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  1. Article ; Online: Eosinophilic cationic protein as marker for response to antibody therapy in severe asthma

    Elisa Franceschi / Nora Drick / Jan Fuge / Tobias Welte / Hendrik Suhling

    ERJ Open Research, Vol 8, Iss

    2022  Volume 3

    Keywords Medicine ; R
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The impact of anti-eosinophilic therapy on exercise capacity and inspiratory muscle strength in patients with severe asthma

    Elisa Franceschi / Nora Drick / Jan Fuge / Pierachille Santus / Bettina Fischer / Moritz Kayser / Tobias Welte / Hendrik Suhling

    ERJ Open Research, Vol 9, Iss

    2023  Volume 2

    Abstract: Introduction Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary exercise testing (CPET) does not have an ... ...

    Abstract Introduction Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary exercise testing (CPET) does not have an established role in the management of severe asthma. The aim of our study was to investigate the role of CPET and inspiratory pressure measurement in exercise capacity and muscle strength in severe asthmatic patients treated with anti-IL-5 therapy. Methods A monocentric observational study was conducted at Hanover Medical School, Germany, from April 2018 to June 2019. Patients affected by severe asthma treated with either mepolizumab or benralizumab were included. All patients underwent CPET before the initiation of antibody therapy and after 3 months, and follow-up visits were scheduled at 3, 6 and 12 months with plethysmography, inspiratory pressure measurement and blood gas analysis. Results 14 patients were enrolled: 10 (71.4%) females, median age 52 years (IQR 47–61). Seven patients were treated with benralizumab, seven with mepolizumab. Oxygen uptake (V′O2 peak) did not change significantly after 3 months of antibody treatment, while the mean value of the breathing reserve exhaustion reduced significantly from 78% to 60% (p=0.004). Whereas at baseline seven patients depleted the breathing reserve and two of them experienced oxygen desaturation during exercise, at 3 months no one presented any desaturation or breathing reserve exhaustion. The inspiratory pressure remained unchanged before and after the antibody therapy. Conclusion CPET could show hints of alveolar recruitment and ventilatory efficiency in severe asthma patients treated with antibody therapy.
    Keywords Medicine ; R
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: COVID-19 in lung transplant recipients-Risk prediction and outcomes.

    Jan C Kamp / Jan B Hinrichs / Jan Fuge / Raphael Ewen / Jens Gottlieb

    PLoS ONE, Vol 16, Iss 10, p e

    2021  Volume 0257807

    Abstract: Patients after lung transplantation are at risk for life-threatening infections. Recently, several publications on COVID-19 outcomes in this patient population appeared, but knowledge on optimal treatment, mortality, outcomes, and appropriate risk ... ...

    Abstract Patients after lung transplantation are at risk for life-threatening infections. Recently, several publications on COVID-19 outcomes in this patient population appeared, but knowledge on optimal treatment, mortality, outcomes, and appropriate risk predictors is limited. A retrospective analysis was performed in a German high-volume lung transplant center between 19th March 2020 and 18th May 2021. Impact of COVID-19 on physical and psychological health, clinical outcomes, and mortality were analyzed including follow-up visits up to 12 weeks after infection in survivors. Predictive parameters on survival were assessed using univariate and multivariate proportional hazards regression models. Out of 1,046 patients in follow-up, 31 acquired COVID-19 during the pandemic. 12 of 31 (39%) died and 26 (84%) were hospitalized. In survivors a significant decline in exercise capacity (p = 0.034), TLC (p = 0.02), and DLCO (p = 0.007) was observed at follow-up after 3 months. Anxiety, depression, and self-assessed quality of life remained stable. Charlson comorbidity index predicted mortality (HR 1.5, 1.1-2.2; p = 0.023). In recipients with pre-existing CLAD, mortality and clinical outcomes were inferior. However, pre-existing CLAD did not predict mortality. COVID-19 remains a life-threatening disease for lung transplant recipients, particularly in case comorbidities. Further studies on long term outcomes and impact on pre-existing CLAD are needed.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Treatment with interleukin (IL)-5/IL-5 receptor antibodies in patients with severe eosinophilic asthma and COPD

    Nora Drick / Jan Fuge / Benjamin Seeliger / Milan Speth / Jens Vogel-Claussen / Tobias Welte / Hendrik Suhling

    ERJ Open Research, Vol 8, Iss

    2022  Volume 4

    Abstract: Background Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies represents an established treatment for patients with severe eosinophilic asthma (SEA) but did not show clinical efficacy in patients with COPD. The objective of ... ...

    Abstract Background Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies represents an established treatment for patients with severe eosinophilic asthma (SEA) but did not show clinical efficacy in patients with COPD. The objective of the present study was to evaluate treatment response to anti-eosinophilic antibody therapy in patients with asthma and COPD. Methods A retrospective comparison of pulmonary function testing, oral corticosteroid intake, quality of life and pulmonary symptom control in patients with SEA and COPD and 1:1 propensity score matched patients suffering from SEA alone was performed. All patients received treatment with either mepolizumab or benralizumab. Data were assessed prior to antibody treatment start and after 6 months of therapy. Results Data from 84 patients (42 patients with SEA and COPD and 42 patients with SEA) were analysed. After 6 months of treatment, patients in both groups showed improved forced expiratory volume in 1 s (improvement by 11% (IQR 5–18) in the SEA and COPD group versus 15% (IQR −3–23); p=0.637) and decreased oral corticosteroid dosages (median reduction by 3 mg in the SEA and COPD group versus 5 mg; p=0.070), without significant differences between groups. Pulmonary symptom control and quality of life improved in both groups. A significant decrease in eosinophils could be measured in both groups with similar cell numbers prior to treatment initiation (600 cells·µL−1 in the SEA and COPD group versus 500 cells·µL−1). Conclusion Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies shows clinical efficacy in patients with SEA and COPD comparable to treatment response in patients with SEA alone.
    Keywords Medicine ; R
    Subject code 616 ; 610
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Computed Tomography in Adults with Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease

    Sabine Dettmer / Felix C. Ringshausen / Jan Fuge / Hannah Louise Maske / Tobias Welte / Frank Wacker / Jessica Rademacher

    Journal of Clinical Medicine, Vol 10, Iss 2736, p

    Typical Imaging Findings

    2021  Volume 2736

    Abstract: Among patients with bronchiectasis, nontuberculous mycobacterial pulmonary disease (NTM-PD) ranged between 1 and 6% and it is suspected that its prevalence is underestimated. Our aim was to evaluate differences in computed tomography (CT) features in ... ...

    Abstract Among patients with bronchiectasis, nontuberculous mycobacterial pulmonary disease (NTM-PD) ranged between 1 and 6% and it is suspected that its prevalence is underestimated. Our aim was to evaluate differences in computed tomography (CT) features in patients with bronchiectasis, with and without NTM-PD, in order to facilitate earlier diagnosis in the future. In addition, we evaluated longitudinal changes after successful NTM-PD treatment. One hundred and twenty-eight CTs performed in adults with bronchiectasis were scored for the involvement, type, and lobar distribution of bronchiectasis, bronchial dilatation, and bronchial wall thickening according to Reiff. In addition, associated findings, such as mucus plugging, tree-in-bud, consolidations, ground-glass opacities, interlobular thickening, intralobular lines, cavities, and atelectasis, were registered. Patients with NTM-PD ( n = 36), as defined by ATS/IDSA diagnostic criteria, were compared to bronchiectasis patients without NTM-PD ( n = 92). In twelve patients with an available consecutive CT scan after microbiological cure of NTM-PD imaging findings were also scored according to Kim and compared in the course. In patients with NTM-PD, there was a higher prevalence of bronchiectasis in the middle lobes ( p < 0.001), extended bronchiolitis ( p = 0.032) and more small and large nodules ( p < 0.001). Furthermore, cavities turned out to be larger ( p = 0.038), and walls thickened ( p = 0.019) and extended ( p = 0.016). Patients without NTM more often showed peripheral ground-glass opacities (0.003) and interstitial changes ( p = 0.001). CT findings decreased after successful NTM-PD treatment in the follow-up CT; however, without statistical significance for most features ( p = 0.056), but bronchiolitis was the only significantly reduced score item ( p = 0.043). CT patterns in patients with bronchiectasis and NTM-PD differ from those of patients with bronchiectasis without NTM-PD, although the findings are non-specific radiological features. Follow-up CT ...
    Keywords bronchiectasis ; diagnostic imaging ; nontuberculous mycobacteria ; computed tomography ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Adherence is associated with a favorable outcome after lung transplantation.

    Anna Bertram / Jan Fuge / Hendrik Suhling / Igor Tudorache / Axel Haverich / Tobias Welte / Jens Gottlieb

    PLoS ONE, Vol 14, Iss 12, p e

    2019  Volume 0226167

    Abstract: Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was assessed in 427 patients undergoing lung transplantation ...

    Abstract Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was assessed in 427 patients undergoing lung transplantation from 2010 to 2013. Objective criteria of adherence were judged by health care workers on every visit on a five item Likert scale including trough level monitoring, home spirometry and contact with an overall rating of adherence between 0 and 100%. Cut-off values for good vs. suboptimal adherence were defined retrospectively. Primary outcome was allograft survival, secondary outcomes were patient survival, prevalence of chronic lung allograft dysfunction, hospitalizations, renal function and quality of life. Follow-up ended on 31st December 2018. Median adherence was 86% on 6,623 visits, this cut-off was used as a discriminator between good and suboptimal adherers. Patients with good adherence within the first three years showed better 5-year allograft (74% vs. 60%, p = 0.003) and patient survival (79% vs. 64%, p<0.001) and lower prevalence of chronic allograft dysfunction (33% vs. 45%, p = 0.011) after 5 years compared to patients with suboptimal adherence. A multidimensional adherence score proved to be a simple tool to assess adherence in clinical practice. Suboptimal adherence was associated with impaired outcome in lung transplant patients.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses

    Jan C. Kamp / Naomi N. Kappe / Carlos Fernández Moro / Jan Fuge / Mark P. Kuehnel / Sabine Wrenger / Tobias Welte / Bart van Hoek / Danny D. Jonigk / Padmini P. S. J. Khedoe / Pavel Strnad / Mikael Björnstedt / Jan Stolk / Sabina Janciauskiene / Antal Nemeth

    International Journal of Molecular Sciences, Vol 24, Iss 2485, p

    2023  Volume 2485

    Abstract: PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not ... ...

    Abstract PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses. Liver biopsies obtained during 1979–2010 at the Department of Paediatrics, Karolinska University Hospital, Sweden, were subjected to histological re-evaluation, immunohistochemistry and NanoString-based transcriptome profiling using a panel of 760 fibrosis plus 8 bile acid-related genes. Subjects were divided into three groups based on clinical outcomes: NCH (neonatal cholestasis, favourable outcome, n = 5), NCC (neonatal cholestasis, early cirrhosis and liver transplantation, n = 4), and NNCH (no neonatal cholestasis, favourable outcome, n = 5, six biopsies). Hepatocytes containing Z-AAT polymers were abundant in all groups whereas NCC showed higher expression of genes related to liver fibrosis/cirrhosis and lower expression of genes related to lipid, aldehyde/ketone, and bile acid metabolism. Z-AAT accumulation per se cannot explain the clinical outcomes of PiZZ children; however, changes in the expression of specific genes and pathways involved in lipid, fatty acid, and steroid metabolism appear to reflect the degree of liver injury.
    Keywords PiZZ deficiency ; liver ; cholestasis ; cirrhosis ; Z-AAT polymers ; mRNA expression ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Validity of echocardiographic tricuspid regurgitation gradient to screen for new definition of pulmonary hypertension

    Henning Gall / Athiththan Yogeswaran / Jan Fuge / Natascha Sommer / Friedrich Grimminger / Werner Seeger / Karen M. Olsson / Marius M. Hoeper / Manuel J. Richter / Khodr Tello / Hossein Ardeschir Ghofrani

    EClinicalMedicine, Vol 34, Iss , Pp 100822- (2021)

    2021  

    Abstract: Background: Currently an echocardiographic threshold for the tricuspid regurgitation gradient (TRG) of > 31 mmHg is recommended for screening for pulmonary hypertension (PH). Invasively diagnosed PH was recently redefined as mean pulmonary arterial ... ...

    Abstract Background: Currently an echocardiographic threshold for the tricuspid regurgitation gradient (TRG) of > 31 mmHg is recommended for screening for pulmonary hypertension (PH). Invasively diagnosed PH was recently redefined as mean pulmonary arterial pressure (mPAP) > 20 mmHg instead of ≥ 25 mmHg. We investigated the ability of TRG to screen for the new PH-definition. Methods: Retrospective assessment of echocardiography and right heart catheterisation data from 1572 patients entering the Giessen PH-Registry during 2008–2018. Accuracy of different TRG thresholds and other echocardiographic parameters was evaluated using receiver operating characteristic curves. Findings: 1264 patients fulfilled the new PH-definition. Positive (PPV) and negative predictive values and accuracy of TRG > 46 mmHg were 95%, 39%, and 73%, respectively, for the new PH-definition. Lowering the TRG cut-off to 31 mmHg and below worsened PPV to ≤ 89%. The PPV of TRG for pre-capillary PH (mPAP > 20 mmHg and pulmonary vascular resistance ≥ 3 Wood Units) was ≤ 85%. In patients with TRG ≤ 46 mmHg, tricuspid annular plane systolic excursion/TRG and TRG/right ventricular outflow tract acceleration time were superior to TRG in screening for newly defined pre-capillary PH. Interpretation: In patients with suspected PH referred to a tertiary care centre, the PPV of TRG to meet the new PH-definition depended strongly on the TRG cut-off used. Our data do not support lowering the TRG cut-off. Combining TRG with other echocardiographic parameters might improve the validity of echocardiographic screening for PH.
    Keywords Pulmonary hypertension ; Screening ; Echocardiography ; Diagnostic algorithm ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Time-Dependent Molecular Motifs of Pulmonary Fibrogenesis in COVID-19

    Jan C. Kamp / Lavinia Neubert / Maximilian Ackermann / Helge Stark / Christopher Werlein / Jan Fuge / Axel Haverich / Alexandar Tzankov / Konrad Steinestel / Johannes Friemann / Peter Boor / Klaus Junker / Marius M. Hoeper / Tobias Welte / Florian Laenger / Mark P. Kuehnel / Danny D. Jonigk

    International Journal of Molecular Sciences, Vol 23, Iss 1583, p

    2022  Volume 1583

    Abstract: 1) Background: In COVID-19 survivors there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood; (2) Methods: In this multicentric study, n = 12 patients who succumbed to COVID-19 due to ... ...

    Abstract (1) Background: In COVID-19 survivors there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood; (2) Methods: In this multicentric study, n = 12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within ≤7 and >7 days of hospitalization, respectively) and compared to n = 11 healthy controls; mRNA and protein expression as well as biological pathway analysis were performed to gain insights into the evolution of pulmonary fibrogenesis in COVID-19; (3) Results: Median duration of hospitalization until death was 3 (IQR25-75, 3–3.75) and 14 (12.5–14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of BST2 and IL1R1 , independent of hospitalization time. In the early group there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB ) and pathways dominated in the late group; (4) Conclusions: After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.
    Keywords COVID-19 ; SARS-CoV-2 ; pulmonary fibrosis ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Topical Nasal Anesthesia in Flexible Bronchoscopy--A Cross-Over Comparison between Two Devices.

    Thomas Fuehner / Jan Fuge / Meike Jungen / Anna Buck / Hendrik Suhling / Tobias Welte / Jens Gottlieb / Mark Greer

    PLoS ONE, Vol 11, Iss 3, p e

    2016  Volume 0150905

    Abstract: INTRODUCTION:Topical airway anesthesia is known to improve tolerance and patient satisfaction during flexible bronchoscopy (FB). Lidocaine is commonly used, delivered as an atomized spray. The current study assesses safety and patient satisfaction for ... ...

    Abstract INTRODUCTION:Topical airway anesthesia is known to improve tolerance and patient satisfaction during flexible bronchoscopy (FB). Lidocaine is commonly used, delivered as an atomized spray. The current study assesses safety and patient satisfaction for nasal anesthesia of a new atomization device during outpatient bronchoscopy in lung transplant recipients. METHODS:Using a prospective, non-blinded, cross-over design, patients enrolled between 01-10-2014 and 24-11-2014 received 2% lidocaine using the standard reusable nasal atomizer (CRNA). Those enrolled between 25-11-2014 and 30-01-2015, received a disposable intranasal mucosal atomization device (DIMAD). After each procedure, the treating physician, their assistant and the patient independently rated side-effects and satisfaction, basing their responses on visual analogue scales (VAS). At their next scheduled bronchoscopy during the study period, patients then received the alternative atomizer. Written consent was obtained prior to the first bronchoscopy, and the study approved by the institutional ethics committee. RESULTS:Of the 252 patients enrolled between 01-10-2014 and 30-01-2015, 80 (32%) received both atomizers. Physicians reported better efficacy (p = 0.001) and fewer side effects (p< = 0.001) for DIMAD in patients exposed to both procedures. Among patients with one visit, physicians and their assistants reported improved efficacy (p = 0.018, p = 0.002) and fewer side effects (p< = 0.001, p = 0.029) for the disposable atomizer, whereas patients reported no difference in efficacy or side effects (p = 0.72 and p = 0.20). No severe adverse events were noted. The cost of the reusable device was 4.08€ per procedure, compared to 3.70€ for the disposable device. DISCUSSION:Topical nasal anesthesia via a disposable intranasal mucosal atomization device (DIMAD) offers comparable safety and patient comfort, compared to conventional reusable nasal atomizers (CRNA) in lung transplant recipients. Procedural costs were reduced by 0.34€ per procedure. TRIAL ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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