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2. Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD

Author

Fortis, Spyridon, Quibrera, Pedro M, Comellas, Alejandro P, Bhatt, Surya P, Tashkin, Donald P, Hoffman, Eric A, Criner, Gerard J, Han, MeiLan K, Barr, R Graham, Arjomandi, Mehrdad, Dransfield, Mark B, Peters, Stephen P, Dolezal, Brett A, Kim, Victor, Putcha, Nirupama, Rennard, Stephen I, Paine, Robert, Kanner, Richard E, Curtis, Jeffrey L, Bowler, Russell P, Martinez, Fernando J, Hansel, Nadia N, Krishnan, Jerry A, Woodruff, Prescott G, Barjaktarevic, Igor Z, Couper, David, Anderson, Wayne H, Cooper, Christopher B, Investigators, Subpopulations and Intermediate Outcome Measures in COPD Study, Alexis, Neil E, Barjaktarevic, Igor, Basta, Patricia, Bateman, Lori A, Bleecker, Eugene R, Boucher, Richard C, Christenson, Stephanie A, Couper, David J, Crystal, Ronald G, Doerschuk, Claire M, Dransfield, Mark T, Drummond, Brad, Freeman, Christine M, Galban, Craig, Hastie, Annette T, Huang, Yvonne, Kaner, Robert J, Kleerup, Eric C, LaVange, Lisa M, Lazarus, Stephen C, Meyers, Deborah A, Moore, Wendy C, Newell, John D, Paulin, Laura, Pirozzi, Cheryl, Oelsner, Elizabeth C, O’Neal, Wanda K, Ortega, Victor E, Raman, Sanjeev, Wells, J Michael, and Wise, Robert A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Lung, Chronic Obstructive Pulmonary Disease, Respiratory, Good Health and Well Being, Humans, Bronchodilator Agents, Nicotiana, Retrospective Studies, Forced Expiratory Volume, Pulmonary Disease, Chronic Obstructive, Asthma, Vital Capacity, bronchodilator, bronchodilator response, bronchodilator responsiveness, bronchodilator reversibility, COPD, Subpopulations and Intermediate Outcome Measures in COPD Study Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundBronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Research questionIs consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?Study design and methodsWe retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEV1 (FEV1-BDR), change in FVC (FVC-BDR), and change in in FEV1, FVC or both (ATS-BDR). Using generalized linear models adjusted for demographics, smoking history, FEV1 % predicted after bronchodilator administration, and number of visits that the participant completed, we assessed the association of BDR group: (1) consistent BDR, (2) inconsistent BDR, and (3) never BDR with asthma, CT scan features, blood eosinophil levels, and FEV1 decline in participants without COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) and the entire cohort (participants with or without COPD).ResultsBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEV1-BDR and FVC-BDR definitions. Eosinophils did not vary consistently among BDR groups. Consistent BDR was associated with FEV1 decline over time relative to never BDR in the entire cohort. In participants with GOLD stage 0 disease, both the inconsistent ATS-BDR group (OR, 3.20; 95% CI, 2.21-4.66; P < .001) and consistent ATS-BDR group (OR, 9.48; 95% CI, 3.77-29.12; P < .001) were associated with progression to COPD relative to the never ATS-BDR group.InterpretationDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Published
2023

3. Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial

Author

Nakamura, Kenta, Henry, Timothy D., Traverse, Jay H., Latter, David A., Mokadam, Nahush A., Answini, Geoffrey A., Williams, Adam R., Sun, Benjamin C., Burke, Christopher R., Bakaeen, Faisal G., DiCarli, Marcelo F., Chaitman, Bernard R., Peterson, Mark W., Byrnes, Dawn G., Ohman, E. Magnus, Pepine, Carl J., Crystal, Ronald G., Rosengart, Todd K., Kowalewski, Elaine, Koch, Gary G., Dittrich, Howard C., and Povsic, Thomas J.

Published
2024
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4. Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD

Author

Esther, Charles R, O’Neal, Wanda K, Anderson, Wayne H, Kesimer, Mehmet, Ceppe, Agathe, Doerschuk, Claire M, Alexis, Neil E, Hastie, Annette T, Barr, R Graham, Bowler, Russell P, Wells, J Michael, Oelsner, Elizabeth C, Comellas, Alejandro P, Tesfaigzi, Yohannes, Kim, Victor, Paulin, Laura M, Cooper, Christopher B, Han, MeiLan K, Huang, Yvonne J, Labaki, Wassim W, Curtis, Jeffrey L, Boucher, Richard C, Study, Subpopulations and Intermediate Outcome Measures in COPD, Arjomandi, Mehrdad, Barjaktarevic, Igor, Bateman, Lori A, Bhatt, Surya P, Bleecker, Eugene R, Christenson, Stephanie A, Couper, David J, Criner, Gerard J, Crystal, Ronald G, Dransfield, Mark T, Drummond, Brad, Freeman, Christine M, Galban, Craig, Hansel, Nadia N, Hoffman, Eric A, Huang, Yvonne, Kaner, Robert J, Kanner, Richard E, Kleerup, Eric C, Krishnan, Jerry A, LaVange, Lisa M, Lazarus, Stephen C, Martinez, Fernando J, Meyers, Deborah A, Moore, Wendy C, Newell, John D, Paine, Robert, Paulin, Laura, Peters, Stephen P, Pirozzi, Cheryl, Putcha, Nirupama, Ortega, Victor E, Raman, Sanjeev, Rennard, Stephen I, Tashkin, Donald P, Wise, Robert A, and Woodruff, Prescott G

Subjects
Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, Respiratory, Good Health and Well Being, Biomarkers, Humans, Hypoxanthines, N-Acetylneuraminic Acid, Pulmonary Disease, Chronic Obstructive, Sputum, adenosine, glutathione, inflammation, metabolomics, methionine salvage, mucus, Subpopulations and Intermediate Outcome Measures in COPD Study, Clinical Sciences, Respiratory System
Abstract

BackgroundImproved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets.Research questionWhich physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations?Study design and methodsWe applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations.ResultsSputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.InterpretationBiomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations.Trial registryClinicalTrials.gov; No.: NCT01969344; URL: www.Clinicaltrialsgov.

Published
2022

5. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author

Mason, Stefanie E, Moreta-Martinez, Rafael, Labaki, Wassim W, Strand, Matthew J, Regan, Elizabeth A, Bon, Jessica, San Jose Estepar, Ruben, Casaburi, Richard, McDonald, Merry-Lynn, Rossiter, Harry B, Make, Barry, Dransfield, Mark T, Han, MeiLan K, Young, Kendra, Curtis, Jeffrey L, Stringer, Kathleen, Kinney, Greg, Hokanson, John E, San Jose Estepar, Raul, Washko, George R, Crapo, James D, Silverman, Edwin K, Cummings, Sara, Madden, Kelley, Make, Barry J, Nabbosa, Juliet, Port, Emily, Rashdi, Serine, Stepp, Lori, Watts, Shandi, Weaver, Michael, Beaty, Terri, Bowler, Russell P, Lynch, David A, Regan, Elizabeth, Anderson, Gary, Bleecker, Eugene R, Coxson, Harvey O, Crystal, Ronald G, Hogg, James C, Province, Michael A, Rennard, Stephen I, Croxton, Thomas, Gan, Weiniu, Postow, Lisa A, Viviano, Lisa M, Costa-Davis, Corinne, Malanga, Elisha, Prieto, Delia, Tal-Singer, Ruth, Farzadegan, Homayoon, Hadji, Akila, Sathe, Leena, Baraghoshi, David, Chen, Grace, Crooks, James, Knowles, Ruthie, Pratte, Katherine, Wilson, Carla, Zelarney, Pearlanne T, Kechris, Katerina J, Leach, Sonia, Hokanson, Co-Chair John E, Austin, Erin E, Czizik, Annika, Kinney, Gregory, Li, Yisha, Lutz, Sharon M, Ragland, Margaret F, Richmond, Nicole, Young, Kendra A, Cho, Michael, Castaldi, Peter J, Glass, Kimberly, Hersh, Craig, Kim, Wonji, Liu, Yang-Yu, Hersh, Craig P, Bidinger, Jacqueline, Cho, Michael H, Conrad, Douglas, and DeMeo, Dawn L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Nutrition, Prevention, 2.1 Biological and endogenous factors, Good Health and Well Being, Body Composition, Body Mass Index, Humans, Longitudinal Studies, Lung, Pectoralis Muscles, Pulmonary Disease, Chronic Obstructive, Smokers, COPD, mortality, muscle wasting, sarcopenia, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1% (95% CI, 2.4%-3.7%; P < .001) in COPDGene, and 2.4% (95% CI, 0.9%-4.0%; P < .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Published
2022

6. Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease.

Author

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

Subjects
Clinical Research, Behavioral and Social Science, Depression, Chronic Obstructive Pulmonary Disease, Mental Health, Lung, Respiratory, Good Health and Well Being, Female, Forced Expiratory Volume, Humans, Pulmonary Disease, Chronic Obstructive, Quality of Life, Respiratory Function Tests, Smoking, Surveys and Questionnaires, depression, COPD, patient reported outcome measures, SPIROMICS Investigators
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 FEV1% 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 FEV1% 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 FEV1% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV1% 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 FEV1%, explaining 30-67% of heterogeneity. FEV1% 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, FEV1% 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 FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.

Published
2022

8. Increased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS.

Author

Zhang, William Z, Oromendia, Clara, Kikkers, Sarah Ann, Butler, James J, O'Beirne, Sarah, Kim, Kihwan, O'Neal, Wanda K, Freeman, Christine M, Christenson, Stephanie A, Peters, Stephen P, Wells, J Michael, Doerschuk, Claire, Putcha, Nirupama, Barjaktarevic, Igor, Woodruff, Prescott G, Cooper, Christopher B, Bowler, Russell P, Comellas, Alejandro P, Criner, Gerard J, Paine, Robert, Hansel, Nadia N, Han, Meilan K, Crystal, Ronald G, Kaner, Robert J, Ballman, Karla V, Curtis, Jeffrey L, Martinez, Fernando J, and Cloonan, Suzanne M

Subjects
Lung, Bronchoalveolar Lavage Fluid, Humans, Pulmonary Disease, Chronic Obstructive, Disease Progression, Iron, Iron-Binding Proteins, Respiratory Function Tests, Forced Expiratory Volume, Severity of Illness Index, Risk Factors, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Ferritins, Biomarkers
Abstract

Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls. Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown. We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195). BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV1 % predicted and exacerbation frequency. Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates. BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers. BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively. Similar associations were not observed with plasma ferritin. Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals.

Published
2020

9. The Effects of Rare SERPINA1 Variants on Lung Function and Emphysema in SPIROMICS

Author

Ortega, Victor E, Li, Xingnan, O’Neal, Wanda K, Lackey, Lela, Ampleford, Elizabeth, Hawkins, Gregory A, Grayeski, Philip J, Laederach, Alain, Barjaktarevic, Igor, Barr, R Graham, Cooper, Christopher, Couper, David, Han, MeiLan K, Kanner, Richard E, Kleerup, Eric C, Martinez, Fernando J, Paine, Robert, Peters, Stephen P, Pirozzi, Cheryl, Rennard, Stephen I, Woodruff, Prescott G, Hoffman, Eric A, Meyers, Deborah A, Bleecker, Eugene R, Alexis, Neil E, Anderson, Wayne H, Arjomandi, Mehrdad, Bateman, Lori A, Bhatt, Surya P, Boucher, Richard C, Bowler, Russell P, Christenson, Stephanie A, Comellas, Alejandro P, Criner, Gerard J, Crystal, Ronald G, Curtis, Jeffrey L, Doerschuk, Claire M, Dransfield, Mark T, Freeman, Christine M, Galban, Craig, Hansel, Nadia N, Hastie, Annette T, Huang, Yvonne, Kaner, Robert J, Krishnan, Jerry A, LaVange, Lisa M, Lazarus, Stephen C, Moore, Wendy C, Paulin, Laura, Putcha, Nirupama, Oelsner, Elizabeth C, Raman, Sanjeev, Tashkin, Donald P, Wells, J Michael, and Wise, Robert A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Tobacco, Emphysema, Clinical Research, Genetics, Tobacco Smoke and Health, Lung, Chronic Obstructive Pulmonary Disease, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Adult, Black or African American, Aged, Aged, 80 and over, Female, Forced Expiratory Volume, Genotype, Heterozygote, Hispanic or Latino, Humans, Isoelectric Focusing, Male, Maximal Midexpiratory Flow Rate, Middle Aged, Phenotype, Polymorphism, Genetic, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Smoking, Tomography, X-Ray Computed, Vital Capacity, White People, alpha 1-Antitrypsin, chronic obstructive pulmonary disease, alpha-1 antitrypsin, SERPINA1, rare variant, emphysema, NHLBI Subpopulations and Intermediate Outcomes Measures in COPD Study, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Rationale: The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, SERPINA1 (serpin peptidase inhibitor, clade A, member 1), in determining chronic obstructive pulmonary disease risk and severity is controversial.Objectives: To comprehensively evaluate the effects of rare SERPINA1 variants on lung function and emphysema phenotypes in subjects with significant tobacco smoke exposure using deep gene resequencing and alpha-1 antitrypsin concentrations.Methods: DNA samples from 1,693 non-Hispanic white individuals, 385 African Americans, and 90 Hispanics with ≥20 pack-years smoking were resequenced for the identification of rare variants (allele frequency

Published
2020

10. Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD

Author

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

Published
2023
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12. EXACT Trial: Results of the Phase 1 Dose-Escalation Study

Author

Povsic, Thomas J., Henry, Timothy D., Traverse, Jay H., Anderson, R. David, Answini, Geoffrey A., Sun, Benjamin C., Arnaoutakis, George J., Boudoulas, Konstantinos D., Williams, Adam R., Dittrich, Howard C., Tarka, Elizabeth A., Latter, David A., Ohman, E. Magnus, Peterson, Mark W., Byrnes, Dawn, Pepine, Carl J., DiCarli, Marcelo F., Crystal, Ronald G., Rosengart, Todd K., and Mokadam, Nahush A.

Published
2023
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13. Management of Select Adverse Events Following Delandistrogene Moxeparvovec Gene Therapy for Patients With Duchenne Muscular Dystrophy

Author

Zaidman, Craig M., primary, Goedeker, Natalie L., additional, Aqul, Amal A., additional, Butterfield, Russell J., additional, Connolly, Anne M., additional, Crystal, Ronald G., additional, Godwin, Kara E., additional, Hor, Kan N., additional, Mathews, Katherine D., additional, Proud, Crystal M., additional, Smyth, Elizabeth Kula, additional, Veerapandiyan, Aravindhan, additional, Watkins, Paul B., additional, and Mendell, Jerry R., additional

Published
2024
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14. The Qatar Genome: A Population-Specific Tool for Precision Medicine in the Middle East

Author

Fakhro, Khalid A., Staudt, Michelle R., Ramstetter, Monica Denise, Robay, Amal, Malek, Joel A., Badii, Ramin, Al-Marri, Ajayeb Al-Nabet, Khalil, Charbel Abi, Al-Shakaki, Alya, Chidiac, Omar, Stadler, Dora, Zirie, Mahmoud, Jayyousi, Amin, Salit, Jacqueline, Mezey, Jason G., Crystal, Ronald G., and Rodriguez-Flores, Juan L.

Subjects
Quantitative Biology - Genomics
Abstract

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific reference genome for the indigenous Arab popula-tion of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million SNP and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual ge-nome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%), and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in the QTRG reference. The benefit for using QTRG varies across ances-tries, a factor that should be taken into consideration when selecting an appropriate reference for analysis., Comment: Includes supplementary figures missing from publisher website

Published
2018
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16. Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD

Author

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

Published
2022
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17. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author

Crapo, James D., Silverman, Edwin K., Cummings, Sara, Madden, Kelley, Make, Barry J., Nabbosa, Juliet, Port, Emily, Rashdi, Serine, Regan, Elizabeth A., Stepp, Lori, Watts, Shandi, Weaver, Michael, Beaty, Terri, Bowler, Russell P., Curtis, Jeffrey L., Han, MeiLan K., Hokanson, John E., Lynch, David A., Strand, Matthew J., Anderson, Gary, Bleecker, Eugene R., Coxson, Harvey O., Crystal, Ronald G., Hogg, James C., Province, Michael A., Rennard, Stephen I., Croxton, Thomas, Gan, Weiniu, Postow, Lisa A., Viviano, Lisa M., Costa-Davis, Corinne, Malanga, Elisha, Prieto, Delia, Tal-Singer, Ruth, Farzadegan, Homayoon, Hadji, Akila, Sathe, Leena, Baraghoshi, David, Chen, Grace, Crooks, James, Knowles, Ruthie, Pratte, Katherine, Wilson, Carla, Zelarney, Pearlanne T., Kechris, Katerina J., Leach, Sonia, Austin, Erin E., Czizik, Annika, Kinney, Gregory, Li, Yisha, Lutz, Sharon M., Ragland, Margaret F., Richmond, Nicole, Young, Kendra A., Cho, Michael, Castaldi, Peter J., Glass, Kimberly, Hersh, Craig, Kim, Wonji, Liu, Yang-Yu, Hersh, Craig P., Bidinger, Jacqueline, Cho, Michael H., Conrad, Douglas, DeMeo, Dawn L., El-Boueiz, Adel R., Foreman, Marilyn G., Ghosh, Auyon, Hahn, Georg, Hansel, Nadia N., Hayden, Lystra P., Hobbs, Brian, Kim, Woori, Lange, Christoph, McDonald, Merry- Lynn, McGeachie, Michael, Moll, Matthew, Morris, Melody, Patsopoulos, Nikolaos A., Qiao, Dandi, Ruczinski, Ingo, Wan, Emily S., Dy, Jennifer G., Fain, Sean B., Ginsburg, Shoshana, Hoffman, Eric A., Humphries, Stephen, Judy, Philip F., Stefanie Mason, Alex Kluiber, Oh, Andrea, Poynton, Clare, Reinhardt, Joseph M., Ross, James, San Jose Estepar, Raul, Schroeder, Joyce D., Sitek, Arkadiusz, Steiner, Robert M., van Beek, Edwin, Ginneken, Bram van, van Rikxoort, Eva, Washko, George R., Jensen, Robert, John E. Hokanson, Co-Chair, Bhatt, Surya P., Casaburi, Richard, Kim, Victor, Putcha, Nirupama, Han, MeiLan, Bon, Jessica, Diaz, Alejandro A., Regan, Elizabeth, Anzueto, Antonio, Bailey, William C., Criner, Gerard J., Dransfield, Mark T., Kinney, Greg, Sprenger, Kim, Benos, Takis, Hanania, Nicola A., Hoth, Karin F., Lambert, Allison, Lowe, Katherine, Oates, Gabriela, Parekh, Trisha, Westney, Gloria, Young, Kendra, Balasubramanian, Aparna, Boriek, Aladin, Fawzy, Ashraf, Jacobson, Francine, LaFon, David C., MacIntyre, Neil, Maselli-Caceres, Diego, McCormack, Meredith C., McDonald, Merry-Lynn, Sciurba, Frank, Soler, Xavier, Tejwani, Vickram, van Beek, Edwin JR., Wade, Raymond C., Wells, Mike, Wendt, Chris H., Yun, Jeong H., Zhang, Jingzhou, Gillenwater, Lucas, Lowe, Katherine E., Pratte, Katherine A., Ragland, Margaret, Attaway, Amy, Mason, Stefanie, Rossiter, Harry B., Saha, Punam Kumar, Wilson, Ava, Amaza, Hannatu, Baldomero, Adrienne, Mamary, A. James, O’Brien, James, Wise, Robert A., Eakin, Michelle, Fiedorowicz, Jess G., Henkle, Ben, Holm, Kristen, Iyer, Anand, Kunisaki, Ken M., McEvoy, Charlene, Mkorombindo, Takudzwa, Shinozaki, Gen, Yohannes, Abebaw, Hobbs, Brian D., Miller, Bruce E., Retson, Tara, McCloskey, Lisa, Pernicano, Perry G., Atik, Mustafa, Bertrand, Laura, Monaco, Thomas, Narendra, Dharani, Lenge de Rosen, Veronica V., Badu-Danso, Kwame, Jacobson, Francine L., Kaufman, Laura, Maguire, Cherie, Struble, Sophie, Wilson, Seth, Barr, R. Graham, Almonte, Casandra, Austin, John H.M., Gomez Blum, Maria Lorena, D’Souza, Belinda M., Florez, Emilay, Martinez, Rodney, MacIntyre, Neil, Jr., Curry, Wendy, McAdams, H. Page, Reikofski, Charlotte V., Washington, Lacey, Brown, Robert, Clare, Cheryl, Daniel, Marie, Horton, Karen, Ting “Tony” Lin, Cheng, Mirza, Tahira, Scott, Meagan, Shade, Becky, Budoff, Matt, Calmelat, Robert, Cavanaugh, Deborah, Dailing, Chris, Diaz, Leticia, Fischer, Hans, Indelicato, Renee Love, Porszasz, Janos, Soriano, April, Stringer, William, Urrutia, Miriam, Baldomero, Arianne, Bell, Brian, Deconcini, Miranda, Loes, Linda, Phelan, Jonathan, Robichaux, Camille, Sasse, Cheryl, Tashjian, Joseph H., Flenaugh, Eric L., Abson, Kema, Gebrekristos, Hirut, Johnson, Priscilla, Jordan, Jessica, Ponce, Mario, Terpenning, Silanath, Wilson, Derrick, Broadhurst, Grace, Dyer, Debra, Engel, Elena, Finigan, Jay, Hill, Andrew, Jones, Alex, Jones, Ryan, Owen, Jordan, Rosiello, Richard, Andries, Nicole, Charpentier, Mary, Kirk, Diane, Pace, David, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Davis, Valena, Desai, Parag, Fehrle, Dee, Grabianowski, Carla, Jacobs, Michael, Jameson, Laurie, Jones, Gayle M., Kelsen, Steven, Marchetti, Nathaniel, McGonagle, Francine, Satti, Aditi, Shenoy, Kartik, Sheridan, Regina, Vega-Sanchez, Maria, Wallace, Samantha, Akinseye-kolapo, Samuel, Baker, Matthew, Goggins, Arnissa, McClain, Anny, Nath, Hrudaya, Singh, Satinder P., Sonavane, Sushil K., Westfall, Elizabeth, Gil, Marissa, El Hajjaoui, Tarek, Hsiao, Albert, Martineau, Amber, Mielke, Jenna, Perez, Karl, Querido, Gabriel, Reston, Tara, Yen, Andrew, Comellas, Alejandro, Fortis, Spyridon, Galizia, Mauricio, Garcia, Eric, Keating, Janet, Laroia, Archana, Lee, Changhyun, Meyer, Amber, Mullan, Brian, Nagpal, Prashant, Ofori, Oloigbe, Suiter, Sierra, Mason, Stefanie E., Moreta-Martinez, Rafael, Labaki, Wassim W., San Jose Estepar, Ruben, Make, Barry, and Stringer, Kathleen

Published
2022
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20. The QChip1 knowledgebase and microarray for precision medicine in Qatar

Author

Rodriguez-Flores, Juan L., Messai-Badji, Radja, Robay, Amal, Temanni, Ramzi, Syed, Najeeb, Markovic, Monika, Al-khayat, Eiman, Qafoud, Fatima, Nawaz, Zafar, Badii, Ramin, Al-Sarraj, Yasser, Mbarek, Hamdi, Al-Muftah, Wadha, Alvi, Muhammad, Rostami, Mahboubeh R., Cruzado, Juan Carlos Martinez, Mezey, Jason G., Shakaki, Alya Al, Malek, Joel A., Greenblatt, Matthew B., Fakhro, Khalid A., Machaca, Khaled, Al-Nabet, Ajayeb, Afifi, Nahla, Brooks, Andrew, Ismail, Said I., Althani, Asmaa, and Crystal, Ronald G.

Published
2022
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21. A Novel STK4 Mutation Impairs T Cell Immunity Through Dysregulation of Cytokine-Induced Adhesion and Chemotaxis Genes

Author

Guennoun, Andrea, Bougarn, Salim, Khan, Taushif, Mackeh, Rafah, Rahman, Mahbuba, Al-Ali, Fatima, Ata, Manar, Aamer, Waleed, Prosser, Debra, Habib, Tanwir, Chin-Smith, Evonne, Al-Darwish, Khawla, Zhang, Qian, Al-Shakaki, Alya, Robay, Amal, Crystal, Ronald G., Fakhro, Khalid, Al-Naimi, Amal, Al Maslamani, Eman, Tuffaha, Amjad, Janahi, Ibrahim, Janahi, Mohammad, Love, Donald R., Karim, Mohammed Yousuf, Lo, Bernice, Hassan, Amel, Adeli, Mehdi, and Marr, Nico

Published
2021
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22. Rural Residence and Chronic Obstructive Pulmonary Disease Exacerbations. Analysis of the SPIROMICS Cohort

Author

Burkes, Robert M, Gassett, Amanda J, Ceppe, Agathe S, Anderson, Wayne, O’Neal, Wanda K, Woodruff, Prescott G, Krishnan, Jerry A, Barr, R Graham, Han, MeiLan K, Martinez, Fernando J, Comellas, Alejandro P, Lambert, Allison A, Kaufman, Joel D, Dransfield, Mark T, Wells, J Michael, Kanner, Richard E, Paine, Robert, Bleecker, Eugene R, Paulin, Laura M, Hansel, Nadia N, Drummond, M Bradley, Alexis, Neil E, Anderson, Wayne H, Boucher, Richard C, Bowler, Russell P, Carretta, Elizabeth E, Christenson, Stephanie A, Cooper, Christopher B, Couper, David J, Criner, Gerard J, Crystal, Ronald G, Curtis, Jeffrey L, Doerschuk, Claire M, Freeman, Christine M, Hastie, Annette T, Hoffman, Eric A, Kaner, Robert J, Kleerup, Eric C, LaVange, Lisa M, Lazarus, Stephen C, Meyers, Deborah A, Moore, Wendy C, Newell, John D, Paulin, Laura, Peters, Stephen, Oelsner, Elizabeth C, Ortega, Victor E, Putcha, Nirupama, Rennard, Stephen I, Tashkin, Donald P, Scholand, Mary Beth, Wise, Robert A, Postow, Lisa, and Croxton, Thomas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Rural Health, Chronic Obstructive Pulmonary Disease, Clinical Research, Respiratory, chronic obstructive pulmonary disease, exacerbation, rural health, Current and former investigators of the SPIROMICS sites and reading centers, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Rationale: Rural residence is associated with poor outcomes in several chronic diseases. The association between rural residence and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear.Objectives: In this work, we sought to determine the independent association between rural residence and COPD-related outcomes, including COPD exacerbations, airflow obstruction, and symptom burden.Methods: A total of 1,684 SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) participants with forced expiratory volume in 1 second/forced vital capacity < 0.70 had geocoding-defined rural-urban residence status determined (N = 204 rural and N = 1,480 urban). Univariate and multivariate logistic and negative binomial regressions were performed to assess the independent association between rurality and COPD outcomes, including exacerbations, lung function, and symptom burden. The primary exposure of interest was rural residence, determined by geocoding of the home address to the block level at the time of study enrollment. Additional covariates of interest included demographic and clinical characteristics, occupation, and occupational exposures. The primary outcome measures were exacerbations determined over a 1-year course after enrollment by quarterly telephone calls and at an annual research clinic visit. The odds ratio (OR) and incidence rate ratio (IRR) of exacerbations that required treatment with medications, including steroids or antibiotics (total exacerbations), and exacerbations leading to hospitalization (severe exacerbations) were determined after adjusting for relevant covariates.Results: Rural residence was independently associated with a 70% increase in the odds of total exacerbations (OR, 1.70 [95% confidence interval (CI), 1.13-2.56]; P = 0.012) and a 46% higher incidence rate of total exacerbations (IRR 1.46 [95% CI, 1.02-2.10]; P = 0.039). There was no association between rural residence and severe exacerbations. Agricultural occupation was independently associated with increased odds and incidence of total and severe exacerbations. Inclusion of agricultural occupation in the analysis attenuated the association between rural residence and the odds and incidence rate of total exacerbations (OR, 1.52 [95% CI, 1.00-2.32]; P = 0.05 and IRR 1.39 [95% CI, 0.97-1.99]; P = 0.07). There was no difference in symptoms or airflow obstruction between rural and urban participants.Conclusions: Rural residence is independently associated with increased odds and incidence of total, but not severe, COPD exacerbations. These associations are not fully explained by agriculture-related exposures, highlighting the need for future research into potential mechanisms of the increased risk of COPD exacerbations in the rural population.

Published
2018

23. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

Author

Hastie, Annette T, Martinez, Fernando J, Curtis, Jeffrey L, Doerschuk, Claire M, Hansel, Nadia N, Christenson, Stephanie, Putcha, Nirupama, Ortega, Victor E, Li, Xingnan, Barr, R Graham, Carretta, Elizabeth E, Couper, David J, Cooper, Christopher B, Hoffman, Eric A, Kanner, Richard E, Kleerup, Eric, O'Neal, Wanda K, Paine, Richard, Peters, Stephen P, Alexis, Neil E, Woodruff, Prescott G, Han, MeiLan K, Meyers, Deborah A, Bleecker, Eugene R, investigators, SPIROMICS, Anderson, Wayne H, Boucher, Richard C, Bowler, Russell P, Christenson, Stephanie A, Comellas, Alejandro P, Criner, Gerard J, Crystal, Ronald G, Dransfield, Mark T, Freeman, Christine M, Kaner, Robert J, Kleerup, Eric C, Krishnan, Jerry A, LaVange, Lisa M, Lazarus, Stephen C, Newell, John D, Oelsner, Elizabeth C, Paine, Robert, Rennard, Stephen I, Tashkin, Donald P, Scholand, Mary Beth, Wells, J Michael, and Wise, Robert A

Subjects
Clinical Research, Lung, Chronic Obstructive Pulmonary Disease, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Respiratory, Adrenal Cortex Hormones, Aged, Biomarkers, Bronchodilator Agents, Eosinophils, Female, Forced Expiratory Volume, Humans, Leukocyte Count, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, ROC Curve, Severity of Illness Index, Sputum, SPIROMICS investigators, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundIncreased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils.MethodsWe did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344).FindingsOf the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (

Published
2017

26. Genetic Evaluation of Male Infertility

Author

Fakhro, Khalid A., Robay, Amal, Rodriguez-Flores, Juan L., Crystal, Ronald G., Arafa, Mohamed, editor, Elbardisi, Haitham, editor, Majzoub, Ahmad, editor, and Agarwal, Ashok, editor

Published
2020
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27. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

Author

Han, MeiLan K, Quibrera, Pedro M, Carretta, Elizabeth E, Barr, R Graham, Bleecker, Eugene R, Bowler, Russell P, Cooper, Christopher B, Comellas, Alejandro, Couper, David J, Curtis, Jeffrey L, Criner, Gerard, Dransfield, Mark T, Hansel, Nadia N, Hoffman, Eric A, Kanner, Richard E, Krishnan, Jerry A, Martinez, Carlos H, Pirozzi, Cheryl B, O'Neal, Wanda K, Rennard, Stephen, Tashkin, Donald P, Wedzicha, Jadwiga A, Woodruff, Prescott, Paine, Robert, Martinez, Fernando J, investigators, SPIROMICS, Alexis, Neil E, Anderson, Wayne H, Boucher, Richard C, Christenson, Stephanie A, Comellas, Alejandro P, Criner, Gerard J, Crystal, Ronald G, Doerschuk, Claire M, Freeman, Christine M, Hastie, Annette T, Kaner, Robert J, Kleerup, Eric C, LaVange, Lisa M, Lazarus, Stephen C, Meyers, Deborah A, Newell, John D, Oelsner, Elizabeth C, Putcha, Nirupama, Rennard, Stephen I, Scholand, Mary Beth, Wells, J Michael, Wise, Robert A, and Woodruff, Prescott G

Subjects
Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 2.4 Surveillance and distribution, Aetiology, Respiratory, Adult, Aged, Aged, 80 and over, Biomarkers, Disease Progression, Female, Forced Expiratory Volume, Humans, Interleukin-15, Interleukin-8, Logistic Models, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Spirometry, Time Factors, Tomography, X-Ray Computed, SPIROMICS investigators, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundPresent treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time.MethodsIn this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40-80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1-4) on the basis of post-bronchodilator FEV1. Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344.Findings2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations.InterpretationAlthough acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations.FundingNational Institutes of Health, and National Heart, Lung, and Blood Institute.

Published
2017

28. Associations Among 25-Hydroxyvitamin D Levels, Lung Function, and Exacerbation Outcomes in COPD: An Analysis of the SPIROMICS Cohort

Author

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

Published
2020
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31. Predicted Deleterious Variants in the Human Genome with the Potential to Influence Effectiveness of Gene Therapy with Adeno-associated Virus Vectors

Author

Rostami, Mahboubeh R., primary, Leopold, Philip L., additional, Vasquez, Jenifer M., additional, de Mulder Rougvie, Miguel, additional, Al Shakaki, Alya, additional, Hssain, Ali Ait, additional, Robay, Amal, additional, Hackett, Neil R., additional, Mezey, Jason G., additional, and Crystal, Ronald G., additional

Published
2023
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39. Aspirin Use and Respiratory Morbidity in COPD: A Propensity Score-Matched Analysis in Subpopulations and Intermediate Outcome Measures in COPD Study

Author

Alexis, Neil E., Anderson, Wayne H., Barjaktarevic, Igor, Barr, R. Graham, Bleecker, Eugene R., Boucher, Richard C., Bowler, Russell P., Carretta, Elizabeth E., Christenson, Stephanie A., Comellas, Alejandro P., Cooper, Christopher B., Couper, David J., Criner, Gerard J., Crystal, Ronald G., Curtis, Jeffrey L., Doerschuk, Claire M., Dransfield, Mark T., Freeman, Christine M., Han, MeiLan K., Hansel, Nadia N., Hastie, Annette T., Hoffman, Eric A., Kaner, Robert J., Kanner, Richard E., Kleerup, Eric C., Krishnan, Jerry A., LaVange, Lisa M., Lazarus, Stephen C., Martinez, Fernando J., Meyers, Deborah A., Moore, Wendy C., Newell, John D., Jr., Paulin, Laura, Peters, Stephen, Pirozzi, Cheryl, Oelsner, Elizabeth C., O’Neal, Wanda K., Ortega, Victor E., Paine, Robert, III, Putcha, Nirupama, Raman, Sanjeev, Rennard, Stephen I., Tashkin, Donald P., Wells, J. Michael, Wise, Robert A., Woodruff, Prescott G., Fawzy, Ashraf, Aaron, Carrie P., Labaki, Wassim W., Paulin, Laura M., Peters, Stephen P., and Wise, Robert

Published
2019
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40. Gene therapy: charting a future course--summary of a National Institutes of Health Workshop, April 12, 2013.

Author

O'Reilly, Marina, Federoff, Howard J, Fong, Yuman, Kohn, Donald B, Patterson, Amy P, Ahmed, Nabil, Asokan, Aravind, Boye, Shannon E, Crystal, Ronald G, De Oliveira, Satiro, Gargiulo, Linda, Harper, Scott Q, Ikeda, Yasuhiro, Jambou, Robert, Montgomery, Maureen, Prograis, Lawrence, Rosenthal, Eugene, Sterman, Daniel H, Vandenberghe, Luk H, Zoloth, Laurie, Abedi, Mehrdad, Adair, Jennifer, Adusumilli, Prasad S, Goins, William F, Gray, Jhanelle, Monahan, Paul, Popplewell, Leslie, Sena-Esteves, Miguel, Tannous, Bakhos, Weber, Thomas, Wierda, William, Gopal-Srivastava, Rashmi, McDonald, Cheryl L, Rosenblum, Daniel, and Corrigan-Curay, Jacqueline

Subjects
Animals, Education, Continuing, Genetic Research, Genetic Therapy: economics, ethics, legislation & jurisprudence, Genetic Vectors, Humans, National Institutes of Health (U.S.), Stem Cell Research, Stem Cell Transplantation, Transduction, Genetic, United States
Abstract

Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances.

Published
2014

41. Repeatability of Pulmonary Quantitative Computed Tomography Measurements in Chronic Obstructive Pulmonary Disease

Author

Motahari, Amin, primary, Barr, R. Graham, additional, Han, MeiLan K., additional, Anderson, Wayne H., additional, Barjaktarevic, Igor, additional, Bleecker, Eugene R., additional, Comellas, Alejandro P., additional, Cooper, Christopher B., additional, Couper, David J., additional, Hansel, Nadia N., additional, Kanner, Richard E., additional, Kazerooni, Ella A., additional, Lynch, David A., additional, Martinez, Fernando J., additional, Newell, John D., additional, Schroeder, Joyce D., additional, Smith, Benjamin M., additional, Woodruff, Prescott G., additional, Hoffman, Eric A., additional, Alexis, Neil E., additional, Arjomandi, Mehrdad, additional, Basta, Patricia, additional, Bateman, Lori A., additional, Bellinger, Christina, additional, Bhatt, Surya P., additional, Boucher, Richard C., additional, Bowler, Russell P., additional, Buhr, Russell G., additional, Christenson, Stephanie A., additional, Criner, Gerard J., additional, Crystal, Ronald G., additional, Curtis, Jeffrey L., additional, Doerschuk, Claire M., additional, Dransfield, Mark T., additional, Drummond, M. Bradley, additional, Freeman, Christine M., additional, Galban, Craig, additional, Gershner, Katherine, additional, Hastie, Annette T., additional, Huang, Yvonne J., additional, Kaner, Robert J., additional, Kesimer, Mehmet, additional, Kleerup, Eric C., additional, Krishnan, Jerry A., additional, Labaki, Wassim W., additional, LaVange, Lisa M., additional, Lazarus, Stephen C., additional, McDonald, Merry-Lynn, additional, Meyers, Deborah A., additional, Moore, Wendy C., additional, Oelsner, Elizabeth C., additional, Ohar, Jill, additional, O’Neal, Wanda K., additional, Ortega, Victor E., additional, Paine, Robert, additional, Paulin, Laura, additional, Peters, Stephen P., additional, Pirozzi, Cheryl, additional, Putcha, Nirupama, additional, Raman, Sanjeev, additional, Rennard, Stephen I., additional, Tashkin, Donald P., additional, Wells, J. Michael, additional, Wise, Robert A., additional, Postow, Lisa, additional, and Viviano, Lisa, additional

Published
2023
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42. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease

Author

De, Bishnu P., primary, Rosenberg, Jonathan B., additional, Selvan, Nithya, additional, Wilson, Isabelle, additional, Yusufzai, Nadir, additional, Greco, Alessandria, additional, Kaminsky, Stephen M., additional, Heier, Linda A., additional, Ricart Arbona, Rodolfo J., additional, Miranda, Ileana C., additional, Monette, Sebastien, additional, Nair, Anju, additional, Khanna, Richie, additional, Crystal, Ronald G., additional, and Sondhi, Dolan, additional

Published
2023
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46. List of Contributors

Author

Abramson, Jakub, primary, Ahmed, S. Sohail, additional, Alba, Marco A., additional, Ali, Youssif M., additional, Ambrus, Julian L., additional, Andersson Svärd, Agnes, additional, Aringer, Martin, additional, Assassi, Shervin, additional, Aung, Thanda, additional, Ayzenberg, Ilya, additional, Barker, Robert N., additional, Baxter, Alan G., additional, Betterle, Corrado, additional, Birlea, Stanca A., additional, Björkström, Niklas K., additional, Blair, Paul A., additional, Blüml, Stephan, additional, Bosch, Xavier, additional, Brodsky, Robert A., additional, Bryceson, Yenan T., additional, Burkett, Patrick R., additional, Bussel, James B., additional, Caricchio, Roberto, additional, Casciola-Rosen, Livia, additional, Caturegli, Patrizio, additional, Chaigne-Delalande, Benjamin, additional, Chalan, Paulina, additional, Chatenoud, Lucienne, additional, Cohen, Philip L., additional, Cooper, Megan A., additional, Coppieters, Ken, additional, Crystal, Ronald G., additional, Culton, Donna A., additional, Damato, Valentina, additional, Davidson, Anne, additional, Delfino, Lorenzo, additional, Delves, Peter J., additional, Di Dalmazi, Giulia, additional, Diamond, Betty, additional, Diaz, Luis A., additional, Falk, Ronald J., additional, Fritzler, Marvin J., additional, Gallucci, Stefania, additional, Gangaputra, Sapna, additional, Gelbman, Brian, additional, Gershwin, M. Eric, additional, Gery, Igal, additional, Getts, Daniel R., additional, Gold, Ralf, additional, Goldfarb, Yael, additional, Gong, Jing, additional, Gordon, Siamon, additional, Goronzy, Jörg J., additional, Greer, Judith M., additional, Guazzone, Vanesa A., additional, Guilherme, Luiza, additional, Hafler, David A., additional, Hahn, Bevra H., additional, Hamad, Abdel Rahim A., additional, Hamano, Hideaki, additional, Harrison, Leonard C., additional, Homann, Dirk, additional, Husebye, Eystein S., additional, Jennette, J. Charles, additional, Jones, Richard J., additional, Jordan, Margaret A., additional, Kalil, Jorge, additional, Kawa, Shigeyuki, additional, Kaya, Ziya, additional, Keller, Christian W., additional, King, Nicholas J.C., additional, Kitcharoensakkul, Maleewan, additional, Kiyosawa, Kendo, additional, Königs, Christoph, additional, Kronenberg, Mitchell, additional, Kuchroo, Vijay K., additional, Laurence, Arian, additional, Lee, Eun-Ju, additional, Lehmann, Helmar C., additional, Lernmark, Åke, additional, Lindbladh, Ida, additional, Liu, Zhi, additional, Ljunggren, Hans-Gustaf, additional, Lunardi, Claudio, additional, Lundin, Knut E.A., additional, Lünemann, Jan D., additional, Lunn, Michael P.T., additional, Lustig, Livia, additional, Mackay, Charles R., additional, Mackay, Ian R., additional, Malattia, Clara, additional, Martinez-Pomares, Luisa, additional, Martini, Alberto, additional, Mauri, Claudia, additional, McCombe, Pamela A., additional, Melchers, Fritz, additional, Mieli-Vergani, Giorgina, additional, Miller, Frederick W., additional, Miller, Stephen D., additional, Mizui, Masayuki, additional, Mjösberg, Jenny, additional, Münz, Christian, additional, Nijjar, Jagtar Singh, additional, Norris, David A., additional, Oleinika, Kristine, additional, Oppenheim, Joost J., additional, Pawlak, Mathias, additional, Peligero-Cruz, Cristina, additional, Peters, Anneli, additional, Peterson, Pärt, additional, Pitarokoili, Kalliopi, additional, Presotto, Fabio, additional, Puccetti, Antonio, additional, Rabb, Hamid, additional, Raczek, Patricia, additional, Rahman, M. Jubayer, additional, Ramos-Casals, Manuel, additional, Rose, Noel R., additional, Rosen, Antony, additional, Sadasivam, Mohanraj, additional, Schiffenbauer, Adam, additional, Schwaeble, Wilhelm J., additional, Sen, H. Nida, additional, Serota, Marc, additional, Sheikh, Kazim A., additional, Shoenfeld, Yehuda, additional, Shovman, Ora, additional, Sieper, Joachim, additional, Silverstein, Arthur M., additional, Sim, Robert B., additional, Smith, Kenneth G C, additional, Smolen, Josef S., additional, Sollid, Ludvig M., additional, Spiteri, Alanna, additional, Steinman, Lawrence, additional, Stone, John H., additional, Syrbe, Uta, additional, Tamhaney, Ami, additional, Tanaka, Atsushi, additional, Taneja, Veena, additional, Tarbell, Kristin V., additional, Tinazzi, Elisa, additional, Tiong, Benedict K., additional, Toh, Ban-Hock, additional, Tsokos, George C., additional, Tung, Kenneth S.K., additional, Varga, John, additional, Vergani, Diego, additional, Vickers, Mark A., additional, Viegas, Stuart, additional, Vincent, Angela, additional, von Herrath, Matthias, additional, Weetman, Anthony P., additional, Weinstock, Joel V., additional, Wentworth, John M., additional, Wesley, Sarah, additional, Weyand, Cornelia M., additional, Wingender, Gerhard, additional, Winter, Michael W., additional, Zanchetta, Renato, additional, and Zouali, Moncef, additional

Published
2020
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48. List of contributors

Author

Abe, Masashi, primary, Ahlstrom, Jon D., additional, Albon, Julie, additional, Allickson, Julie, additional, Almeida-Porada, Graça, additional, Altschuler, Richard A., additional, Anderson, Daniel G., additional, Annabi, Nasim, additional, Arcidiacono, Judith, additional, Ashammakhi, Nureddin, additional, Atala, Anthony, additional, Athanasiou, Kyriacos A., additional, Awad, Hani A., additional, Badylak, Stephen F, additional, Balachander, Gowri, additional, Balkan, Wayne, additional, Bara, Jennifer J., additional, Barry, Michael P., additional, Baskaran, Harihara, additional, Bedell, Matthew L., additional, Belcher, Donald Andrew, additional, Berry, David B., additional, Bhat, Hina, additional, Bhat, Zuhaib F., additional, Bhatia, Sangeeta N., additional, Blackburn, Catherine Clare, additional, Blocki, Anna, additional, Blum, Kevin M., additional, Bochenek, Matthew A., additional, Bonassar, Lawrence J., additional, Bonventre, Joseph V., additional, Borrelli, Mimi R., additional, Bowles, Robby D., additional, Bradshaw, Amy D., additional, Bratt-Leal, Andres M., additional, Breuer, Christopher K., additional, Brewster, Luke, additional, Brey, Eric M., additional, Briquez, Priscilla S., additional, Buckwalter, J.A., additional, Burg, Karen J.L., additional, Burg, Timothy C., additional, Byambaa, Batzaya, additional, Chandra, Prafulla K., additional, Chen, Amanda X., additional, Chen, Fa-Ming, additional, Chen, Shaochen, additional, Chesterman, Julian, additional, Chhabra, Arnav, additional, Chong, Seow Khoon, additional, Clark, Richard A.F., additional, Cleary, Muriel A., additional, Coleman, M., additional, Cotsarelis, George, additional, Crystal, Ronald G., additional, Dagnelie, Gislin, additional, Darabi, Mohammad Ali, additional, Davidson, Jeffrey M., additional, Davidson, Joseph, additional, De Coppi, Paolo, additional, Delcassian, Derfogail, additional, de Vos, Paul, additional, Dominijanni, Anthony, additional, Donahue, Ryan, additional, Drain, Allison P., additional, Duvall, Craig L., additional, Dziki, Jenna L., additional, Elgalad, Abdelmotagaly, additional, Eng, George, additional, Falanga, Vincent, additional, Farhang, Niloofar, additional, Ferreira, Lino, additional, Fink, Donald W., additional, Fleming, Heather E., additional, Fong, Peter, additional, Frey, Mark R., additional, Gay, Denise, additional, Gerecht, Sharon, additional, Gersbach, Charles A., additional, Gibbs, D.M.R., additional, Gidwani, Simran, additional, González Morales, Shaimar R., additional, Goyal, Ritu, additional, Grant, Maria B., additional, Gray, Andrea, additional, Greisler, Howard P., additional, Grikscheit, Tracy C., additional, Grosh, Karl, additional, Guilak, Farshid, additional, Guo, Jason L., additional, Han, Yingli, additional, Hare, Joshua M., additional, Hassanbhai, Ammar Mansoor, additional, Hatzistergos, Konstantinos, additional, Hay, David C., additional, He, Xiao-Tao, additional, Henderson, Timothy, additional, Hickerson, Darren, additional, Hickerson, Darren H.M., additional, Hmadcha, Abdelkrim, additional, Hochman-Mendez, Camila, additional, Huang, Chao, additional, Hubbell, Jeffrey A., additional, Huelsmann, Joern, additional, Huh, Jun Tae, additional, Hunsberger, Joshua G., additional, Iannucci, Leanne E., additional, Inoue, Haruhisa, additional, Jackson, John, additional, Jiang, Yangzi, additional, Kalinichenko, Vladimir V., additional, Kanczler, J.M., additional, Karp, Jeffrey M., additional, Kasper, F. Kurtis, additional, Khademhosseini, Ali, additional, Kim, Ji Hyun, additional, Kimbrel, Erin A., additional, Klimanskaya, Irina, additional, Kohn, Joachim, additional, Kumar, Sunil, additional, Kyriakides, Themis R., additional, Lake, Spencer P., additional, Lam, Johnny, additional, Langer, Robert, additional, Lanza, Robert, additional, Leach, Timothy S., additional, Lee, Benjamin W., additional, Lee, Iris, additional, Lee, Sang Jin, additional, Li, David, additional, Li, Linheng, additional, Liu, Qian, additional, Ljubimov, Alexander V., additional, Lo, Chi, additional, Longaker, Michael T., additional, López-Beas, Javier, additional, Loring, Jeanne F., additional, Luo, Ying, additional, MacArthur, Ben D., additional, Madigan, Nicolas N., additional, Madry, Henning, additional, Magalhaes, Renata S., additional, Manley, Nancy Ruth, additional, Mansbridge, Jonathan, additional, Mao, Jeremy J., additional, Marshall, K.M., additional, Martin, J.A., additional, Martins-Green, M., additional, Maselli, Kathryn M., additional, Maxfield, Mark W., additional, McCracken, Kyle W., additional, Melville, James, additional, Mikos, Antonios G., additional, Millán, José del R., additional, Mirotsou, Maria, additional, Montoro, Daniel T., additional, Murphy, Matthew P., additional, Murphy, Sean V., additional, Musillo, Michael, additional, Muthukumaran, Padmalosini, additional, Navara, Adam M., additional, Nelson, Christopher E., additional, Niklason, Laura E., additional, Nowell, Craig Scott, additional, O’Keefe, Regis J., additional, O’Neill, Kathy E., additional, Oreffo, Richard O.C., additional, Ortiz, Ophir, additional, Palmer, Andre Francis, additional, Perdikis, Serafeim, additional, Petreaca, M., additional, Plikus, Maksim V., additional, Porada, Christopher D., additional, Post, Mark, additional, Prokop, Aleš, additional, Puri, Raj K., additional, Qian, Pengxu, additional, Radisic, Milica, additional, Raredon, Micha Sam Brickman, additional, Richie, Ellen Rothman, additional, Rouse, Paul, additional, Sadri-Ardekani, Hooman, additional, Saltzman, W. Mark, additional, Sampaio, Luiz C., additional, Schlieve, Christopher R., additional, Sha, Su-Hua, additional, Sharpe, Paul T., additional, Shastri, V. Prasad, additional, Shi, Yanhong, additional, Shupe, Thomas, additional, Sirabella, Dario, additional, Skardal, Aleksander, additional, Slack, J.M.W., additional, Sloan, Stephen R., additional, Soker, Shay, additional, Soria, Bernat, additional, Soria-Juan, Bárbara, additional, Stockdale, Frank E., additional, Stover, Josh, additional, Stransky, Thomas, additional, Stronks, H. Christiaan, additional, Stumpf, Patrick S., additional, Sung, Kyung Eun, additional, Swarr, Daniel, additional, Szkolnicka, Dagmara, additional, Takahashi, Jun, additional, Tang, D.K.O., additional, Tang, Winson, additional, Taylor, Doris A., additional, Teng, Yao, additional, Teoh, Swee Hin, additional, Smith, Anthony J., additional, Treffeisen, Elsa, additional, Tuan, Rocky S., additional, Vacanti, Joseph P., additional, van der Weele, Cor, additional, Vincent, Matthew, additional, Vunjak-Novakovic, Gordana, additional, Wahlberg, Lars U., additional, Wan, Derrick C., additional, Wang, Anne, additional, Wang, Dan, additional, Wang, Qiwei, additional, Wang, Yanling, additional, Wang, Yu-li, additional, Wang, Zhanwen, additional, Weaver, Valerie M., additional, Wells, J.A., additional, Welter, Jean F., additional, Wen, Feng, additional, Weston, Jake, additional, Whitsett, Jeffrey A., additional, Williams, James K., additional, Windebank, Anthony J., additional, Wong, Mark Eu-Kien, additional, Worgall, Stefan, additional, Wu, Iwen, additional, Wu, Rui-Xin, additional, Xie, Virginia Y., additional, Xing, Malcolm, additional, Yamada, Kenneth M., additional, Yamanaka, Shinya, additional, Yoo, James J., additional, Young, Simon, additional, Yu, Claire, additional, Yu, Hanry, additional, Yuan, Yifan, additional, Zacharias, William, additional, Zakko, Jason, additional, Zhang, Ai, additional, Zhang, Yuanyuan, additional, Zhang, Zheng, additional, Zhao, Chunfeng, additional, Zhao, Yimu, additional, and Zoloth, Laurie, additional

Published
2020
Full Text
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49. LB-2 | VEGF Gene Therapy Improves Exercise Time, Ischemia, and Symptoms in Patients with Refractory Angina: Results of the Phase II EXACT Trial

Author

Nakamura, Kenta, Henry, Timothy D., Traverse, Jay H., Latter, David A., Mokadam, Nahush A., Answini, Geoffrey A., Williams, Adam R., Sun, Benjamin, Burke, Christopher R., Bakaeen, Faisal G., DiCarli, Marcelo F., Chaitman, Bernard R., Peterson, Mark W., Byrnes, Dawn G., Ohman, E.M., Pepine, Carl J., Crystal, Ronald G., Rosengart, Todd K., Kowalewski, Elaine, Koch, Gary G., Dittrich, Howard C., and Povsic, Thomas Joseph

Published
2024
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