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1. Differentially co‐expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease

Author

Joe W. Chiles III, Ava C. Wilson, Rachel Tindal, Kaleen Lavin, Samuel Windham, Harry B. Rossiter, Richard Casaburi, Anna Thalacker‐Mercer, Thomas W. Buford, Rakesh Patel, J. Michael Wells, Marcas M. Bamman, Beatriz Y. Hanaoka, Mark Dransfield, and Merry‐Lynn N. McDonald

Subjects
COPD, fibre‐type shift, myofibre proportions, sex differences, skeletal muscle, transcriptomics, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD. Methods Forty‐six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre‐type distribution and cross‐sectional area via immunofluorescence microscopy and RNA‐sequenced to generate transcriptome‐wide gene expression data. Sex‐stratified k‐means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co‐expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype. Results Abnormal myofibre proportion was defined in males with COPD (n = 29) as 22% type IIx/IIax fibres and in females with COPD (n = 17) as 12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6‐min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s‐to‐forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty‐nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co‐expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co‐expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density. Conclusions Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co‐expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

Published
2024
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2. Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease

Author

Preeti Lakshman Kumar, Ava C. Wilson, Alison Rocco, Michael H. Cho, Emily Wan, Brian D. Hobbs, George R. Washko, Victor E. Ortega, Stephanie A. Christenson, Xingnan Li, J. Michael Wells, Surya P. Bhatt, Dawn L. DeMeo, Sharon M. Lutz, Harry Rossiter, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Wassim W. Labaki, Ruth Tal‐Singer, Russel P. Bowler, Craig P. Hersh, Hemant K. Tiwari, Mark Dransfield, Anna Thalacker‐Mercer, Deborah A. Meyers, Edwin K. Silverman, Merry‐Lynn N. McDonald, and COPDGene, ECLIPSE and SPIROMICS investigators

Subjects
GWAS, Cachexia, Weight loss, COPD, Genetics, Biomarkers, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome‐wide association study approach. Methods Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self‐reported unintentional weight loss > 5% in the past year or low BMI (BMI

Published
2021
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3. Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial

Author

Nicola C. Day, Subramanya Kumar, Gerard Criner, Mark Dransfield, David M. G. Halpin, MeiLan K. Han, C. Elaine Jones, Morrys C. Kaisermann, Sally Kilbride, Peter Lange, David A. Lomas, Neil Martin, Fernando J. Martinez, Dave Singh, Robert Wise, and David A. Lipson

Subjects
COPD, Triple therapy, LAMA/LABA, ICS/LABA, Cardiovascular safety, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy. Methods IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death. Results Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments. Conclusions In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10–11% and 1–3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI. Trial registration NCT02164513 (GSK study number CTT116855).

Published
2020
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4. It’s more than low BMI: prevalence of cachexia and associated mortality in COPD

Author

Merry-Lynn N. McDonald, Emiel F. M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, and Edwin K. Silverman

Subjects
COPD, Cachexia, BODE, Weight loss, BMI, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE. Methods In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months. The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index. Mortality was assessed using Kaplan-Meier survival and Cox Regression. Performance of models was compared using C-statistics. Results Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively. Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function. The CODE index predicted mortality slightly more accurately than the BODE and WODE indices. Conclusions Cachexia is associated with increased mortality among COPD patients. Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.

Published
2019
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5. The influence of social support on COPD outcomes mediated by depression.

Author

Leonard Turnier, Michelle Eakin, Han Woo, Mark Dransfield, Trisha Parekh, Jerry A Krishnan, Richard Kanner, Christopher B Cooper, Prescott G Woodruff, Robert Wise, MeiLan K Han, Karina Romero, Laura M Paulin, Stephen Peters, Brad Drummond, Eugene R Bleecker, Russell Bowler, Alejandro P Comellas, David Couper, Robert Paine, Fernando Martinez, Graham Barr, Nirupama Putcha, and Nadia N Hansel

Subjects
Medicine, Science
Abstract

BackgroundThe purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms.MethodsSubjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period. In both cross-sectional and longitudinal analyses, we examined the association of social support as measured by the FACIT-F with COPD outcomes. Cross sectional analyses used multivariable linear or logistic regression, adjusting for covariates. For longitudinal analyses, generalized linear mixed models with random intercepts were used. Models were adjusted with and without depressive symptoms and mediation analyses performed.ResultsOf the 1831 subjects with COPD, 1779 completed the FACIT- F questionnaire. In adjusted cross-sectional analysis without depressive symptoms, higher perceived social support was associated with better quality of life, well-being, 6 minute walk distance, and less dyspnea. When also adjusting for depressive symptoms, all associations between social support and COPD outcomes were attenuated and no longer statistically significant. Mediation analysis suggested that depressive symptoms explained the majority (> = 85%) of the association between social support and measured COPD outcomes. Results of the longitudinal analysis were consistent with the cross-sectional analyses. There was no association between social support and odds of exacerbations.ConclusionHigher social support was associated with better COPD outcomes across several measures of morbidity including quality of life, respiratory symptoms, and functional status. In addition, these associations were largely attenuated when accounting for depressive symptoms suggesting that the beneficial association of social support with COPD outcomes may be largely mediated by the association between social support and depression.Trial registrationSPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov: NCT01969344).

Published
2021
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6. Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD)

Author

Sean Duffy, Robert Marron, Helen Voelker, Richard Albert, John Connett, William Bailey, Richard Casaburi, J. Allen Cooper, Jeffrey L. Curtis, Mark Dransfield, MeiLan K. Han, Barry Make, Nathaniel Marchetti, Fernando Martinez, Stephen Lazarus, Dennis Niewoehner, Paul D. Scanlon, Frank Sciurba, Steven Scharf, Robert M. Reed, George Washko, Prescott Woodruff, Charlene McEvoy, Shawn Aaron, Don Sin, Gerard J. Criner, and the NIH COPD Clinical Research Network and the Canadian Institutes of Health Research

Subjects
COPD, Exacerbation, Beta-blocker, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. Methods We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Results Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. Conclusion We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

Published
2017
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7. Impact of pre-enrolment medication use on clinical outcomes in SUMMIT

Author

Jørgen Vestbo, Mark Dransfield, Julie A. Anderson, Robert D. Brook, Peter M.A. Calverley, Bartolome R. Celli, Nicholas J. Cowans, Courtney Crim, Fernando Martinez, David E. Newby, Julie Yates, and Peter Lange

Subjects
Medicine
Abstract

The impact of prior treatment on results of clinical trials in chronic obstructive pulmonary disease (COPD) has been debated. We used data from the Study to Understand Mortality and Morbidity in COPD Trial to examine the impact of prior treatment on the effects of randomised study drugs on mortality and exacerbations. We used data on 16 417 patients with moderate COPD and heightened cardiovascular risk and information on prior medications to examine the effects of fluticasone furoate (FF), vilanterol (VI) and combined FF/VI compared to placebo on moderate and severe exacerbation as well as mortality. The study was event-driven with a median study exposure of 1.8 years. This study was registered with ClinicalTrials.gov, number NCT01313676. There were no consistent associations between treatment prior to study entry and the effects of FF, VI or FF/VI on exacerbations during the study. However, patients taking inhaled corticosteroids and one or more bronchodilators prior to study entry seemed to have a better effect of active treatments than of placebo on mortality (hazard ratio for FF/VI 0.65, 95% CI 0.48–0.89). Survival in those randomised to placebo was independent of treatment prior to study enrolment. Prior treatment appears to affect treatment effects on mortality but not exacerbations in a randomised controlled trial of patients with COPD and heightened cardiovascular risk.

Published
2019
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8. Sequential comparison of tiotropium to high-dose ipratropium in patients with chronic obstructive pulmonary disease in a practice setting

Author

Umair Gauhar, Mark Dransfield, and J Allen D Cooper

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Umair Gauhar, Mark Dransfield, J Allen D CooperPulmonary Section, Birmingham Veterans Affairs Medical Center and Division of Allergy, Pulmonary and Critical Medicine University of Alabama at Birmingham, AL, USAObjective: To determine the effect of changing anticholinergic therapy in patients with COPD from ipratropium to tiotropium on pulmonary function.Methods: We examined records of patients prescribed high-dose ipratropium, who were subsequently converted to tiotropium. Spirometric values were obtained within 2 days of the change in medication and after 56 to 224 days of the switch to tiotropium.Results: 15 subjects were documented to have filled a prescription for ipratropium-containing medications the month prior to the change. Medication compliance over the 6 months prior to the switch in these patients was 72% ± 31% (mean ± SD) for ipratropium compared to 87% ± 14% for tiotropium over the 6-month period after the switch (P = 0.1). FEV1 improved from 1.12 ± 0.39 L at baseline to 1.37 ± 0.49 L after the change to tiotropium (P = 0.01). FVC also improved from 2.45 ± 0.73 L at baseline to 2.72 ± 0.69 L after the change (P = 0.04). Maximal voluntary ventilation was also increased from 39.67 ± 10.7 L/min to 45.13 ± 15.8 L/min (P = 0.045).Conclusions: We conclude that replacing high-dose ipratropium with tiotropium therapy significantly improves pulmonary function in a clinical setting.Keywords: ipratropium, tiotropium, COPD, pulmonary function, exacerbation rate

Published
2009

9. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

Author

Brigid A. Adviento, Elizabeth A. Regan, Barry J. Make, MeiLan K. Han, Marilyn G. Foreman, Anand S. Iyer, Surya P. Bhatt, Victor Kim, Jessica Bon, Xavier Soler, Gregory L. Kinney, Nicola A. Hanania, Katherine E. Lowe, Kristen E. Holm, Abebaw M. Yohannes, Gen Shinozaki, Karin F. Hoth, Jess G. Fiedorowicz, James D. Crapo, Edwin K. Silverman, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Emily S. Wan, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Matthew Strand, Jim Crooks, Katherine Pratte, Aastha Khatiwada, Erin Austin, Gregory Kinney, Kendra A. Young, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2023
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10. Cystic Fibrosis Transmembrane Conductance Regulator: Roles in Chronic Obstructive Pulmonary Disease

Author

Mark Dransfield, Steven Rowe, Claus F. Vogelmeier, Jadwiga Wedzicha, Gerard J. Criner, MeiLan K. Han, Fernando J. Martinez, and Peter Calverley

Subjects
Inflammation, Pulmonary and Respiratory Medicine, Pulmonary Disease, Chronic Obstructive, Ion Transport, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Humans, Critical Care and Intensive Care Medicine
Abstract

Chronic obstructive pulmonary disease (COPD) manifests with a variety of clinical presentations, reflecting its complex pathology. Currently, care focuses on symptom amelioration and prevention of complications and thus is generally tailored to disease severity rather than targeting specific pathophysiologic mechanisms. Chronic inflammation and mucus hypersecretion are key features of COPD. Epithelial ion channel dysfunction may be important, as it results in airway dehydration and defective host defense, contributing to chronic airway inflammation. Recent evidence suggests considerable similarities between COPD and cystic fibrosis (CF), a disease in which chloride ion channel dysfunction has been extensively studied (in particular CFTR [CF transmembrane conductance regulator]). Understanding commonalities between CF and COPD, and the role of CFTR in CF, may help in designing strategies targeting ion channel dysfunction and lead to new treatments with potential to alter the natural history of disease progression. Here, we review the roles of airway mucus and CFTR in normal lung function, the previously underestimated contribution of mucus stasis to the development of COPD, and the evidence for targeting CFTR to counteract mucus accumulation.

Published
2022
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11. Following the yellow brick road? Developing inspiring learning and teaching in the pursuit of teaching excellence in higher education

Author

Margaret Wood, Mark Dransfield, and Feng Su

Subjects
LB2300, LB, Education
Abstract

Inspiring learning and teaching are a matter of growing importance in today’s marketised higher education sector. To date, much research in this area has a focus on reviewing literature or adopting a single-stakeholder perspective – typically that of staff or students. This paper reports on the findings of a qualitative study adopting a multi-stakeholder perspective on inspiring learning and teaching. The study sought to address the following questions – what is inspiring learning and teaching, and what are the conditions under which universities might achieve it? Thirty-two participants from three English universities took part in the study including heads of learning and teaching [n = 4], academic staff [n = 13], and students [n = 15]. Adopting a phenomenological position using interviews and focus groups, the study found that rather than being a tangible ‘something’, inspiring learning and teaching is the outcome of a complex interplay between all relevant stakeholders, requiring an authentic commitment to learning. Drawing on the findings, the authors propose a model that captures the multi-faceted and multilateral nature of inspiring learning and teaching, demonstrating the inter-relatedness of the following factors: authentic relationships, partnership and collaboration, student reciprocity, and pedagogical leadership. The authors conclude by exploring the necessary institutional conditions required to apply the framework in practice in order to foster inspiring learning and teaching, such as recognising and rewarding inspiring teaching; providing professional development opportunities for staff who are keen to develop inspiring teaching; and having time and space to nurture authentic and trusting relationships with students in learning and teaching.

Published
2022
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12. CONQUEST: A Quality Improvement Program for Defining and Optimizing Standards of Care for Modifiable High-Risk COPD Patients

Author

Luis Alves, Rachel Pullen, John R Hurst, Marc Miravitlles, Victoria Carter, Rongchang Chen, Amy Couper, Mark Dransfield, Alexander Evans, Antony Hardjojo, David Jones, Rupert Jones, Margee Kerr, Konstantinos Kostikas, Jonathan Marshall, Fernando Martinez, Marije van Melle, Ruth Murray, Shigeo Muro, Clementine Nordon, Michael Pollack, Chris Price, Anita Sharma, Dave Singh, Tonya Winders, David B Price, Institut Català de la Salut, [Alves L] EPIUnit - Epidemiology Research Unit, ITR - Laboratory for Integrative and Translational Research in Population Health, Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal. [Pullen R] Observational and Pragmatic Research Institute, Singapore, Singapore. [Hurst JR] UCL Respiratory, University College London, London, UK. [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain. [Carter V] Optimum Patient Care, Cambridge, UK. [Chen R] Key Laboratory of Respiratory Disease of Shenzhen, Shenzhen Institute of Respiratory Disease, Shenzhen People’s Hospital, Shenzen, China, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [DISEASES], administración de los servicios de salud::calidad de la atención sanitaria::mejora de la calidad [ATENCIÓN DE SALUD], atención a la salud (salud pública)::atención a la salud (salud pública)::prestación sanitaria::atención integral de salud::atención primaria de la salud [SALUD PÚBLICA], Hospitals - Serveis de teràpia respiratòria, Health Services Administration::Quality of Health Care::Quality Improvement [HEALTH CARE], Other subheadings::/therapy [Other subheadings], Pulmons - Malalties obstructives - Tractament, Serveis sanitaris - Administració, Health Care (Public Health)::Health Care (Public Health)::Delivery of Health Care::Comprehensive Health Care::Primary Health Care [PUBLIC HEALTH], Otros calificadores::/terapia [Otros calificadores], enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES]
Abstract

Patient-reported outcome; Clinical decision support; Quality standards Resultado informado por el paciente; Apoyo a la decisión clínica; Estándares de calidad Resultat informat pel pacient; Suport a la decisió clínica; Estàndards de qualitat The COllaboration on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) aims to improve the quality of COPD care in primary care. The CONQUEST target population includes patients diagnosed with COPD, and those undiagnosed but with COPD-like exacerbations, who are at high but modifiable risk of COPD exacerbations, increased morbidity, and mortality. Timely diagnosis and optimized management to reduce these risks is vital. There is a need for a quality improvement program (QIP) that enables long-term improvement of patient clinical outcomes via integration of the program into routine clinical care. Core to the CONQUEST program is the adoption of four specifically designed, globally applicable, and expert-agreed quality standards (QS) for modifiable high-risk COPD patients. Translation of the QS into clinical practice, and implementation of the QIP, is guided by the CONQUEST global operational protocol provided to sites meeting the minimum healthcare system requirements. Initial analyses of current practices are conducted to generate baseline assessments of need within healthcare systems and sites looking to implement the QIP. Implementation is supported by the provision of CONQUEST resources and tools, such as clinical decision support, that promote prompt identification and treatment of patients. Utilization of electronic medical record (EMR) and patient-reported data are integral components of the QIP. Regular, automated collection and analysis of data, combined with a cyclical review of the implementation process, will be conducted for long-term, continuous improvement and health impact evaluation. The CONQUEST QIP will be an important resource in the identification and management of patients with modifiable high-risk COPD. Embedding the CONQUEST QS into routine clinical practice with regular evaluation and feedback will result in long-term quality of care improvement. This study was conducted by Optimum Patient Care Global and the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was co-funded by Optimum Patient Care Global and AstraZeneca. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Published
2022
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13. Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease

Author

Jacqueline O’Toole, Han Woo, Nirupama Putcha, Christopher B. Cooper, Prescott Woodruff, Richard E. Kanner, Robert Paine, Russell P. Bowler, Alejandro Comellas, Karin F. Hoth, Jerry A. Krishnan, Meilan Han, Mark Dransfield, Anand S. Iyer, David Couper, Stephen P. Peters, Gerard Criner, Victor Kim, R. Graham Barr, Fernando J. Martinez, Nadia N. Hansel, Michelle N. Eakin, Neil E. Alexis, Wayne H. Anderson, Mehrdad Arjomandi, Igor Barjaktarevic, Lori A. Bateman, Surya P. Bhatt, Eugene R. Bleecker, Richard C. Boucher, Stephanie A. Christenson, Alejandro P. Comellas, David J. Couper, Gerard J. Criner, Ronald G. Crystal, Jeffrey L. Curtis, Claire M. Doerschuk, Mark T. Dransfield, Brad Drummond, Christine M. Freeman, Craig Galban, MeiLan K. Han, Annette T. Hastie, Eric A. Hoffman, Yvonne Huang, Robert J. Kaner, Eric C. Kleerup, Lisa M. LaVange, Stephen C. Lazarus, Deborah A. Meyers, Wendy C. Moore, John D. Newell, Laura Paulin, Cheryl Pirozzi, Elizabeth C. Oelsner, Wanda K. O’Neal, Victor E. Ortega, Sanjeev Raman, Stephen I. Rennard, Donald P. Tashkin, J Michael Wells, Robert A. Wise, and Prescott G. Woodruff

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Internal medicine, medicine, Pulmonary disease, medicine.disease, business, Depressive symptoms, Depression (differential diagnoses), respiratory tract diseases
Abstract

Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives:...

Published
2022
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14. Comparative Impact of Depressive Symptoms and FEV

Author

Jacqueline, O'Toole, Han, Woo, Nirupama, Putcha, Christopher B, Cooper, Prescott, Woodruff, Richard E, Kanner, Robert, Paine, Russell P, Bowler, Alejandro, Comellas, Karin F, Hoth, Jerry A, Krishnan, Meilan, Han, Mark, Dransfield, Anand S, Iyer, David, Couper, Stephen P, Peters, Gerard, Criner, Victor, Kim, R Graham, Barr, Fernando J, Martinez, Nadia N, Hansel, Michelle N, Eakin, and Prescott G, Woodruff

Subjects
Pulmonary Disease, Chronic Obstructive, Depression, Forced Expiratory Volume, Surveys and Questionnaires, Smoking, Quality of Life, Humans, Female, Respiratory Function Tests, Original Research
Abstract

RATIONALE: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. OBJECTIVES: Examine the impact of depressive symptoms compared with FEV(1)% on COPD morbidity. METHODS: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV(1)% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. RESULTS: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV(1)% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV(1)% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV(1)%, explaining 30–67% of heterogeneity. FEV(1)% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16–32% of heterogeneity. Depressive symptoms accounted for 3–17% variance in change over time in PROs. In contrast, FEV(1)% accounted for 1–4% variance over time in PROs. CONCLUSIONS: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV(1)%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.

Published
2023

15. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A Post Hoc Analysis of the COPDGene and SPIROMICS Cohorts

Author

Anand S. Iyer, Trisha M. Parekh, Jacqueline O’Toole, Surya P. Bhatt, Michelle N. Eakin, Jerry A. Krishnan, Abebaw M. Yohannes, Prescott G. Woodruff, Christopher B. Cooper, Richard E. Kanner, Nicola A. Hanania, Mark T. Dransfield, Elizabeth A. Regan, Karin F. Hoth, Victor Kim, James D. Crapo, Edwin K. Silverman, Barry J. Make, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Huries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San José Estépar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Los Angeles, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Comorbid anxiety, business.industry, Internal medicine, Post-hoc analysis, Medicine, Respiratory system, business, Depressive symptoms
Published
2022
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16. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Divay Chandra, Aman Gupta, Gregory L. Kinney, Carl R. Fuhrman, Joseph K. Leader, Alejandro A. Diaz, Jessica Bon, R. Graham Barr, George Washko, Matthew Budoff, John Hokanson, Frank C. Sciurba, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Adel R. Boueiz, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Carla G. Wilson, Robert Jensen, Jim Crooks, Douglas Everett, Camille Moore, null Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Carlos Martinez, Susan Murray, Xavier Soler, Farnoush Banaei-Kashani, Russell P. Bowler, Katerina Kechris, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Michael E. DeBakey, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya P. Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Carlos H. Martinez, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronary Artery Disease, Critical Care and Intensive Care Medicine, COPD: Original Research, Coronary artery disease, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Functional residual capacity, Risk Factors, Internal medicine, medicine, Humans, Lung volumes, 030212 general & internal medicine, Myocardial infarction, Lung, Subclinical infection, COPD, business.industry, Smoking, Organ Size, Middle Aged, respiratory system, medicine.disease, Coronary Vessels, United States, Respiratory Function Tests, respiratory tract diseases, Airway Obstruction, Plethysmography, Biological Variation, Population, Pulmonary Emphysema, 030228 respiratory system, Asymptomatic Diseases, Cohort, Cardiology, Airway Remodeling, Female, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Published
2021
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17. The Air We Breathe: Respiratory Impact of Indoor Air Quality in Chronic Obstructive Pulmonary Disease

Author

Takudzwa Mkorombindo, Adnan Custovic, John Balmes, and Mark Dransfield

Subjects
Pulmonary and Respiratory Medicine, Pulmonary Disease, Chronic Obstructive, Air Pollution, Indoor, Humans, Particulate Matter, Original Articles, Critical Care and Intensive Care Medicine
Abstract

RATIONALE: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. OBJECTIVES: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. METHODS: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV(1) of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (β, −8.29; 95% confidence interval [CI], −14.80 to −1.77), higher St. George’s Respiratory Questionnaire Total Score (β, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. CONCLUSIONS: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD outcomes.

Published
2022
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18. Bronchodilators in Symptomatic Tobacco-exposed Persons with Preserved Spirometry for the RETHINC Study Group

Author

MeiLan K. Han, Wen Ye, Di Wang, Emily White, Mehrdad Arjomandi, Igor Barjaktarevic, Stacey-Ann Brown, Russell Buhr, Alejandro Comellas, Christopher Cooper, Gerard Criner, Mark Dransfield, Frank Drescher, Rodney Folz, Nadia Hansel, Robert Kaner, Richard Kanner, Jerry Krishnan, Stephen Lazarus, Veeranna Maddipati, Fernando Martinez, Anne Matthews, Catherine Meldrum, Charlene Mcevoy, Toru Nyunoya, Linda Rogers, William Stringer, Christine Wendt, Robert Wise, Stephen Wisniewski, Frank Sciurba, and Prescott Woodruff

Published
2022
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19. Tick-box, weasel words, or a transformative experience? Insights into what educators consider the real impact of HEA Fellowships

Author

Sarah Floyd, Fiona Smart, Abby Cathcart, Rachael Carkett, Ros Duhs, Mark Dransfield, Laurie-Anne Campbell, and Vicky Davies

Subjects
Scheme (programming language), Self-efficacy, LB2300, Focus (computing), ComputingMilieux_THECOMPUTINGPROFESSION, biology, Education, LB1705-2286, Professional Standards Framework (PSF), Self-efficacy, HEA Fellow, Teaching Excellence, Reflection, Impact, Intangible benefits, Transformative learning, Weasel, biology.animal, Pedagogy, Sociology, Reflection (computer graphics), computer, computer.programming_language
Abstract

Global membership of the HEA fellowship scheme is increasing. Despite the focus by academic developers on supporting staff to achieve fellowship, there is limited research that examines whether it improves teaching and the learning experience. Our detailed survey of educators in the UK and Australia indicates perceptions of impact on individuals, practice, and community. Importantly for academic developers, the reflective act of developing a fellowship has potential to shape the student learning experience. However, some staff are frustrated and disillusioned by their experience. We call for institutions to design development and recognition that maximise impact and acknowledge the benefits valued by educators.

Published
2021
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20. Reconsidering the Utility of Race-Specific Lung Function Prediction Equations

Author

Aaron D. Baugh, Stephen Shiboski, Nadia N. Hansel, Victor Ortega, Igor Barjaktarevic, R. Graham Barr, Russell Bowler, Alejandro P. Comellas, Christopher B. Cooper, David Couper, Gerard Criner, Jeffrey L. Curtis, Mark Dransfield, Chinedu Ejike, MeiLan K. Han, Eric Hoffman, Jamuna Krishnan, Jerry A. Krishnan, David Mannino, Robert Paine, Trisha Parekh, Stephen Peters, Nirupama Putcha, Stephen Rennard, Neeta Thakur, and Prescott G. Woodruff

Subjects
Pulmonary and Respiratory Medicine, Chronic Obstructive, respiratory function tests, Chronic Obstructive Pulmonary Disease, Vital Capacity, Respiratory System, Original Articles, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Respiratory Function Tests, Pulmonary Disease, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Clinical Research, Forced Expiratory Volume, Respiratory, Humans, Lung, racism, health disparities
Abstract

Rationale: African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives: To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods: In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George's Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. Measurements and Main Results: Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson's Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P

Published
2022

22. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease

Author

Thuonghien V. Tran, Gregory L. Kinney, Alejandro Comellas, Karin F. Hoth, Arianne K. Baldomero, A. James Mamary, Jeffrey L. Curtis, Nicola Hanania, Richard Casaburi, Kendra A. Young, Victor Kim, Barry Make, Emily S. Wan, Alejandro A. Diaz, John Hokanson, James D. Crapo, Edwin K. Silverman, Surya P. Bhatt, Elizabeth Regan, Spyridon Fortis, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Marilyn G. Foreman, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Jessica Bon, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush BanaeiKashani, Perry G. Pernicano, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine
Published
2023
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23. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

Author

Auyon J. Ghosh, Brian D. Hobbs, Matthew Moll, Aabida Saferali, Adel Boueiz, Jeong H. Yun, Frank Sciurba, Lucas Barwick, Andrew H. Limper, Kevin Flaherty, Gerard Criner, Kevin K. Brown, Robert Wise, Fernando J. Martinez, David Lomas, Peter J. Castaldi, Vincent J. Carey, Dawn L. DeMeo, Michael H. Cho, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Adel El-Boueiz, Marilyn G. Foreman, Lystra P. Hayden, Jacqueline Hetmanski, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Jarrett Morrow, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Richard Rosiello, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Male, Endotype, Respiratory System, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Gastroenterology, Loss of heterozygosity, Pulmonary Disease, Chronic Obstructive, Genotype, 80 and over, 2.1 Biological and endogenous factors, Medicine, Longitudinal Studies, Aetiology, Lung, Aged, 80 and over, COPD, RNA sequencing, Middle Aged, Respiratory Function Tests, medicine.anatomical_structure, Phenotype, Meta-analysis, Respiratory, Female, alpha-1 antitrypsin, Genetic Markers, Adult, Pulmonary and Respiratory Medicine, Chronic Obstructive, Heterozygote, medicine.medical_specialty, Chronic Obstructive Pulmonary Disease, Pulmonary disease, Pulmonary Disease, Clinical Research, Internal medicine, alpha 1-Antitrypsin Deficiency, Humans, Allele, Aged, Emphysema, COPDGene Investigators, Whole Genome Sequencing, business.industry, Original Articles, medicine.disease, Survival Analysis, respiratory tract diseases, meta-analysis, alpha 1-Antitrypsin, Case-Control Studies, business
Abstract

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Published
2021

25. Dialogic assessment in the context of professional recognition: perspectives from the canoe

Author

Fiona Smart, Sarah Floyd, Vicky Davies, and Mark Dransfield

Subjects
LB1705-2286, LB2300, Assessment, HEA Fellowship, professional dialogues, scaffolded support, reciprocal learning, LC5201
Abstract

This paper draws on the reflective evaluations of four experienced academic practitioners who each have roles in leading or contributing to Fellowship Schemes in a UK context (United Kingdom Professional Standards Framework, 2011) and are all Advance HE accreditors. The focus for the evaluation was the use of a dialogic approach within their respective Fellowship Schemes. The aim of the project was to better understand the conditions in which dialogues can thrive, and to surface the challenges. A collective autoethnographic method was decided upon to frame the evaluative process. Four one-hour online meetings were scheduled over a period of six weeks. The data were transcribed and analysed using a mind-map process and resulted in the emergence of a metaphor – that of a canoe trip in which five phases were identified: designing the vessel, getting aboard, settling in/ settling down, navigating the space and forward-wash. These five phases are overviewed here with the intention of provoking discussion in the academic practice community, drawing into conversation individuals who are concerned with assessment for learning generally, and those who have particular interest in the potential of dialogic assessments which culminate in a summative judgement. It adds to the literature focused on assessment in higher education by drawing to the fore the conditions in which dialogic approaches can thrive for the individual being assessed, while also facilitating reciprocal learning.

Published
2021

26. Bronchial Thermoplasty in Patients With Severe Asthma at 5 Years: The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma Study

Author

Geoffrey, Chupp, Joel N, Kline, Sumita B, Khatri, Charlene, McEvoy, Gerard A, Silvestri, Adrian, Shifren, Mario, Castro, Sundeep, Bansal, Marc, McClelland, Mark, Dransfield, Jennifer, Trevor, Nick, Kahlstrom, Michael, Simoff, Momen M, Wahidi, Carla R, Lamb, J Scott, Ferguson, Andrew, Haas, D Kyle, Hogarth, Richard, Tejedor, Jennifer, Toth, Jamie, Hey, Adnan, Majid, Peter, LaCamera, J Mark, Fitzgerald, Kyle, Enfield, G Mark, Grubb, Edmund A, McMullen, Jennifer L, Olson, and Michel, Laviolette

Subjects
Bronchial Thermoplasty, Adrenal Cortex Hormones, Quality of Life, Humans, Prospective Studies, Asthma
Abstract

Bronchial thermoplasty is a device-based treatment for subjects ≥ 18 years of age with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on patients with severe asthma undergoing this procedure.What are the 5-year efficacy and safety results in patients with severe asthma who have undergone bronchial thermoplasty?This was a prospective, open-label, observational, multicenter study conducted in the United States and Canada. Subjects 18 to 65 years of age who were taking inhaled corticosteroids ≥ 1,000 μg/d (beclomethasone or equivalent) and long-acting beta-agonists ≥ 80 μg/d (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, ED visits, and medication usage were evaluated for the 12 months prior to and at years 1 through 5 posttreatment. Spirometry was evaluated at baseline and at years 1 through 5 posttreatment.A total of 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 posttreatment, the proportion of subjects with severe exacerbations, ED visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared with 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups.Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes.ClinicalTrials.gov; No.: NCT01350336; URL: www.gov.

Published
2021

27. Ambient ozone effects on respiratory outcomes among smokers modified by neighborhood poverty: An analysis of SPIROMICS AIR

Author

Daniel C. Belz, Han Woo, Nirupama Putcha, Laura M. Paulin, Kirsten Koehler, Ashraf Fawzy, Neil E. Alexis, R. Graham Barr, Alejandro P. Comellas, Christopher B. Cooper, David Couper, Mark Dransfield, Amanda J. Gassett, MeiLan Han, Eric A. Hoffman, Richard E. Kanner, Jerry A. Krishnan, Fernando J. Martinez, Robert Paine, Roger D. Peng, Stephen Peters, Cheryl S. Pirozzi, Prescott G. Woodruff, Joel D. Kaufman, and Nadia N. Hansel

Subjects
Air Pollutants, Smokers, Environmental Engineering, Environmental Exposure, Middle Aged, Pollution, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Ozone, Air Pollution, Humans, Environmental Chemistry, Poverty, Waste Management and Disposal
Abstract

Neighborhood poverty has been associated with poor health outcomes. Previous studies have also identified adverse respiratory effects of long-term ambient ozone. Factors associated with neighborhood poverty may accentuate the adverse impact of ozone on respiratory health.To evaluate whether neighborhood poverty modifies the association between ambient ozone exposure and respiratory morbidity including symptoms, exacerbation risk, and radiologic parameters, among participants of the SPIROMICS AIR cohort study.Spatiotemporal models incorporating cohort-specific monitoring estimated 10-year average outdoor ozone concentrations at participants' homes. Adjusted regression models were used to determine the association of ozone exposure with respiratory outcomes, accounting for demographic factors, education, individual income, body mass index (BMI), and study site. Neighborhood poverty rate was defined by percentage of families living below federal poverty level per census tract. Interaction terms for neighborhood poverty rate with ozone were included in covariate-adjusted models to evaluate for effect modification.1874 participants were included in the analysis, with mean (± SD) age 64 (± 8.8) years and FEVIndividuals with COPD in high poverty neighborhoods have higher susceptibility to adverse respiratory effects of ambient ozone exposure, after adjusting for individual factors. These findings highlight the interaction between exposures associated with poverty and their effect on respiratory health.

Published
2022
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28. Lung Volumes Changes Across GOLD Stages of COPD

Author

Mehrdad Arjomandi, Siyang Zeng, Jianhong Chen, Surya P. Bhatt, Robert Paine III, Fereidoun Abtin, Christopher B. Cooper, Igor Barjaktarevic, R. Graham Barr, Eugene R. Bleecker, Russell G. Buhr, Gerard J. Criner, Alejandro P. Comellas, David Couper, Jeffrey L. Curtis, Mark Dransfield, Spyridon Fortis, Meilan K. Han, Nadia N. Hansel, Eric A. Hoffman, John E. Hokanson, Robert J. Kaner, Richard E. Kanner, Jerry Krishnan, Wassim Labaki, David A. Lynch, Victor E. Ortega, Stephen P. Peters, Prescott Woodruff, Steven I. Rennard, Russell P. Bowler, Donald P. Tashkin, and COPDGene and SPIROMICS Investigators

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2021
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29. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author

Vickram Tejwani, Ashraf Fawzy, Nirupama Putcha, Peter J. Castaldi, Michael H. Cho, Katherine A. Pratte, Surya P. Bhatt, David A. Lynch, Stephen M. Humphries, Gregory L. Kinney, Franco R. D’Alessio, Nadia N. Hansel, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bramvan Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, KenM. Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, and Joel Weissfeld

Subjects
Pulmonary and Respiratory Medicine, Male, Angiotensin receptor, medicine.medical_specialty, Population, Vital Capacity, Angiotensin-Converting Enzyme Inhibitors, Walk Test, Critical Care and Intensive Care Medicine, Cohort Studies, 03 medical and health sciences, Angiotensin Receptor Antagonists, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Forced Expiratory Volume, Medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Prospective Studies, education, Aged, COPD, education.field_of_study, Lung, biology, business.industry, Angiotensin-converting enzyme, respiratory system, Middle Aged, Protective Factors, medicine.disease, Angiotensin II, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Genetic epidemiology, Pulmonary Emphysema, Spirometry, Cohort, biology.protein, Cardiology, Disease Progression, Female, Cardiology and Cardiovascular Medicine, business, Lung Volume Measurements, Tomography, X-Ray Computed
Abstract

Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov

Published
2020

30. Current Smoking With or Without Chronic Bronchitis is Independently Associated With Goblet Cell Hyperplasia in Healthy Smokers and COPD Subjects: an Analysis of the SPIROMICS Cohort

Author

Victor Kim, Stephanie Jeong, Huaqing Zhao, Jennifer Kraft, Mehmet Kesimer, Richard Boucher, James Michael Wells, Stephanie Christenson, Meilan K Han, Mark Dransfield, Robert Paine, Christopher B Cooper, Igor Barjaktarevic, Russell P Bowler, Jeffrey L Curtis, Robert J Kaner, Sara L O'Beirne, Wanda K O'Neal, Stephen I Rennard, Fernando J Martinez, and Prescott G Woodruff

Abstract

Background: COPD, chronic bronchitis (CB) and active smoking have all been associated with large airway goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Methods: Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects] in which endobronchial mucosal biopsies were obtained during the SPIROMICS bronchoscopy substudy. Biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane by two independent observers in a blinded fashion. GCD was divided into tertiles (1=low, 2=medium, 3=high) based on log10 transformed values. Multivariable logistic and linear regressions were performed with CB and current smoking as the independent variables of interest and demographics and FEV1% predicted smoking as covariates.Results: Log10 GCD was greater in current smokers compared to former smokers (1.16±0.28 [n=31] vs. 0.85±0.42 [n=40], p=0.001). Those with classically defined CB had a greater log10 GCD compared to those without CB (1.21±0.31 [n=13] vs. 0.94±0.39 [n=58], p=0.024). Similarly, those with CB by the SGRQ definition had a greater log10 GCD compared to those without CB (1.13±0.39 [n=25] vs. 0.91±0.39 [n=43], p=0.028). Tertiles 2 and 3 had a greater percent of current smokers compared to tertile 1 (16.7, 50.0 and 63.6% in tertiles 1, 2 and 3, respectively, p=0.004). Current smoking was independently associated with tertile 3 (high GCD) (OR 4.15, 95% CI 1.17, 14.71) whereas CB was not in multivariable logistic regression. Similar results were found with multivariable linear regression for log10 GCD.Conclusions: GCD is higher in current smokers with and without airflow obstruction and in CB. However, current smoking, but not CB, is independently associated with GCD. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

Published
2020
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31. Heli‐borne gravity gradiometry in rugged terrain

Author

Mark Dransfield and Tianyou Chen

Subjects
Gravity (chemistry), Data processing, 010504 meteorology & atmospheric sciences, Terrain, Survey research, 010502 geochemistry & geophysics, Curvature, 01 natural sciences, Gravity gradiometry, Gradiometer, Geophysics, Geochemistry and Petrology, Image resolution, Geology, 0105 earth and related environmental sciences, Remote sensing
Abstract

For airborne gravity gradiometry in rugged terrain, helicopters offer a significant advantage over fixed‐wing aircraft: their ability to maintain much lower ground clearances. Crucially, this provides both better signal‐to‐noise and better spatial resolution than is possible with a fixed‐wing survey in the same terrain. Comparing surveys over gentle terrain at Margaret Lake, Canada, and over rugged terrain at Mount Aso, Japan, demonstrates that there is some loss of spatial resolution in the more rugged terrain. The slightly higher altitudes forced by rugged terrain make the requirements for terrain correction easier than for gentle terrain. Transforming the curvature gradients measured by the Falcon gravity gradiometer into gravity and the complete set of tensor components is done by a Fourier method over gentle terrain and an equivalent source method for rugged terrain. The Fourier method is perfectly stable and uses iterative padding to improve the accuracy of the longer wavelengths. The equivalent source method relies on a smooth model inversion, and the source distribution must be designed to suit the survey design.

Published
2019
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32. Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial

Author

Mark T. Dransfield, Justin L. Garner, Surya P. Bhatt, Dirk-Jan Slebos, Karin Klooster, Frank C. Sciurba, Pallav L. Shah, Nathaniel T. Marchetti, Richard D. Sue, Shawn Wright, Hiram Rivas-Perez, Tanya A. Wiese, Momen M. Wahidi, Hugo Goulart de Oliveira, Brian Armstrong, Sri Radhakrishnan, Narinder S. Shargill, Gerard J. Criner, Lewis Katz, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H. Criner, Richard Sue, Aaron Thornburg, Terry Thomas, Mark Dransfield, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Umair Gauhar, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Brian Morrissey, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F. Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Steven Hays, Eric Seeley, Pavan Shrestha, Gabriela R. Dincheva, Adnan Majid, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Nicholas Pastis, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Lisa Kopas, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Mark Vollenweider, Luis Herrera, Rumi Khan, Kristine Sernulka, P. Michael McFadden, Richard Barbers, Michelle Hernandez, Michael Machuzak, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Arthur Sung, Meghan Ramsey, Ryan Van Wert, Karen Morris, Nabil Jarad, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Stephen Hazelrigg, Kristal Adams, Karen Bade, Ganesh Krishna, Bryan S. Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Dirk-Ja n Slebos, Nick H. T. ten Hacken, Jorine Hartman, Sonja Augustijn, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Exacerbation, medicine.medical_treatment, EMPHYSEMA, Bronchoscopic lung volume reduction, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Forced Expiratory Volume, Surveys and Questionnaires, interventional bronchoscopy, Medicine, PREDICTS MORTALITY, 030212 general & internal medicine, LUNG-VOLUME-REDUCTION, Pneumonectomy, Zephyr Valve, Lung function, Original Research, Rehabilitation, Exercise Tolerance, Patient-centered outcomes, Prostheses and Implants, respiratory system, Middle Aged, Treatment Outcome, Pulmonary Emphysema, patient-reported outcomes, Anesthesia, Female, Pulmonary and Respiratory Medicine, REHABILITATION, Adult, Bronchi, Severe copd, OBSTRUCTIVE PULMONARY-DISEASE, CAPACITY, chronic obstructive pulmonary disease, 03 medical and health sciences, severe emphysema, SEVERE COPD, Bronchoscopy, PATIENT-CENTERED OUTCOMES, Humans, Aged, business.industry, respiratory tract diseases, PHYSICAL-ACTIVITY, 030228 respiratory system, EXACERBATION, Quality of Life, business, Adult Pulmonary
Abstract

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool–PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P

Published
2020

33. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Author

Emily S. Wan, Spyridon Fortis, Elizabeth A. Regan, John Hokanson, MeiLan K. Han, Richard Casaburi, Barry J. Make, James D. Crapo, Dawn L. DeMeo, Edwin K. Silverman, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Sungho Won, Phuwanat Sakornsakolpat, Dmitry Prokopenko, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Jessica Bon, Barry Make, Carlos Martinez, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Follow up studies, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Cardiology, medicine, 030212 general & internal medicine, Prism, business
Abstract

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...

Published
2018
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34. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)

Author

Gerard J. Criner, Richard Sue, Shawn Wright, Mark Dransfield, Hiram Rivas-Perez, Tanya Wiese, Frank C. Sciurba, Pallav L. Shah, Momen M. Wahidi, Hugo Goulart de Oliveira, Brian Morrissey, Paulo F. G. Cardoso, Steven Hays, Adnan Majid, Nicholas Pastis, Lisa Kopas, Mark Vollenweider, P. Michael McFadden, Michael Machuzak, David W. Hsia, Arthur Sung, Nabil Jarad, Malgorzata Kornaszewska, Stephen Hazelrigg, Ganesh Krishna, Brian Armstrong, Narinder S. Shargill, Dirk-Jan Slebos, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H. Criner, Aaron Thornburg, Terry Thomas, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Umair Gauhar, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F. Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Eric Seeley, Pavan Shrestha, Gabriela R. Dincheva, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Luis Herrera, Rumi Khan, Kristine Sernulka, Richard Barbers, Michelle Hernandez, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Meghan Ramsey, Ryan Van Wert, Karen Morris, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Kristal Adams, Karen Bade, Bryan S. Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Nick H. T. ten Hacken, Karin Klooster, Jorine Hartman, Sonja Augustijn, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Pulmonary and Respiratory Medicine, CLINICAL-OUTCOMES, medicine.medical_specialty, Randomization, SURGERY, lung reduction, Bronchi, Critical Care and Intensive Care Medicine, OBSTRUCTIVE PULMONARY-DISEASE, chronic obstructive pulmonary disease, MEDICAL THERAPY, Collateral ventilation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Randomized controlled trial, law, Forced Expiratory Volume, Surveys and Questionnaires, Internal medicine, Bronchoscopy, Correspondence, Humans, COPD, Medicine, 030212 general & internal medicine, LUNG-VOLUME-REDUCTION, Respiratory system, Exercise Tolerance, IMPORTANT DIFFERENCE, business.industry, Walk distance, OPERATIVE MORTALITY, Endobronchial valve, Equipment Design, Prostheses and Implants, Middle Aged, NATIONAL EMPHYSEMA, medicine.disease, Treatment Outcome, emphysema, Pulmonary Emphysema, 030228 respiratory system, TESTS, Female, business
Abstract

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

Published
2018
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35. Measuring gravity gradient in rugged terrain: HeliFalcon survey in Aso-Oguni, Japan

Author

Mark Dransfield and Tianyou Chen

Subjects
Regional geology, Geophysics, Hydrogeology, Terrain, Gemology, Economic geology, Gravity gradiometry, Image resolution, Geothermal gradient, Geology, Remote sensing
Abstract

Since the first Falcon AGG survey in 1999 (van Leuwen et al., 2000), fixed-wing airborne gravity gradiometry (AGG) has proved to be a valuable tool for mining and oil and gas explora¬tion (Dransfield, 2007). The more compact digital Falcon AGG allowed the system to be installed in a helicopter and helicopter AGG surveys began in 2006 (Boggs et al., 2007). Compared with fixed-wing aircraft, the helicopter platform can fly surveys low and slow, offering superior spatial resolution as well as an improved signal-to-noise ratio (Dransfield, 2007). The superior spatial resolution and improved signal-to-noise ratio provided by helicopter AGG enhances its capability to detect smaller targets and better delineate subtler features. Dransfield and Christensen (2013) reported a HeliFalcon performance of 6 Eo RMS at 45 m resolution in vertical gravity gradient, by far the finest spatial resolution of any airborne AGG system. Another advantage afforded by helicopter AGG is its capa¬bility to follow terrains more closely especially in areas of high relief. Christensen and Hodges (2013) compared the vertical grav¬ity gradient from HeliFalcon with the simulated fixed-wing result over the Iron Range survey in the Canadian Rocky Mountains where the terrain variation reaches 1900 m. They showed that in this terrain, a fixed-wing survey would have to fly at ground clearances of more than 1000 m for much of the survey area. This high ground clearance would have greatly suppressed the signal at short wavelengths and degraded the spatial resolution. In this paper, we look at the HeliFalcon AGG survey conducted in the Aso-Oguni area exploring for geothermal fields, examin the technical challenges presented by the rugged terrains, describe some aspects of the data acquisition and processing, and present the survey results.

Published
2018
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36. Benralizumab for the Prevention of COPD Exacerbations

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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
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37. Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression

Author

Adel Boueiz, Yale Chang, Michael H. Cho, George R. Washko, Raul San José Estépar, Russell P. Bowler, James D. Crapo, Dawn L. DeMeo, Jennifer G. Dy, Edwin K. Silverman, Peter J. Castaldi, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Robert Busch, Dandi Qiao, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Sharon Lutz, David A. Lynch, Harvey O. Coxson, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, John D. Newell, James C. Ross, Raul José Estépar, Berend C. Stoel, Juerg Tschirren, Eva van Rikxoort, Bram van Ginneken, Carla G. Wilson, Mustafa Al Qaisi, Teresa Gray, Alex Kluiber, Tanya Mann, Jered Sieren, Douglas Stinson, Joyce Schroeder, Edwin Van Beek, Robert Jensen, Douglas Everett, Anna Faino, Matt Strand, Carla Wilson, John E. Hokanson, Gregory Kinney, Kendra Young, Katherine Pratte, Lindsey Duca, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun Nachiappan, Francine Jacobson, R. Graham Barr, Byron Thomashow, John Austin, Belinda D’Souza, Gregory D.N. Pearson, Anna Rozenshtein, Neil MacIntyre, Lacey Washington, H. Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Janos Porszasz, Hans Fischer, Matthew Budoff, Harry Rossiter, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, J. Michael Wells, Surya Bhatt, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro Cornellas, John Newell, Brad Thompson, MeiLan Han, Ella Kazerooni, Carlos Martinez, Joanne Billings, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Genome-wide association study, Comorbidity, Critical Care and Intensive Care Medicine, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Forced Expiratory Volume, Internal medicine, medicine, Humans, COPD, Distribution (pharmacology), 030212 general & internal medicine, Aged, business.industry, Middle Aged, respiratory system, medicine.disease, respiratory tract diseases, Pulmonary Emphysema, 030228 respiratory system, Genetic epidemiology, Radiological weapon, Cohort, Disease Progression, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Female, Metabolic syndrome, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Published
2018
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38. Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease

Author

Spyridon Fortis, Alejandro Comellas, Barry J. Make, Craig P. Hersh, Sandeep Bodduluri, Dimitris Georgopoulos, Victor Kim, Gerard J. Criner, Mark T. Dransfield, Surya P. Bhatt, James D. Crapo, Edwin K. Silverman, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Pulmonary and Respiratory Medicine, Spirometry, Male, Vital capacity, medicine.medical_specialty, medicine.drug_class, Vital Capacity, Pulmonary disease, Risk Assessment, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Bronchodilator, Forced Expiratory Volume, medicine, Humans, 030212 general & internal medicine, Respiratory system, Asthma, Aged, Proportional Hazards Models, Retrospective Studies, Original Research, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Survival Analysis, respiratory tract diseases, Bronchodilator Agents, Respiratory Function Tests, Logistic Models, Treatment Outcome, 030228 respiratory system, Volume (thermodynamics), Multivariate Analysis, Cardiology, Disease Progression, Female, business, Tomography, X-Ray Computed
Abstract

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

Published
2019

39. Full Spectrum Gravity - Improving AGG data quality at both ends of the spectrum

Author

Chris van Galder and Mark Dransfield

Subjects
Gravity (chemistry), Gravimeter, Noise (signal processing), Noise reduction, Physics::Medical Physics, General Engineering, Gravity gradiometry, Gradiometer, Physics::Geophysics, General Relativity and Quantum Cosmology, Wavelength, Image resolution, Geology, Remote sensing
Abstract

Three major developments provide improvements in the spatial resolution, long wavelength response and noise reduction in airborne gravity gradiometer data. The world’s first commercial strap down gravimeter, sGrav, has achieved the same levels of data quality at long wavelengths as stabilized platform systems. With a repeatability of 0.71 mGal RMS at 300 s filtering, it is ideally suited to augment the long wavelength airborne gravity gradiometer data. The sGrav data is incorporated into the airborne gravity gradiometer processing stream by a modified conforming technique that first converts the gravity data to gravity gradients and then merges the result with the gradients from the gravity gradiometer. This improved process has advantages for conforming gravity gradiometer data to any regional gravity data. Processing gravity gradient data routinely involves low-pass filtering which limits the spatial resolution. A new processing method increases this resolution by splitting the acquisition noise from the geologic noise and then removing the acquisition noise. This method has reduced noise amplitude densities, in some cases by 50%.

Published
2016
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40. The St. George's Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

Author

Victor Kim, Huaqing Zhao, Elizabeth Regan, MeiLan K. Han, Barry J. Make, James D. Crapo, Paul W. Jones, Jeffrey L. Curtis, Edwin K. Silverman, Gerard J. Criner, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Jean-Paul Charbonnier, Harvey O. Coxson, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Eric L. Flenaugh, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, Gabriela Oates, Sushil Sonavane, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Chronic bronchitis, Exacerbation, Critical Care and Intensive Care Medicine, Severity of Illness Index, 03 medical and health sciences, Diagnostic Self Evaluation, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Medicine, Humans, Per patient per year, 030212 general & internal medicine, Respiratory system, Aged, COPD, Normal spirometry, business.industry, Severe exacerbation, Middle Aged, medicine.disease, Prognosis, humanities, Obstructive lung disease, respiratory tract diseases, Bronchitis, Chronic, 030228 respiratory system, Disease Progression, Female, Cardiology and Cardiovascular Medicine, business, human activities
Abstract

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

Published
2018

41. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

Author

Magnus Ekström, Anna Bornefalk-Hermansson, Nicholas Wysham, David C. Currow, Neil MacIntyre, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs Pharm.D, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Airflow, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Correspondence, Cardiology, Medicine, business, Lung function
Abstract

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.

Published
2018

42. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Author

Jeong H. Yun, Andrew Lamb, Robert Chase, Dave Singh, Margaret M. Parker, Aabida Saferali, Jørgen Vestbo, Ruth Tal-Singer, Peter J. Castaldi, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D'Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, P. de Mallorca, Y. Feschenko, V. Gavrisyuk, L. Yashina Kiev, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal Singer, J. Yates, B. Miller, R. Tal-Singer, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, and MUMC+: MA Longziekten (3)

Subjects
Male, Exacerbation, Allergy, AIRWAY INFLAMMATION, INHALED CORTICOSTEROIDS, Rate ratio, Leukocyte Count, 0302 clinical medicine, exacerbation, CLINICAL CHARACTERISTICS, Immunology and Allergy, 030212 general & internal medicine, Longitudinal Studies, Lung, COPD, medicine.diagnostic_test, Chronic obstructive pulmonary disease, Complete blood count, Middle Aged, RANDOMIZED CONTROLLED-TRIAL, Observational Studies as Topic, medicine.anatomical_structure, Disease Progression, Respiratory, Female, SHORT-TERM RESPONSE, medicine.medical_specialty, Chronic Obstructive, Chronic Obstructive Pulmonary Disease, Immunology, Pulmonary Disease, 03 medical and health sciences, FEV1/FVC ratio, Clinical Research, Internal medicine, White blood cell, medicine, Humans, eosinophil, Asthma, Aged, business.industry, COPDGene and ECLIPSE Investigators, Eosinophil, asthma, medicine.disease, Eosinophils, 030228 respiratory system, SPUTUM-EOSINOPHILIA, OVERLAP SYNDROME, business, COPENHAGEN GENERAL-POPULATION
Abstract

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Published
2018

43. The Long-Term Oxygen Treatment Trial for Chronic Obstructive Pulmonary Disease: Rationale, Design, and Lessons Learned

Author

Roger D. Yusen, Gerard J. Criner, Alice L. Sternberg, David H. Au, Anne L. Fuhlbrigge, Richard K. Albert, Richard Casaburi, James K. Stoller, Kathleen F. Harrington, J. Allen D. Cooper, Philip Diaz, Steven Gay, Richard Kanner, Neil MacIntyre, Fernando J. Martinez, Steven Piantadosi, Frank Sciurba, David Shade, Thomas Stibolt, James Tonascia, Robert Wise, William C. Bailey, Ernestina Sampong, Karin Sloan, Ashley Wagner, Susan Anderson, Marilyn Moy, Osarenoma Okunbor, Scott Marlow, Yvonne Meli, Richard Rice, Loutfi S. Aboussouan, Robert Castele, Joseph Parambil, Sumita Khatri, Aman Pande, Joe Zein, Thomas Olbrych, Stephan Alkins, Christine Jocko, Franck Rahaghi, Jean Barton, Jennifer Underwood, Barry Make, John Davies, Richard Mularski, Allison Naleway, Sarah Vertrees, Janos Porszasz, Peggy Walker, Renee Indelicato, Lennard Specht, Kathleen Ellstrom, Jamie Portillo, David Horak, Brian Tiep, Mary Barnett, Janice Drake, Mahasti Rittinger, Rachael Compton, Scott Miller, Ralph J. Panos, Laura A. Lach, Gerard Criner, Carla Grabianowski, Francis Cordova, Parag Desai, Samuel Krachman, James Mamary, Nathaniel Marchetti, Aditi Satti, Eileen Mumm, Michelle Vega-Olivo, Jenny Hua, Vanna Tauch, Lii-Yoong Criner, Michael Jacobs, Peter Rising, Paul Simonelli, Michele Mitchell, Matthew Lammi, Connie Romaine, Howard Lee, Mary Ianacone, Steven Scharf, Wanda Bell-Farrell, M. Jeffery Mador, Ayesha Rahman, Mumtaz Zaman, Lisa Hill, Alec Platt, J. Allen Cooper, Kathleen Harrington, Mark Dransfield, Patti Smith, Donald Davis, Peruvemba Sriram, Katherine Herring, Fernando Martinez, Meilan Han, Kelly Rysso, Catherine Meldrum, K. P. Ravikrishnan, Daniel Keena, Jennifer DeRidder, Beth Kring, Antonio Anzueto, Alex Aguilera, Timothy Houlihan, Reda Girgis, Jennifer Cannestra, Benjamin Kelly, Mary Beth Scholand, G. Martin Villegas, Judy Carle, Edmunds Udris, Randall Curtis, David Au, Laura C. Feemster, Richard Goodman, Brianna Moss, Lynn Reinke, Moira Aitken, Bruce Culver, Mario Castro, Brigitte Mittler, Jeanne Heaghney, Myron Jacobs, Min Joo, Nina Bracken, Edward Diamond, Mary K. Joseph, Xavier Soler, Arianna Villa, Daniel Layish, Edwin Silverman, Roxanne Kelly, Daniel Cossette, Patricia Belt, Amanda Blackford, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, K Patrick May, Jill Meinert, Girlie Reyes, Michael Smith, Mark Van Natta, Laura Wilson, Annette Wagoner, Katherine P. Yates, Rosemarie Hakim, Antonello Punturieri, Julie Bamdad, Thomas Croxton, Joanne Deshler, Pamela McCord-Reynolds, Mario Stylianou, Gail Weinmann, Gordon Bernard, James Anderson, Bernard Lo, Andrew Ries, Stuart Stoloff, Byron Thomashow, Barbara Tilley, and Kevin Weiss

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Randomization, Time Factors, medicine.medical_treatment, Population, law.invention, Hypoxemia, Treatment and control groups, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Patient Admission, Randomized controlled trial, law, Oxygen therapy, Medicine, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, education, Aged, Randomized Controlled Trials as Topic, Clinical Study Design, Aged, 80 and over, education.field_of_study, Geography, business.industry, Oxygen Inhalation Therapy, Middle Aged, Long-Term Care, United States, Clinical trial, Oxygen, 030228 respiratory system, Sample size determination, Emergency medicine, Physical therapy, Quality of Life, Female, medicine.symptom, business
Abstract

The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).

Published
2018

44. Searchlights for gravity and magnetics

Author

Mark Dransfield

Subjects
Wavefront, Physics, Field line, Gravimeter, Magnetometer, Equipotential surface, Geophysics, law.invention, Magnetic field, Electromagnetic induction, Gravitation, Geochemistry and Petrology, law
Abstract

The development of mental schemata is important in developing an understanding of physical phenomena and processes. Gravitational and magnetic fields are often visualized by geophysicists as equipotential surfaces (for gravity) and field lines (for magnetics). In these cases, the schemata treat the geology as the source of the field. In seismic and electromagnetic prospecting, one instead visualizes a field that is emitted by the instrument. Example schemata are traveling wavefronts (seismic) and smoke rings (electromagnetic induction in the dissipative limit). I carried this instrument-focused conceptualization over to potential field prospecting by a schema, which envisages the instrument as a probe, illuminating the earth in a manner analogous to a searchlight. Different potential-field instruments (potentiometers, gravimeters, magnetometers, and gradiometers) each have different beam characteristics and consequently illuminate the earth in different ways. This schema provides a new way of visualizing potential fields in prospecting with applications in instrument development, data acquisition and processing, and interpretation.

Published
2015
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45. Full spectrum falcon: Measuring broadband airborne gravity

Author

Chris van Galder, Tianyou Chen, and Mark Dransfield

Subjects
Engineering, Gravity (chemistry), 010504 meteorology & atmospheric sciences, business.industry, Gravimeter, 010502 geochemistry & geophysics, Geodesy, 01 natural sciences, Broadband, business, Falcon, computer, 0105 earth and related environmental sciences, computer.programming_language, Remote sensing
Published
2017
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46. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

Author

Robert Busch, Brian D. Hobbs, Jin Zhou, Peter J. Castaldi, Michael J. McGeachie, Megan E. Hardin, Iwona Hawrylkiewicz, Pawel Sliwinski, Jae-Joon Yim, Woo Jin Kim, Deog K. Kim, Alvar Agusti, Barry J. Make, James D. Crapo, Peter M. Calverley, Claudio F. Donner, David A. Lomas, Emiel F. Wouters, Jørgen Vestbo, Ruth Tal-Singer, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David Sparrow, Peter D. Paré, Robert D. Levy, Stephen I. Rennard, Terri H. Beaty, John Hokanson, Edwin K. Silverman, Michael H. Cho, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Adel El-Bouiez, Dandi Qiao, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Sharon Lutz, David A. Lynch, Harvey O. Coxson, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, John D. Newell, James C. Ross, Raul San Jose Estepar, Berend C. Stoel, Juerg Tschirren, Eva van Rikxoort, Bram van Ginneken, George Washko, Carla G. Wilson, Mustafa Al Qaisi, Teresa Gray, Alex Kluiber, Tanya Mann, Jered Sieren, Douglas Stinson, Joyce Schroeder, Edwin Van Beek, Robert Jensen, Douglas Everett, Anna Faino, Matt Strand, Carla Wilson, John E. Hokanson, Gregory Kinney, Kendra Young, Katherine Pratte, Lindsey Duca, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun Nachiappan, Francine Jacobson, R. Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Gregory D. N. Pearson, Anna Rozenshtein, Neil MacIntyre, Lacey Washington, H. Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Janos Porszasz, Hans Fischer, Matthew Budoff, Harry Rossiter, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, J. Michael Wells, Surya Bhatt, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro Comellas, John Newell, Brad Thompson, MeiLan Han, Ella Kazerooni, Carlos Martinez, Joanne Billings, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, Jaume Sauleda, Peter M. A. Calverley, Stephen Rennard, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, Y. Feschenko, V. Gavrisyuk, L. Yashina, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal Singer, J. Yates, B. Miller, R. Tal-Singer, J. Benditt, G. Criner, M. DeCamp, P. Diaz, M. Ginsburg, L. Kaiser, M. Katz, M. Krasna, N. MacIntyre, R. McKenna, F. Martinez, Z. Mosenifar, J. Reilly, A. Ries, J. Utz, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, MUMC+: MA Longziekten (3), and RS: NUTRIM - R3 - Chronic inflammatory disease and wasting

Subjects
0301 basic medicine, Male, Clinical Biochemistry, EMPHYSEMA, SUSCEPTIBILITY, AIR-FLOW OBSTRUCTION, Pulmonary Disease, Chronic Obstructive, Risk Factors, Medicine, EPIDEMIOLOGY, Genetic epidemiology, Original Research, COPD, COMPLEX DISEASE, RECLASSIFICATION, Chronic obstructive pulmonary disease, Middle Aged, Genetic risk score, Respiratory Function Tests, LUNG-FUNCTION, Genetic risk factors, alpha-1 antitrypsin, Meta-analysis, Female, SMOKING, Pulmonary and Respiratory Medicine, medicine.medical_specialty, genetic epidemiology, Pulmonary disease, Single-nucleotide polymorphism, genetic risk score, chronic obstructive pulmonary disease, 03 medical and health sciences, Internal medicine, Genetic variation, genetic risk factors, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Genetic association, Aged, business.industry, Cell Biology, Heritability, medicine.disease, respiratory tract diseases, 030104 developmental biology, Physical therapy, business, Genome-Wide Association Study
Abstract

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Published
2017
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47. Development and Maintenance of a Biospecimen Repository for Clinical Samples Derived from Pulmonary Patients

Author

Joao A. de Andrade, Lisa M. Schwiebert, B S Kim Estell, R N Tonja Meadows, Amit Gaggar, Mark Dransfield, Victor J. Thannickal, W. Thomas Harris, Steven Rowe, and Eric J. Sorscher

Subjects
medicine.medical_specialty, Lung, Biospecimen, medicine.diagnostic_test, business.industry, General Neuroscience, Health Insurance Portability and Accountability Act, Translational research, General Medicine, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Surgery, Idiopathic pulmonary fibrosis, medicine.anatomical_structure, Bronchoalveolar lavage, Internal medicine, medicine, Sample collection, General Pharmacology, Toxicology and Pharmaceutics, business, Asthma
Abstract

The Pulmonary Biospecimen Repository (PBR) at the University of Alabama at Birmingham (UAB) was launched in 2009. The purpose of the UAB PBR is to provide investigators within the pulmonary community at UAB and elsewhere with clinical samples derived from multiple lung diseases, including transplant recipients, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Cell and fluid samples isolated from bronchoalveolar lavage (BAL), plasma, and serum are collected and stored; samples are assessed routinely for viability. Each sample is linked directly with the respective patient information via the Pulmonary Translational Research and Clinical Database, a Health Insurance Portability and Accountability Act compliant database that includes detailed information allowing for the study of specific patient cohorts. To access samples, investigators must complete a request form, which is reviewed by the UAB PBR Steering Committee. To date, more than 800 patients have provided approximately 7,000 BAL, serum and plasma fluid, and cell samples. Over the past 4 years, nearly 800 of these samples have been distributed to investigators at UAB and elsewhere. Future plans for the UAB PBR include expanding sample collection to additional pulmonary diseases, such as mycobacterial infections, increasing the number of sample users and obtaining external funding to ensure its continued sustainability.

Published
2014
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48. Performance of airborne gravity gradiometers

Author

Mark Dransfield and Asbjorn Norlund Christensen

Subjects
Gravity (chemistry), Geophysics, Rapid acquisition, High spatial resolution, Geology, Geodesy, Gravity gradiometry, Gradiometer, Remote sensing
Abstract

Airborne gravity gradiometry (AGG) is becoming a widely accepted tool in exploration. It provides rapid acquisition of accurate gravity data at high spatial resolution with complete coverage over large areas. The data are of significant value to explorers for a wide range of commodities throughout the world. With the advent of airborne gravity gradiometer technology, it is now possible to collect high-resolution gravity with all the attendant advantages.

Published
2013
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49. Application of curvatures to airborne gravity gradients

Author

Jacqueline Hope, Heather Carey, Mark Dransfield, and Carlos Cevallos

Subjects
Gravity (chemistry), Mean curvature, Gravitational field, Equipotential surface, Line (geometry), General Engineering, Equipotential, Mathematics::Differential Geometry, Curvature, Geodesy, Geology, Gradiometer, Physics::Geophysics
Abstract

The application of equipotential surface curvatures to airborne gravity gradient data is presented. The differential curvature, as measured by the FALCON? airborne gravity gradiometer system, the mean curvature, and the direction of maximum curvature of the equipotential surface should improve the understanding and geological interpretation of gravity gradient data. It has been shown that the horizontal gradients of the vertical component of the gravity vector form the curvature of the gravity field line. As this line is orthogonal to the equipotential surface, its curvature is related to how successive equipotential surfaces change and it may not be needed to interpret. The theoretical basis for the method is discussed. Practical applications of utilising the curvature method are presented on a synthetic model and FALCON? airborne gravity gradiometer data from the western zone of the Halls Creek Orogen, Western Australia.

Published
2012
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50. Interpretation of airborne gravity gradiometry and magnetic data using cross-gradients

Author

Mark Dransfield, Jacqueline Hope, Carlos Cevallos, and Heather Carey

Subjects
Gravity (chemistry), Basis (linear algebra), Magnetic intensity, General Engineering, Geophysics, Cross product, Geodesy, Gravity gradiometry, Geology, Gradiometer, Interpretation (model theory)
Abstract

SUMMARY Computing the cross-gradient product of airborne vertical gravity and magnetic intensity data provides a means to combine information about two different physical properties into the same image, thereby aiding interpretation. The method utilises the angle and cross-product values between the horizontal gradients of each dataset to produce two images in which structural similarities are enhanced. The theoretical basis for the method and results of its application to the survey data are discussed. The cross-gradient method was tested on a synthetic model and applied to FALCON™ airborne gravity gradiometer data from the Halls Creek Orogen, Western Australia. The vertical component of the gravity vector and the reduced to magnetic pole total magnetic intensity, were used as inputs.

Published
2012
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