Author: "Eugene Bleecker" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Eugene Bleecker"' showing total 22 results

Start Over Author "Eugene Bleecker"

22 results on '"Eugene Bleecker"'

1. Imaging-based clusters in former smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and intermediate outcome measures in COPD study (SPIROMICS)

Author: Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A. C. Kleerup, Fernando J. Martinez, Wanda O’Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, and Ching-Long Lin
Subjects: COPD, Emphysema, Functional small airway disease, Former smokers, Imaging-based cluster analysis, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping. Methods An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration. Results We derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema. Conclusions QCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.
Published: 2019
Full Text: View/download PDF

2. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations

Author: Michelle Daya, Nicholas Rafaels, Tonya M. Brunetti, Sameer Chavan, Albert M. Levin, Aniket Shetty, Christopher R. Gignoux, Meher Preethi Boorgula, Genevieve Wojcik, Monica Campbell, Candelaria Vergara, Dara G. Torgerson, Victor E. Ortega, Ayo Doumatey, Henry Richard Johnston, Nathalie Acevedo, Maria Ilma Araujo, Pedro C. Avila, Gillian Belbin, Eugene Bleecker, Carlos Bustamante, Luis Caraballo, Alvaro Cruz, Georgia M. Dunston, Celeste Eng, Mezbah U. Faruque, Trevor S. Ferguson, Camila Figueiredo, Jean G. Ford, Weiniu Gan, Pierre-Antoine Gourraud, Nadia N. Hansel, Ryan D. Hernandez, Edwin Francisco Herrera-Paz, Silvia Jiménez, Eimear E. Kenny, Jennifer Knight-Madden, Rajesh Kumar, Leslie A. Lange, Ethan M. Lange, Antoine Lizee, Pissamai Maul, Trevor Maul, Alvaro Mayorga, Deborah Meyers, Dan L. Nicolae, Timothy D. O’Connor, Ricardo Riccio Oliveira, Christopher O. Olopade, Olufunmilayo Olopade, Zhaohui S. Qin, Charles Rotimi, Nicolas Vince, Harold Watson, Rainford J. Wilks, James G. Wilson, Steven Salzberg, Carole Ober, Esteban G. Burchard, L. Keoki Williams, Terri H. Beaty, Margaret A. Taub, Ingo Ruczinski, Rasika A. Mathias, Kathleen C. Barnes, and CAAPA
Subjects: Science
Abstract: The burden of asthma varies between ancestries, but GWAS have so far focused on mainly European ancestry populations. Here, Daya et al. perform GWAS for asthma in 14,654 individuals of African ancestry and, besides confirming previously known loci, identify two potentially African ancestry-specific loci.
Published: 2019
Full Text: View/download PDF

3. Imaging-based clusters in current smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)

Author: Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A. C. Kleerup, Fernando J. Martinez, Wanda O’Neal, Stephen I. Rennard, Prescott G. Woodruff, and Ching-Long Lin
Subjects: COPD, Current smokers, Emphysema, Functional small airway disease, Imaging-based cluster analysis, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD. Methods Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers. Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%). Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter. We employed an unsupervised method for clustering. Results Four clusters were identified. Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema. Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations. Cluster 4 showed relatively low FEV1/FVC and high exacerbations. While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters. Conclusions Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.
Published: 2018
Full Text: View/download PDF

4. A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome

Author: Rasika Ann Mathias, Margaret A. Taub, Christopher R. Gignoux, Wenqing Fu, Shaila Musharoff, Timothy D. O'Connor, Candelaria Vergara, Dara G. Torgerson, Maria Pino-Yanes, Suyash S. Shringarpure, Lili Huang, Nicholas Rafaels, Meher Preethi Boorgula, Henry Richard Johnston, Victor E. Ortega, Albert M. Levin, Wei Song, Raul Torres, Badri Padhukasahasram, Celeste Eng, Delmy-Aracely Mejia-Mejia, Trevor Ferguson, Zhaohui S. Qin, Alan F. Scott, Maria Yazdanbakhsh, James G. Wilson, Javier Marrugo, Leslie A. Lange, Rajesh Kumar, Pedro C. Avila, L. Keoki Williams, Harold Watson, Lorraine B. Ware, Christopher Olopade, Olufunmilayo Olopade, Ricardo Oliveira, Carole Ober, Dan L. Nicolae, Deborah Meyers, Alvaro Mayorga, Jennifer Knight-Madden, Tina Hartert, Nadia N. Hansel, Marilyn G. Foreman, Jean G. Ford, Mezbah U. Faruque, Georgia M. Dunston, Luis Caraballo, Esteban G. Burchard, Eugene Bleecker, Maria Ilma Araujo, Edwin Francisco Herrera-Paz, Kimberly Gietzen, Wendy E. Grus, Michael Bamshad, Carlos D. Bustamante, Eimear E. Kenny, Ryan D. Hernandez, Terri H. Beaty, Ingo Ruczinski, Joshua Akey, CAAPA, and Kathleen C. Barnes
Subjects: Science
Abstract: The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) aims to better understand population genetics of the African diaspora. Here, it uses deeply sequenced whole-genomes to describe the impact of admixture and potential disease burden of deleterious variants.
Published: 2016
Full Text: View/download PDF

5. Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations

Author: Michelle Daya, Nicholas Rafaels, Tonya M. Brunetti, Sameer Chavan, Albert M. Levin, Aniket Shetty, Christopher R. Gignoux, Meher Preethi Boorgula, Genevieve Wojcik, Monica Campbell, Candelaria Vergara, Dara G. Torgerson, Victor E. Ortega, Ayo Doumatey, Henry Richard Johnston, Nathalie Acevedo, Maria Ilma Araujo, Pedro C. Avila, Gillian Belbin, Eugene Bleecker, Carlos Bustamante, Luis Caraballo, Alvaro Cruz, Georgia M. Dunston, Celeste Eng, Mezbah U. Faruque, Trevor S. Ferguson, Camila Figueiredo, Jean G. Ford, Weiniu Gan, Pierre-Antoine Gourraud, Nadia N. Hansel, Ryan D. Hernandez, Edwin Francisco Herrera-Paz, Silvia Jiménez, Eimear E. Kenny, Jennifer Knight-Madden, Rajesh Kumar, Leslie A. Lange, Ethan M. Lange, Antoine Lizee, Pissamai Maul, Trevor Maul, Alvaro Mayorga, Deborah Meyers, Dan L. Nicolae, Timothy D. O’Connor, Ricardo Riccio Oliveira, Christopher O. Olopade, Olufunmilayo Olopade, Zhaohui S. Qin, Charles Rotimi, Nicolas Vince, Harold Watson, Rainford J. Wilks, James G. Wilson, Steven Salzberg, Carole Ober, Esteban G. Burchard, L. Keoki Williams, Terri H. Beaty, Margaret A. Taub, Ingo Ruczinski, Rasika A. Mathias, Kathleen C. Barnes, and CAAPA
Subjects: Science
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
Full Text: View/download PDF

6. Asthma heterogeneity and severity

Author: Tara F. Carr and Eugene Bleecker
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Asthma is a common, chronic inflammatory airways disease characterized by a clinical syndrome of bronchial hyperresponsiveness, inflammation, and reversible airflow obstruction. Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. The incident factors, pathogenesis, prognosis, and treatment of asthma remain incompletely understood. Utilizing measurable characteristics of asthmatic patients, including demographic, physiologic, and biologic markers, can however identify meaningful phenotypic categories in asthma. Identification of these phenotypes may help improve precision therapeutics targeted toward an individual’s’ disease, and may identify strategies for preventing progression of disease severity. Keywords: Severe asthma, Phenotype, Heterogeneity
Published: 2016
Full Text: View/download PDF

7. A Between-Sex Comparison of the Genomic Architecture of Asthma

Author: Joe G. Zein, Peter Bazeley, Deborah Meyers, Eugene Bleecker, Benjamin Gaston, Bo Hu, Amy Attaway, and Victor Ortega
Subjects: Pulmonary and Respiratory Medicine, Clinical Biochemistry, Cell Biology, Molecular Biology
Published: 2023

8. Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

Author: Xiaowei Hu, Dandi Qiao, Wonji Kim, Matthew Moll, Pallavi P. Balte, Leslie A. Lange, Traci M. Bartz, Rajesh Kumar, Xingnan Li, Bing Yu, Brian E. Cade, Cecelia A. Laurie, Tamar Sofer, Ingo Ruczinski, Deborah A. Nickerson, Donna M. Muzny, Ginger A. Metcalf, Harshavardhan Doddapaneni, Stacy Gabriel, Namrata Gupta, Shannon Dugan-Perez, L. Adrienne Cupples, Laura R. Loehr, Deepti Jain, Jerome I. Rotter, James G. Wilson, Bruce M. Psaty, Myriam Fornage, Alanna C. Morrison, Ramachandran S. Vasan, George Washko, Stephen S. Rich, George T. O’Connor, Eugene Bleecker, Robert C. Kaplan, Ravi Kalhan, Susan Redline, Sina A. Gharib, Deborah Meyers, Victor Ortega, Josée Dupuis, Stephanie J. London, Tuuli Lappalainen, Elizabeth C. Oelsner, Edwin K. Silverman, R. Graham Barr, Timothy A. Thornton, Heather E. Wheeler, Michael H. Cho, Hae Kyung Im, and Ani Manichaikul
Subjects: Pulmonary Disease, Chronic Obstructive, Risk Factors, Genetics, Humans, National Heart, Lung, and Blood Institute (U.S.), Transcriptome, Lung, Article, United States, Genetics (clinical)
Abstract: While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV(1)] and its ratio to forced vital capacity [FEV(1)/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV(1) and FEV(1)/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08–1.43] for PTRS versus 1.10 [0.96–1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p
Published: 2022

9. Novel Privacy Considerations for Large Scale Proteomics

Author: Andrew C. Hill, Elizabeth M. Litkowski, Ani Manichaikul, Bing Yu, Betty A. Gorbet, Leslie Lange, Katherine A. Pratte, Katerina J. Kechris, Matthew DeCamp, Marilyn Coors, Victor E. Ortega, Stephen S. Rich, Jerome I. Rotter, Robert E. Gerzsten, Clary B. Clish, Jeffrey Curtis, Xiaowei Hu, Debby Ngo, Wanda K. O'Neal, Deborah Meyers, Eugene Bleecker, Brian D. Hobbs, Michael H. Cho, Farnoush Banaei-Kashani, Claire Guo, and Russell Bowler
Abstract: Privacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level genotype probabilities, and then applied a naïve Bayesian approach to match proteomes to genomes for 2,812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA). We were able to correctly match 90%-95% of proteomes to their correct genome and for 95%-99% we could match the proteome to the 1% most likely genome. The accuracy of matching in subjects with African ancestry was lower (~ 60%) unless training included diverse subjects. With larger profiling (SomaScan 5K) in the Atherosclerosis Risk Communities (ARIC) correct identification was > 99% even in mixed ancestry populations. When serial proteomes are available, the matching algorithm can be used to identify and correct mislabeled samples. This work also demonstrates the importance of including diverse populations in omics research and that large proteomic datasets (> 1,000 proteins) can be accurately linked to a specific genome through pQTL knowledge and should not be considered unidentifiable.
Published: 2022

10. DNA Sequencing Analysis of Cystic Fibrosis Transmembrane Regulator Gene Identifies Cystic Fibrosis-Associated Variants in the Severe Asthma Research Program

Author: Manuel E. Izquierdo, Chad R. Marion, Wendy Moore, Karen Raraigh, Jennifer Taylor-Cousar L, Gary Cutting, E. Ampleford, Gregory A. Hawkins, Joe Zein, Mario Castro, Loren C. Denlinger, Serpil Erzurum, John Fahy, Elliot Israel, Nizar Jarjour, David Mauger, Bruce D. Levy, Sally Wenzel, Prescott Woodruff, Eugene Bleecker, Deborah A. Meyers, and Victor E. Ortega
Abstract: Background: Heterozygote carriers of potentially pathogenic variants in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene have increased asthma risk. However, the frequency and impact of CFTR variation among individuals with asthma is unknown. Objective: To determine whether potentially pathogenic CFTR variants associate with disease severity and whether individuals with two potentially pathogenic variants exist in a severe asthma-enriched cohort . Methods: We analyzed sequencing data spanning a 190.5Kb region of CFTR in participants from the Severe Asthma Research Program (SARP1-3). Potentially pathogenic, rare CFTR variants (frequencyCFTR genotypes (0-2 potentially pathogenic variants) and severity outcomes. Results: Of 1401 participants, 9.5% (134) had one potentially pathogenic variant, occurring more frequently in non-Hispanic white (NHW, 10.1% [84 of 831]) compared to African American individuals (AA, 5.2% [22 of 426]). We found ≥2 potentially pathogenic CFTR variants in 1.4% (19); 0.5% (4) of NHW and 2.8% (12) of AA. Potentially pathogenic CFTR variant genotypes (≥1 or ≥2 variants) were not cumulatively associated with lung function or exacerbations. In NHW, we found three F508del compound heterozygotes with F508del and a VVCC (two 5T;TG12[c.1210-11T>G] and one Arg1070Trp) and a homozygote for the VVCC, 5T;TG12. Conclusions: We found potentially pathogenic CFTR variants within a severe asthma-enriched cohort , including three compound heterozygote genotypes variably associated with CF in NHW individuals. These findings provide the rationale for CFTR sequencing and phenotyping of CF-related traits in individuals with severe asthma.
Published: 2022

11. How cytokines co-occur across asthma patients: From bipartite network analysis to a molecular-based classification.

Author: Suresh K. Bhavnani, Sundar Victor, William J. Calhoun, William W. Busse, Eugene Bleecker, Mario Castro, Hyunsu Ju, Regina Pillai, Numan Oezguen, Gowtham Bellala, and Allan R. Brasier
Published: 2011
Full Text: View/download PDF

12. Estimated Ventricular Size, Asthma Severity, and Exacerbations

Author: Samuel Y. Ash, Gonzalo Vegas Sanchez-Ferrero, Mark L. Schiebler, Farbod N. Rahaghi, Ashish Rai, Carolyn E. Come, James C. Ross, Alysha G. Colon, Juan Carlos Cardet, Eugene R. Bleecker, Mario Castro, John V. Fahy, Sean B. Fain, Benjamin M. Gaston, Eric A. Hoffman, Nizar N. Jarjour, Jason K. Lempel, David T. Mauger, Matthew C. Tattersall, Sally E. Wenzel, Bruce D. Levy, George R. Washko, Elliot Israel, Raul San Jose Estepar, Bruce Levy, George Washko, Manuela Cernadas, Wanda Phipatanakul, Sally Wenzel, Merritt Fajt, Benjamin Gaston, James Chmiel, W. Gerald Teague, Anne-Marie Irani, Serpil Erzurum, Sumita Khatri, Suzy Comhair, Raed Dweik, Kristie Ross, Ross Myers, Wendy Moore, Deborah Meyers, Eugene Bleecker, Stephen Peters, Annette Hastie, Victor Ortega, Greg Hawkins, Xingan Li, Anne Fitzpatrick, Nazar Jarjour, Loren Denlinger, Sean Fain, Ronald Sorkness, Leonard Bacharier, David Gierada, Kenneth Schechtman, Jason Woods, John Fahy, Prescott Woodruff, Ngoc Ly, and David Mauger
Subjects: Pulmonary and Respiratory Medicine, COPD, medicine.medical_specialty, Aorta, Exacerbation, business.industry, Critical Care and Intensive Care Medicine, medicine.disease, Cystic fibrosis, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, medicine.artery, Internal medicine, Cohort, Pulmonary artery, medicine, Cardiology, 030212 general & internal medicine, Respiratory system, Cardiology and Cardiovascular Medicine, business, Asthma
Abstract: Background Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. Methods We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Results Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. Conclusions In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. Trial Registry ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov
Published: 2020

13. Clinical and molecular implications of RGS2 promoter genetic variation in severe asthma

Author: Juan Carlos Cardet, Donghwa Kim, Eugene Bleecker, Thomas Casale, Elliot Israel, David Mauger, Deborah Meyers, Yaping Tu, Stephen Liggett, and Victor Ortega
Subjects: Immunology, Immunology and Allergy
Published: 2022

14. Benralizumab for the Prevention of COPD Exacerbations

Author: Criner, G. J., Celli, B. R., Brightling, C. E., Agusti, A., Papi, A., Singh, D., Sin, D. D., Vogelmeier, C. F., Sciurba, F. C., Bafadhel, M., Backer, V., Kato, M., Ramirez-Venegas, A., Wei, Y. -F., Bjermer, L., Shih, V. H., Jison, M., O'Quinn, S., Makulova, N., Newbold, P., Goldman, M., Martin, U. J., GALATHEA Study Investigators, TERRANOVA Study Investigators, Otto, Burghuber, Bernhard, Forstner, Gerhard, Köberl, Bernd, Lamprecht, Judith, Löffler-Ragg, Horst, Olschewski, Michael, Studnicka, Francois, Beaucage, Guy, Chouinard, Anthony, Dechant, Anthony, Dowell, Jacques, Hebert, Sohail, Khattak, Kieran, Killian, William, Killorn, Andy, Lam, Francois, Maltais, Darcy, Marciniuk, Lyle, Melenka, Bonavuth, Pek, Jeremy, Road, Donald, Sin, Alain, Vaugeois, Brandie, Walker, Tomas, Dvorak, Stanislav, Holub, Otakar, Hokynar, Vitezslav, Kolek, Daniela, Kopecka, Jan, Krepelka, Jaroslav, Mares, Josef, Veverka, Vladimir, Zindr, Sabine, Ballenberger, Rolf, Dichmann, Christian, Geßner, Margret, Jandl, Claus, Keller, Joachim, Kirschner, Marc, Kornmann, Petra, Mikloweit, Ingomar, Naudts, Axel, Overlack, Isabelle, Schenkenberger, Volker, Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan, Zielen, István, Albert, Beatrix, Bálint, Mária Csilla Hangonyi, Teréz, Kecskés, Anikó, Kurucz, Balázs, Medgyasszay, Lajos, Molnár, János, Mucsi, Márta, Papp, Magdolna, Póczi, Éva, Radeczky, Zsolt Pápai Székely, Csilla, Szabó, Gyöngyi, Szabó, Melinda, Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio, Donazzan, Federica, Meloni, Elisabetta, Pace, Pierluigi, Paggiaro, Alberto, Papi, Ricciardolo, Fabio Luigi Massimo, Antonio, Spanevello, Fumiaki, Aoki, Ryosuke, Eda, Takeo, Endo, Yasushi, Fukushima, Kenichi, Gemba, Naoki, Hagimoto, Hiromasa, Harada, Yasuko, Harada, Norihiko, Hata, Osamu, Hataji, Nobuo, Hatakeyama, Takahiko, Horiguchi, Gen, Ideura, Motoyasu, Iikura, Azusa, Ikegami, Shirou, Imokawa, Yoshikazu, Inoue, Takeshi, Isobe, Ryoji, Ito, Susumu, Iwata, Tadashi, Kamei, Motokazu, Kato, Hideki, Katsura, Yuji, Kawarada, Norio, Kihara, Masaharu, Kinoshita, Takashi, Kinoshita, Tomoo, Kishaba, Hideo, Kita, Arihiro, Kiyosue, Shigeru, Komatsu, Kazuki, Konishi, Sekiya, Koyama, Makoto, Kudo, Kazuhiko, Machida, Hironi, Makita, Hiroto, Matsuse, Naoki, Miyazawa, Hiroyuki, Nakamura, Yuji, Nakatani, Kazuyuki, Nishimura, Takashi, Nishimura, Junichi, Ogawa, Hiroyuki, Ohbayashi, Tetsuro, Ohdaira, Tsukasa, Ohnishi, Kazuhiko, Oki, Masahiko, Saito, Kenji, Sakamoto, Osamu, Sakamoto, Hisakuni, Sekino, Noriharu, Shijubo, Masaharu, Shinkai, Hideo, Soto, Yoshitaka, Sugawara, Noriaki, Suko, Hisaho, Takahashi, Masamitsu, Takahashi, Tsuneyuki, Takahashi, Hiroshi, Tanaka, Hiroyuki, Taniguchi, Tadayuki, Terada, Takao, Tochigi, Kazuyo, Tohyama, Hirokazu, Tokuyasu, Keisuke, Tomii, Tomomasa, Tsuboi, Mitsuyoshi, Utsugi, Katsumaru, Yamamoto, Michiko, Yamamoto, Shuichi, Yano, Makoto, Yoshida, Frank, Custers, Richard, Dekhuijzen, Remco, Djamin, Jan Willem Van Dan Berg, Lowie, Vanfleteren, Pascal, Wielders, Bogusława, Cimoszko, Anna, Doboszyńska, Andrzej, Dyczek, Andrzej, Fal, Krystyna, Folcik, Łukasz, Goliński, Marek, Jutel, Andrzej, Kolczyński, Piotr, Kuna, Ewa, Łączyńska, Wojciech, Machowiak, Maciej, Marczak, Joanna, Markiewicz, Janusz, Milanowski, Grzegorz, Mincewicz, Maria, Nittner-Marszalska, Wojciech, Papiewski, Małgorzata, Pawlukiewicz, Witold, Pomiećko, Barbara, Rewerska, Cezary, Rybacki, Wojciech, Skucha, Ewa, Trębas-Pietraś, Ewa, Uhryn, Małgorzata, Żurowska-Gębala, Laurentia, Andrei, Traian, Mihaescu, Stefan, Mihaicuta, Eniko Vera Pall, Ioan, Petrui, Angelica, Savu, Claudia, Toma, Ana, Trailescu, Vladimir, Abrosimov, Nataliya, Astafyeva, Evgenyi, Bazdyrev, Nadezhda, Berdnikova, Laura, Bolieva, Ekaterina, Bukreeva, Valery, Chistyakov, Anna, Galustyan, Halida, Gantseva, Svetlana, Goncharova, Sergey, Grigoriev, Galina, Ignatova, Inna, Ilyashevich, Nadezhda, Izmozherova, Magomed, Kamalov, Yaroslava, Khovaeva, Natalia, Kuzubova, Lyudmila, Kvitkova, Liudmila, Lenskaya, Igor, Leshchenko, Olga, Magnitskaya, Boris, Molotilov, Artem, Molotkov, Svetlana, Myasoedova, Sergey, Nedogoda, Vladimir, Nosov, Marina, Osipenko, Andrey, Peskov, Veronika, Popova, Oksana, Ratushnay, Irina, Ryzhova, Olga, Shangina, Natalia, Shaporova, Evgeny, Shmelev, Lybov, Shpagina, Alexander, Shutkin, Yuri, Shvarts, Mikhail, Smirnov, Irina, Stitsenko, Maksim, Vasilev, Arkadiy, Vertkin, Elena, Vishneva, Alexander, Vizel, Anna, Zateyschikova, Mohamed, Abdool-Gaffar, Ismail, Abdullah, Axel, Bruning, Nyda, Fourie, Michael, Greenblatt, Mohammed, Tayob, Venter, K, An Soo Jang, Kwan Ho Lee, Sang Haak Lee, Sook Young Lee, Suk Joong Yong, Kwang Ha Yoo, Soo Taek Uh, Ramón Agüero Balbín, David Ramos Barbón, Álvar Agustí García-Navarro, José Luis Velasco Garrido, Sergi Pascual Guardia, Eduard Monso Molas, Luis De Teresa Parreño, Borja García-Cosio Piqueras, German Peces-Barba Romero, Myriam Calle Rubio, Fernando Sánchez-Toril López, Alicia Marín Tapia, Heidi Martin Braschler, Martin, Brutsche, Michael, Grob, Jörg, Leuppi, Daiana, Stolz, Alexander, Turk, Nawar, Bakerley, Mona, Bafadhel, Christopher, Brightling, Rekha, Chaudhuri, Gourab, Choudhury, Graham, Devereux, Imran, Hussain, Kai, Lee, William, Macnee, Ravindran, Mahadeva, Matthew, Masoli, Monica, Nordstrom, Manish, Patel, Allan, Reid, Dinesh, Saralaya, Tariq, Sethi, Sukh Dave Singh, Anthony, G de Soyza, Tom, Wilkinson, Alice, Turner, Helen, Ward, Chandar, Abboy, Ivan, Ackerman, Idalia, Acosta, Arun, Adlakha, Bassil, Aish, Mohamed, Ali, Charles, Andrews, Robby, Ayoub, Anil, Badhwar, Dennis, Bassetti, Sherif El Bayadi, Richard, Beasley, Shashi, Bellam, Jonathan, Bernstein, Maria, Blahey, Scott, Bloom, Eugene, Bleecker, Wesley, Bray, Johnathan, Brewer, Robert, Buynak, William, Calhoun, Edward, Campbell, Anthony, Captain, Birjis, Chinoy, Kenneth, Chinsky, Geoffrey, Chupp, Arsenio, Columbie, Clinton, Corder, Gerard, Criner, Humberto, Cruz, Edward, Cullen, Kevin, Deboer, Michael, Denenberg, Mark, Dransfield, Leonard, Dunn, Miles, Elmore, David, Erb, Faisal, Fakih, Gary, Ferguson, Charles, Fogarty, Mark, Freed, Stephen, Fritz, David, Fuentes, Shariar, Cohen-Gadol, Robert, Garver, John, Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert, Gordon, Gregory, Gottschlich, Donald, Graham, David, Grant, Gary, Greenwald, James, Greenwald, Kenneth, Haft, Gregory, Hammond, Nadia, Hansel, Jeffrey, Harris, Humberto, Hernandez, Marvin, Heuer, Albrecht, Heyder, David, Hill, Willis, Holloway, Octavian, Ioachimescu, Richard, Jackson, Ajay, Jain, Nan, Jiang, Thomas, Kaelin, Adolfo, Kaplan, Mitchell, Kaye, Akram, Khan, Yekaterina, Khronusova, Ryan, Klein, Joel, Kline, Firas, Koura, Ritsu, Kuno, Ware, Kuschner, Jean Claude Labissiere, David Laman Jr, John, Lee, Mitchell, Lee, Lawrence, Levinson, Njira, Lugogo, Mador, M, Nathaniel, Marchetti, Rafael, Martinez, Richard, Martinez, Peter, Mattar, David, Maybee, Dennis, Mcgraw, Michael, Mcguire, Curtis, Mello, Aaron, Milstone, John, Mitchell, Wendy, Moore, Timothy, Moriarty, Cheta, Nand, Brooke, Nevins, Ikeadi, Ndukwu, Rachel, Nisbet, David, Nyanjom, Maria, Nualart, Thomas, O'Brien, Mikhail, Palatnik, Gnyandev, Patel, Amit, Patel, Guido, Perez, Christopher, Perry, Michael, Pfeffer, Krishna, Pudi, Marina, Raikhel, Murali, Ramaswamy, Joe, Ramsdell, Donato, Ricci, Gary, Richmond, Eugene, Ryan, Fadi, Saba, Boris, Sagalovich, C Andrew Schroeder, Timothy, Scialla, Frank, Sciurba, Amit, Shah, Nirav, Shah, Zeeshan, Shaikh, Akhtar, Siddiqui, Barry, Sigal, Thomas, Siler, Howard, Silverboard, William, Sims, Clyde, Southwell, Selwyn, Spangenthal, Peruvemba, Sriram, James, Stocks, Tony, Su, John, Suen, Robert, Sussman, Horia, Tatu, Antonio, Terrelonge, Alan, Thomas, Mario, Torres, Rodolfo, Trejo, Miguel, Trevino, Banks, Turner, Manuel, Villareal, Janine, Vintch, Neal, Warshoff, Jan, Westerman, Philip, Wexler, Thomas, Yunger, Amir, Zeki, Mariano Fernandez Acquier, Norma, Aramayo, German, Arce, Juan, Belloni, Víctor, Cambursano, Carlos De La Vega, Fernando Rodriguez Chariarse, Pedro, Elias, Marcelo, Fernández, Ana, Lopez, Andrea, Medina, María, Otaola, Maria Salazan Saez, Maria De Salvo, Fernando, Scherbovsky, Ana, Stok, Jorge, Taborda, Alberto, Tolcachier, Fernando, Verra, Carlos, Victorio, Rita Gisela Delgado Vizcarra, Philip, Bardin, Peter, Bremner, Martin, Phillips, John, Upham, Peter, Wark, Antoine, Bolly, Alain, Delobbe, Peter, Driesen, Eduard, Janssens, Wim, Janssens, Olivier, Michel, Bernard, Vandooren, Martti, Antila, Jussara, Fiterman, Carlos, Fritscher, Jorge, Hetzel, Jose, Jardim, Waldo De Mattos, Rafael, Martins, Maria Eunice De Oliveira, Andreia, Pez, Maria, Sales, Rafael, Stelmach, Priscila, Wolff, Svetla, Andreeva, Reneta, Antonova, Ana, Dancheva, Yuliya, Ivanova, Slavcho, Ivanov, Hristo, Metev, Iveta, Naydenova, Tatyana, Petkova, Galina, Petrova, Kostadinka, Sotirova, Mariyana, Stoyanova, Rumen, Tiholov, Iliyana, Valkanova, Oleg, Yakov, Rosa, Feijoo, Juana, Pavie, Patricia, Schönffeldt, Absalon, Silva, Victor, Martinez, David, Espinosa, Alejandro, Londono, Dora, Molina, Gonzalo, Prada, Andrés, Rico, Gregorio Sanchez Vallejo, Alvaro, Urbina, Ana, Vanegas, Maria, Villegas, Josip, Aralica, Gordana, Stjepanovic, Vibeke, Backer, Uffe, Bødtger, Christian, Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid, Titlestad, Nathalie, Bautin, Arnaud, Bourdin, Pascal, Chanez, Francis, Couturaud, Antoine, Cuvelier, Gilles, Devouassoux, Pierre-Olivier, Girodet, Jean-François, Muir, Jean-Louis, Pépin, Alain, Proust, Azzedine, Yaici, Yochai, Adir, Gershon, Fink, Zvi, Fridlender, Gabriel, Izbicki, Mordechai, Kramer, Yehuda, Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra, Ramirez-Venegas, Paul, Dawkins, Syed, Hussain, Benedict, Brockway, John, Richmond, Colin, Helm, Catherina, Chang, Jørn, Ahlqvist, Terje, Tollåli, Tadeusz, Tomala, Socorro, Castro, William, Chavez, Octavio, Cubas, Rolando, Estrella, Efrain, Felix, Ronal, Gamarra, Alfredo, Guerreros, Alberto, Matsuno, Danilo, Salazar, Miguel, Tsukayama, Albert Albay Jr, Teresita, Aquino, Tito, Atienza, Joven Roque Gonong, Ronnie, Samoro, Joel, Santiaguel, Beata, Asankowicz-Bargiel, Ewa, Pisarczyk-Bogacka, Renata, Bijata-Bronisz, Marta, Chełmińska, Małgorzata, Dobryniewska, Anna, Olech-Cudzik, Tomasz, Fijołek, Krzysztof, Filipek, Agata, Kot, Bożena, Kucińska, Krzysztof, Lis, Elżbieta, Rybicka-Liszewska, Marzenna, Tarnowska-Matusiak, Robert, Mróz, Piotr, Napora, Wojciech, Naumnik, Artur, Niemiec, Władysław, Pierzchała, Grzegorz, Przybylski, Katarzyna, Styka, Danuta, Wrońska, Branislava, Milenkovic, Dobrivoje, Novkovic, Matijaz, Flezar, Niksa, Segota, Snezana Ulcar Kostic, Albert, Klobucar, Leif, Bjermer, Dan, Curiac, Christer, Janson, Pekka, Koskinen, Lundback, Bo, Åke, Olsson, Shih-Lung, Cheng, Ming-Lin, Ho, Jeng-Yuan, Hsu, Wu-Huei, Hsu, Ping-Hung, Kuo, Chin-Chou, Wang, Yu-Feng, Wei, Kuang-Yao, Yang, Watchara, Boonsawat, Somchai, Chantarothorn, Warangkana, Keeratichananont, Kittipong, Maneechotesuwan, Kanok, Pipatvech, Piamlarp, Sangsayunh, Sibel, Arinc, Sermin, Borekci, Arzu Kaner Erturk, Filiz, Kosar, Hakan, Gunen, Ismail, Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel, Nayci, Serir Aktogu Ozkan, Abdullah, Sayiner, Esra, Uzaslan, Viktor, Blazhko, Volodymyr, Gavrysyuk, Olena, Golub, Liudmyla, Iashyna, Tetiana, Ilashchuk, Volodymyr, Koshlia, Olena, Krakhmalova, Vitali, Kryvenko, Lesia, Kuryk, Olena, Levchenko, Yuriy, Mostovoy, Mykola, Ostrovskyy, Tetyana, Pertseva, Olena, Piura, Nadiya, Rudnytska, Ganna, Stupnytska, Nataliia, Velychko, Oleh, Yakovenko, Lilia Rodriguez Ables, Roger, Abrahams, Jose, Alvarez, Fernando, Arencibia, Chander, Arora, Samir, Arora, Francis, Averill, Kwabena, Ayesu, Stephen, Basheda, Steven, Bauer, Jose, Bautista, Matthew, Beacom, Hernando, Bernal, Subodh, Bhuchar, J'Cinda, Bitters, John, Burk, Elizabeth, Burkett, James, Cain, Robert, Call, Christopher, Chappel, Bartolome, Celli, Tom, Christensen, Jeremy, Cole, Jerome, Daniel, Nguyen, Dang, Enrique, Davis, Samuel, Deleon, Robert, Deluca, Ernesto, Diaz, Anthony, Dimarco, Calvin, Dixon, Ankur, Doshi, Hugh, Durrence, Alain, Eid, John, Elsen, Herbon, Fleming, May, Flores, Scott, Franczek, Gregory, Funk, Stuart, Garay, Bernard, Garcia, Joseph, Graif, Carl, Griffin, Yamirka Duardo Guerra, David, Headley, Mitzie, Hewitt, Susan, Hole, Robert, Holladay, Ira, Horowitz, Yu-Luen, Hsu, Jonathan, Ilowite, Stephen, Jones, Ravindra, Kashyap, Edward, Kerwin, Ahtaram, Khan, Nicole, Kimzey, James, Krainson, Flory, Kreutter, Kannappan, Krishnaswamy, Shahrukh, Kureishy, Albert, Lai, Alex, Lechin, Daria, Lee, Marcus, Lee, Williams, Leeds, Joseph, Lillo, Edward, Lisberg, Lawrence, Madoff, Narendra, Maheskwari, Mujibur, Majumder, Sashi, Makam, Douglas, Mapel, Matthew, Mardiney, Jennifer, Martin, Isaac, Melamed, Elvin, Mendez, Stuart, Millstone, Joseph, Montes, Lee, Morrow, Frank, Murphy, Dany, Obeid, France, Occy, Godson, Oguchi, Juan, Ortiz, Francisco, Padron, Ward, Paine, James, Pearle, Enrique, Pelayo, Vandely, Perez, David, Pham, Carlos, Piniella, Kevin, Pritchett, Padmashri, Rastogi, Stephen, Ryan, Syed, Rehman, Jackson, Rhudy, Eustace, Riley, James, Riser, Clifford, Risk, Emory, Robinette, Christopher, Roney, Gary, Ruoff, David, Russian, Mercedes, Samson, Jay, Sandberg, Jose, Santiago, William, Sargeant, Alan, Schecter, Jeffrey, Scott, Ilia, Segal, Sudhir, Sehgal, Frederic, Seifer, Sudhir, Sekhsaria, Richard, Sellman, Paul, Shapero, Jeffrey, Shea, Lawrence, Sher, John, Sibille, Jawed, Siddiqui, Toniya, Singh, Deren, Sinkowitz, Denise, Smyth, Daniel, Soteres, Daniel, Sousa, Ralph, Steele, Thomas, Stern, Jose, Suarez, Sever, Surdulescu, Ricardo, Tan, Tonny, Tanus, Raymond, Tidman, Aurelio, Torres-Consuegra, Barry, Troyan, John, Updegrove, Sanjay, Vadgama, Armando, Pineda-Velez, Eduardo, Viera, Andrew, Wachtel, Ralph, Wade, Jimin, Wang, Dave, Webster, Paul, Weinberg, Terry, Wells, Jeffrey, White, Bram, Wieskopf, Hugh, Windom, Patrick, Wright, David, Wyatt, Bassam, Yousef, Zahid, Zafar, Chau, Ngo, Huong, Le, Lan, Nguyen, Thanh, Nguyen, Nhung, Nguyen, SALAS, Danielle, Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Harvard Medical School [Boston] (HMS), University of Leicester, University of Barcelona, Università degli Studi di Ferrara = University of Ferrara (UniFE), University of Manchester [Manchester], St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada] (SPH-UBC), Philipps Universität Marburg = Philipps University of Marburg, University of Pittsburgh School of Medicine, University of Oxford, Bispebjerg University Hospital [Copenhagen, Denmark] (BUH), Kishiwada City Hospital [Osaka, Japan] (KCH), Instituto Nacional de Enfermedades Respiratorias [México, Mexico], I-Shou University [Kaohsiung, Taiwan] (ISU), Lund University [Lund], AstraZeneca [Gaithersburg, MD, USA] (AZ), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Otto Burghuber, Bernhard Forstner, Gerhard Köberl, Bernd Lamprecht, Judith Löffler-Ragg, Horst Olschewski, Michael Studnicka, Francois Beaucage, Guy Chouinard, Anthony Dechant, Anthony Dowell, Jacques Hebert, Sohail Khattak, Kieran Killian, William Killorn, Andy Lam, Francois Maltais, Darcy Marciniuk, Lyle Melenka, Bonavuth Pek, Jeremy Road, Donald Sin, Alain Vaugeois, Brandie Walker, Tomas Dvorak, Stanislav Holub, Otakar Hokynar, Vitezslav Kolek, Daniela Kopecka, Jan Krepelka, Jaroslav Mares, Josef Veverka, Vladimir Zindr, Sabine Ballenberger, Rolf Dichmann, Christian Geßner, Margret Jandl, Claus Keller, Joachim Kirschner, Marc Kornmann, Petra Mikloweit, Ingomar Naudts, Axel Overlack, Isabelle Schenkenberger, Volker Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan Zielen, István Albert, Beatrix Bálint, Mária Csilla Hangonyi, Teréz Kecskés, Anikó Kurucz, Balázs Medgyasszay, Lajos Molnár, János Mucsi, Márta Papp, Magdolna Póczi, Éva Radeczky, Zsolt Pápai Székely, Csilla Szabó, Gyöngyi Szabó, Melinda Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio Donazzan, Federica Meloni, Elisabetta Pace, Pierluigi Paggiaro, Alberto Papi, Fabio Luigi, Massimo Ricciardolo, Antonio Spanevello, Fumiaki Aoki, Ryosuke Eda, Takeo Endo, Yasushi Fukushima, Kenichi Gemba, Naoki Hagimoto, Hiromasa Harada, Yasuko Harada, Norihiko Hata, Osamu Hataji, Nobuo Hatakeyama, Takahiko Horiguchi, Gen Ideura, Motoyasu Iikura, Azusa Ikegami, Shirou Imokawa, Yoshikazu Inoue, Takeshi Isobe, Ryoji Ito, Susumu Iwata, Tadashi Kamei, Motokazu Kato, Hideki Katsura, Yuji Kawarada, Norio Kihara, Masaharu Kinoshita, Takashi Kinoshita, Tomoo Kishaba, Hideo Kita, Arihiro Kiyosue, Shigeru Komatsu, Kazuki Konishi, Sekiya Koyama, Makoto Kudo, Kazuhiko Machida, Hironi Makita, Hiroto Matsuse, Naoki Miyazawa, Hiroyuki Nakamura, Yuji Nakatani, Kazuyuki Nishimura, Takashi Nishimura, Junichi Ogawa, Hiroyuki Ohbayashi, Tetsuro Ohdaira, Tsukasa Ohnishi, Kazuhiko Oki, Masahiko Saito, Kenji Sakamoto, Osamu Sakamoto, Hisakuni Sekino, Noriharu Shijubo, Masaharu Shinkai, Hideo Soto, Yoshitaka Sugawara, Noriaki Suko, Hisaho Takahashi, Masamitsu Takahashi, Tsuneyuki Takahashi, Hiroshi Tanaka, Hiroyuki Taniguchi, Tadayuki Terada, Takao Tochigi, Kazuyo Tohyama, Hirokazu Tokuyasu, Keisuke Tomii, Tomomasa Tsuboi, Mitsuyoshi Utsugi, Katsumaru Yamamoto, Michiko Yamamoto, Shuichi Yano, Makoto Yoshida, Frank Custers, Richard Dekhuijzen, Remco Djamin, Jan Willem Van Dan Berg, Lowie Vanfleteren, Pascal Wielders, Bogusława Cimoszko, Anna Doboszyńska, Andrzej Dyczek, Andrzej Fal, Krystyna Folcik, Łukasz Goliński, Marek Jutel, Andrzej Kolczyński, Piotr Kuna, Ewa Łączyńska, Wojciech Machowiak, Maciej Marczak, Joanna Markiewicz, Janusz Milanowski, Grzegorz Mincewicz, Maria Nittner-Marszalska, Wojciech Papiewski, Małgorzata Pawlukiewicz, Witold Pomiećko, Barbara Rewerska, Cezary Rybacki, Wojciech Skucha, Ewa Trębas-Pietraś, Ewa Uhryn, Małgorzata Żurowska-Gębala, Laurentia Andrei, Traian Mihaescu, Stefan Mihaicuta, Eniko Vera Pall, Ioan Petrui, Angelica Savu, Claudia Toma, Ana Trailescu, Vladimir Abrosimov, Nataliya Astafyeva, Evgenyi Bazdyrev, Nadezhda Berdnikova, Laura Bolieva, Ekaterina Bukreeva, Valery Chistyakov, Anna Galustyan, Halida Gantseva, Svetlana Goncharova, Sergey Grigoriev, Galina Ignatova, Inna Ilyashevich, Nadezhda Izmozherova, Magomed Kamalov, Yaroslava Khovaeva, Natalia Kuzubova, Lyudmila Kvitkova, Liudmila Lenskaya, Igor Leshchenko, Olga Magnitskaya, Boris Molotilov, Artem Molotkov, Svetlana Myasoedova, Sergey Nedogoda, Vladimir Nosov, Marina Osipenko, Andrey Peskov, Veronika Popova, Oksana Ratushnay, Irina Ryzhova, Olga Shangina, Natalia Shaporova, Evgeny Shmelev, Lybov Shpagina, Alexander Shutkin, Yuri Shvarts, Mikhail Smirnov, Irina Stitsenko, Maksim Vasilev, Arkadiy Vertkin, Elena Vishneva, Alexander Vizel, Anna Zateyschikova, Mohamed Abdool-Gaffar, Ismail Abdullah, Axel Bruning, Nyda Fourie, Michael Greenblatt, Mohammed Tayob, K Venter, An Soo Jang, Kwan Ho Lee, Sang Haak Lee, Sook Young Lee, Suk Joong Yong, Kwang Ha Yoo, Soo Taek Uh, Ramón Agüero Balbín, David Ramos Barbón, Álvar Agustí García-Navarro, José Luis Velasco Garrido, Sergi Pascual Guardia, Eduard Monso Molas, Luis De Teresa Parreño, Borja García-Cosio Piqueras, German Peces-Barba Romero, Myriam Calle Rubio, Fernando Sánchez-Toril López, Alicia Marín Tapia, Heidi Martin Braschler, Martin Brutsche, Michael Grob, Jörg Leuppi, Daiana Stolz, Alexander Turk, Nawar Bakerley, Mona Bafadhel, Christopher Brightling, Rekha Chaudhuri, Gourab Choudhury, Graham Devereux, Imran Hussain, Kai Lee, William MacNee, Ravindran Mahadeva, Matthew Masoli, Monica Nordstrom, Manish Patel, Allan Reid, Dinesh Saralaya, Tariq Sethi, Sukh Dave Singh, Anthony G de Soyza, Tom Wilkinson, Alice Turner, Helen Ward, Chandar Abboy, Ivan Ackerman, Idalia Acosta, Arun Adlakha, Bassil Aish, Mohamed Ali, Charles Andrews, Robby Ayoub, Anil Badhwar, Dennis Bassetti, Sherif El Bayadi, Richard Beasley, Shashi Bellam, Jonathan Bernstein, Maria Blahey, Scott Bloom, Eugene Bleecker, Wesley Bray, Johnathan Brewer, Robert Buynak, William Calhoun, Edward Campbell, Anthony Captain, Birjis Chinoy, Kenneth Chinsky, Geoffrey Chupp, Arsenio Columbie, Clinton Corder, Gerard Criner, Humberto Cruz, Edward Cullen, Kevin Deboer, Michael Denenberg, Mark Dransfield, Leonard Dunn, Miles Elmore, David Erb, Faisal Fakih, Gary Ferguson, Charles Fogarty, Mark Freed, Stephen Fritz, David Fuentes, Shariar Cohen-Gadol, Robert Garver, John Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert Gordon, Gregory Gottschlich, Donald Graham, David Grant, Gary Greenwald, James Greenwald, Kenneth Haft, Gregory Hammond, Nadia Hansel, Jeffrey Harris, Humberto Hernandez, Marvin Heuer, Albrecht Heyder, David Hill, Willis Holloway, Octavian Ioachimescu, Richard Jackson, Ajay Jain, Nan Jiang, Thomas Kaelin, Adolfo Kaplan, Mitchell Kaye, Akram Khan, Yekaterina Khronusova, Ryan Klein, Joel Kline, Firas Koura, Ritsu Kuno, Ware Kuschner, Jean Claude Labissiere, David Laman Jr, John Lee, Mitchell Lee, Lawrence Levinson, Njira Lugogo, M Mador, Nathaniel Marchetti, Rafael Martinez, Richard Martinez, Peter Mattar, David Maybee, Dennis McGraw, Michael McGuire, Curtis Mello, Aaron Milstone, John Mitchell, Wendy Moore, Timothy Moriarty, Cheta Nand, Brooke Nevins, Ikeadi Ndukwu, Rachel Nisbet, David Nyanjom, Maria Nualart, Thomas O'Brien, Mikhail Palatnik, Gnyandev Patel, Amit Patel, Guido Perez, Christopher Perry, Michael Pfeffer, Krishna Pudi, Marina Raikhel, Murali Ramaswamy, Joe Ramsdell, Donato Ricci, Gary Richmond, Eugene Ryan, Fadi Saba, Boris Sagalovich, C Andrew Schroeder, Timothy Scialla, Frank Sciurba, Amit Shah, Nirav Shah, Zeeshan Shaikh, Akhtar Siddiqui, Barry Sigal, Thomas Siler, Howard Silverboard, William Sims, Clyde Southwell, Selwyn Spangenthal, Peruvemba Sriram, James Stocks, Tony Su, John Suen, Robert Sussman, Horia Tatu, Antonio Terrelonge, Alan Thomas, Mario Torres, Rodolfo Trejo, Miguel Trevino, Banks Turner, Manuel Villareal, Janine Vintch, Neal Warshoff, Jan Westerman, Philip Wexler, Thomas Yunger, Amir Zeki, Mariano Fernandez Acquier, Norma Aramayo, German Arce, Juan Belloni, Víctor Cambursano, Carlos De La Vega, Fernando Rodriguez Chariarse, Pedro Elias, Marcelo Fernández, Ana Lopez, Andrea Medina, María Otaola, Maria Salazan Saez, Maria De Salvo, Fernando Scherbovsky, Ana Stok, Jorge Taborda, Alberto Tolcachier, Fernando Verra, Carlos Victorio, Rita Gisela Delgado Vizcarra, Philip Bardin, Peter Bremner, Martin Phillips, John Upham, Peter Wark, Antoine Bolly, Alain Delobbe, Peter Driesen, Eduard Janssens, Wim Janssens, Olivier Michel, Bernard Vandooren, Martti Antila, Jussara Fiterman, Carlos Fritscher, Jorge Hetzel, Jose Jardim, Waldo De Mattos, Rafael Martins, Maria Eunice De Oliveira, Andreia Pez, Maria Sales, Rafael Stelmach, Priscila Wolff, Svetla Andreeva, Reneta Antonova, Ana Dancheva, Yuliya Ivanova, Slavcho Ivanov, Hristo Metev, Iveta Naydenova, Tatyana Petkova, Galina Petrova, Kostadinka Sotirova, Mariyana Stoyanova, Rumen Tiholov, Iliyana Valkanova, Oleg Yakov, Rosa Feijoo, Juana Pavie, Patricia Schönffeldt, Absalon Silva, Victor Martinez, David Espinosa, Alejandro Londono, Dora Molina, Gonzalo Prada, Andrés Rico, Gregorio Sanchez Vallejo, Alvaro Urbina, Ana Vanegas, Maria Villegas, Josip Aralica, Gordana Stjepanovic, Vibeke Backer, Uffe Bødtger, Christian Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid Titlestad, Nathalie Bautin, Arnaud Bourdin, Pascal Chanez, Francis Couturaud, Antoine Cuvelier, Gilles Devouassoux, Pierre-Olivier Girodet, Jean-François Muir, Jean-Louis Pépin, Alain Proust, Azzedine Yaici, Yochai Adir, Gershon Fink, Zvi Fridlender, Gabriel Izbicki, Mordechai Kramer, Yehuda Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra Ramirez-Venegas, Paul Dawkins, Syed Hussain, Benedict Brockway, John Richmond, Colin Helm, Catherina Chang, Jørn Ahlqvist, Terje Tollåli, Tadeusz Tomala, Socorro Castro, William Chavez, Octavio Cubas, Rolando Estrella, Efrain Felix, Ronal Gamarra, Alfredo Guerreros, Alberto Matsuno, Danilo Salazar, Miguel Tsukayama, Albert Albay Jr, Teresita Aquino, Tito Atienza, Joven Roque Gonong, Ronnie Samoro, Joel Santiaguel, Beata Asankowicz-Bargiel, Ewa Pisarczyk-Bogacka, Renata Bijata-Bronisz, Marta Chełmińska, Małgorzata Dobryniewska, Anna Olech-Cudzik, Tomasz Fijołek, Krzysztof Filipek, Agata Kot, Bożena Kucińska, Krzysztof Lis, Elżbieta Rybicka-Liszewska, Marzenna Tarnowska-Matusiak, Robert Mróz, Piotr Napora, Wojciech Naumnik, Artur Niemiec, Władysław Pierzchała, Grzegorz Przybylski, Katarzyna Styka, Danuta Wrońska, Branislava Milenkovic, Dobrivoje Novkovic, Matijaz Flezar, Niksa Segota, Snezana Ulcar Kostic, Albert Klobucar, Leif Bjermer, Dan Curiac, Christer Janson, Pekka Koskinen, Bo Lundback, Åke Olsson, Shih-Lung Cheng, Ming-Lin Ho, Jeng-Yuan Hsu, Wu-Huei Hsu, Ping-Hung Kuo, Chin-Chou Wang, Yu-Feng Wei, Kuang-Yao Yang, Watchara Boonsawat, Somchai Chantarothorn, Warangkana Keeratichananont, Kittipong Maneechotesuwan, Kanok Pipatvech, Piamlarp Sangsayunh, Sibel Arinc, Sermin Borekci, Arzu Kaner Erturk, Filiz Kosar, Hakan Gunen, Ismail Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel Nayci, Serir Aktogu Ozkan, Abdullah Sayiner, Esra Uzaslan, Viktor Blazhko, Volodymyr Gavrysyuk, Olena Golub, Liudmyla Iashyna, Tetiana Ilashchuk, Volodymyr Koshlia, Olena Krakhmalova, Vitali Kryvenko, Lesia Kuryk, Olena Levchenko, Yuriy Mostovoy, Mykola Ostrovskyy, Tetyana Pertseva, Olena Piura, Nadiya Rudnytska, Ganna Stupnytska, Nataliia Velychko, Oleh Yakovenko, Lilia Rodriguez Ables, Roger Abrahams, Bassil Aish, Jose Alvarez, Fernando Arencibia, Chander Arora, Samir Arora, Francis Averill, Kwabena Ayesu, Stephen Basheda, Steven Bauer, Jose Bautista, Matthew Beacom, Richard Beasley, Hernando Bernal, Subodh Bhuchar, J'Cinda Bitters, John Burk, Elizabeth Burkett, James Cain, Robert Call, Christopher Chappel, Bartolome Celli, Tom Christensen, Jeremy Cole, Jerome Daniel, Nguyen Dang, Enrique Davis, Samuel Deleon, Robert DeLuca, Ernesto Diaz, Anthony DiMarco, Calvin Dixon, Ankur Doshi, Hugh Durrence, Alain Eid, John Elsen, Herbon Fleming, May Flores, Charles Fogarty, Scott Franczek, Stephen Fritz, Gregory Funk, Stuart Garay, Bernard Garcia, Luis Ramos Gonez, Gregory Gottschlich, Joseph Graif, Carl Griffin, Yamirka Duardo Guerra, David Headley, Mitzie Hewitt, Susan Hole, Robert Holladay, Ira Horowitz, Yu-Luen Hsu, Jonathan Ilowite, Stephen Jones, Ravindra Kashyap, Edward Kerwin, Ahtaram Khan, Nicole Kimzey, James Krainson, Flory Kreutter, Kannappan Krishnaswamy, Shahrukh Kureishy, Albert Lai, Alex Lechin, Daria Lee, Marcus Lee, Williams Leeds, Joseph Lillo, Edward Lisberg, Lawrence Madoff, Narendra Maheskwari, Mujibur Majumder, Sashi Makam, Douglas Mapel, Matthew Mardiney, Jennifer Martin, David Maybee, Isaac Melamed, Elvin Mendez, Stuart Millstone, Joseph Montes, Lee Morrow, Frank Murphy, Dany Obeid, France Occy, Godson Oguchi, Juan Ortiz, Francisco Padron, Ward Paine, James Pearle, Enrique Pelayo, Vandely Perez, David Pham, Carlos Piniella, Kevin Pritchett, Padmashri Rastogi, Stephen Ryan, Syed Rehman, Jackson Rhudy, Eustace Riley, James Riser, Clifford Risk, Emory Robinette, Christopher Roney, Gary Ruoff, David Russian, Mercedes Samson, Jay Sandberg, Jose Santiago, William Sargeant, Alan Schecter, Frank Sciurba, Jeffrey Scott, Ilia Segal, Sudhir Sehgal, Frederic Seifer, Sudhir Sekhsaria, Richard Sellman, Paul Shapero, Jeffrey Shea, Lawrence Sher, John Sibille, Jawed Siddiqui, William Sims, Toniya Singh, Deren Sinkowitz, Denise Smyth, Daniel Soteres, Daniel Sousa, Ralph Steele, Thomas Stern, Jose Suarez, Sever Surdulescu, Ricardo Tan, Tonny Tanus, Raymond Tidman, Aurelio Torres-Consuegra, Barry Troyan, John Updegrove, Sanjay Vadgama, Armando Pineda-Velez, Eduardo Viera, Andrew Wachtel, Ralph Wade, Jimin Wang, Dave Webster, Paul Weinberg, Terry Wells, Jeffrey White, Bram Wieskopf, Hugh Windom, Patrick Wright, David Wyatt, Bassam Yousef, Zahid Zafar, Chau Ngo, Huong Le, Lan Nguyen, Thanh Nguyen, Nhung Nguyen
Subjects: Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Anti-asthmatic Agent, law.invention, Pulmonary Disease, Chronic Obstructive, Leukocyte Count, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Medicine, Anti-Asthmatic Agents, 030212 general & internal medicine, Humanized, COPD Exacerbations, benralizumab, clinical trials, COPD, Subcutaneous, General Medicine, Middle Aged, anti–IL-5Rα, Benralizumab, Pulmonary Disease, Chronic Obstructive/drug therapy, [SDV] Life Sciences [q-bio], Female, Antibodies, Monoclonal, Humanized/administration & dosage, Chronic Obstructive, Benralizumab COPD exacerbations, Injections, Subcutaneous, Socio-culturale, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Eosinophils, Humans, Patient Acuity, Receptors, Interleukin-5, Antibodies, chronic obstructive pulmonary disease, Injections, Pulmonary Disease, 03 medical and health sciences, Phase III, Anti-Asthmatic Agents/administration & dosage, In patient, business.industry, Eosinophils/metabolism, medicine.disease, Clinical trial, Receptors, Interleukin-5/antagonists & inhibitors, chemistry, Multicenter study, randomized controlled trial, Immunology, Interleukin-5, business
Abstract: BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).
Published: 2019

15. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

Author: William W Busse, Eugene R Bleecker, J Mark FitzGerald, Gary T Ferguson, Peter Barker, Stephanie Sproule, Richard F Olsson, Ubaldo J Martin, Mitchell Goldman, Anahí Yañez, Marcelo Fernández, Alberto Tolcachier, Juan Belloni, Jorge Taborda, Maria De Salvo, Jorge Maspero, Carlos Victorio, Miguel Chirino Navarta, Monica Grilli, Pablo Rodríguez, María Otaola, Víctor Cambursano, Patricia Malamud, Ana Stok, German Arce, Osiris Roza, Fernando Scherbovsky, Pedro Elias, Maria Salazan Saez, Matthew Peters, Martin Phillips, John Upham, Peter Gibson, Francis Thien, Jo Douglass, Paul Thomas, Philip Bardin, Dimitar Sajkov, Mark Hew, David Langton, Andreia Pez, Carlos Fritscher, Jorge Hetzel, Waldo Mattos, Rafael Stelmach, Martti Antila, Ana Luisa Fernandes, Hristo Metev, Yavor Ivanov, Aneliya Bogdanova, Ana Dancheva Markova, Marinka Peneva, Rumyana Veselinova, Tatyana Petkova, Vanushka Petrova, Elena Shopova, Yuliya Ivanova, Rumyana Yotsova, Ginka Kirkova, Galina Petrova, Svetoslav Dachev, Kostadinka Sotirova, Mariyana Stoyanova, Oleg Yakov, Vanya Ilieva-Fartunova, Catherine Lemiere, Michel Laviolette, William Yang, Bonavuth Pek, William Patrick Killorn, Claude Poirier, Guy Chouinard, Lyle Melenka, Richard Leigh, Parameswaran Nair, Delbert Dorscheid, James Martin, Juana Pavie, Andres Rosenblut, Claudia Cartagena, Carlos Quilodran, Silvia Muñoz, Ivana Malkusova, Josef Veverka, Stanislav Holub, Jaroslav Mares, Radovan Kozel, Daniela Kopecka, Vladimir Zindr, Pavel Cerva, Pascal Chanez, Arnaud Bourdin, Gilles Devouassoux, Camille Taille, Frédéric De Blay, Francois Goupil, Christophe Leroyer, Delphine Gourcerol, Toufik Didi, Alain Didier, Gilles Garcia, Philippe Bonniaud, Riazate Rossanaly Vasram, Marek Lommatzsch, Ulf Harnest, Anneliese Linnhoff, Claus Keller, Gerhard Hoheisel, Karin Förster, Thomas Schultz, Isabelle Schenkenberger, Joachim Kirschner, Tibor Schmoller, Stefan Zielen, Marc Kornmann, Ekkehard Beck, Lutz Volgmann, Rolf Dichmann, Axel Overlack, Jörg Winkler, Petra Mikloweit, Sabine Ballenberger, Mathias Rolke, Stephanie Korn, Helmut Pabel, Martin Hoffmann, Jan Feimer, Klaus Rabe, Regina Deckelmann, Tobias Welte, Hiroyuki Ohbayashi, Soichiro Hozawa, Terufumi Shimoda, Makoto Yoshida, Toshikazu Nagakura, Tadashi Kamei, Yasuyuki Sano, Shinichiro Kagami, Hisaho Takahashi, Michiko Haida, Goro Kimura, Hiroyuki Nakamura, Yasuo To, Masaharu Shinkai, Tadasuke Shimokawaji, Makoto Kudo, Noriharu Shijyubo, Takao Tochigi, Motokazu Kato, Akihiko Tanaka, Yasuhiro Gon, Norihisa Sasaki, Tetsuro Ohdaira, Chiharu Omori, Toshiki Takahashi, Satomi Takeuchi, Kiyotaka Nakajima, Hironi Makita, Masahiro Kaneko, Kenjiro Furuta, Masami Taniguchi, Yoshito Inobe, Hiroshi Miki, Yoichi Nakamura, Naoki Miyazawa, Shuichi Yano, Masayuki Iijima, Tsuyoshi Yamato, Javier Diaz, Alberto Matsuno, Efrain Felix, Alfredo Guerreros, Alejandro Daly, Fernando Rodriguez Chariarse, Danilo Salazar, Socorro Castro, William Chavez, Rolando Estrella, Teresita Aquino, Tito Atienza, Ronnie Samoro, Marie Grace Dawn Isidro, Piotr Kuna, Adam Antczak, Michał Bednarek, Danuta Mądra-Rogacka, Teresa Hofman, Marek Jutel, Ewa Pisarczyk-Bogacka, Agata Kot, Robert Mróz, Małgorzata Czupryńska-Borkowska, Małgorzata Żurowska-Gębala, Andrzej Dyczek, Grażyna Jasieniak-Pinis, Piotr Wojnowski, Ewa Trębas-Pietraś, Małgorzata Dobryniewska, Marcin Stobiecki, Marzenna Tarnowska-Matusiak, Alina Magner, Andrzej Kolczyński, Tomasz Kachel, Zbigniew Bartuzi, Bernadetta Majorek-Olechowska, Paweł Śliwiński, Violetta Balicka, Elżbieta Hajoł, Jacek Stachera, Marta Rachel, Marek Michnar, Jarosław Tałałaj, Ewa Springer, Piotr Napora, Tomasz Grzelewski, Renata Bijata-Bronisz, Anna Świderska, Grzegorz Mincewicz, Zbigniew Sankowski, Tomasz Fijołek, Artur Kwaśniewski, Joanna Jerzyńska, Jerzy Cygler, Ryszard Olesiejuk, Iwona Von Steiner, Wojciech Machowiak, Krzysztof Filipek, Piotr Piskorz, Ewa Uhryn, Marita Nittner-Marszalska, Elżbieta Rybicka-Liszewska, Anna Bodzenta-Łukaszyk, Marta Chełmińska, Izabella Krupa-Borek, Wojciech Skucha, Anna Płoszczuk, Traian Mihaescu, Ioan Dorin Petrui, Angelica Savu, Ghiulten Apti, Claudia Toma, Ana Trailescu, Sergei Sokurenko, Vasiliy Trofimov, Igor Leshchenko, Natalia Shaporova, Inna Ilyashevich, Irina Stitsenko, Alexander Vizel, Yulia Ilkovich, Dmitrii Tikhanov, Svetlana Goncharova, Andrey Ezhov, Galina Ignatova, Nadezhda Izmozherova, Nadezhda Berdnikova, Ludmila Goryachkina, Veronika Popova, Laura Bolieva, Andrey Rebrov, Vladimir Nosov, Olga Magnitskaya, Sergey Nedogoda, Vladimir Abrosimov, Artem Molotkov, Galina Reshedko, Mikhail Smirnov, Marina Osipenko, Elena Pavlysh, Svetlana Myasoedova, Liudmila Lenskaya, Valery Chistyakov, Elena Vishneva, Liliya Uon, Anna Zateyschikova, Svetlana Laleko, Tatiana Pak, Axel Bruning, Visvakuren Naidoo, Jeevren Reddy, Richard Van Zyl Smit, Hae-Sim Park, Young Joo Cho, Sang-Heon Cho, Sang Haak Lee, Byung Jae Lee, Ju Sang Kim, You Sook Cho, Choon-Sik Park, Mi-Kyeong Kim, Young-Il Koh, Joo-Hee Kim, Sook Young Lee, Sang Pyo Lee, Jung Won Park, Kwang Ha Yoo, Hyoungkyu Yoon, Jaechun Lee, Gyu-Young Hur, Soo Keol Lee, HeeKyoo Kim, David Ramos Barbón, Elena Laffond Yges, Eva Martínez Moragón, Miguel Arias Guillen, Alberto Saura Vinuesa, Fernando Sánchez-Toril López, José Luis Velasco Garrido, Borja García-Cosio Piqueras, Luis Pérez de Llano, Antonio Luis Valero Santiago, Myriam Calle Rubio, Leif Bjermer, Bo Lundbäck, Bilun Gemicioglu, Sevim Bavbek, Dane Ediger, Munevver Erdinc, Ismail Hanta, Sibel Nayci, Sibel Arinc, Liudmyla Iashyna, Yuriy Mostovoy, Mykola Ostrovskyy, Lesia Kuryk, Ivan Lemko, Tetyana Ospanova, Liubov Moskalenko, Oleksii Korzh, Viktor Blazhko, Olena Krakhmalova, Liliia Romaniuk, Yevgeniya Dytyatkovs'ka, Oleh Yakovenko, Volodymyr Gavrysyuk, Hassan Burhan, Dinesh Saralaya, Stephen Scott, Alyn Morice, Ewart Jackson-Voyzey, Thida Win, Shuab Nasser, Richard Harrison, Rekha Chaudhuri, Monica Nordstrom, Pradip De, Matthew Masoli, Adel Mansur, Anthony Gunstone, Robert Niven, Timothy Harrison, Suresh Babu, Subodh Bhuchar, Shahrukh Kureishy, John Zwetchkenbaum, Lawrence Kaplan, Eugene Bleecker, Santiago Reyes, Faisal Fakih, Marvin Heuer, Ryan Klein, Michael Marcus, Iftikhar Hussain, Tonny Tanus, Hengameh Raissy, Sady Alpizar, Hector Rodriguez, Gerald Gleich, Tracy Bridges, Joe Pouzar, Gary Steven, Jonathan Matz, Shana Krstevska, Dama Ziworitin, Adolfo Kaplan, James Sublett, James DeAngelo, Amy Darter, John Agaiby, John Hagan, Enrique Davis, Dareen Siri, Charlene Mcevoy, Chrisette Dharma, Najmuddin Karimjee, Steven Kelsen, Manuel Frade, Amy Silverthorn, Joel Kline, Francis Averill, Jose Ruiz, Emory Robinette, Zeeshan Shaikh, Carlos Aguilar, William Nish, German Alvarez, Younus Ismail, Purvi Parikh, Mila Leong, Dennis Murphy, Francisco Garcia, Alan Goldsobel, Antonio Blanco, Edward Campbell, Guido Perez, Geoffrey Chupp, Toby Bates, Vandely Perez, Sally Wenzel, Kartik Shenoy, Rohit Katial, David Bernstein, Neil Parikh, William Sims, Gary Ferguson, David Pham, Anu George, Richard Beasley, Gilberto Perez, Robert Garver, Miriam Garcia-Portela, Stephen Wong, Weily Soong, Richard Guillot, Golda Hudes, Ahmed Arif, Josefa Binker, Manuel Villareal, Ulrike Ziegner, Joseph Ojile, Sanjeev Goswami, Carlos Piniella, Ilia Segal, Heidi Zafra, Mitchell Lee, Martha Tarpay, John Panuto, Rajan Merchant, Peter Springsteen, Timothy Scialla, Paul Shapero, Karen Allen, Mark Moss, Humberto Cruz, Jeffrey Rumbyrt, Amy Boyd, Robert Nathan, Jonathan Bernstein, Joshua Jacobs, Elliot Ginchansky, Janice Johnston, Barbara Baxter, Thomas Johnson II, Stephen Apaliski, Clinton Corder, David Fuentes, Joseph Diaz, Chau Ngo, Lan Le, Department of Medicine, University of Wisconsin-Madison-School of Medicine and Public Health, Fundación Cidea Allergy and Respiratory Research Unit, University of Oxford [Oxford], University of Newcastle, Newcastle, NSW Australia., Defence Science and Technology Laboratory (Dstl), Ministry of Defence (UK) (MOD), Organização Multinacional de Formação, Agence Universitaire de la Francophonie (AUF), University of Calgary, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), laboratoire du sommeil, CHU Grenoble, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Centre Hospitalier du Mans, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Service de pneumologie, Centre hospitalier de la région d'Annecy, Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-IFR13-Institut National de la Santé et de la Recherche Médicale (INSERM), J.W. Goethe Universität, Institut für Geowissenschaften, Altenhöferallee 1, D-60438 Frankfurt am Main, Germany, Department of Pulmonary Medicine, Leiden University Medical Center (LUMC), Hannover Medical School [Hannover] (MHH), Japan Energy Corporation, Medical University of Łódź (MUL), Wroclaw Medical University, Saint-Petersburg State University, Physical Department, Petrodvoretz, 194508 St.-Petersburg, Russia, Physical Department (PD), St Petersburg State University (SPbU)-St Petersburg State University (SPbU), Ankara University, Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC, Department of Earth Sciences, University of Cambridge, University of Cambridge [UK] (CAM), Center for Genomics and Personalized Medicine, Wake Forest University, Mayo Clinic [Rochester], Department of Wildlife Management, Pir Mehr Ali Shah Arid Agriculture University, Lab Biotecnol Bacteriana, Inst Ciencia & Tecnol Alimentos & Nutr ICTAN, Universidade da Coruña, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre recherche en CardioVasculaire et Nutrition (C2VN), Université de Brest (UBO), University of Oxford, University of Newcastle [Callaghan, Australia] (UoN), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Universiteit Leiden-Universiteit Leiden, Wrocław Medical University, Department of Earth Sciences [University of Cambridge], and Pir Mehr Ali Shah Arid Agriculture University = PMAS-Arid Agriculture University Rawalpindi (AAUR)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Antibodies, Monoclonal, Humanized, Placebo, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Time, law.invention, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Clinical endpoint, Humans, Medicine, Anti-Asthmatic Agents, 030212 general & internal medicine, Child, Adverse effect, ComputingMilieux_MISCELLANEOUS, Aged, Asthma, business.industry, Middle Aged, medicine.disease, Benralizumab, 3. Good health, Clinical trial, Treatment Outcome, 030228 respiratory system, Tolerability, chemistry, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma.We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12-17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542).Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14-16%) and worsening asthma (7-10%). The most common serious adverse events were worsening asthma (3-4%), pneumonia (1% to 1%), and pneumonia caused by bacterial infection (0-1%). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71-75%; benralizumab group only) and BORA (65-71%), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2% in SIROCCO and CALIMA vs 2-3% in BORA).The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year.AstraZeneca and Kyowa Hakko Kirin.
Published: 2019

16. Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci

Author: Michelle Daya, Nicholas Rafaels, Sameer Chavan, Henry Richard Johnston, Aniket Shetty, Christopher R. Gignoux, Meher Preethi Boorgula, Monica Campbell, Pissamai Maul, Trevor Maul, Candelaria Vergara, Albert M. Levin, Genevieve Wojcik, Dara G. Torgerson, Victor E. Ortega, Ayo Doumatey, Maria Ilma Araujo, Pedro C. Avila, Eugene Bleecker, Carlos Bustamante, Luis Caraballo, Georgia M. Dunston, Mezbah U. Faruque, Trevor S. Ferguson, Camila Figueiredo, Jean G. Ford, Pierre-Antoine Gourraud, Nadia N. Hansel, Ryan D. Hernandez, Edwin Francisco Herrera-Paz, Eimear E. Kenny, Jennifer Knight-Madden, Rajesh Kumar, Lesli A. Lange, Ethan M. Lange, Antoine Lizee, Alvaro Mayorga, Deborah Meyers, Dan L. Nicolae, Timothy D. O’Connor, Ricardo Riccio Oliveira, Christopher O. Olopade, Olufunmilayo Olopade, Zhaohui S. Qin, Charles Rotimi, Harold Watson, Rainford J. Wilks, L. Keoki Williams, James G. Wilson, Carole Ober, Esteban G. Burchard, Terri H. Beaty, Margaret A. Taub, Ingo Ruczinski, Rasika Ann Mathias, Kathleen C. Barnes, Ayola Akim Adegnika, Ganiyu Arinola, Ulysse Ateba-Ngoa, Gerardo Ayestas, Adolfo Correa, Francisco M. De La Vega, Celeste Eng, Said Omar Leiva Erazo, Marilyn G. Foreman, Cassandra Foster, Li Gao, Jingjing Gao, Kimberly Gietzen, Leslie Grammer, Linda Gutierrez, Mark Hansen, Tina Hartert, Yijuan Hu, Kwang-Youn A. Kim, Pamela Landaverde-Torres, Javier Marrugo, Beatriz Martinez, Rosella Martinez, Luis F. Mayorga, Delmy-Aracely Mejia-Mejia, Catherine Meza, Solomon Musani, Shaila Musharoff, Oluwafemi Oluwole, Maria Pino-Yanes, Hector Ramos, Allan Saenz, Steven Salzberg, Maureen Samms-Vaughan, Robert Schleimer, Alan F. Scott, Suyash S. Shringarpure, Wei Song, Zachary A. Szpiech, Raul Torres, Gloria Varela, Olga Marina Vasquez, Lorraine B. Ware, and Maria Yazdanbakhsh
Subjects: Genetics, Genotype, medicine, Chromosome, SNP, Genetic admixture, Single-nucleotide polymorphism, Genome-wide association study, Allele, Biology, medicine.disease, Asthma
Abstract: BACKGROUNDAsthma is a complex disease with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. One of the main goals of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to discover genes conferring risk to asthma in populations of African descent.METHODSWe performed a genome-wide meta-analysis of asthma across 11 CAAPA datasets (4,827 asthma cases and 5,397 controls), genotyped on the African Diaspora Power Chip (ADPC) and including existing GWAS array data. The genotype data were imputed up to a whole genome sequence reference panel from n=880 African ancestry individuals for a total of 61,904,576 SNPs. Statistical models appropriate to each study design were used to test for association, and results were combined using the weighted Z-score method. We also used admixture mapping as a complementary approach to identify loci involved in asthma pathogenesis in subjects of African ancestry.RESULTSSNPs rs787160 and rs17834780 on chromosome 2q22.3 were significantly associated with asthma (p=6.57 × 10−9 and 2.97 × 10−8, respectively). These SNPs lie in the intergenic region between the Rho GTPase Activating Protein 15 (ARHGAP15) and Glycosyltransferase Like Domain Containing 1 (GTDC1) genes. Four low frequency variants on chromosome 1q21.3, which may be involved in the “atopic march” and which are not polymorphic in Europeans, also showed evidence for association with asthma (1.18 ×10−6 ≤ p ≤ 3.06 ×10−6). SNP rs11264909 on chromosome 1q23.1, close to a region previously identified by the EVE asthma meta-analysis as having a putative African ancestry specific effect, only showed differences in counts in subjects homozygous for alleles of African ancestry. Admixture mapping also identified a significantly associated region on chromosome 6q23.2, which includes the Transcription Factor 21 (TCF21) gene, previously shown to be differentially expressed in bronchial tissues of asthmatics and non-asthmatics.CONCLUSIONSWe have identified a number of novel asthma association signals warranting further investigation.
Published: 2017
Full Text: View/download PDF

17. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Gary T Ferguson, J Mark FitzGerald, Eugene R Bleecker, Michel Laviolette, David Bernstein, Craig LaForce, Lyndon Mansfield, Peter Barker, Yanping Wu, Maria Jison, Mitchell Goldman, Guy Chouinard, Maryam Rostami, Jean Oosthuizen, Bonavuth Pek, Deepen Patel, Pierre-Alain Houle, Sohail Khattak, Patrick Killorn, Claus Keller, Isabelle Schenkenberger, Stefan Zielen, Sabine Ballenberger, Martin Hoffmann, Joachim Kirschner, Márta Papp, Teréz Kecskés, Magdolna Póczi, Lajos Molnár, Éva Radeczky, Judit Schlezák, Ewa Springer, Violetta Balicka, Jadwiga Kaczmarek, Danuta Madra-Rogacka, Ewa Pisarczyk-Bogacka, Malgorzata Zurowska-Gebala, Maciej Marczak, Piotr Napora, Witold Pomiecko, Erika Pribulova, Svetlana Kurthova, Maria Drugdova, Denisa Kavkova, Luboslava Frajtova, Alexander Golubov, Dagmar Paulinyova, Daniela Hasicova, Miriam Michalickova, Miguel Trevino, Charles Campbell, Andrew Wachtel, Eugene Bleecker, Selwyn Spangenthal, Edward Kerwin, Paul Ratner, Samir Arora, Gregory Feldman, Benedict Okwara, Humberto Cruz, Lawrence Sher, Andrew Pedinoff, and Clinton Corder
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, Injections, Subcutaneous, Population, Placebo, Antibodies, Monoclonal, Humanized, Severity of Illness Index, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Forced Expiratory Volume, Severity of illness, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Anti-Asthmatic Agents, Pulmonary Eosinophilia, education, Asthma, Aged, education.field_of_study, Biological Products, Intention-to-treat analysis, Dose-Response Relationship, Drug, business.industry, Middle Aged, Benralizumab, medicine.disease, Bronchodilator Agents, 030228 respiratory system, chemistry, Chronic Disease, Disease Progression, Female, business
Abstract: Summary Background Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma. Methods In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18–75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV 1 ) of at least 12% at screening, from 52 clinical research centres in six countries. Patients must have been receiving either low- to medium-dosage inhaled corticosteroids (ICS) or low-dosage ICS plus long-acting β 2 agonist fixed-combination therapy at screening, had a morning prebronchodilator FEV 1 of more than 50% to 90% predicted at screening, and had one or more of the following symptoms within the 7 days before randomisation: a daytime or night-time asthma symptom score of at least 1 for at least 2 days, rescue short-acting β 2 agonist use for at least 2 days, or night-time awakenings due to asthma for at least one night. We converted patients' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients' respective countries and randomly allocated them (1:1; stratified by blood eosinophil count [ vs ≥300 cells per μL] and region [USA vs the rest of the world]) with an interactive web-based voice response system to receive subcutaneous placebo or benralizumab 30 mg injections every 4 weeks for 12 weeks. All patients and investigators involved in patient treatment or clinical assessment and those assessing outcomes were masked to treatment allocation. The primary endpoint was change from baseline prebronchodilator FEV 1 at week 12. Efficacy analyses used an intention to treat approach. This trial is registered with ClinicalTrials.gov, number NCT02322775. Findings Between Feb 2, 2015, and April 24, 2015, we enrolled 351 patients, with 211 (60%) randomly assigned (105 [50%] to placebo and 106 [50%] to benralizumab). Benralizumab resulted in an 80 mL (95% CI 0–150; p=0·04) greater improvement (least-squares mean difference) in prebronchodilator FEV 1 after 12 weeks than did placebo (placebo group: 2246 mL [SD 768] at baseline vs 2261 mL [796] at week 12, change from baseline of 0 mL; benralizumab group: 2248 mL [606] vs 2310 mL [670], 70 mL). 44 (42%) patients in the benralizumab group had adverse events compared with 49 (47%) in the placebo group. The most common adverse events for both groups were nasopharyngitis (eight [8%] patients in each group) and upper respiratory tract infections (five [5%] patients in each group). Serious adverse events occurred in two (2%) patients each in the benralizumab (pancytopenia and a suicide attempt, both considered unrelated to treatment) and placebo (cervix carcinoma and colon adenoma) groups. Interpretation This study suggests that active and modifiable disease processes might be ongoing in patients with mild to moderate, persistent asthma receiving ICS. Although the lung function improvement observed does not warrant use of benralizumab in this population because it did not reach the minimum clinically important difference of 10%, further studies to assess this finding should be considered. Funding AstraZeneca.
Published: 2016

18. Effect of β2-adrenergic receptor polymorphism on response to longacting β2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial

Author: Michael E, Wechsler, Susan J, Kunselman, Vernon M, Chinchilli, Eugene, Bleecker, Homer A, Boushey, William J, Calhoun, Bill T, Ameredes, Mario, Castro, Timothy J, Craig, Loren, Denlinger, John V, Fahy, Nizar, Jarjour, Shamsah, Kazani, Sophia, Kim, Monica, Kraft, Stephen C, Lazarus, Robert F, Lemanske, Amy, Markezich, Richard J, Martin, Perdita, Permaul, Stephen P, Peters, Joe, Ramsdell, Christine A, Sorkness, E Rand, Sutherland, Stanley J, Szefler, Michael J, Walter, Stephen I, Wasserman, Elliot, Israel, and Cheryl, Wilmoth
Subjects: Adult, Male, Agonist, medicine.medical_specialty, Genotype, medicine.drug_class, Peak Expiratory Flow Rate, Placebo, Gastroenterology, Double-Blind Method, Internal medicine, Administration, Inhalation, medicine, Humans, Albuterol, Glucocorticoids, Salmeterol Xinafoate, Asthma, Cross-Over Studies, Polymorphism, Genetic, Intention-to-treat analysis, business.industry, Beclomethasone, General Medicine, Adrenergic beta-Agonists, Middle Aged, medicine.disease, Crossover study, respiratory tract diseases, Treatment Outcome, Anesthesia, Corticosteroid, Female, Methacholine, Receptors, Adrenergic, beta-2, Salmeterol, business, medicine.drug
Abstract: Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid.In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting beta2 agonist (salmeterol 50 microg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 microg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00200967.After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21.4 L/min (95% CI 11.8-31.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p0.0001). In Gly/Gly participants, morning PEF was 21.5 L/min (11.0-32.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p0.0001). The improvement in PEF did not differ between genotypes (difference [Arg/Arg-Gly/Gly] -0.1, -14.4 to 14.2; p=0.99). In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a prespecified secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p0.0001). Responsiveness to methacholine did not differ between salmeterol and placebo in Arg/Arg participants (p=0.87). The 2.5 times higher genotype-specific difference in responsiveness to methacholine was significant (1.32 doubling dose difference between genotypes, 0.43-2.21, p=0.0038). Seven Arg/Arg participants (placebo, n=5; salmeterol, n=2) and six Gly/Gly participants (placebo, n=3; salmeterol, n=3) had an asthma exacerbation. Five serious adverse events were reported, one each during the pre-match and run-in phases on open-label inhaled corticosteroid, two during double-blind treatment with salmeterol/inhaled corticosteroid, and one during double-blind treatment with placebo/inhaled corticosteroid. None of the serious events was asthma-related or related to study drugs or procedures.In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. These findings suggest that patients should continue to be treated with longacting beta2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. Further investigation is needed to establish the importance of the genotype-specific difference in responsiveness to methacholine.National Institutes of Health.
Published: 2009

19. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

Author: Leslie A. Lange, Youna Hu, He Zhang, Chenyi Xue, Ellen M. Schmidt, Zheng-Zheng Tang, Chris Bizon, Ethan M. Lange, Joshua D. Smith, Emily H. Turner, Goo Jun, Hyun Min Kang, Gina Peloso, Paul Auer, Kuo-ping Li, Jason Flannick, Ji Zhang, Christian Fuchsberger, Kyle Gaulton, Cecilia Lindgren, Adam Locke, Alisa Manning, Xueling Sim, Manuel A. Rivas, Oddgeir L. Holmen, Omri Gottesman, Yingchang Lu, Douglas Ruderfer, Eli A. Stahl, Qing Duan, Yun Li, Peter Durda, Shuo Jiao, Aaron Isaacs, Albert Hofman, Joshua C. Bis, Adolfo Correa, Michael E. Griswold, Johanna Jakobsdottir, Albert V. Smith, Pamela J. Schreiner, Mary F. Feitosa, Qunyuan Zhang, Jennifer E. Huffman, Jacy Crosby, Christina L. Wassel, Ron Do, Nora Franceschini, Lisa W. Martin, Jennifer G. Robinson, Themistocles L. Assimes, David R. Crosslin, Elisabeth A. Rosenthal, Michael Tsai, Mark J. Rieder, Deborah N. Farlow, Aaron R. Folsom, Thomas Lumley, Ervin R. Fox, Christopher S. Carlson, Ulrike Peters, Rebecca D. Jackson, Cornelia M. van Duijn, André G. Uitterlinden, Daniel Levy, Jerome I. Rotter, Herman A. Taylor, Vilmundur Gudnason, David S. Siscovick, Myriam Fornage, Ingrid B. Borecki, Caroline Hayward, Igor Rudan, Y. Eugene Chen, Erwin P. Bottinger, Ruth J.F. Loos, Pål Sætrom, Kristian Hveem, Michael Boehnke, Leif Groop, Mark McCarthy, Thomas Meitinger, Christie M. Ballantyne, Stacey B. Gabriel, Christopher J. O’Donnell, Wendy S. Post, Kari E. North, Alexander P. Reiner, Eric Boerwinkle, Bruce M. Psaty, David Altshuler, Sekar Kathiresan, Dan-Yu Lin, Gail P. Jarvik, L. Adrienne Cupples, Charles Kooperberg, James G. Wilson, Deborah A. Nickerson, Goncalo R. Abecasis, Stephen S. Rich, Russell P. Tracy, Cristen J. Willer, David M. Altshuler, Gonçalo R. Abecasis, Hooman Allayee, Sharon Cresci, Mark J. Daly, Paul I.W. de Bakker, Mark A. DePristo, Peter Donnelly, Tim Fennell, Kiran Garimella, Stanley L. Hazen, Daniel M. Jordan, Adam Kiezun, Guillaume Lettre, Bingshan Li, Mingyao Li, Christopher H. Newton-Cheh, Sandosh Padmanabhan, Sara Pulit, Daniel J. Rader, David Reich, Muredach P. Reilly, Steve Schwartz, Laura Scott, John A. Spertus, Nathaniel O. Stitziel, Nina Stoletzki, Shamil R. Sunyaev, Benjamin F. Voight, Ermeg Akylbekova, Larry D. Atwood, Maja Barbalic, R. Graham Barr, Emelia J. Benjamin, Joshua Bis, Donald W. Bowden, Jennifer Brody, Matthew Budoff, Greg Burke, Sarah Buxbaum, Jeff Carr, Donna T. Chen, Ida Y. Chen, Wei-Min Chen, Pat Concannon, Ralph D’Agostino, Anita L. DeStefano, Albert Dreisbach, Josée Dupuis, J. Peter Durda, Jaclyn Ellis, Caroline S. Fox, Ervin Fox, Vincent Funari, Santhi K. Ganesh, Julius Gardin, David Goff, Ora Gordon, Wayne Grody, Myron Gross, Xiuqing Guo, Ira M. Hall, Nancy L. Heard-Costa, Susan R. Heckbert, Nicholas Heintz, David M. Herrington, DeMarc Hickson, Jie Huang, Shih-Jen Hwang, David R. Jacobs, Nancy S. Jenny, Andrew D. Johnson, Craig W. Johnson, Steven Kawut, Richard Kronmal, Raluca Kurz, Martin G. Larson, Mark Lawson, Cora E. Lewis, Dalin Li, Honghuang Lin, Chunyu Liu, Jiankang Liu, Kiang Liu, Xiaoming Liu, Yongmei Liu, William T. Longstreth, Cay Loria, Kathryn Lunetta, Aaron J. Mackey, Rachel Mackey, Ani Manichaikul, Taylor Maxwell, Barbara McKnight, James B. Meigs, Alanna C. Morrison, Solomon K. Musani, Josyf C. Mychaleckyj, Jennifer A. Nettleton, Kari North, Daniel O’Leary, Frank Ong, Walter Palmas, James S. Pankow, Nathan D. Pankratz, Shom Paul, Marco Perez, Sharina D. Person, Joseph Polak, Aaron R. Quinlan, Leslie J. Raffel, Vasan S. Ramachandran, Kenneth Rice, Jill P. Sanders, Pamela Schreiner, Sudha Seshadri, Steve Shea, Stephen Sidney, Kevin Silverstein, Nicholas L. Smith, Nona Sotoodehnia, Asoke Srinivasan, Kent Taylor, Fridtjof Thomas, Michael Y. Tsai, Kelly A. Volcik, Chrstina L. Wassel, Karol Watson, Gina Wei, Wendy White, Kerri L. Wiggins, Jemma B. Wilk, O. Dale Williams, Gregory Wilson, Phillip Wolf, Neil A. Zakai, John Hardy, James F. Meschia, Michael Nalls, Andrew Singleton, Brad Worrall, Michael J. Bamshad, Kathleen C. Barnes, Ibrahim Abdulhamid, Frank Accurso, Ran Anbar, Terri Beaty, Abigail Bigham, Phillip Black, Eugene Bleecker, Kati Buckingham, Anne Marie Cairns, Daniel Caplan, Barbara Chatfield, Aaron Chidekel, Michael Cho, David C. Christiani, James D. Crapo, Julia Crouch, Denise Daley, Anthony Dang, Hong Dang, Alicia De Paula, Joan DeCelie-Germana, Allen DozorMitch Drumm, Maynard Dyson, Julia Emerson, Mary J. Emond, Thomas Ferkol, Robert Fink, Cassandra Foster, Deborah Froh, Li Gao, William Gershan, Ronald L. Gibson, Elizabeth Godwin, Magdalen Gondor, Hector Gutierrez, Nadia N. Hansel, Paul M. Hassoun, Peter Hiatt, John E. Hokanson, Michelle Howenstine, Laura K. Hummer, Jamshed Kanga, Yoonhee Kim, Michael R. Knowles, Michael Konstan, Thomas Lahiri, Nan Laird, Christoph Lange, Lin Lin, Xihong Lin, Tin L. Louie, David Lynch, Barry Make, Thomas R. Martin, Steve C. Mathai, Rasika A. Mathias, John McNamara, Sharon McNamara, Deborah Meyers, Susan Millard, Peter Mogayzel, Richard Moss, Tanda Murray, Dennis Nielson, Blakeslee Noyes, Wanda O’Neal, David Orenstein, Brian O’Sullivan, Rhonda Pace, Peter Pare, H. Worth Parker, Mary Ann Passero, Elizabeth Perkett, Adrienne Prestridge, Nicholas M. Rafaels, Bonnie Ramsey, Elizabeth Regan, Clement Ren, George Retsch-Bogart, Michael Rock, Antony Rosen, Margaret Rosenfeld, Ingo Ruczinski, Andrew Sanford, David Schaeffer, Cindy Sell, Daniel Sheehan, Edwin K. Silverman, Don Sin, Terry Spencer, Jackie Stonebraker, Holly K. Tabor, Laurie Varlotta, Candelaria I. Vergara, Robert Weiss, Fred Wigley, Robert A. Wise, Fred A. Wright, Mark M. Wurfel, Robert Zanni, Fei Zou, Phil Green, Jay Shendure, Joshua M. Akey, Carlos D. Bustamante, Evan E. Eichler, P. Keolu Fox, Wenqing Fu, Adam Gordon, Simon Gravel, Jill M. Johnsen, Mengyuan Kan, Eimear E. Kenny, Jeffrey M. Kidd, Fremiet Lara-Garduno, Suzanne M. Leal, Dajiang J. Liu, Sean McGee, Timothy D. O’Connor, Bryan Paeper, Peggy D. Robertson, Jeffrey C. Staples, Jacob A. Tennessen, Gao Wang, Qian Yi, Rebecca Jackson, Garnet Anderson, Hoda Anton-Culver, Paul L. Auer, Shirley Beresford, Henry Black, Robert Brunner, Robert Brzyski, Dale Burwen, Bette Caan, Cara L. Carty, Rowan Chlebowski, Steven Cummings, J. David Curb, Charles B. Eaton, Leslie Ford, Stephanie M. Fullerton, Margery Gass, Nancy Geller, Gerardo Heiss, Barbara V. Howard, Li Hsu, Carolyn M. Hutter, John Ioannidis, Karen C. Johnson, Lewis Kuller, Andrea LaCroix, Kamakshi Lakshminarayan, Dorothy Lane, Norman Lasser, Erin LeBlanc, Kuo-Ping Li, Marian Limacher, Benjamin A. Logsdon, Shari Ludlam, JoAnn E. Manson, Karen Margolis, Lisa Martin, Joan McGowan, Keri L. Monda, Jane Morley Kotchen, Lauren Nathan, Judith Ockene, Mary Jo O’Sullivan, Lawrence S. Phillips, Ross L. Prentice, John Robbins, Jacques E. Rossouw, Haleh Sangi-Haghpeykar, Gloria E. Sarto, Sally Shumaker, Michael S. Simon, Marcia L. Stefanick, Evan Stein, Hua Tang, Kira C. Taylor, Cynthia A. Thomson, Timothy A. Thornton, Linda Van Horn, Mara Vitolins, Jean Wactawski-Wende, Robert Wallace, Sylvia Wassertheil-Smoller, Donglin Zeng, Deborah Applebaum-Bowden, Michael Feolo, Weiniu Gan, Dina N. Paltoo, Phyliss Sholinsky, Anne Sturcke, Epidemiology, and Internal Medicine
Subjects: Male, Genome-wide association study, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Gene Frequency, Receptors, Genotype, Dyslipidemias/blood, Receptors, LDL/genetics, Genetics(clinical), Exome, Genetics (clinical), Exome sequencing, Genetics, 0303 health sciences, Serine Endopeptidases, Single Nucleotide, Middle Aged, 3. Good health, Cholesterol, Phenotype, Genetic Code, Cholesterol, LDL/genetics, Female, lipids (amino acids, peptides, and proteins), Proprotein Convertases, Proprotein Convertase 9, Sequence Analysis, Adult, Apolipoproteins E/blood, LDL/genetics, Serine Endopeptidases/genetics, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Apolipoproteins E, SDG 3 - Good Health and Well-being, Humans, Polymorphism, Allele frequency, 030304 developmental biology, Genetic association, Aged, Dyslipidemias, PCSK9, DNA, Cholesterol, LDL, Lipase, Sequence Analysis, DNA, Receptors, LDL, Lipase/genetics, Proprotein Convertases/genetics, Follow-Up Studies, Genome-Wide Association Study
Abstract: Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or
Published: 2014

20. Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS)

Author: David, Couper, Lisa M, LaVange, MeiLan, Han, R Graham, Barr, Eugene, Bleecker, Eric A, Hoffman, Richard, Kanner, Eric, Kleerup, Fernando J, Martinez, Prescott G, Woodruff, Stephen, Rennard, and Fred A, Wright
Subjects: Adult, Aged, 80 and over, Male, Disease Management, Middle Aged, Prognosis, Article, respiratory tract diseases, Pulmonary Disease, Chronic Obstructive, Spirometry, Surveys and Questionnaires, Humans, Female, Prospective Studies, Tomography, X-Ray Computed, Biomarkers, Aged, Follow-Up Studies
Abstract: SPIROMICS is a multi-center observational study of chronic obstructive pulmonary disease (COPD) designed to guide future development of therapies for COPD by 1) providing robust criteria for sub-classifying COPD participants into groups most likely to benefit from a given therapy during a clinical trial, thereby improving the chances of successful outcome; and 2) identifying biomarkers/phenotypes that can be used as intermediate outcomes to reliably predict clinical benefit during therapeutic trials, thus reducing costs. The goal is to enroll 3,200 participants in four strata: severe COPD, mild/moderate COPD, smokers without airflow obstruction and non-smoking controls. Participants undergo a baseline visit including morphometric measures, spirometry, six-minute walk, an inspiratory and expiratory chest CT, and a set of standardized questionnaires. Biospecimens, including plasma, serum, DNA, urine and induced sputum, are collected and stored. There are three annual follow-up examinations, with quarterly telephone calls to assess for exacerbations, hospitalizations and mortality. Bronchoscopy is being performed in a subset of participants and a subset of COPD patients will be assessed during exacerbations. Adjudication of exacerbations and mortality will be undertaken. SPIROMICS is designed so that sub-studies and ancillary studies testing additional hypotheses can be added.
Published: 2013

21. Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the Severe Asthma Research Program

Author: Chitra K, Rao, Charity G, Moore, Eugene, Bleecker, William W, Busse, William, Calhoun, Mario, Castro, Kian Fan, Chung, Serpil C, Erzurum, Elliot, Israel, Douglas, Curran-Everett, and Sally E, Wenzel
Subjects: Adult, Adolescent, Aspirin, Vital Capacity, Middle Aged, Models, Biological, Severity of Illness Index, Asthma, Menstruation, Young Adult, Phenotype, Treatment Outcome, Surveys and Questionnaires, Prostaglandins, Humans, Female, Anti-Asthmatic Agents, Original Research
Abstract: Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control.Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control.Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization.PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype.
Published: 2013

22. Airways reactivity and functional deterioration in relatives of COPD patients

Author: E. James Britt, Bernice Cohen, Harold Menkes, Eugene Bleecker, Solbert Permutt, Richard Rosenthal, and Philip Norman
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Forced Expiratory Volume, Vital Capacity, Humans, Methacholine Compounds, Family, Lung Diseases, Obstructive, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 1980

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

22 results on '"Eugene Bleecker"'

1. Imaging-based clusters in former smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and intermediate outcome measures in COPD study (SPIROMICS)

2. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations

3. Imaging-based clusters in current smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)

4. A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome

5. Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations

6. Asthma heterogeneity and severity

7. A Between-Sex Comparison of the Genomic Architecture of Asthma

8. Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

9. Novel Privacy Considerations for Large Scale Proteomics

10. DNA Sequencing Analysis of Cystic Fibrosis Transmembrane Regulator Gene Identifies Cystic Fibrosis-Associated Variants in the Severe Asthma Research Program

11. How cytokines co-occur across asthma patients: From bipartite network analysis to a molecular-based classification.

12. Estimated Ventricular Size, Asthma Severity, and Exacerbations

13. Clinical and molecular implications of RGS2 promoter genetic variation in severe asthma

14. Benralizumab for the Prevention of COPD Exacerbations

15. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

16. Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci

17. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial

18. Effect of β2-adrenergic receptor polymorphism on response to longacting β2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial

19. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

20. Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS)

21. Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the Severe Asthma Research Program

22. Airways reactivity and functional deterioration in relatives of COPD patients

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

22 results on '"Eugene Bleecker"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources