high-flow versus noninvasive ventilation in patients with chronic hypercapnic COPD.

Int J Chron Obstruct Pulmon Dis 2019 5;14:1411-1421. Epub 2019 Jul 5.

Department of Respiratory Medicine, University of Leipzig AöR, Leipzig, Germany.

Background: Despite the encouraging results of noninvasive ventilation (NIV) in chronic hypercapnic COPD patients, it is also evident that some patients do not tolerate NIV or do not benefit from it. We conducted a study in which COPD patients with stable, chronic hypercapnia were treated with NIV and nasal high-flow (NHF) to compare effectiveness.

Methods: In a multi-centered, randomized, controlled, cross-over design, patients received 6 weeks of NHF ventilation followed by 6 weeks of NIV ventilation or vice-versa (TIBICO) between 2011 and 2016. COPD patients with stable daytime hypercapnia (pCO≥50 mmHg) were recruited from 13 German centers. The primary endpoint was pCO changes from baseline blood gas, lung function, quality of life (QoL), the 6 min walking test, and duration of device use were secondary endpoints.

Results: A total of 102 patients (mean±SD) age 65.3±9.3 years, 61% females, body mass index 23.1±4.8 kg/m, 90% GOLD D, pCO 56.5±5.4 mmHg were randomized. PCO levels decreased by 4.7% (n=94; full analysis set; 95% CI 1.8-7.5, =0.002) using NHF and 7.1% (95% CI 4.1-10.1, <0.001) from baseline using NIV (indistinguishable to intention-to-treat analysis). The difference of pCO changes between the two devices was -1.4 mmHg (95% CI -3.1-0.4, =0.12). Both devices had positive impact on blood gases and respiratory scores (St. George's Respiratory Questionnaire, Severe Respiratory Insufficiency Questionnaire).

Conclusions: NHF may constitute an alternative to NIV in COPD patients with stable chronic hypercapnia, eg, those not tolerating or rejecting NIV with respect to pCO reduction and improvement in QoL.
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http://dx.doi.org/10.2147/COPD.S206111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615713PMC
February 2020

Use of psychosocial services by lung cancer survivors in Germany : Results of a German multicenter study (LARIS).

Strahlenther Onkol 2019 Nov 10;195(11):1018-1027. Epub 2019 Jul 10.

Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany.

Purpose: Little is known about the use of psychosocial services in lung cancer survivors and patients who have survived the diagnosis for at least one year. We investigated the frequency of use, stratified by radiation therapy received, its associated factors, and the reasons for non-use of those services.

Methods: We performed a multicenter (n = 6 hospitals) cross-sectional study using data from medical records, patient reported questionnaires, and computer-assisted telephone interviews. Odds ratios (OR) for factors potentially associated with the use of any type of psychosocial services were calculated using multivariable logistic regression.

Results: We included 604 lung cancer patients/survivors. Of them, 60% (69% of those who had received radiotherapy) had used some kind of psychological and/or social service in the past (47% psychological, 42% social); 39% had used inpatient care, 24% outpatient care (cancer counselling center, general counselling center, psychological counselling by family doctor, psychotherapy, patient support group, pastoral work). Of those who visited a rehabilitation clinic, 66% received psychosocial care there. Factors associated with using psychosocial services in general were female gender (OR 1.96, 95% CI 1.32-2.93), poor emotional functioning (per unit decrease: OR 0.99, 95% CI 0.98-0.996), and younger age (per year decrease: OR 0.95, 95% CI 0.93-0.97).

Conclusions/implications: The high proportion of psychosocial care users among lung cancer survivors in Germany indicates that patients are interested in using it and that an unmet need exists. The creation of a broad spectrum of easily accessible services with high quality is important to enable and facilitate use.
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http://dx.doi.org/10.1007/s00066-019-01490-1DOI Listing
November 2019

High amplitude stretching of ATII cells and fibroblasts results in profibrotic effects.

Exp Lung Res 2019 09 10;45(7):167-174. Epub 2019 Jul 10.

a Department of Respiratory Medicine, University of Leipzig , Leipzig , Germany.

Inappropriate mechanical forces act on alveolar epithelial cells during mechanical ventilation e.g. in ARDS and possibly in patients with pulmonary fibrosis. These forces can cause lung injury and may contribute to the development or aggravation of pulmonary fibrosis. We investigated the hypothesis that high amplitude mechanical stretching of alveolar type II (ATII) cells and lung fibroblasts promotes profibrotic processes. ATII cells and fibroblasts were stretched on elastic membranes using a pattern of higher amplitudes ("unphysiological"). The production of profibrotic cytokines and extra cellular matrix (ECM) proteins were investigated in supernatants. In addition, we determined the expression of relevant microRNAs (miRNA) and the process of epithelial-mesenchymal transition (EMT) in ATII cells. Unphysiological stretch of ATII cells led to increased release of TGF-β1 into supernatants. We also found elevated protein levels of collagen I and IV in supernatants of stretched cells. By contrast, stretching of fibroblasts changed neither the expression of fibrosis-modulating factors nor ECM-proteins. However, fibroblasts significantly withstood stretch-induced cell injury and seemed to have a survival benefit. Further, stretched ATII cells exhibited a higher expression of miRNAs (miR-15b, miR-25, let-7d) relevant to EMT. The process of EMT, which is characterized by an increase of vimentin and a decrease of cytokeratin expression, was significantly accelerated due to stretching of ATII cells. These data provide evidence that unphysiological mechanical stretching of lung cells induced several profibrotic effects and accelerated EMT, which may have critical implications in terms of development or aggravation of pulmonary fibrosis in the clinical context.
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http://dx.doi.org/10.1080/01902148.2019.1636424DOI Listing
September 2019

The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry.

Respir Res 2019 Mar 15;20(1):59. Epub 2019 Mar 15.

Medizinische Klinik und Poliklinik V, Klinikum der LMU, Munich, Germany.

Background: Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry.

Methods: Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George's Respiratory Questionnaire (SGRQ) were used.

Results: Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DL% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DL predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DL. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations.

Conclusions: QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality.
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http://dx.doi.org/10.1186/s12931-019-1020-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420774PMC
March 2019

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

Z Gastroenterol 2019 Mar 12;57(3):312-316. Epub 2019 Mar 12.

University Hospital Leipzig, Division of Gastroenterology, Leipzig, Germany.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.
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http://dx.doi.org/10.1055/a-0829-7050DOI Listing
March 2019

The association of socioeconomic status with quality of life in cancer patients over a 6-month period using individual growth models.

Support Care Cancer 2019 Sep 9;27(9):3347-3355. Epub 2019 Jan 9.

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre of Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 69, 55131, Mainz, Germany.

Purpose: Studies examining longitudinal associations between socioeconomic factors and quality of life (QoL) in cancer patients are rare. This study investigates changes in QoL over a 6-month period.

Methods: Four hundred forty-two cancer patients (mean age 64, SD = 11, 70% male) completed standardized questionnaires at the beginning (t1) and end (t2) of their hospital stay and 3 (t3) and 6 months (t4) thereafter. QoL was assessed with the EORTC QLQ-C30 core questionnaire. Mixed effect models were employed to analyze individual changes in QoL in relation to socioeconomic status (education, income, job status) over the four timepoints. Age, sex, cohabitation, disease and treatment factors, and comorbidity were included as covariates in the models.

Results: Income was a predictive factor for QoL. Patients with a low income had 8.8 percentage points (PP) lower physical, 4.9 PP lower emotional, and 11.4 PP lower role functioning. They also had 6.6 PP lower global QoL. Lower social functioning (6.2 PP) was found in patients with higher education or university degrees compared with those who were less educated or had not undergone an apprenticeship. Income also influenced trajectories of role functioning. There was no evidence that primary or secondary education and job type were related to QoL.

Conclusions: The fact that income is negatively associated with many aspects of quality of life should be considered during and after treatment with a focus on patients with special needs.
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http://dx.doi.org/10.1007/s00520-018-4634-yDOI Listing
September 2019

A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation.

Am J Transplant 2019 06 5;19(6):1759-1769. Epub 2019 Feb 5.

Department of Cardiothoracic Surgery, Newark Beth Israel Medical Center, Children's Hospital of New Jersey, Newark, New Jersey.

Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus-based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open-label, 12-month multicenter trial was conducted at 8 German sites. Patients 3-18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3-5 ng/mL) with reduced CNI (tacrolimus 3-5 ng/mL or cyclosporine 25-75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint (eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy-proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT01404325.
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http://dx.doi.org/10.1111/ajt.15251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590654PMC
June 2019

Nasal high-flow in acute hypercapnic exacerbation of COPD.

Int J Chron Obstruct Pulmon Dis 2018 30;13:3895-3897. Epub 2018 Nov 30.

Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany,

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http://dx.doi.org/10.2147/COPD.S185001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280891PMC
April 2019

Quality of Life in NSCLC Survivors - A Multicenter Cross-Sectional Study.

J Thorac Oncol 2019 03 30;14(3):420-435. Epub 2018 Nov 30.

University Medical Center, Johannes Gutenberg University, Mainz, Germany; University Cancer Center Mainz, Mainz, Germany.

Introduction: The objective was to assess quality of life (QoL) in lung cancer survivors, compare it to the general population, and identify factors associated with global QoL, physical functioning, emotional functioning, fatigue, pain, and dyspnea.

Methods: Data from NSCLC patients who had survived 1 year or longer after diagnosis were collected cross-sectionally in a multicenter study. QoL was assessed with the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer module QLQ-LC13 across different clinical subgroups and compared to age- and sex-standardized general population reference values. Multivariable linear regression analyses were performed to test the associations of patient-, tumor-, and treatment-related factors with the six primary QoL scales.

Results: Six hundred fifty-seven NSCLC patients participated in the study with a median time since diagnosis of 3.7 years (range, 1.0-21.2 years). Compared to the age- and sex-standardized general population, clinically meaningful differences in the QoL detriment were found on almost all domains: lung cancer survivors had clinically relevant poorer global QoL (10 points, p < 0.001). Whereas in 12 months or longer treatment-free patients this detriment was small (8.3), it was higher in patients currently in treatment (16.0). Regarding functioning and symptom scales, respective detriments were largest for dyspnea (41 points), role function (33 points), fatigue (27 points), social function (27 points), physical function (24 points), and insomnia (21 points) observed across all subgroups. The main factor associated with poorer QoL in all primary QoL scales was mental distress (β |19-31|, all p < 0.001). Detriments in QoL across multiple primary QoL scales were also observed with current treatment (β |8-12|, p < 0.01), respiratory comorbidity (β |4-5|, p < 0.01), and living on a disability pension (β |10-11|, p < 0.01). The main factor associated with better QoL in almost all primary QoL scales was higher physical activity (β |10-20|, p < 0.001). Better QoL was also observed in patients with high income (β |10-14|, p < 0.01).

Conclusions: Lung cancer survivors experience both functional restrictions and symptoms that persist long term after active treatment ends. This substantiates the importance of providing long-term supportive care.
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http://dx.doi.org/10.1016/j.jtho.2018.11.019DOI Listing
March 2019

Daytime Sleepiness in Patients Diagnosed with Sarcoidosis Compared with the General Population.

Can Respir J 2018 10;2018:6853948. Epub 2018 Jul 10.

Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany.

Background: The aim of this study was to analyze daytime sleepiness in a sample of patients diagnosed with sarcoidosis.

Methods: A sample of 1197 German sarcoidosis patients was examined with the Epworth Sleepiness Scale (ESS), the Fatigue Assessment Scale, the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Short-Form Health Survey (SF-8). The patients' ESS mean scores were compared with those obtained from a large general population sample.

Results: Exactly 50% of the patients reached the criterion (ESS > 10) for excessive daytime sleepiness, compared with only 22.1% in the general population. The effect size for the mean score difference between both samples was =0.62. The number of affected organs and the number of concomitant diseases proved to be significant independent predictors of daytime sleepiness. Sleepiness was associated with fatigue (=0.45), anxiety (=0.23), depression (=0.28), sleep problems (=0.23), and detriments in physical (=-0.29) and mental (=-0.28) quality of life.

Conclusions: The issue of excessive daytime sleepiness should be considered in the management of sarcoidosis.
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http://dx.doi.org/10.1155/2018/6853948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079447PMC
April 2019

Electrical Impedance Tomography for Confirmation of Lung Isolation during One-lung Ventilation.

Anesthesiology 2018 09;129(3):580

From the Department of Anesthesiology and Intensive Care Medicine (G.H., H.Wrigge) the Department of Pulmonary Medicine (G.S., H.Wirtz), University of Leipzig, Leipzig, Germany.

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http://dx.doi.org/10.1097/ALN.0000000000002189DOI Listing
September 2018

Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

BMC Health Serv Res 2018 03 1;18(1):147. Epub 2018 Mar 1.

Medical Oncology Service, Hospital Universitario La Paz (IDIPAZ), Madrid, Spain.

Background: Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC.

Methods: This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC.

Results: The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements.

Conclusions: HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries. Comparative findings and an understanding of country-specific clinical practices can help to identify areas of need and guide future resource allocation for patients with advanced NSCLC. Further studies evaluating the costs associated with resource use are warranted.
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http://dx.doi.org/10.1186/s12913-018-2946-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831211PMC
March 2018

The revised GOLD 2017 COPD categorization in relation to comorbidities.

Respir Med 2018 01 5;134:79-85. Epub 2017 Dec 5.

Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Comprehensive Pneumology Center Munich (CPC-M), Ludwig-Maximilians-Universität München, Ziemssenstr. 1, 80336 Munich, Germany.

Introduction: The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities.

Methods: We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations.

Results: Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations.

Conclusions: These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates.
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http://dx.doi.org/10.1016/j.rmed.2017.12.003DOI Listing
January 2018

Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage dependent.

BMC Pulm Med 2018 Jan 24;18(1):14. Epub 2018 Jan 24.

Department of Respiratory Medicine, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.

Background: Nasal Highflow (NHF) delivers a humidified and heated airflow via nasal prongs. Current data provide evidence for efficacy of NHF in patients with hypoxemic respiratory failure. Preliminary data suggest that NHF may decrease hypercapnia in hypercapnic respiratory failure. The aim of this study was to evaluate the mechanism of NHF mediated PCO reduction in patients with chronic obstructive pulmonary disease (COPD).

Methods: In 36 hypercapnic COPD patients (PCO > 45 mmHg), hypercapnia was evaluated by capillary gas sampling 1 h after NHF breathing under four conditions A to D with different flow rates and different degrees of leakage (A = 20 L/min, low leakage, two prongs, both inside; B = 40 L/min, low leakage, two prongs, both inside; C = 40 L/min, high leakage, two prongs, one outside and open; D = 40 L/min, high leakage, two prongs, one outside and closed). Under identical conditions, mean airway pressure was measured in the hypopharynx of 10 COPD patients.

Results: Hypercapnia significantly decreased in all patients. In patients with capillary PCO > 55 mmHg (n = 26), PCO additionally decreased significantly by increased leakage and/or flow rate in comparison to lower leakage/ flow rate conditions (A = 94.2 ± 8.2%; B = 93.5 ± 4.4%; C = 90.5 ± 7.2%; D = 86.8 ± 3.8%). The highest mean airway pressure was observed in patients breathing under condition B (2.3 ± 1.6 mbar; p < 0.05).

Conclusions: This study demonstrates effective PCO reduction with NHF therapy in stable hypercapnic COPD patients. This effect does not correlate with an increase in mean airway pressure but with increased leakage and airflow, indicating airway wash out and reduction of functional dead space as important mechanisms of NHF therapy. These results may be useful when considering NHF treatment in hypercapnic COPD patients.

Trial Registration: Clinical Trials: NCT02504814; First posted July 22, 2015.
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http://dx.doi.org/10.1186/s12890-018-0576-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784698PMC
January 2018

Oral Versus Nasal High-Flow Bronchodilator Inhalation in Chronic Obstructive Pulmonary Disease.

J Aerosol Med Pulm Drug Deliv 2018 08 20;31(4):248-254. Epub 2017 Dec 20.

Department of Respiratory Medicine, University of Leipzig , Leipzig, Germany .

Background: Nasal high flow (NHF) alters breathing patterns, stabilizes fraction of inspired oxygen (FiO2) during respiratory distress, helps to keep up hemostasis in the airways, and washes out the upper airways. Particularly the support of inspiratory flow and decrease in functional dead space are interesting mechanisms of action with regard to aerosol delivery. Several laboratory investigations have studied aerosol delivery via the nasal route by using NHF, whereas clinical benefits are poorly evaluated.

Methods: Thirty patients with stable chronic obstructive pulmonary disease Gold D were recruited. In a randomized order, they inhaled a salbutamol 2.5 mg/ipratropium bromide 500 μg solution oral or NHF adapted on the second study day. A jet nebulizer was used as aerosol delivery device. The chosen flow rate was 35 L/min.

Results: Four patients refused to repeat the procedure, for example, for inconvenience or fear of delayed discharge, and were not included in the intention-to-treat analysis. All remaining patients tolerated both inhalation systems well. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), airway resistance (Rtot), and residual volume (RV) were significantly altered after bronchodilator inhalation with each of the both devices. The two different ways of combined bronchodilator inhalation resulted in very comparable changes in FVC, FEV1, relative 1 second-capacity (FEV1%FVC), Rtot, total lung capacity (TLC), RV, and residual volume expressed as percent of TLC (RV%TLC). However, in between devices, no difference was observed on comparing the postinhalational measurements of FVC, FEV1, Rtot, and RV.

Conclusions: We conclude from this proof-of-principle kind of study that inhalation of combined bronchodilators adapted to an NHF device is similarly effective to inhalation with a standard oral aerosol nebulizer. (Clinical Trails NCT02885103).
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http://dx.doi.org/10.1089/jamp.2017.1432DOI Listing
August 2018