19 results on '"Kronsbein, Juliane"'
Search Results
2. Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial
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White, R James, Jerjes-Sanchez, Carlos, Bohns Meyer, Gisela Martina, Pulido, Tomas, Sepulveda, Pablo, Wang, Kuo Yang, Grünig, Ekkehard, Hiremath, Shirish, Yu, Zaixin, Gangcheng, Zhang, Yip, Wei Luen James, Zhang, Shuyang, Khan, Akram, Deng, CQ, Grover, Rob, Tapson, Victor F, Svetliza, Graciela Noemi, Lescano, Adrian Jose, Bortman, Guillermo Roberto, Diez, Fabian Antonio, Botta, Christian Edgardo, Fitzgerald, John, Feenstra, Eelke, Kermeen, Fiona Dawn, Keogh, Anne Margaret, Williams, Trevor John, Yousseff, Peter Paul, Ng, Benjamin Joh-Han, Smallwood, David McNaughton, Dwyer, Nathan Brent, Brown, Martin Russell, Lang, Irene M, Steringer-Mascherbauer, Regina, Arakaki, Jaquelina Sonoe Ota, Campos, Frederico Thadeu Assis Figueiredo, de Amorim Correa, Ricardo, de Souza, Rogerio, Bohns Meyer, Gisela M, Moreira, Maria Auxiliadora Carmo, Yoo, Hugo Hyung Bok, Lapa, Monica Silveira, Swiston, John, Hirani, Naushad, Mehta, Sanjay, Michelakis, Evangelos, Sepulveda, Pablo Andres, Blancaire, Monica Maria Zagolin, Liu, Jimming, Shuyang, Zhang, Pan, Lei, Chunde, Bao, Qun, Yi, Xiaoshu, Cheng, Zaixin, Yu, Li, Xinli, Hua, Yao, Zhu, Xianyang, Chen, Yundai, Zhaozhong, Cheng, Yang, Yuanhua, Daxin, Zhou, Jieyan, Shen, Nielsen-Kudsk, Jens Erik, Carlsen, Jorn, Bourdin, Arnaud, Hachulla, Eric, Dromer, Claire, Chaouat, Ari, Reynaud-Gauber, Martine, Seronde, Marie-France, Klose, Hans, Halank, Michael, Hoffken, Gert, Ewert, Ralf, Rosenkranz, Stephan, Grunig, Ekkehard, Kruger, Ulrich, Kronsbein, Juliane, Hauptmeier, Barbara Monika, Koch, Andrea, Held, Matthias, Lange, Tobias Johannes, Neurohr, Claus, Wilkens, Heinrike, Wilhelm Wirtz, Hubert Rolf, Konstantinides, Stavros, Argyropoulou-Pataka, Paraskevi, Orfanos, Stylianos, Kerkar, Prafulla Gopinath, Suresh, Pujar Venkateshacharya, Baxi, Hemang Ashwinkumar, Oomman, Abraham, Abhaichand, Rajpal Kanaklal, Arjun, Padma Kumar Edla, Chopra, Vijay, Mehrotra, Rahul, Rajput, Rajeev Kumar, and Sawhney, Jitendra Pal Singh
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Rare Diseases ,Patient Safety ,Digestive Diseases ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Administration ,Oral ,Adolescent ,Adult ,Aged ,Antihypertensive Agents ,Double-Blind Method ,Epoprostenol ,Female ,Humans ,Male ,Middle Aged ,Placebos ,Pulmonary Arterial Hypertension ,Young Adult ,FREEDOM-EV Investigators ,clinical study ,combination therapy ,oral treprostinil ,pulmonary arterial hypertension ,sequential therapy ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).
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- 2020
3. OR2AT4 and OR1A2 counterregulate molecular pathophysiological processes of steroid-resistant inflammatory lung diseases in human alveolar macrophages
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Weidinger, Daniel, Jamal Jameel, Kaschin, Alisch, Desiree, Jacobsen, Julian, Bürger, Paul, Ruhe, Matthias, Yusuf, Faisal, Rohde, Simon, Störtkuhl, Klemens, Kaufmann, Peter, Kronsbein, Juliane, Peters, Marcus, Hatt, Hanns, Giannakis, Nikolaos, and Knobloch, Jürgen
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- 2022
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4. The monocyte-dependent immune response to bacteria is suppressed in smoking-induced COPD
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Knobloch, Jürgen, Panek, Susanne, Yanik, Sarah Derya, Jamal Jameel, Kaschin, Bendella, Zeynep, Jungck, David, Bürger, Paul, Bülthoff, Eike, Struck, Birte, Giannakis, Nikolaos, Rupp, Jan, Kronsbein, Juliane, Peters, Marcus, and Koch, Andrea
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- 2019
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5. Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment
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Kahnert, Kathrin, Andreas, Stefan, Kellerer, Christina, Lutter, Johanna I., Lucke, Tanja, Yildirim, Önder, Lehmann, Mareike, Seissler, Jochen, Behr, Jürgen, Frankenberger, Marion, Bals, Robert, Watz, Henrik, Welte, Tobias, Trudzinski, Franziska C., Vogelmeier, Claus F., Alter, Peter, Jörres, Rudolf A., Bahmer, Thomas, Bewig, Burkhard, Ewert, Ralf, Stubbe, Beate, Ficker, Joachim H., Grohé, Christian, Held, Matthias, Henke, Markus, Herth, Felix, Kirsten, Anne-Marie, Koczulla, Rembert, Kronsbein, Juliane, Kropf-Sanchen, Cornelia, Herzmann, Christian, Pfeifer, Michael, Randerath, Winfried J., Seeger, Werner, Studnicka, Michael, Taube, Christian, Timmermann, Hartmut, Schmeck, Bernd, Vogelmeier, Claus, and Wirtz, Hubert
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Male ,Epidemiology ,Science ,Vital Capacity ,Medizin ,Article ,Body Mass Index ,Cohort Studies ,Pulmonary Disease, Chronic Obstructive ,Sex Factors ,Forced Expiratory Volume ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,Lung ,Aged ,Multidisciplinary ,Smoking ,Age Factors ,Middle Aged ,respiratory system ,Metformin ,respiratory tract diseases ,Pulmonary Emphysema ,Pulmonary Diffusing Capacity ,Medicine ,Female ,Drug therapy - Abstract
We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p 1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.
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- 2022
6. The association of cognitive functioning as measured by the DemTect with functional and clinical characteristics of COPD: results from the COSYCONET cohort
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von Siemens, Sarah Marietta, Perneczky, Robert, Waschki, Benjamin, Lutter, Johanna I, Welte, Tobias, Jörres, Rudolf A, Kahnert, Kathrin, group, COSYCONET study, Andreas, Stefan, Bals, Robert, Behr, Jürgen, Vogelmeier, Claus F, Bewig, Burkhard, Buhl, Roland, Ewert, Ralf, Stubbe, Beate, Gogol, Manfred, Grohé, Christian, Hauck, Rainer, Held, Matthias, Jany, Berthold, Henke, Markus, Herth, Felix, Höffken, Gerd, Katus, Hugo A, Kirsten, Anne-Marie, Watz, Henrik, Koczulla, Rembert, Kenn, Klaus, Kronsbein, Juliane, Kropf-Sanchen, Cornelia, Lange, Christoph, Kauffmann-Guerrero, Diego, Zabel, Peter, Pfeifer, Michael, Randerath, Winfried J, Seeger, Werner, Studnicka, Michael, Taube, Christian, Teschler, Helmut, Timmermann, Hartmut, Virchow, J Christian, Vogelmeier, Claus, Alter, Peter, Wagner, Ulrich, Wirtz, Hubert, Trudzinski, Franziska C, and Söhler, Sandra
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Male ,medicine.medical_specialty ,epidemiology [Cognitive Dysfunction] ,psychology [Pulmonary Disease, Chronic Obstructive] ,Medizin ,Comorbidity ,Cohort Studies ,03 medical and health sciences ,FEV1/FVC ratio ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Cognition ,epidemiology [Pulmonary Disease, Chronic Obstructive] ,Surveys and Questionnaires ,medicine ,Dementia ,Humans ,COPD ,Cognitive Dysfunction ,ddc:610 ,Cognitive skill ,Path analysis (statistics) ,Aged ,lcsh:RC705-779 ,business.industry ,Research ,physiology [Cognition] ,diagnosis [Pulmonary Disease, Chronic Obstructive] ,lcsh:Diseases of the respiratory system ,Middle Aged ,medicine.disease ,Mental Status and Dementia Tests ,humanities ,Cross-Sectional Studies ,Cognitive impairment ,diagnosis [Cognitive Dysfunction] ,030228 respiratory system ,Cohort ,Physical therapy ,Female ,psychology [Cognitive Dysfunction] ,business ,030217 neurology & neurosurgery ,Cognitive load - Abstract
Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL).Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL.DemTect scores were =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment.We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.
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- 2022
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7. Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET
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Trudzinski, F.C., Jörres, R.A., Alter, P., Kahnert, K., Waschki, B., Herr, C., Kellerer, C., Omlor, A., Vogelmeier, C.F., Fähndrich, S., Watz, H., Welte, T., Jany, B., Söhler, S., Biertz, F., Herth, F., Kauczor, H.-U., Bals, R., Andreas, Stefan, Behr, Jürgen, Bewig, Burkhard, Buhl, Roland, Ewert, Ralf, Stubbe, Beate, Ficker, Joachim H., Gogol, Manfred, Grohé, Christian, Hauck, Rainer, Held, Matthias, Henke, Markus, Höffken, Gerd, Katus, Hugo A., Kirsten, Anne-Marie, Koczulla, Rembert, Kenn, Klaus, Kronsbein, Juliane, Kropf-Sanchen, Lange, Christoph, Zabel, Peter, Pfeifer, Michael, Randerath, Winfried J., Seeger, Werner, Studnicka, Michael, Taube, Christian, Teschler, Helmut, Timmermann, Hartmut, Virchow, J. Christian, Wagner, and Wirtz, Hubert
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Adult ,Male ,medicine.medical_specialty ,Exacerbation ,Medizin ,lcsh:Medicine ,Severity of Illness Index ,Gastroenterology ,Article ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,Medical research ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Signs and symptoms ,lcsh:Science ,Survival rate ,Aged ,Oxygen saturation (medicine) ,Aged, 80 and over ,Inflammation ,COPD ,Oxygenated Hemoglobin ,Multidisciplinary ,Proportional hazards model ,business.industry ,Hazard ratio ,lcsh:R ,Middle Aged ,Prognosis ,medicine.disease ,Comorbidity ,Survival Rate ,Risk factors ,030228 respiratory system ,Oxyhemoglobins ,Female ,lcsh:Q ,Blood Gas Analysis ,business ,Biomarkers - Abstract
We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1–4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO2, PaO2, PaCO2, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO2, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85–4.15, p 8000/µL was 2.33 (95% CI: 1.60–3.39, p 2. It thus appears well suited for clinical use with minimal equipment, especially for GPs.
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- 2020
8. Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD
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Jameel, Kaschin Jamal, Gallert, Willem-Jakob, Yanik, Sarah D., Panek, Susanne, Kronsbein, Juliane, Jungck, David, Koch, Andrea, and Knobloch, Jürgen
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Male ,Smokers ,QH301-705.5 ,T-Lymphocytes ,T-cells ,Smoking ,Comorbidity ,Middle Aged ,comorbidities ,Article ,Pulmonary Disease, Chronic Obstructive ,Chemistry ,Case-Control Studies ,Germany ,Cytokines ,Humans ,COPD ,Female ,ddc:610 ,Biology (General) ,QD1-999 ,Biomarkers - Abstract
In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total n = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP, chemokine (C-C motif) ligand 18, CCL18, C-X3-C motif chemokine ligand 1, CX3CL1, interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22, epidermal growth factor, EGF, IL-17, periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFNγ and TNFα without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma— and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations.
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- 2021
9. Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD
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Jamal Jameel, Kaschin, primary, Gallert, Willem-Jakob, additional, Yanik, Sarah D., additional, Panek, Susanne, additional, Kronsbein, Juliane, additional, Jungck, David, additional, Koch, Andrea, additional, and Knobloch, Jürgen, additional
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- 2021
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10. Relationship between clinical and radiological signs of bronchiectasis in COPD patients: Results from COSYCONET
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Kirsten Anne-Marie, Anne Wirz, Erich Traugott, Ficker Joachim H, Bertram J. Jobst, Vivien Janke, Stubbe Beate, Johanna I. Lutter, Barbara Ziss, Franziska C. Trudzinski, Patricia Berger, Henrik Watz, Gogol Manfred, Thomas Bahmer, Beate Polte, Kronsbein Juliane, Campus Kiel, Lange Christoph, Martina Seibert, Rudolf A. Jörres, Pfeifer Michael, Timmermann Hartmut, Grohé Christian, Tobias Welte, Studnicka Michael, Petra Hundack-Winter, Jana Graf, Jürgen Behr, Diana Schottel, Buhl Roland, Virchow J. Christian, Bewig Burkhard, Ruhrlandklinik gGmbH. Essen, Wirtz Hubert, Rosalie Untsch, Birte Struck, Peter Alter, Kathrin Kahnert, Gudrun Hübner, Vogelmeier Claus, Sabine Michalewski, Kropf-Sanchen Cornelia, Kenn Klaus, Pontus Mertsch, Sonja Rohweder, Hauck Rainer, Andreas Stefan, Ilona Kietzmann, Zabel Peter, Michaela Schrade-Illmann, Höffken Gerd, Julia Tobias, Frank Biertz, Seeger Werner, Manuel Klöser, Kahnert Kathrin, Teschler Helmut, Anita Reichel, Gina Spangel, Ulrike Rieber, Randerath Winfried J, Julia Teng, Tanja Lucke, Herth Felix, Jeanette Pieper, Lenka Krabbe, Taube Christian, Jürgen Biederer, Wagner Ulrich, Doris Lehnert, Claus Vogelmeier, Katrin Schwedler, Henke Markus, Jany Berthold, Katus Hugo A, Bals Robert, Zaklina Hinz, Cornelia Böckmann, Ellen Burmann, Margret Gleiniger, Behr Jürgen, Britta Markworth, Ewert Ralf, Gertraud Weiß, Katrin Wons, Barbara Arikan, Watz Henrik, Beate Schaufler, Lena Sterk, Robert Bals, Hans-Ulrich Kauczor, Koczulla Rembert, Held Matthias, and Welte Tobias
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Copd patients ,Medizin ,Comorbidity ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,Medicine ,Humans ,In patient ,Lung ,Aged ,Aged, 80 and over ,COPD ,Bronchiectasis ,business.industry ,Phlegm ,Middle Aged ,medicine.disease ,Radiological weapon ,Clinical diagnosis ,Cohort ,Female ,Radiography, Thoracic ,Radiology ,medicine.symptom ,business ,Tomography, X-Ray Computed - Abstract
Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.
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- 2020
11. CAT score single item analysis in patients with COPD: results from COSYCONET
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J. Randerath Winfried, Pfeifer Michael, Kenn Klaus, Joachim H. Ficker, Gogol Manfred, Grohé Christian, Höffken Gerd, Zaklina Hinz, Julia Tobias, Henke Markus, Teschler Helmut, Welte Tobias, Benjamin Waschki, Buhl Roland, Paul W. Jones, Kirsten Anne-Marie, A. Katus Hugo, Taube Christian, Bewig Burkhard, Beate Polte, Kronsbein Juliane, Stubbe Beate, Bals Robert, Johanna I. Lutter, Sarah Marietta von Siemens, Lange Christoph, Vogelmeier Claus, Ellen Burmann, Wirtz Hubert, Kathrin Kahnert, Erich Traugott, Behr Jürgen, Birte Struck, Vivien Janke, Lenka Krabbe, Timmermann Hartmut, Wagner Ulrich, Anita Reichel, Sabine Michalewski, Gudrun Hübner, Seeger Werner, Doris Lehnert, Jany Berthold, Kropf-Sanchen Cornelia, Sandra Söhler, Jeanette Pieper, Ulrike Rieber, Peter Alter, Herth Felix, Zabel Peter, Andreas Stefan, Koczulla Rembert, Held Matthias, Tobias Welte, Franziska C. Trudzinski, Patricia Berger, Kahnert Kathrin, Jana Graf, Jürgen Behr, Rosalie Untsch, Rudolf A. Jörres, Kornelia Speth, Britta Markworth, Ewert Ralf, Gertraud Weiß, Hans-Ulrich Kauczor, Claus Vogelmeier, Katrin Schwedler, Katrin Wons, Bertram J. Jobst, Barbara Arikan, Margret Gleiniger, Henrik Watz, Watz Henrik, Studnicka Michael, Beate Schaufler, Diana Schottel, Sonja Rohweder, Robert Bals, Ilona Kietzmann, Virchow J. Christian, Burkhard Bewig, Hauck Rainer, and Michaela Schrade-Illmann
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Pulmonary and Respiratory Medicine ,Percentile ,medicine.medical_specialty ,Medizin ,Diagnostic Techniques, Respiratory System ,Single item ,CAT score ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Internal medicine ,medicine ,COPD ,In patient ,030212 general & internal medicine ,Lung function ,Emphysema ,business.industry ,Regression analysis ,Cat Score ,Copd ,medicine.disease ,Exploratory factor analysis ,respiratory tract diseases ,030228 respiratory system ,Cohort ,business - Abstract
The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items against a panel of comorbidities, lung function, or CT characteristics (qualitative score, 15th percentile of mean lung density), with age, BMI and gender as covariates. This was supported by exploratory factor analysis. Regarding the relationship to comorbidities and emphysema, there were marked differences between CAT items, especially items 1 and 2 versus 3 to 8. This grouping was basically confirmed by factor analysis. Items 4 and 5, and to a lower degree 1, 2 and 6, appeared to be informative regarding the presence of emphysema, whereas the total score was not or less informative. Regarding comorbidities, similar findings as for the total CAT score were obtained for the modified Medical Research Council scale (mMRC) which was also informative regarding emphysema. Our findings suggest that the usefulness of the CAT can be increased if evaluated on the basis of single items which may be indicating the presence of comorbidities and emphysema.
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- 2020
12. LABAs and p38MAPK Inhibitors Reverse the Corticosteroid-Insensitivity of IL-8 in Airway Smooth Muscle Cells of COPD
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Knobloch, Jürgen (PD Dr. rer. nat.), Jungck, David (Dr. med.), Kronsbein, Juliane (Dr. med.), Stölben, Erich (Prof. Dr. med.), Ito, Kazuhiro (Dr.), and Koch, Andrea (Prof. Dr. med.)
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p38mapk isoforms ,Communication ,long-acting-β2-agonist (laba) ,reversion of corticosteroid resistance ,non-type 2 inflammation ,lcsh:R ,copd phenotypes ,lcsh:Medicine ,ddc:610 ,hormones, hormone substitutes, and hormone antagonists ,respiratory tract diseases - Abstract
Airway inflammation in chronic obstructive pulmonary disease (COPD) is partially insensitive/resistant to inhaled corticosteroids (ICS). ICS plus bronchodilator therapy has been discussed for COPD phenotypes with frequent exacerbations and participation of corticosteroid-sensitive type 2/eosinophilic inflammation. Neutralization of non-type 2/IL-8-associated airway inflammation by reversion of its corticosteroid-resistance might be a future strategy for other phenotypes. Human airway smooth muscle cells (HASMCs) produce corticosteroid-insensitive IL-8 in response to TNF\(\alpha\) or LPS in stable disease stages or bacteria-induced exacerbations, respectively. p38-mitogen-activated-protein-kinases (p38MAPKs) are alternative therapeutic targets. Hypothesis: long-acting-\(\beta\)2-agonists (LABAs) reverse the corticosteroid-insensitivity of IL-8 by p38MAPK inhibition in HASMCs. Cultivated HASMCs from COPD subjects were pre-incubated with formoterol, salmeterol, fluticasone-propionate, BIRB796 (p38MAPK\(\alpha\), -\(\gamma\), -\(\delta\) inhibitor), and/or SB203580 (p38MAPK\(\alpha\) and -\(\beta\) inhibitor) before stimulation with TNF\(\alpha\) or LPS. IL-8 and MAPK-activities were measured by ELISA. Formoterol, salmeterol, and fluticasone did not or hardly reduced TNF\(\alpha\)- or LPS-induced IL-8. BIRB796 and SB203580 reduced TNF\(\alpha\)-induced IL-8. SB203580 reduced LPS-induced IL-8. Fluticasone/formoterol, fluticasone/salmeterol, and fluticasone/BIRB796, but not fluticasone/SB203580 combinations, reduced TNF\(\alpha\)-induced IL-8 stronger than single treatments. All combinations including fluticasone/SB203580 reduced LPS-induced IL-8 stronger than single treatments. TNF\(\alpha\) induced p38MAPK\(\alpha\) and -\(\gamma\) activity. LPS induced p38MAPK\(\alpha\) activity. Formoterol reduced TNF\(\alpha\)-induced p38MAPK\(\gamma\) and LPS-induced p38MAPK\(\alpha\) activity. LABAs reverse the corticosteroid-insensitivity of IL-8 in airway smooth muscles via p38MAPK\(\gamma\) in stable disease and via p38MAPK\(\alpha\) in exacerbations. Our pre-clinical data indicate a utility for also adding ICS in non-type 2 inflammatory COPD phenotypes to bronchodilator therapy. Depending on phenotype and disease stage, isoform-specific p38MAPK blockers might also reverse corticosteroid-resistance in COPD.
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- 2019
13. Exposure to welding fumes suppresses the activity of T-helper cells
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Knobloch, Jürgen, primary, Casjens, Swaantje, additional, Lehnert, Martin, additional, Yanik, Sarah D., additional, Körber, Sandra, additional, Lotz, Anne, additional, Rupp, Jan, additional, Raulf, Monika, additional, Zschiesche, Wolfgang, additional, Weiss, Tobias, additional, Kronsbein, Juliane, additional, Koch, Andrea, additional, Brüning, Thomas, additional, and Pesch, Beate, additional
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- 2020
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14. Combined effects of lung function, blood gases and kidney function on the exacerbation risk in stable COPD: Results from the COSYCONET cohort
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F.C. Trudzinski, K. Kahnert, C.F. Vogelmeier, P. Alter, F. Seiler, S. Fähndrich, H. Watz, T. Welte, T. Speer, S. Zewinger, F. Biertz, H.-U. Kauczor, R.A. Jörres, R. Bals, Andreas Stefan, Bals Robert, Behr Jürgen, Kahnert Kathrin, Bewig Burkhard, Buhl Roland, Ewert Ralf, Stubbe Beate, Ficker Joachim H, Gogol Manfred, Grohé Christian, Hauck Rainer, Held Matthias, Jany Berthold, Henke Markus, Herth Felix, Höffken Gerd, Katus Hugo A, Kirsten Anne-Marie, Watz Henrik, Koczulla Rembert, Kenn Klaus, Kronsbein Juliane, Kropf-Sanchen Cornelia, Lange Christoph, Zabel Peter, Pfeifer Michael, Randerath Winfried J, null eeger Werner, Studnicka Michael, Taube Christian, Teschler Helmut, Timmermann Hartmut, Virchow J. Christian, Vogelmeier Claus, Wagner Ulrich, Welte Tobias, and Wirtz Hubert
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Exacerbation ,Partial Pressure ,Medizin ,Renal function ,Comorbidity ,Acid-Base Imbalance ,Kidney Function Tests ,Risk Assessment ,Cohort Studies ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,DLCO ,Diffusing capacity ,Internal medicine ,Forced Expiratory Volume ,medicine ,Humans ,Respiratory function ,030212 general & internal medicine ,Aged ,COPD ,Carbon Monoxide ,business.industry ,Middle Aged ,medicine.disease ,respiratory tract diseases ,Respiratory Function Tests ,Cross-Sectional Studies ,030228 respiratory system ,Cohort ,Cardiology ,Disease Progression ,Pulmonary Diffusing Capacity ,Female ,Blood Gas Analysis ,Risk assessment ,business ,Glomerular Filtration Rate - Abstract
Rationale Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. Methods We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. Results 1506 patients with stable COPD (GOLD grade 1–4; mean age 64.5 ± 8.1 y; mean FEV1 54 ± 18 %predicted, mean eGFR 82.3 ± 16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. Conclusion Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.
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- 2019
15. No evidence for WU polyomavirus infection in chronic obstructive pulmonary disease
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Ringshausen Felix C, Heckmann Marei, Weissbrich Benedikt, Neske Florian, Borg Irmgard, Knoop Umut, Kronsbein Juliane, Hauptmeier Barbara M, Schultze-Werninghaus Gerhard, and Rohde Gernot
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Human polyomaviruses are known to cause persistent or latent infections, which are reactivated under immunosuppression. Polyomaviruses have been found to immortalize cell lines and to possess oncogenic properties. Moreover, the recently discovered Merkel cell polyomavirus shows a strong association with human Merkel cell carcinomas. Another novel human polyomavirus, WU polyomavirus (WUPyV), has been identified in respiratory specimens from patients with acute respiratory tract infections (ARTI). WUPyV has been proposed to be a pathogen in ARTI in early life and immunocompromised individuals, but so far its role as a causative agent of respiratory disease remains controversial. The objective of our study was to determine the prevalence of WUPyV infections in adult hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and to establish its potential clinical relevance by comparison to patients with stable COPD hospitalized for other reasons than acute exacerbation of COPD (AE-COPD). A total of 378 respiratory specimens, each 189 induced sputum and nasal lavage samples from 189 patients, who had been recruited in a prospective 2:1 ratio case-control set-up between 1999 and 2003, were evaluated for the presence of WUPyV DNA by real-time PCR. In the present study we could not detect WUPyV DNA in 378 respiratory specimens from 189 adult hospitalized patients with AE-COPD and stable COPD in four consecutive years. Persistence of viral replication or reactivation of latent WUPyV infection did not occur. WUPyV may not play a major role in adult immunocompetent patients with AE-COPD and stable COPD.
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- 2009
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16. Einfluß einer RSV-Exposition auf das Zytokinmuster humaner T-Lymphozyten und PBMC \(\textit {in vitro}\)
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Kronsbein, Juliane (Dr. med.)
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Interleukin 10 ,Interferon (gamma) ,Interleukin 5 ,ddc:610 ,Durchflusscytometrie ,Interleukin 4 - Abstract
Die Bedeutung von Respiratory Syncytial Virus (RSV) für die Pathogenese und Exazerbation der chronisch obstruktiven Lungenerkrankung (COPD) wird zunehmend diskutiert. Insbesondere T-Zellen werden angeschuldigt, an der virusinduzierten Immunantwort wesentlich beteiligt zu sein. In der vorliegenden Arbeit wurden daher mononukleäre Zellen des peripheren Blutes (PBMC) sowie T-Zellen von gesunden Kontrollpersonen und klinisch stabilen COPD-Patienten im Hinblick auf ihr Zytokinprofil unter RSV-Einfluß und verschiedenen Stimulationsbedingungen untersucht. Eine RSV-/T-Zell-Interaktion konnte hierbei durchflußzytometrisch gezeigt werden. Auch das Zytokinprofil von T-Zellen und PBMC wird durch RSV beeinflußt. Die beobachtete, signifikante Zunahme des IL-10/IFN-\(\gamma\)-Quotienten könnte Ausdruck einer abgeschwächten antiviralen Immunantwort sein, die bei COPD-Patienten eine Bahnung der Infektion mit anderen Atemwegspathogenen bewirkt, die dann ihrerseits Auslöser einer Exazerbation sein können.
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- 2005
17. Einfluß einer RSV-Exposition auf das Zytokinmuster humaner T-Lymphozyten und PBMC in vitro
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Kronsbein, Juliane and Medizin
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Interleukin 4 ,Interleukin 5 ,Interleukin 10 ,Interferon (gamma) ,Durchflusscytometrie - Abstract
Die Bedeutung von Respiratory Syncytial Virus (RSV) für die Pathogenese und Exazerbation der chronisch obstruktiven Lungenerkrankung (COPD) wird zunehmend diskutiert. Insbesondere T-Zellen werden angeschuldigt, an der virusinduzierten Immunantwort wesentlich beteiligt zu sein. In der vorliegenden Arbeit wurden daher mononukleäre Zellen des peripheren Blutes (PBMC) sowie T-Zellen von gesunden Kontrollpersonen und klinisch stabilen COPD-Patienten im Hinblick auf ihr Zytokinprofil unter RSV-Einfluß und verschiedenen Stimulationsbedingungen untersucht. Eine RSV-/T-Zell-Interaktion konnte hierbei durchflußzytometrisch gezeigt werden. Auch das Zytokinprofil von T-Zellen und PBMC wird durch RSV beeinflußt. Die beobachtete, signifikante Zunahme des IL-10/IFN-γ-Quotienten könnte Ausdruck einer abgeschwächten antiviralen Immunantwort sein, die bei COPD-Patienten eine Bahnung der Infektion mit anderen Atemwegspathogenen bewirkt, die dann ihrerseits Auslöser einer Exazerbation sein können.
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- 2005
18. Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease
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Ringshausen, Felix C., primary, Ringshausen, Felix C., additional, Tan, Ai-Yui, additional, Allander, Tobias, additional, Borg, Irmgard, additional, Arinir, Umut, additional, Kronsbein, Juliane, additional, Hauptmeier, Barbara, additional, Schultze-Werninghaus, Gerhard, additional, and Rohde, Gernot, additional
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- 2009
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19. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial
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Harrison, Tim W, Chanez, Pascal, Menzella, Francesco, Canonica, Giorgio Walter, Louis, Renaud, Cosio, Borja G, Lugogo, Njira L, Mohan, Arjun, Burden, Annie, McDermott, Lawrence, Garcia Gil, Esther, Zangrilli, James G, Wolfgang Pohl, Robert Voves, Maud Deschampheleire, Renaud Louis, Jean-Benoit Martinot, Rudi Peché, Kenneth Chapman, Amarjit Cheema, Delbert Dorscheid, J Mark FitzGerald, Remi Gagnon, William Patrick Killorn, Ronald Olivenstein, George Philteos, Clare Ramsey, J Douglass Rolf, Brandie Walker, Ole Hilberg, Tina Skjold, Ingrid Titlestad, Auli Hakulinen, Maritta Kilpeläinen, Michèle Ben Hayoun, Philippe Bonniaud, Arnaud Bourdin, Pascal Chanez, Frédéric De Blay, Gaëtan Deslee, Gilles Devouassoux, Alain Didier, Youcef Douadi, Stéphanie Fry, Gilles Garcia, Pierre-Olivier Girodet, Christophe Leroyer, Antoine Magnan, Guillaume Mahay, Cécilia Nocent, Christophe Pison, Pauline-Marie Roux, Camille Taillé, Juliana-Angelica Tiotiu, Ekkehard Beck, Margret Jandl, Christian Kaehler, Frank Kässner, Frank Koesters, Juliane Kronsbein, Thomas Schaum, Christian Schulz, Dirk Skowasch, Christian Taube, Tobias Welte, Andrés de Roux, Bianca Beghé, Francesco Blasi, Giorgio Walter Canonica, Giovanna Carpagnano, Cristiano Caruso, Angelo Guido Corsico, Elio Constantino, Nunzio Crimi, Piero Maestrelli, Francesco Menzella, Manlio Milanese, Alberto Papi, Girolamo Pelaia, Laura Pini, Pierachille Santus, Eleonora Savi, Nicola Scichilone, Gianenrico Senna, Giuseppe Spadaro, Adriano Vaghi, Steven Gans, Jurgen Hölters, B Langeveld, Willem Pieters, G H A Staaks, Ilonka van Veen, J W K van den Berg, Gunnar Einvik, Sverre Lehmann, Ismael Ali García, Carlos Almonacid, Irina Bobolea, Paloma Campo Mozo, Gustavo de Luiz, Christian Domingo Ribas, José María Echave-Sustaeta María-Tomé, Juan Luis García Rivero, Borja García-Cosío Piqueras, Ana Gómez-Bastero Fernández, Ruperto González Pérez, Aythamy Henríquez Santa, Carlos Martínez Rivera, Xavier Muñoz Gall, Jacinto Ramos, Jose Gregorio Soto Campos, Carmen Vidal Pan, Nikolai Stenfors, Alf Tunsäter, Ines Vinge, Rekha Chaudhuri, Timothy Harrison, Adel Mansur, Shuaib Nasser, Monica Nordstrom, Paul Pfeffer, Dinesh Saralaya, Philip Short, Arun Adlakha, Oral Alpan, Francis Averill, Anil Badhwar, Jose Bardelas, Barbara Baxter, George Bensch, William Berger, Jonathan Bernstein, Tracy Bridges, Ryan Brimeyer, William Calhoun, Edward Campbell, William Brett Cherry, Geoffrey Chupp, Lee Clore, John Cohn, Jeremy Cole, John Condemi, James Cury, Benjamin Davis, Samuel DeLeon, Luis Delacruz, Joseph Diaz, David Erb, Emeka Eziri, Faisal Fakih, Douglas Fiedler, David Fost, Stephen Fritz, Erika Gonzalez, Brad Goodman, Peter Gottlieb, Gregory Gottschlich, Richard Gower, Rizan Hajal, James Harris, Hengameh Heidarian-Raissy, Albrecht Heyder, David Hill, Fernando Holguin, Iftikhar Hussain, Jonathan Illowite, Joshua Jacobs, Mikell Jarratt, Harold Kaiser, Neil Kao, Ravindra Kashyap, David Kaufman, Edward Kent, Kenneth Kim, Ryan Klein, Monica Kraft, Ritsu Kono, Shahrukh Kureishy, Jeffrey Leflein, Mila Leong, Huamin Li, Robert Lin, Njira Lugogo, Michael Marcus, Diego Jose Maselli Caceres, Vinay Mehta, Curtis Mello, Mark Millard, Aaron Milstone, Arjun Mohan, Wendy Moore, Mark Moss, Nayla Mumneh, Thomas O'Brien, David Ostransky, Michael Palumbo, Purvi Parikh, Sudhir Parikh, Amit Patel, Guido Perez, Warren Pleskow, Bruce Prenner, Dileep Puppala, John Ramey, Joan Reibman, Ramon Reyes, Emory Robinette, Ileana Rodicio, Stephen Ryan, Sudhir Sekhsaria, Barry Sigal, Vinay Sikand, Weily Soong, Selwyn Spangenthal, Roy St John, Gary Steven, Vijay Subramaniam, Kaharu Sumino, Eric Sztejman, Ricardo A Tan, Tonny Tanus, Charles Thompson, Carl Thornblade, Manuel Villareal, Sally Wenzel, Heidi Zafra, Tomasz Ziedalski, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tim W, Harrison, Pascal, Chanez, Francesco, Menzella, Giorgio Walter, Canonica, Renaud, Loui, Borja G, Cosio, Njira L, Lugogo, Arjun, Mohan, Annie, Burden, Lawrence, Mcdermott, Esther, Garcia Gil, Zangrilli, G, Jame, Pohl, Wolfgang, Voves, Robert, Deschampheleire, Maud, Louis, Renaud, Martinot, Jean-Benoit, Peché, Rudi, Chapman, Kenneth, Cheema, Amarjit, Dorscheid, Delbert, Mark FitzGerald, J, Gagnon, Remi, Patrick Killorn, William, Olivenstein, Ronald, Philteos, George, Ramsey, Clare, Douglass Rolf, J, Walker, Brandie, Hilberg, Ole, Skjold, Tina, Titlestad, Ingrid, Hakulinen, Auli, Kilpeläinen, Maritta, Ben Hayoun, Michèle, Bonniaud, Philippe, Bourdin, Arnaud, Chanez, Pascal, De Blay, Frédéric, Deslee, Gaëtan, Devouassoux, Gille, Didier, Alain, Douadi, Youcef, Fry, Stéphanie, Garcia, Gille, Girodet, Pierre-Olivier, Leroyer, Christophe, Magnan, Antoine, Mahay, Guillaume, Nocent, Cécilia, Pison, Christophe, Roux, Pauline-Marie, Taillé, Camille, Tiotiu, Juliana-Angelica, Beck, Ekkehard, Jandl, Margret, Kaehler, Christian, Kässner, Frank, Koesters, Frank, Kronsbein, Juliane, Schaum, Thoma, Schulz, Christian, Skowasch, Dirk, Taube, Christian, Welte, Tobia, de Roux, André, Beghé, Bianca, Blasi, Francesco, Walter Canonica, Giorgio, Carpagnano, Giovanna, Caruso, Cristiano, Guido Corsico, Angelo, Constantino, Elio, Crimi, Nunzio, Maestrelli, Piero, Menzella, Francesco, Milanese, Manlio, Papi, Alberto, Pelaia, Girolamo, Pini, Laura, Santus, Pierachille, Savi, Eleonora, Scichilone, Nicola, Senna, Gianenrico, Spadaro, Giuseppe, Vaghi, Adriano, Gans, Steven, Hölters, Jurgen, Langeveld, B, Pieters, Willem, A Staaks, G H, van Veen, Ilonka, K van den Berg, J W, Einvik, Gunnar, Lehmann, Sverre, Ali García, Ismael, Almonacid, Carlo, Bobolea, Irina, Campo Mozo, Paloma, de Luiz, Gustavo, Domingo Ribas, Christian, María Echave-Sustaeta María-Tomé, José, Luis García Rivero, Juan, García-Cosío Piqueras, Borja, Gómez-Bastero Fernández, Ana, González Pérez, Ruperto, Henríquez Santa, Aythamy, Martínez Rivera, Carlo, Muñoz Gall, Xavier, Ramos, Jacinto, Gregorio Soto Campos, Jose, Vidal Pan, Carmen, Stenfors, Nikolai, Tunsäter, Alf, Vinge, Ine, Chaudhuri, Rekha, Harrison, Timothy, Mansur, Adel, Nasser, Shuaib, Nordstrom, Monica, Pfeffer, Paul, Saralaya, Dinesh, Short, Philip, Adlakha, Arun, Alpan, Oral, Averill, Franci, Badhwar, Anil, Bardelas, Jose, Baxter, Barbara, Bensch, George, Berger, William, Bernstein, Jonathan, Bridges, Tracy, Brimeyer, Ryan, Calhoun, William, Campbell, Edward, Brett Cherry, William, Chupp, Geoffrey, Clore, Lee, Cohn, John, Cole, Jeremy, Condemi, John, Cury, Jame, Davis, Benjamin, Deleon, Samuel, Delacruz, Lui, Diaz, Joseph, Erb, David, Eziri, Emeka, Fakih, Faisal, Fiedler, Dougla, Fost, David, Fritz, Stephen, Gonzalez, Erika, Goodman, Brad, Gottlieb, Peter, Gottschlich, Gregory, Gower, Richard, Hajal, Rizan, Harris, Jame, Heidarian-Raissy, Hengameh, Heyder, Albrecht, Hill, DAVID STANLEY, Holguin, Fernando, Hussain, Iftikhar, Illowite, Jonathan, Jacobs, Joshua, Jarratt, Mikell, Kaiser, Harold, Kao, Neil, Kashyap, Ravindra, Kaufman, David, Kent, Edward, Kim, Kenneth, Klein, Ryan, Kraft, Monica, Kono, Ritsu, Kureishy, Shahrukh, Leflein, Jeffrey, Leong, Mila, Li, Huamin, Lin, Robert, Lugogo, Njira, Marcus, Michael, Jose Maselli Caceres, Diego, Mehta, Vinay, Mello, Curti, Millard, Mark, Milstone, Aaron, Mohan, Arjun, Moore, Wendy, Moss, Mark, Mumneh, Nayla, O'Brien, Thoma, Ostransky, David, Palumbo, Michael, Parikh, Purvi, Parikh, Sudhir, Patel, Amit, Perez, Guido, Pleskow, Warren, Prenner, Bruce, Puppala, Dileep, Ramey, John, Reibman, Joan, Reyes, Ramon, Robinette, Emory, Rodicio, Ileana, Ryan, Stephen, Sekhsaria, Sudhir, Sigal, Barry, Sikand, Vinay, Soong, Weily, Spangenthal, Selwyn, St John, Roy, Gary, Steven, Subramaniam, Vijay, Sumino, Kaharu, Sztejman, Eric, A Tan, Ricardo, Tanus, Tonny, Thompson, Charle, Thornblade, Carl, Villareal, Manuel, Wenzel, Sally, Zafra, Heidi, Ziedalski, Tomasz, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie, Harrison T.W., Chanez P., Menzella F., Canonica G.W., Louis R., Cosio B.G., Lugogo N.L., Mohan A., Burden A., McDermott L., Garcia Gil E., Zangrilli J.G., Pohl W., Voves R., Deschampheleire M., Martinot J.-B., Peche R., Chapman K., Cheema A., Dorscheid D., FitzGerald J.M., Gagnon R., Killorn W.P., Olivenstein R., Philteos G., Ramsey C., Rolf J.D., Walker B., Hilberg O., Skjold T., Titlestad I., Hakulinen A., Kilpelainen M., Ben Hayoun M., Bonniaud P., Bourdin A., De Blay F., Deslee G., Devouassoux G., Didier A., Douadi Y., Fry S., Garcia G., Girodet P.-O., Leroyer C., Magnan A., Mahay G., Nocent C., Pison C., Roux P.-M., Taille C., Tiotiu J.-A., Beck E., Jandl M., Kaehler C., Kassner F., Koesters F., Kronsbein J., Schaum T., Schulz C., Skowasch D., Taube C., Welte T., de Roux A., Beghe B., Blasi F., Carpagnano G., Caruso C., Corsico A.G., Constantino E., Crimi N., Maestrelli P., Milanese M., Papi A., Pelaia G., Pini L., Santus P., Savi E., Scichilone N., Senna G., Spadaro G., Vaghi A., Gans S., Holters J., Langeveld B., Pieters W., Staaks G.H.A., van Veen I., van den Berg J.W.K., Einvik G., Lehmann S., Ali Garcia I., Almonacid C., Bobolea I., Campo Mozo P., de Luiz G., Domingo Ribas C., Echave-Sustaeta Maria-Tome J.M., Garcia Rivero J.L., Garcia-Cosio Piqueras B., Gomez-Bastero Fernandez A., Gonzalez Perez R., Henriquez Santa A., Martinez Rivera C., Munoz Gall X., Ramos J., Gregorio Soto Campos J., Vidal Pan C., Stenfors N., Tunsater A., Vinge I., Chaudhuri R., Harrison T., Mansur A., Nasser S., Nordstrom M., Pfeffer P., Saralaya D., Short P., Adlakha A., Alpan O., Averill F., Badhwar A., Bardelas J., Baxter B., Bensch G., Berger W., Bernstein J., Bridges T., Brimeyer R., Calhoun W., Campbell E., Cherry W.B., Chupp G., Clore L., Cohn J., Cole J., Condemi J., Cury J., Davis B., DeLeon S., Delacruz L., Diaz J., Erb D., Eziri E., Fakih F., Fiedler D., Fost D., Fritz S., Gonzalez E., Goodman B., Gottlieb P., Gottschlich G., Gower R., Hajal R., Harris J., Heidarian-Raissy H., Heyder A., Hill D., Holguin F., Hussain I., Illowite J., Jacobs J., Jarratt M., Kaiser H., Kao N., Kashyap R., Kaufman D., Kent E., Kim K., Klein R., Kraft M., Kono R., Kureishy S., Leflein J., Leong M., Li H., Lin R., Lugogo N., Marcus M., Maselli Caceres D.J., Mehta V., Mello C., Millard M., Milstone A., Moore W., Moss M., Mumneh N., O'Brien T., Ostransky D., Palumbo M., Parikh P., Parikh S., Patel A., Perez G., Pleskow W., Prenner B., Puppala D., Ramey J., Reibman J., Reyes R., Robinette E., Rodicio I., Ryan S., Sekhsaria S., Sigal B., Sikand V., Soong W., Spangenthal S., St. John R., Steven G., Subramaniam V., Sumino K., Sztejman E., Tan R.A., Tanus T., Thompson C., Thornblade C., Villareal M., Wenzel S., Zafra H., Ziedalski T., and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
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Pulmonary and Respiratory Medicine ,Spirometry ,Adult ,Male ,medicine.medical_specialty ,Exacerbation ,[SDV]Life Sciences [q-bio] ,Population ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Placebo ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Anti-Asthmatic Agents ,Patient Reported Outcome Measures ,education ,Sinusitis ,Asthma ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Benralizumab ,3. Good health ,Eosinophils ,030228 respiratory system ,chemistry ,Asthma Control Questionnaire ,Disease Progression ,Quality of Life ,Female ,business - Abstract
Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.
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- 2021
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