Search

Your search keyword '"Celli B"' showing total 545 results
Start Over Author "Celli B"
545 results on '"Celli B"'

1. Blood Eosinophils in Chinese COPD Participants and Response to Treatment with Combination Low-Dose Theophylline and Prednisone: A Post-Hoc Analysis of the TASCS Trial

Author

Bradbury T, Di Tanna GL, Scaria A, Martin A, Wen FQ, Zhong NS, Zheng JP, Barnes PJ, Celli B, Berend N, and Jenkins CR

Subjects
eosinophil, copd, clinical trial, china, theophylline, prednisone, Diseases of the respiratory system, RC705-779
Abstract

Thomas Bradbury,1 Gian Luca Di Tanna,1 Anish Scaria,1 Allison Martin,1 Fu-Qiang Wen,2 Nan-Shan Zhong,3 Jin-Ping Zheng,3 Peter J Barnes,4 Bartolome Celli,5 Norbert Berend,1 Christine R Jenkins1 On behalf of the TASCS Investigators1Respiratory Group, The George Institute for Global Health, Sydney, NSW 2042, Australia; 2West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4National Heart & Lung Institute, Imperial College, London, UK; 5Pulmonary and Critical Care Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Thomas BradburyRespiratory Group, The George Institute for Global Health, Level 5, 1 King St, Newtown, Sydney, NSW 2042, Australia, Tel +61 2 8052 4413, Email tbradbury@georgeinstitute.org.auBackground and Objectives: The burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention.Methods: This was a post-hoc analysis of the TASCS dataset – a double-blinded, placebo-controlled trial conducted in patients with moderate–severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥ 300 eosinophils/μL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate.Results: Of 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (± 8) years and a predicted forced expiratory volume in 1s (FEV1) of 43% (± 16). The annualized moderate–severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06– 1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George’s Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups.Conclusion: Combination low-dose theophylline and prednisone was associated with a significant increase in the annual moderate-severe exacerbation rate in participants with a blood eosinophil count ≥ 300 cells/μL compared to placebo.Keywords: eosinophil, COPD, clinical trial, China, theophylline, prednisone

Published
2022

2. A Delphi Consensus Document on the Use of Single-Inhaler Fixed-Dose Triple Therapies in COPD Patients

Author

López-Campos JL, Alcázar Navarrete B, Riesco Miranda JA, Cosío BG, de-Torres JP, Celli B, Jiménez-Ruiz CA, and Casanova Macario C

Subjects
chronic obstructive pulmonary disease, laba/lama, laba/ics, bronchodilator agents, inhaled corticosteroids, triple therapy, statements, delphi consensus, Diseases of the respiratory system, RC705-779
Abstract

José Luis López-Campos,1,2 Bernardino Alcázar Navarrete,3 Juan Antonio Riesco Miranda,2,4 Borja G Cosío,2,5 Juan P de-Torres,6 Bartolomé Celli,7 Carlos A Jiménez-Ruiz,8 Ciro Casanova Macario9 1Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Sevilla, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Hospital de Loja, Loja, Granada, Spain; 4Hospital Universitario de Cáceres, Cáceres, Spain; 5Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Spain; 6Respirology Division, Queen’s University, Kingston, ON, Canada; 7Brigham and Women’s Hospital, Harvard Medical School Boston, Boston, MA, USA; 8Unidad Especializada en Tabaquismo, Hospital Clínico San Carlos, Madrid, Spain; 9Servicio de Neumología-Unidad de Investigación, Hospital Universitario La Candelaria, Universidad de La Laguna, La Laguna, SpainCorrespondence: José Luis López-CamposHospital Universitario Virgen del Rocio, Avda. Manuel Siurot, S/N, Sevilla 41013, SpainTel +34955013166Email lcampos@separ.esIntroduction: Despite the evidence provided by clinical trials, there are some uncertainties and controversies regarding the use of triple inhaled therapy. With the aim of evaluating clinical practice in specialized respiratory units, a Delphi consensus document was implemented on the use of single-inhaler fixed-dose triple therapies after 1 year of use in Spain.Methods: A scientific committee of COPD experts defined a thematic index, guided a systematic literature review and helped design the Delphi questionnaire. This was sent to the other 45 COPD experts between April and June 2019. Agreement/disagreement on 58 statements was tested in two rounds using a Likert scale. Replies were classified as a consensus when ≥ 80% of the panelists agreed; a majority when a degree of agreement of ≥ 66% was reached; and divergence if agreement was < 66%.Results: After two rounds, 44.44% of the statements reached consensus, 14.81% reached majority and 40.74% were divergent. Panelists agreed that escalating from double bronchodilation should be phenotype-based and aim to prevent exacerbations but not for improving symptoms. The addition of an antimuscarinic to inhaled corticosteroids combinations achieves improvement in lung function, symptoms and exacerbation prevention. Main safety concerns included the increased risk of pneumonia as compared to bronchodilator therapies, with similar cardiovascular effects. There was no consensus agreement on patient type response based on blood eosinophil counts or obstruction severity.Conclusion: The low degree of consensus among panelists may reflect the complexity of severe COPD management. The information provided here may be useful to clinicians implementing personalized medicine for COPD patients.Keywords: chronic obstructive pulmonary disease, LABA/LAMA, LABA/ICS, bronchodilator agents, inhaled corticosteroids, triple therapy, statements, Delphi consensus

Published
2020

3. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal

Author

Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, and Celli B

Subjects
Muscarinic antagonists, adrenergic beta-2 receptor agonists, glucocorticoids, pulmonary disease, chronic obstructive, review, exacerbations, safety, Diseases of the respiratory system, RC705-779
Abstract

Lowie Vanfleteren,1–3 Leonardo M Fabbri,1,4 Alberto Papi,4 Stefano Petruzzelli,5 Bartolome Celli6 1COPD Center, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; 2CIRO, Horn, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Hospital, Maastricht, the Netherlands; 4Section of Cardiorespiratory and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 5Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy; 6Division of Pulmonary and Critical Care, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD. This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations. Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium. Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio. Furthermore, triple therapy showed a promising signal in terms of improved survival. The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia. Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma–COPD overlap. Keywords: muscarinic antagonists, adrenergic β2 receptor agonists, glucocorticoids, pulmonary disease, chronic obstructive, review, exacerbations, safety

Published
2018

4. Impact and prevention of severe exacerbations of COPD: a review of the evidence

Author

Halpin DMG, Miravitlles M, Metzdorf N, and Celli B

Subjects
severe COPD exacerbations, hospitalization, prevention, treatment, bronchodilators, long-acting muscarinic antagonist, Diseases of the respiratory system, RC705-779
Abstract

David MG Halpin,1 Marc Miravitlles,2 Norbert Metzdorf,3 Bartolomé Celli4 1Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 2Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 3Respiratory Medicine, Boehringer Ingelheim Pharma GmBH & Co KG, Ingelheim am Rhein, Germany; 4Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA Abstract: Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. Keywords: severe COPD exacerbations, hospitalization, prevention, treatment, bronchodilators, long-acting muscarinic antagonist

Published
2017

5. Perception of symptoms and quality of life – comparison of patients’ and physicians’ views in the COPD MIRROR study

Author

Celli B, Blasi F, Gaga M, Singh D, Vogelmeier C, Pegoraro V, Caputo N, and Agusti A

Subjects
COPD, perception, QoL, Diseases of the respiratory system, RC705-779
Abstract

Bartolome Celli,1,2 Francesco Blasi,3,4 Mina Gaga,5 Dave Singh,6 Claus Vogelmeier,7,8 Valeria Pegoraro,9 Nicoletta Caputo,10 Alvar Agusti11 1Pulmonary and Critical Care Medicine Division, Brigham and Women’s Hospital, 2Harvard Medical School, Boston, MA, USA; 3Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; 4Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 57th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital, Athens, Greece; 6Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester, Manchester, UK; 7Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany, 8German Center for Lung Research (DZL), Giessen, Germany; 9Real World Insight, QuintilesIMS, Milan, Italy; 10Primary Market Research, QuintilesIMS, Milan, Italy; 11Respiratory Institute, Hospital Clinic, IDIBAPS, CibeRes, University of Barcelona, Barcelona, Spain Objectives: The aim of this study was to compare potential differences between the perception that COPD patients have of their disease and the perception that physicians have of how the disease affects their patients.Methods: Surveys in COPD patients and physicians caring for COPD patients were conducted in Spain, Italy, and Germany. Online questionnaires mirrored to explore the same domains, were administered to patients and physicians. Physicians were asked to respond to the questionnaire taking a recently seen patient who represents the majority of COPD patients usually managed, as a reference. Patients with COPD completed a survey containing the same questions offered to the physicians (Medical Investigation of Respiratory COPD Perception [MIRROR] survey). Comparisons between the responses of patients and general practitioners (GPs) and between patients and pulmonologists (PULs) were run separately using the chi-square, Fisher’s exact, or Student’s t-tests.Results: A total of 334 COPD patients, 333 GPs, and 333 PULs participated in the surveys. The typical perception that PULs have of the COPD patient was that of an older man with more severe disease and less likely to be a smoker, than the included COPD patients. COPD was regarded as a major health problem by patients and physicians, but its impact on overall quality of life among more severe patients was less strongly perceived by physicians than by patients. Instead, physicians paid more attention to domains related to clinical features (cough, phlegm, and dyspnea), while underestimating COPD impact on leisure and social activities. The majority of patients stated not being completely frank with their doctors during visits. Both GPs and PULs seemed to recognize this issue but underestimated its extent.Conclusion: To improve the doctor–patient communication, a more frank reporting by the patients of their symptoms and feelings and an increased awareness of physicians about the impact on nonconventional domains that patients perceive as importantly affected by COPD should be encouraged. Keywords: COPD, perception, QoL

Published
2017

6. Agreement between a simple dyspnea-guided treatment algorithm for stable COPD and the GOLD guidelines: a pilot study

Author

Cabrera C, Casanova C, Martín Y, Mirabal V, Sánchez MC, Álvarez F, Juliá G, Cabrera-Navarro P, García-Bello MA, Marín JM, de-Torres JP, Divo M, and Celli B

Subjects
COPD, Treatment, algorithm, Diseases of the respiratory system, RC705-779
Abstract

Carlos Cabrera,1 Ciro Casanova,2 Yolanda Martín,3 Virginia Mirabal,3 María del Carmen Sánchez,4 Felisa Álvarez,5 Gabriel Juliá,1 Pedro Cabrera-Navarro,1 Miguel Ángel García-Bello,6 José María Marín,7 Juan Pablo de-Torres,8 Miguel Divo,9 Bartolomé Celli9 1University Hospital of Gran Canaria Dr Negrín, Respiratory Service, Las Palmas de Gran Canaria, Spain; 2University Hospital Nuestra Señora de la Candelaria, Respiratory Service, Santa Cruz de Tenerife, Spain; 3Arucas Health Center, Primary Care Las Palmas de Gran Canaria, Spain; 4Cueva Torres Health Center, Primary Care Las Palmas de Gran Canaria, Spain; 5La Feria Health Center, Primary Care Las Palmas de Gran Canaria, Spain; 6University Hospital of Gran Canaria Dr Negrín, Investigation Unit, Las Palmas de Gran Canaria, Spain; 7University Hospital Miguel Servet, Respiratory Service, Zaragoza, Spain; 8Navarra University Clinic, Respiratory Service, Pamplona, Spain; 9Brigham and Women’s Hospital, Pulmonary and Critical Care Service, Boston, MA, USA Introduction: Guidelines recommendations for the treatment of COPD are poorly followed. This could be related to the complexity of classification and treatment algorithms. The purpose of this study was to validate a simpler dyspnea-based treatment algorithm for inhaled pharmacotherapy in stable COPD, comparing its concordance with the current Global Initiative for Obstructive Lung Disease (GOLD) guideline.Methods: We enrolled patients who had been diagnosed with COPD in three primary care facilities and two tertiary hospitals in Spain. We determined anthropometric data, forced expiratory volume in the 1st second (percent), exacerbations, and dyspnea based on the modified Medical Research Council scale. We evaluated the new algorithm based on dyspnea and exacerbations and calculated the concordance with the current GOLD recommendations.Results: We enrolled 100 patients in primary care and 150 attending specialized care in a respiratory clinic. There were differences in the sample distribution between cohorts with 41% vs 26% in grade A, 16% vs 12% in grade B, 16% vs 22% in grade C, and 27% vs 40% in grade D for primary and respiratory care, respectively (P=0.005). The coincidence of the algorithm with the GOLD recommendations in primary care was 93% and 91.8% in the respiratory care cohort.Conclusion: A simple dyspnea-based treatment algorithm for inhaled pharmacotherapy of COPD could be useful in the management of COPD patients and concurs very well with the recommended schema suggested by the GOLD initiative. Keywords: COPD, treatment, algorithm, primary care

Published
2016

7. Comorbidities of patients in tiotropium clinical trials: comparison with observational studies of patients with chronic obstructive pulmonary disease

Author

Miravitlles M, Price D, Rabe KF, Schmidt H, Metzdorf N, and Celli B

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Marc Miravitlles,1 David Price,2 Klaus F Rabe,3,7 Hendrik Schmidt,4 Norbert Metzdorf,5 Bartolome Celli6 1Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 2Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Department of Medicine, Christian-Albrechts-Universität zu Kiel (CAU), Großhansdorf, Germany; 4Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany; 5TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany; 6Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA; 7LungenClinic Grosshansdorf, Großhansdorf, Germany Background: There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD. It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.Methods: We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013. Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline. Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.Results: We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria. The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%–45.8% (RCTs) and 13.7–42.1% (observational studies). The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%–40.0% vs 40.1%–60.6%), other ischemic heart disease (12.3%–14.2% vs 12.5%–41.0%), diabetes (10.3%–10.9% vs 4.0%–38.9%), depression (8.5%–9.5% vs 17.0%–20.6%), and cardiac arrhythmia (7.8%–11.4% vs 11.3%–15.8%).Conclusion: The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for “real-life patients.” The tiotropium RCTs tended to include patients with more severe disease than the observational studies. Keywords: patient population, baseline characteristics, epidemiology, real-life patients, GOLD staging

Published
2015

8. Exacerbation frequency and course of COPD

Author

Halpin DMG, Decramer M, Celli B, Kesten S, Liu D, and Tashkin DP

Subjects
Diseases of the respiratory system, RC705-779
Abstract

David MG Halpin,1 Marc Decramer,2 Bartolome Celli,3 Steven Kesten,4 Dacheng Liu,4 Donald P Tashkin51Royal Devon and Exeter Hospital, Devon, UK; 2Respiratory Division, Katholieke Universiteit Leuven, University Hospital, KU Leuven, Belgium; 3Pulmonary Division, Brigham and Women's Hospital, Boston, MA; 4Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT; 5Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USABackground: Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.Methods: This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo. Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0>0–1, >1–2, and>2). Spirometry and the St George's Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).Results: In total, 5992 patients (mean age 65 years, 75% male) were randomized. Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units). Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium). Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium). The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium). The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.Conclusion: Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD. Increasing rates of hospitalized exacerbations are associated with increasing risk of death.Keywords: chronic obstructive pulmonary disease, exacerbations, forced expiratory volume in one second, health status, tiotropium

Published
2012

9. A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease

Author

Hardin, M, Cho, MH, McDonald, M-L, Wan, E, Lomas, DA, Coxson, HO, MacNee, W, Vestbo, J, Yates, JC, Agusti, A, Calverley, PMA, Celli, B, Crim, C, Rennard, S, Wouters, E, Bakke, P, Bhatt, SP, Kim, V, Ramsdell, J, Regan, EA, Make, BJ, Hokanson, JE, Crapo, JD, Beaty, TH, and Hersh, CP

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Genetics, Lung, Human Genome, Chronic Obstructive Pulmonary Disease, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adrenergic beta-2 Receptor Agonists, Black or African American, Aged, Bronchodilator Agents, Cadherins, Europe, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, New Zealand, North America, Pharmacogenomic Testing, Pharmacogenomic Variants, Phenotype, Potassium Channels, Inwardly Rectifying, Potassium Channels, Tandem Pore Domain, Pulmonary Disease, Chronic Obstructive, Risk Factors, Sarcoglycans, Severity of Illness Index, Spirometry, Treatment Outcome, White People, ECLIPSE and COPDGene Investigators, COPDGene Investigators—clinical centers, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Short-acting β2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.

Published
2016

12. Challenges and Opportunities in Conducting Real-world Chronic Obstructive Pulmonary Disease Studies in a US Healthcare Network: A Qualitative Feasibility Assessment

Author

Rabe, A., primary, Loke, W.J., additional, Ward, G., additional, Khan, Y., additional, Eckerd, M., additional, Barjaktarevic, I., additional, Mapel, D., additional, Roberts, M.H., additional, Linnell, J., additional, Grünfeld Een, T., additional, Pollack, M., additional, and Celli, B., additional

Published
2023
Full Text
View/download PDF

13. Itepekimab significantly reduced hospitalizations or emergency department visits in former smokers with moderate-to-severe COPD

Author

Rabe, K F, primary, Celli, B R, additional, Praestgaard, A, additional, Djandji, M, additional, Soler, X, additional, Abdulai, R M, additional, Lederer, D J, additional, Goulaouic, H, additional, Nivens, M C, additional, Siddiqui, S, additional, Jacob-Nara, J A, additional, Deniz, Y, additional, and Rowe, P J, additional

Published
2022
Full Text
View/download PDF

14. Eosinophils sub-types differ between patients with asthma and COPD

Author

Cabrera Lopez, C, primary, Sánchez Santos, A, additional, Lemes Castellano, A, additional, Cazorla Rivero, S, additional, Breña Atienza, J, additional, González Dávila, E, additional, De Torres Tajes, J P, additional, Divo, M, additional, Pinto-Plata, V, additional, Polverino, F, additional, Marin, J M, additional, Celli, B, additional, and Casanova Macario, C, additional

Published
2022
Full Text
View/download PDF

18. Improving lung health in low-income and middle-income countries: from challenges to solutions

Author

Meghji, J., Mortimer, K., Agusti, A., Allwood, B.W., Asher, I., Bateman, E.D., Bissell, K., Bolton, C.E., Bush, A., Celli, B., Chiang, C.-Y., Cruz, A.A., Dinh-Xuan, A.-T., El Sony, A., Fong, K.M., Fujiwara, P.I., Gaga, M., Garcia-Marcos, L., Halpin, D.M.G., Hurst, J.R., Jayasooriya, S., Kumar, A., Lopez-Varela, M.V., Masekela, R., Mbatchou Ngahane, B.H., Montes de Oca, M., Pearce, N., Reddel, H.K., Salvi, S., Singh, S.J., Varghese, C., Vogelmeier, C.F., Walker, P., Zar, H.J., and Marks, G.B.

Subjects
wf_140, wa_395, wf_200, wf_600
Abstract

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

Published
2021

19. Sputum Biomarkers in Wood and Tobacco Smoke Etiotypes of Chronic Obstructive Pulmonary Disease

Author

Giraldo-Montoya ÁM, Torres-Duque CA, Giraldo-Cadavid LF, Laucho-Contreras ME, González-Flórez A, Santos AM, Tuta-Quintero EA, Celli BR, and González-García M

Subjects
copd, wood smoke, biomass fuels, tobacco smoke, biomarkers, sputum, cytokines., Diseases of the respiratory system, RC705-779
Abstract

Ángela María Giraldo-Montoya,1,2,&ast; Carlos A Torres-Duque,1,3,&ast; Luis F Giraldo-Cadavid,4,5 Maria E Laucho-Contreras,1 Angélica González-Flórez,1 Ana María Santos,3 Eduardo A Tuta-Quintero,1,5 Bartolomé R Celli,6 Mauricio González-García1,7 1CINEUMO, Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 2School of Medicine, Universidad Tecnológica de Pereira, Pereira, Colombia; 3Biosciences Doctoral, Universidad de La Sabana, Chía, Colombia; 4Medical Department, Fundación Neumológica Colombiana, Bogotá, Colombia; 5Epidemiology and Biostatistics Department, Universidad de La Sabana, Chía, Colombia; 6Harvard Medical School, Boston, MA, USA; 7School of Medicine, Universidad de La Sabana, Chía, Colombia&ast;These authors contributed equally to this workCorrespondence: Carlos A Torres-Duque, Research Department, Fundación Neumológica Colombiana, Bogotá, Colombia, Biosciences Doctoral, Universidad de La Sabana, Chía, Colombia, Email ctorres@neumologica.orgIntroduction: There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls.Methods: Eighty-eight women (69± 12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal–Wallis and Mann–Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman’s test.Results: At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p< 0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P< 0.001) and VEGF (rho:-0.22; P=0.04).Conclusion: While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.Keywords: COPD, wood smoke, biomass fuels, tobacco smoke, biomarkers, sputum, cytokines

Published
2023

20. A Delphi Consensus Document on the Use of Single-Inhaler Fixed-Dose Triple Therapies in COPD Patients

Author

López-Campos, J. L., Alcázar Navarrete, Bernardino, Riesco Miranda, J. A., Cosio, Borja G., Torres, Juan Pablo de, Celli, B., Jiménez-Ruiz, Carlos A., and Casanova, Ciro

Subjects
Consensus, statements, bronchodilator agents, Nebulizers and Vaporizers, Muscarinic Antagonists, International Journal of Chronic Obstructive Pulmonary Disease, LABA/LAMA, LABA/ICS, chronic obstructive pulmonary disease, Delphi consensus, Drug Combinations, Pulmonary Disease, Chronic Obstructive, Adrenal Cortex Hormones, Spain, triple therapy, Administration, Inhalation, Humans, inhaled corticosteroids, Adrenergic beta-2 Receptor Agonists, Original Research
Abstract

[Introduction] Despite the evidence provided by clinical trials, there are some uncertainties and controversies regarding the use of triple inhaled therapy. With the aim of evaluating clinical practice in specialized respiratory units, a Delphi consensus document was implemented on the use of single-inhaler fixed-dose triple therapies after 1 year of use in Spain., [Methods] A scientific committee of COPD experts defined a thematic index, guided a systematic literature review and helped design the Delphi questionnaire. This was sent to the other 45 COPD experts between April and June 2019. Agreement/disagreement on 58 statements was tested in two rounds using a Likert scale. Replies were classified as a consensus when ≥ 80% of the panelists agreed; a majority when a degree of agreement of ≥ 66% was reached; and divergence if agreement was < 66%., [Results] After two rounds, 44.44% of the statements reached consensus, 14.81% reached majority and 40.74% were divergent. Panelists agreed that escalating from double bronchodilation should be phenotype-based and aim to prevent exacerbations but not for improving symptoms. The addition of an antimuscarinic to inhaled corticosteroids combinations achieves improvement in lung function, symptoms and exacerbation prevention. Main safety concerns included the increased risk of pneumonia as compared to bronchodilator therapies, with similar cardiovascular effects. There was no consensus agreement on patient type response based on blood eosinophil counts or obstruction severity., [Conclusion] The low degree of consensus among panelists may reflect the complexity of severe COPD management. The information provided here may be useful to clinicians implementing personalized medicine for COPD patients.

Published
2020

21. Validación pronóstica según los criterios de la GesEPOC 2017

Author

Cabrera López, C., Casanova Macario, C., Marín Trigo, J.M., de-Torres, J.P., Torres, R.S., González, J.M., Polverino, F., Divo, M., Pinto Plata, V., Zulueta, J., Callejas, F.J., and Celli, B.

Abstract

Introduction: The Spanish COPD guidelines (GesEPOC) have been recently modified. The aim of this study is to assess this revision and evaluate the prognosis of patients according to the new classification of severity. Methods: A total of 700 COPD patients (83.9% men) were prospectively followed up for a mean period of 5 years in tertiary hospitals in Spain and the USA. Anthropometric data, lung function tests, dyspnea (according to the mMRC scale), BODE and Charlson index were collected. We calculated mortality at 5 years following the risk criteria proposed by the new GesEPOC. Results: Mean age was 66 ± 9.6 years and mean FEV1% was 59.7 ± 20.2. The proportion of patients in the low-risk group was 40.43%. Patients in the high-risk group had a significantly higher BODE index than those in the low-risk group (2.92 ± 0, 66 vs. 0.52 ± 1.91, p < 0.001), while the Charlson index score was similar in both groups. Mortality at 60 months was significantly higher in the high-risk group (31.7% vs. 15.5%, p < 0.001). Dyspnea and FEV1% were also independent predictors of mortality (p < 0.001), and neither was inferior to the risk classification proposed by GesEPOC. Conclusions: The new severity index proposed by GesEPOC accurately predicts 5-year mortality. However, dyspnea and FEV1% have the same strength in predicting mortality.

Published
2020

24. The GOLD Summit on chronic obstructive pulmonary disease in low- and middle-income countries

Author

Halpin, D. M. G., primary, Celli, B. R., additional, Criner, G. J., additional, Frith, P., additional, López Varela, M. V., additional, Salvi, S., additional, Vogelmeier, C. F., additional, Chen, R., additional, Mortimer, K., additional, Montes de Oca, M., additional, Aisanov, Z., additional, Obaseki, D., additional, Decker, R., additional, and Agusti, A., additional

Published
2019
Full Text
View/download PDF

28. 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

35. GOLD 2023 Update: Implications for Clinical Practice

Author

Tamondong-Lachica DR, Skolnik N, Hurst JR, Marchetti N, Rabe APJ, Montes de Oca M, and Celli BR

Subjects
chronic obstructive pulmonary disease, copd, respiratory, implications, clinical practice, primary care, guidelines., Diseases of the respiratory system, RC705-779
Abstract

Diana R Tamondong-Lachica,1 Neil Skolnik,2 John R Hurst,3 Nathaniel Marchetti,4 Adrian Paul J Rabe,5,6 Maria Montes de Oca,7 Bartolome R Celli8 1College of Medicine, University of the Philippines Manila, Manila, Philippines; 2Sidney Kimmel Medical College, Thomas Jefferson University, Abington, Philadelphia, PA, USA; 3UCL Respiratory, University College London, London, UK; 4Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, PA, USA; 5Department of Primary Care and Public Health, Imperial College London, London, UK; 6Biopharmaceuticals Medical, AstraZeneca, Cambridge, UK; 7Pulmonary and Thoracic Surgery Department, Universidad Central de Venezuela, School of Medicine, Centro Médico de Caracas, Caracas, Venezuela; 8Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Diana R Tamondong-Lachica, College of Medicine, University of the Philippines Manila, 547 Pedro Gil Street, Ermita, Manila, 1000 Metro Manila, Philippines, Tel +63285264170, Email drtamondonglachica@up.edu.phAbstract: In 2022, over 3 million people died of chronic obstructive pulmonary disease (COPD) and the global burden of the disease is expected to increase over the coming decades. Recommendations for the treatment and management of patients with COPD are published by the Global Initiative for Chronic Obstructive Lung Disease, and updated annually with scientific evidence-based recommendations. The 2023 updates, published in November 2022, contain key changes to recommendations for diagnosis and treatment of COPD that are anticipated to have a significant impact on clinical practice for patients with COPD. Updates to how COPD is defined and diagnosed, including the expansion of contributing factors beyond tobacco use, have the potential to lead to the diagnosis of more patients and to allow for the implementation of early interventions for patients during early stages of the disease. Simplification of the treatment algorithms, and placement of triple therapy within these algorithms, will support clinicians in providing appropriate, timely treatment for patients with COPD with a focus on reducing the risk of future exacerbations. Finally, recognition of mortality reduction as a treatment goal in COPD supports an increase in the use of triple therapy, the only pharmacological intervention that has been demonstrated to improve survival for patients with COPD. Although further guidance and clarification are needed in some areas, such as use of blood eosinophil counts in guiding treatment decisions and implementation of treatment protocols following hospitalizations, recent updates to the GOLD recommendations will support clinicians in addressing current gaps in patient care. Clinicians should utilize these recommendations to drive the early diagnosis of patients with COPD, the identification of exacerbations, and the selection of appropriate, timely treatments for patients.Keywords: chronic obstructive pulmonary disease, COPD, respiratory, implications, clinical practice, primary care, guidelines

Published
2023

39. Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution

Author

Boueiz, Adel, primary, Pham, Betty, additional, Chase, Robert, additional, Lamb, Andrew, additional, Lee, Sool, additional, Naing, Zun Zar Chi, additional, Cho, Michael H., additional, Parker, Margaret M., additional, Sakornsakolpat, Phuwanat, additional, Hersh, Craig P., additional, Crapo, James D., additional, Stergachis, Andrew B., additional, Tal-Singer, Ruth, additional, DeMeo, Dawn L., additional, Silverman, Edwin K., additional, Zhou, Xiaobo, additional, Castaldi, Peter J., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Cho, Michael, additional, Boueiz, Adel, additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Qiao, Dandi, additional, Wan, Emily S., additional, Won, Sungho, additional, Prokopenko, Dmitry, additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Newell, John D., additional, Ross, James C., additional, Estepar, Raul San Jose, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, Young, Kendra A., additional, Bhatt, Surya, additional, Bon, Jessica, additional, Make, Barry, additional, Martinez, Carlos, additional, Murray, Susan, additional, Regan, Elizabeth, additional, Soler, Xavier, additional, Bowler, Russell P., additional, Kechris, Katerina, additional, Banaei-Kashani, Farnoush, additional, Ivanov, Y., additional, Kostov, K., additional, Bourbeau, J., additional, Fitzgerald, M., additional, Hernandez, P., additional, Killian, K., additional, Levy, R., additional, Maltais, F., additional, O’Donnell, D., additional, Krepelka, J., additional, Vestbo, J., additional, Wouters, E., additional, Quinn, D., additional, Bakke, P., additional, Kosnik, M., additional, Agusti, A., additional, Sauleda, J., additional, Feschenko, Y., additional, Gavrisyuk, V., additional, Yashina, L., additional, Monogarova, N., additional, Calverley, P., additional, Lomas, D., additional, MacNee, W., additional, Singh, D., additional, Wedzicha, J., additional, Anzueto, A., additional, Braman, S., additional, Casaburi, R., additional, Celli, B., additional, Giessel, G., additional, Gotfried, M., additional, Greenwald, G., additional, Mirage, Rancho, additional, Hanania, N., additional, Mahler, D., additional, Make, B., additional, Rennard, S., additional, Rochester, C., additional, Scanlon, P., additional, Schuller, D., additional, Sciurba, F., additional, Sharafkhaneh, A., additional, Siler, T., additional, Silverman, E., additional, Wanner, A., additional, Wise, R., additional, ZuWallack, R., additional, Coxson, H., additional, Crim, C., additional, Edwards, L., additional, Tal-Singer, R., additional, Yates, J., additional, Miller, B., additional, Bakke, Per, additional, and Gulsvik, Amund, additional

Published
2019
Full Text
View/download PDF

40. Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

Author

Leeming, Diana J., Byrjalsen, Inger, Sand, Jannie M.B., Bihlet, Asger R., Lange, Peter, Thal-Singer, Ruth, Miller, Bruce E., Karsdal, Morten A., Vestbo, Jørgen, Ivanov, Y., Kostov, K., Bourbeau, J., Fitzgerald, M., Hernández, P., Killian, K., Levy, R., Maltais, F., O'Donnell, D., Krepelka, J., Vestbo, J., Wouters, E., Quinn, D., Bakke, P., Kosnik, M., Agusti, A., Sauleda, Jaume, Feschenko, Y., Gavrisyuk, V., Yashina, L., MacNee, W., Singh, D., Wedzicha, J., Anzueto, A., Braman, S., Casaburi, R., Celli, B., Giessel, G., Gotfried, M., Greenwald, G., Hanania, N., Mahler, D., Make, B., Rennard, S., Rochester, C., Scanlon, P., Schuller, D., Sciurba, F., Sharafkhaneh, A., Siler, T., and Silverman, E.

Subjects
Pulmonary and Respiratory Medicine, Male, Chronic bronchitis, medicine.medical_specialty, medicine.drug_class, Collagen Type VI, Collagen Type I, Serology, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Bronchodilator, Forced Expiratory Volume, Medicine, Humans, COPD, 030212 general & internal medicine, Serological marker, Lung function change, Aged, lcsh:RC705-779, biology, business.industry, Surrogate endpoint, C-reactive protein, lcsh:Diseases of the respiratory system, Extracellular matrix, respiratory system, Middle Aged, medicine.disease, Prognosis, Matrix Metalloproteinases, Peptide Fragments, respiratory tract diseases, Clinical trial, C-Reactive Protein, 030228 respiratory system, biology.protein, Observational study, Female, business, Biomarkers, Research Article
Abstract

Background Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. Methods One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1. Conclusion We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration NCT00292552, Retrospectively registered, trial registration in February 2006. Electronic supplementary material The online version of this article (10.1186/s12890-017-0505-4) contains supplementary material, which is available to authorized users.

Published
2017

44. Clinical and prognostic heterogeneity of C and D GOLD groups

Author

Agustí, A., Rennard, S., Edwards, L.D., MacNee, W., Wouters, E., Miller, B., Tal-Singer, R., Mullerova, H., Celli, B., Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators, the, Pulmonologie, RS: CAPHRI School for Public Health and Primary Care, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: CAPHRI - R5 - Optimising Patient Care

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cross-sectional study, Pulmonary disease, Kaplan-Meier Estimate, OBSTRUCTIVE PULMONARY-DISEASE, CLASSIFICATION, Pulmonary Disease, Chronic Obstructive, ECLIPSE COHORT, Forced Expiratory Volume, Internal medicine, medicine, Humans, COPD, Longitudinal Studies, Prospective Studies, Prospective cohort study, Aged, Surrogate endpoint, business.industry, Middle Aged, Prognosis, medicine.disease, Obstructive lung disease, respiratory tract diseases, Hospitalization, Cross-Sectional Studies, Treatment Outcome, Cohort, Physical therapy, Female, Observational study, business
Abstract

“High risk” groups for exacerbations of chronic obstructive pulmonary disease (COPD) in the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal ( i.e. groups C and D) [1] include: patients with a forced expiratory volume in 1 s FEV1

Published
2015

49. Continuous fat-free mass decline in COPD: fact or fiction?

Author

Rutten, E.P.A., Spruit, M.A., McDonald, M.L.N., Rennard, S., Agusti, A., Celli, B., Miller, B.E., Crim, C., Calverley, P.M.A., Hanson, C., MacNee, W., Franssen, F.M.E., Vanfleteren, L., ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points)Investigators, the, Wouters, E.F.M., Pulmonologie, RS: CAPHRI School for Public Health and Primary Care, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: CAPHRI - R5 - Optimising Patient Care

Subjects
Male, Pulmonary and Respiratory Medicine, LUNG-DISEASE, business.industry, Environmental ethics, Middle Aged, BODY-MASS, OBSTRUCTIVE PULMONARY-DISEASE, Pulmonary Disease, Chronic Obstructive, Fat free mass, Case-Control Studies, Body Composition, Electric Impedance, Humans, Medicine, Female, Longitudinal Studies, SMOKING, Muscle, Skeletal, business, Humanities, Aged
Abstract

[Rutten, Erica P. A.; Spruit, Martijn A.; Franssen, Frits M. E.; Vanfleteren, Lowie; Wouters, Emiel F. M.] CIRO, Dept Res & Educ, Horn, Netherlands. [Rutten, Erica P. A.; Wouters, Emiel F. M.] Maastricht Univ, Med Ctr, NL-6200 MD Maastricht, Netherlands. [Spruit, Martijn A.] Hasselt Univ, BIOMED Biomed Res Inst, Fac Med & Life Sci, REVAL Rehabil Res Ctr, Diepenbeek, Belgium. [McDonald, Merry-Lynn N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Rennard, Stephen] Univ Nebraska, Nebraska Med Ctr, Div Internal Med, Omaha, NE 68182 USA. [Agusti, Alvar] Univ Barcelona, Thorax Inst, Hosp Clin, IDIBAPS, Barcelona, Spain. [Agusti, Alvar] CIBERES, Madrid, Spain. [Celli, Bartolome] Harvard Univ, Brigham & Womens Hosp, Pulm & Crit Care Med, Sch Med, Boston, MA 02115 USA. [Miller, Bruce E.] GlaxoSmithKline, King Of Prussia, PA USA. [Crim, Courtney] GlaxoSmithKline, Res Triangle Pk, NC USA. [Calverley, Peter M. A.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Hanson, Corrine] Univ Nebraska, Nebraska Med Ctr, Med Nutr Educ, Omaha, NE 68182 USA. [MacNee, William] Univ Edinburgh, Edinburgh, Midlothian, Scotland.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results