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1. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease.

Author

Ghosh, Auyon J, Hobbs, Brian D, Moll, Matthew, Saferali, Aabida, Boueiz, Adel, Yun, Jeong H, Sciurba, Frank, Barwick, Lucas, Limper, Andrew H, Flaherty, Kevin, Criner, Gerard, Brown, Kevin K, Wise, Robert, Martinez, Fernando J, Lomas, David, Castaldi, Peter J, Carey, Vincent J, DeMeo, Dawn L, Cho, Michael H, Silverman, Edwin K, Hersh, Craig P, Crapo, James D, Make, Barry J, Regan, Elizabeth A, Beaty, Terri H, El-Boueiz, Adel, Foreman, Marilyn G, Hayden, Lystra P, Hetmanski, Jacqueline, Hokanson, John E, Kim, Wonji, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Prokopenko, Dmitry, Morrow, Jarrett, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Ross, James C, Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Austin, Erin, Kinney, Gregory, Young, Kendra A, Bhatt, Surya P, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Pernicano, Perry G, and Hanania, Nicola

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Chronic Obstructive Pulmonary Disease, Lung, Emphysema, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Markers, Genotype, Heterozygote, Humans, Longitudinal Studies, Male, Middle Aged, Phenotype, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Survival Analysis, Whole Genome Sequencing, alpha 1-Antitrypsin, COPDGene Investigators, RNA sequencing, alpha-1 antitrypsin, chronic obstructive pulmonary disease, meta-analysis, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
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 FEV1% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV1 was 3.9% lower (95% confidence interval [CI], -6.55% to -1.26%) and emphysema (the percentage of lung attenuation areas

Published
2022

2. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author

Tejwani, Vickram, Fawzy, Ashraf, Putcha, Nirupama, Castaldi, Peter J, Cho, Michael H, Pratte, Katherine A, Bhatt, Surya P, Lynch, David A, Humphries, Stephen M, Kinney, Gregory L, D’Alessio, Franco R, Hansel, Nadia N, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bramvan, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Young, Kendra A, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Pernicano, Perry G, Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, and Guy, Elizabeth

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Emphysema, Lung, Tobacco, Chronic Obstructive Pulmonary Disease, Tobacco Smoke and Health, Cancer, Respiratory, Aged, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Cohort Studies, Disease Progression, Female, Forced Expiratory Volume, Humans, Lung Volume Measurements, Male, Middle Aged, Prospective Studies, Protective Factors, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Spirometry, Tomography, X-Ray Computed, Vital Capacity, Walk Test, angiotensin II, COPD, emphysema progression, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAttenuation 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 questionIs use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema?MethodsFormer 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

Published
2021

3. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Chandra, Divay, Gupta, Aman, Kinney, Gregory L, Fuhrman, Carl R, Leader, Joseph K, Diaz, Alejandro A, Bon, Jessica, Barr, R Graham, Washko, George, Budoff, Matthew, Hokanson, John, Sciurba, Frank C, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Boueiz, Adel R, Castaldi, Peter J, Cho, Michael, DeMeo, Dawn L, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Al Qaisi, Mustafa, Coxson, Harvey O, Gray, Teresa, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Newell, John D, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Wilson, Carla G, Jensen, Robert, Crooks, Jim, Everett, Douglas, Moore, Camille, Strand, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Bhatt, Surya, Martinez, Carlos, Murray, Susan, Soler, Xavier, Banaei-Kashani, Farnoush, Bowler, Russell P, Kechris, Katerina, Curtis, Jeffrey L, Pernicano, Perry G, Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, and Parulekar, Amit

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Tobacco Smoke and Health, Emphysema, Chronic Obstructive Pulmonary Disease, Atherosclerosis, Biomedical Imaging, Clinical Research, Heart Disease - Coronary Heart Disease, Heart Disease, Lung, Tobacco, Cardiovascular, Prevention, Respiratory, Good Health and Well Being, Airway Obstruction, Airway Remodeling, Asymptomatic Diseases, Biological Variation, Population, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, Middle Aged, Organ Size, Plethysmography, Pulmonary Emphysema, Respiratory Function Tests, Risk Factors, Smoking, Tomography, X-Ray Computed, United States, COPD, coronary artery disease, lung hyperinflation, smoking, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundSmokers manifest varied phenotypes of pulmonary impairment.Research questionWhich pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers?Study design and methodsWe 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 (FEV1 to FVC ratio, < 0.70).ResultsPulmonary 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). FEV1 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.InterpretationLung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV1 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

4. Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function The Genetic Epidemiology of COPD Study

Author

Pistenmaa, Carrie L, Nardelli, P, Ash, SY, Come, CE, Diaz, AA, Rahaghi, FN, Barr, RG, Young, KA, Kinney, GL, Simmons, JP, Wade, RC, Wells, JM, Hokanson, JE, Washko, GR, San José Estépar, R, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri H, Castaldi, Peter J, Cho, Michael H, DeMeo, Dawn L, Boueiz, Adel El, Foreman, Marilyn G, Ghosh, Auyon, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Kim, Wonji, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Prokopenko, Dmitry, Moll, Matthew, Morrow, Jarrett, Qiao, Dandi, Regan, Elizabeth, Saferali, Aabida, Sakornsakolpat, Phuwanat, Wan, Emily S, Yun, Jeong, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bramvan, van Rikxoort, Eva, Ferrero, Gonzalo Vegas Sanchez-, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Austin, Erin, Kinney, Gregory, Young, Kendra A, Bhatt, Surya P, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, and Curtis, Jeffrey L

Subjects
Emphysema, Tobacco, Tobacco Smoke and Health, Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, Biomedical Imaging, Respiratory, Disease Progression, Endothelium, Vascular, Female, Humans, Longitudinal Studies, Male, Middle Aged, Pulmonary Artery, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Smokers, Tomography, X-Ray Computed, emphysema, imaging, longitudinal, lung function, pulmonary circulation, COPDGene Investigators, Clinical Sciences, Respiratory System
Abstract

BackgroundPulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema.Research questionIs intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT imaging or decline in lung function over 5 years?Study design and methodsThe Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels < -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5 mm2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema.ResultsAt baseline, the 4,227 participants were 60 ± 9 years of age, 50% were women, 28% were Black, 47% were current smokers, and 41% had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95% CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV1 to FVC ratio was 68.5 ± 14.2% and declined 0.26%/y (95% CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95% CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning also was associated with a faster decline in FEV1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95% CI, -0.008 to -0.001%/y).InterpretationPulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression.Trial registryClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Published
2021

5. Machine Learning Characterization of COPD Subtypes Insights From the COPDGene Study

Author

Castaldi, Peter J, Boueiz, Adel, Yun, Jeong, San Jose Estepar, Raul, Ross, James C, Washko, George, Cho, Michael H, Hersh, Craig P, Kinney, Gregory L, Young, Kendra A, Regan, Elizabeth A, Lynch, David A, Criner, Gerald J, Dy, Jennifer G, Rennard, Stephen I, Casaburi, Richard, Make, Barry J, Crapo, James, Silverman, Edwin K, Hokanson, John E, Crapo, James D, Beaty, Terri, Begum, Ferdouse, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hetmanski, Jacqueline, Hobbs, Brian D, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Bhatt, Surya P, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Soler, Xavier, Bowler, Russell P, and Kechris, Katerina

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Lung, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Cluster Analysis, Diagnostic Imaging, Disease Progression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Machine Learning, Molecular Epidemiology, Phenotype, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, COPD, emphysema, machine learning, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

Published
2020

6. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

Author

Young, Alexandra L, Bragman, Felix JS, Rangelov, Bojidar, Han, MeiLan K, Galbán, Craig J, Lynch, David A, Hawkes, David J, Alexander, Daniel C, Hurst, John R, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Qiao, Dandi, Wan, Emily S, Won, Sungho, Sakornsakolpat, Phuwanat, Prokopenko, Dmitry, Al Qaisi, Mustafa, Coxson, Harvey O, Gray, Teresa, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Newell, John D, Ross, James C, Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Bhatt, Surya, Bon, Jessica, Martinez, Carlos, Murray, Susan, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Barr, R Graham, Austin, John, D’Souza, Belinda, Pearson, Gregory DN, Rozenshtein, Anna, Thomashow, Byron, MacIntyre, Neil, McAdams, H Page, Washington, Lacey, McEvoy, Charlene, and Tashjian, Joseph

Subjects
Biomedical Imaging, Lung, Clinical Research, Chronic Obstructive Pulmonary Disease, Aetiology, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Respiratory, Aged, Disease Progression, Female, Humans, Male, Middle Aged, Models, Theoretical, Pulmonary Disease, Chronic Obstructive, Tomography, X-Ray Computed, clustering, CT imaging, emphysema, bronchitis, chronic obstructive pulmonary disease, COPDGene Investigators, Medical and Health Sciences, Respiratory System
Abstract

Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P

Published
2020

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

Author

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

Published
2023
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8. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure: A Longitudinal Follow-up Study of the COPDGene Cohort

Author

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

Published
2023
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9. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Author

Yun, Jeong H, Lamb, Andrew, Chase, Robert, Singh, Dave, Parker, Margaret M, Saferali, Aabida, Vestbo, Jørgen, Tal-Singer, Ruth, Castaldi, Peter J, Silverman, Edwin K, Hersh, Craig P, Crapo, James D, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Busch, Robert, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hansel, Nadia N, Hardin, Megan E, Hayden, Lystra P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Qiao, Dandi, Santorico, Stephanie, Silverman, E, Wan, Emily S, Won, Sungho, Qaisi, Mustafa Al, Coxson, Harvey O, Gray, Teresa, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Newell, John D, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Hersh, Craig, Barr, R Graham, Austin, John, D'Souza, Belinda, Pearson, Gregory DN, and Rozenshtein, Anna

Subjects
Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, Respiratory, Aged, Disease Progression, Eosinophils, Female, Humans, Leukocyte Count, Longitudinal Studies, Male, Middle Aged, Observational Studies as Topic, Pulmonary Disease, Chronic Obstructive, Chronic obstructive pulmonary disease, asthma, eosinophil, exacerbation, COPDGene and ECLIPSE Investigators, Immunology, Allergy
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). A subset 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 300 cells/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 300 cells/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 300 cells/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 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Published
2018

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

Author

Boueiz, Adel, Chang, Yale, Cho, Michael H, Washko, George R, San José Estépar, Raul, Bowler, Russell P, Crapo, James D, DeMeo, Dawn L, Dy, Jennifer G, Silverman, Edwin K, Castaldi, Peter J, Crapo, James, Silverman, Edwin, Make, Barry, Regan, Elizabeth, Beaty, Terri, Laird, Nan, Lange, Christoph, Santorico, Stephanie, Hokanson, John, DeMeo, Dawn, Hansel, Nadia, Hersh, Craig, Castaldi, Peter, McDonald, Merry-Lynn, Wan, Emily, Hardin, Megan, Hetmanski, Jacqueline, Parker, Margaret, Foreman, Marilyn, Hobbs, Brian, Busch, Robert, Qiao, Dandi, Halper-Stromberg, Eitan, Begum, Ferdouse, Won, Sungho, Lutz, Sharon, Lynch, David A, Coxson, Harvey O, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Newell, John D, Ross, James C, Estépar, Raul José, Stoel, Berend C, Tschirren, Juerg, van Rikxoort, Eva, van Ginneken, Bram, Wilson, Carla G, Qaisi, Mustafa Al, Gray, Teresa, Kluiber, Alex, Mann, Tanya, Sieren, Jered, Stinson, Douglas, Schroeder, Joyce, Van Beek, Edwin, Jensen, Robert, Everett, Douglas, Faino, Anna, Strand, Matt, Wilson, Carla, Hokanson, John E, Kinney, Gregory, Young, Kendra, Pratte, Katherine, Duca, Lindsey, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Bandi, Venkata, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, Nachiappan, Arun, Jacobson, Francine, Barr, R Graham, Thomashow, Byron, Austin, John, D’Souza, Belinda, and Pearson, Gregory DN

Subjects
Clinical Research, Chronic Obstructive Pulmonary Disease, Lung, Emphysema, Prevention, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Aged, Comorbidity, Disease Progression, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Pulmonary Emphysema, Severity of Illness Index, Tomography, X-Ray Computed, clustering, COPD, COPD disease progression, emphysema distribution, machine learning, COPDGene Investigators, Clinical Sciences, Respiratory System
Abstract

BackgroundEmphysema 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.MethodsWe 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.ResultsThree 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.ConclusionsSubgroups 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

11. Machine Learning Characterization of COPD Subtypes: Insights From the COPDGene Study

Author

Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S., Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O., Galban, Craig J., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Nardelli, Pietro, Newell, John D., Jr., Notary, Aleena, Oh, Andrea, Ross, James C., Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R., Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Young, Kendra A., Bhatt, Surya P., Bon, Jessica, Diaz, Alejandro A., Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Bowler, Russell P., Kechris, Katerina, Banaei-Kashani, Farnoush, Boueiz, Adel, Yun, Jeong, Washko, George, Cho, Michael H., Kinney, Gregory L., Criner, Gerald J., Dy, Jennifer G., Rennard, Stephen I., Casaburi, Richard, and Crapo, James

Published
2020
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12. SPIROMICS Protocol for Multicenter Quantitative Computed Tomography to Phenotype the Lungs

Author

Sieren, Jered P, Newell, John D, Barr, R Graham, Bleecker, Eugene R, Burnette, Nathan, Carretta, Elizabeth E, Couper, David, Goldin, Jonathan, Guo, Junfeng, Han, MeiLan K, Hansel, Nadia N, Kanner, Richard E, Kazerooni, Ella A, Martinez, Fernando J, Rennard, Stephen, Woodruff, Prescott G, and Hoffman, Eric A

Subjects
Lung, Clinical Research, Biomedical Imaging, Chronic Obstructive Pulmonary Disease, Respiratory, Asthma, Body Mass Index, Emphysema, Humans, Lung Diseases, Lung Volume Measurements, Multicenter Studies as Topic, Multidetector Computed Tomography, Phenotype, Predictive Value of Tests, Pulmonary Disease, Chronic Obstructive, Sensitivity and Specificity, lung imaging, chronic obstructive pulmonary disease, asthma, pulmonary parenchyma, pulmonary airways, SPIROMICS Research Group, Medical and Health Sciences, Respiratory System
Abstract

Multidetector row computed tomography (MDCT) is increasingly taking a central role in identifying subphenotypes within chronic obstructive pulmonary disease (COPD), asthma, and other lung-related disease populations, allowing for the quantification of the amount and distribution of altered parenchyma along with the characterization of airway and vascular anatomy. The embedding of quantitative CT (QCT) into a multicenter trial with a variety of scanner makes and models along with the variety of pressures within a clinical radiology setting has proven challenging, especially in the context of a longitudinal study. SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), sponsored by the National Institutes of Health, has established a QCT lung assessment system (QCT-LAS), which includes scanner-specific imaging protocols for lung assessment at total lung capacity and residual volume. Also included are monthly scanning of a standardized test object and web-based tools for subject registration, protocol assignment, and data transmission coupled with automated image interrogation to assure protocol adherence. The SPIROMICS QCT-LAS has been adopted and contributed to by a growing number of other multicenter studies in which imaging is embedded. The key components of the SPIROMICS QCT-LAS along with evidence of implementation success are described herein. While imaging technologies continue to evolve, the required components of a QCT-LAS provide the framework for future studies, and the QCT results emanating from SPIROMICS and the growing number of other studies using the SPIROMICS QCT-LAS will provide a shared resource of image-derived pulmonary metrics.

Published
2016

13. Comparison of breathing gated CT images generated using a 5DCT technique and a commercial clinical protocol in a porcine model

Author

O'Connell, Dylan P, Thomas, David H, Dou, Tai H, Lamb, James M, Feingold, Franklin, Low, Daniel A, Fuld, Matthew K, Sieren, Jered P, Sloan, Chelsea M, Shirk, Melissa A, Hoffman, Eric A, and Hofmann, Christian

Subjects
Lung, Bioengineering, Biomedical Imaging, Respiratory, Algorithms, Animals, Male, Models, Animal, Models, Biological, Motion, Radiation Dosage, Respiration, Respiratory-Gated Imaging Techniques, Swine, Tomography, X-Ray Computed, 4DCT, breathing motion modeling, Other Physical Sciences, Biomedical Engineering, Oncology and Carcinogenesis, Nuclear Medicine & Medical Imaging
Abstract

PurposeTo demonstrate that a "5DCT" technique which utilizes fast helical acquisition yields the same respiratory-gated images as a commercial technique for regular, mechanically produced breathing cycles.MethodsRespiratory-gated images of an anesthetized, mechanically ventilated pig were generated using a Siemens low-pitch helical protocol and 5DCT for a range of breathing rates and amplitudes and with standard and low dose imaging protocols. 5DCT reconstructions were independently evaluated by measuring the distances between tissue positions predicted by a 5D motion model and those measured using deformable registration, as well by reconstructing the originally acquired scans. Discrepancies between the 5DCT and commercial reconstructions were measured using landmark correspondences.ResultsThe mean distance between model predicted tissue positions and deformably registered tissue positions over the nine datasets was 0.65 ± 0.28 mm. Reconstructions of the original scans were on average accurate to 0.78 ± 0.57 mm. Mean landmark displacement between the commercial and 5DCT images was 1.76 ± 1.25 mm while the maximum lung tissue motion over the breathing cycle had a mean value of 27.2 ± 4.6 mm. An image composed of the average of 30 deformably registered images acquired with a low dose protocol had 6 HU image noise (single standard deviation) in the heart versus 31 HU for the commercial images.ConclusionsAn end to end evaluation of the 5DCT technique was conducted through landmark based comparison to breathing gated images acquired with a commercial protocol under highly regular ventilation. The techniques were found to agree to within 2 mm for most respiratory phases and most points in the lung.

Published
2015

14. The St. George’s Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

Author

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

Published
2019
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15. Residual Volume versus FRC Computed Tomography Assessment of Functional Small Airway Disease in Smokers with and without Chronic Obstructive Pulmonary Disease

Author

Comellas, Alejandro P., primary, Newell, John D., additional, Kirby, Miranda, additional, Sieren, Jered P., additional, Peterson, Sam, additional, Hatt, Charles, additional, Galban, Craig J., additional, Kazerooni, Ella A., additional, Lynch, David A., additional, Han, MeiLan K., additional, and Hoffman, Eric A., additional

Published
2023
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16. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease

Author

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

Published
2023
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17. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

Author

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

Published
2023
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21. Development of a Blood-based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease

Author

Moll, Matthew, primary, Boueiz, Adel, additional, Ghosh, Auyon J., additional, Saferali, Aabida, additional, Lee, Sool, additional, Xu, Zhonghui, additional, Yun, Jeong H., additional, Hobbs, Brian D., additional, Hersh, Craig P., additional, Sin, Don D., additional, Tal-Singer, Ruth, additional, Silverman, Edwin K., additional, Cho, Michael H., additional, Castaldi, Peter J., additional, Crapo, James D., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Prokopenko, Dmitry, additional, Qiao, Dandi, additional, Sakornsakolpat, Phuwanat, additional, Wan, Emily S., additional, Centeno, Juan Pablo, additional, Charbonnier, Jean-Paul, additional, Coxson, Harvey O., additional, Galban, Craig J., additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Nardelli, Pietro, additional, Newell, John D., additional, Notary, Aleena, additional, Oh, Andrea, additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Vegas Sanchez-Ferrero, Gonzalo, additional, Veitel, Lucas, additional, Washko, George R., additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Pratte, Katherine, additional, Strand, Matt, additional, Kinney, Gregory, additional, Young, Kendra A., additional, Bhatt, Surya P., additional, Bon, Jessica, additional, Diaz, Alejandro A., additional, Murray, Susan, additional, Soler, Xavier, additional, Bowler, Russell P., additional, Kechris, Katerina, additional, and Banaei-Kashani, Farnoush, additional

Published
2022
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22. 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

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

Published
2022
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24. THE ASSOCIATION OF VOXEL-LEVEL LUNG DEFORMATION INDICES WITH AIRFLOW OBSTRUCTION IN POST-HEMATOPOIETIC CELL TRANSPLANTATION BRONCHIOLITIS OBLITERANS SYNDROME

Author

Bertini, Christopher, primary, Hernandez, Maria, additional, Alousi, Amin, additional, Mehta, Rohtesh, additional, Bashoura, Lara, additional, Hasan Arain, Muhammad, additional, Noor, Laila, additional, Montanez, Diana, additional, Popat, Uday, additional, Hosing, Chitra, additional, Rondon, Gabriela, additional, Jennings, Kristofer, additional, Godoy, Myrna, additional, Layman, Rick, additional, McEleney, Stephen, additional, Sieren, Jered, additional, Castro, Mario, additional, Paczesny, Sophie, additional, Hoffman, Eric, additional, Ost, David, additional, Champlin, Richard, additional, Dickey, Burton, additional, and Sheshadri, Ajay, additional

Published
2021
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26. Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts

Author

Trivedi, Abhaya P., Hall, Chase, Goss, Charles W., Lew, Daphne, Krings, James G., McGregor, Mary Clare, Samant, Maanasi, Sieren, Jered P., Li, Huashi, Schechtman, Ken B., Schirm, Joshua, McEleney, Stephen, Peterson, Sam, Moore, Wendy C., Bleecker, Eugene R., Meyers, Deborah A., Israel, Elliot, Washko, George R., Levy, Bruce D., Leader, Joseph K., Wenzel, Sally E., Fahy, John V., Schiebler, Mark L., Fain, Sean B., Jarjour, Nizar N., Mauger, David T., Reinhardt, Joseph M., Newell, John D., Hoffman, Eric A., Castro, Mario, and Sheshadri, Ajay

Abstract

BackgroundClustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes.PurposeTo determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes.Materials and MethodsA retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models.ResultsA total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P< .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P< .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P< .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P< .001).ConclusionQuantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study.© RSNA, 2022Online supplemental material is available for this article.See also the editorial by Verschakelenin this issue.

Published
2022
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29. The St. George’s Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

Author

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

Published
2019
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30. Using Novel Computed Tomography Analysis to Describe the Contribution and Distribution of Emphysema and Small Airways Disease in Chronic Obstructive Pulmonary Disease

Author

Ostridge, Kristoffer, primary, Gove, Kerry, additional, Paas, Karlien H. W., additional, Burke, Hannah, additional, Freeman, Anna, additional, Harden, Stephen, additional, Kirby, Miranda, additional, Peterson, Sam, additional, Sieren, Jered, additional, McCrae, Chris, additional, Vaarala, Outi, additional, Staples, Karl J., additional, and Wilkinson, Tom M. A., additional

Published
2019
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31. Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease

Author

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

Published
2019
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32. Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution

Author

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

Published
2019
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34. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Author

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

Published
2018
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35. Inter‐ and intra‐software reproducibility of computed tomography lung density measurements.

Author

Kirby, Miranda, Hatt, Charles, Obuchowski, Nancy, Humphries, Stephen M., Sieren, Jered, Lynch, David A., and Fain, Sean B.

Subjects
COMPUTED tomography, LUNG volume measurements, SOFTWARE development tools, SOFTWARE measurement, OBSTRUCTIVE lung diseases
Abstract

Purpose: Multiple commercial, open‐source, and academic software tools exist for objective quantification of lung density in computed tomography (CT) images. The purpose of this study was to evaluate the intersoftware reproducibility of CT lung density measurements. Methods: Computed tomography images from 50 participants from the COPDGeneTM cohort study were randomly selected for analysis; n = 10 participants across each global initiative for chronic obstructive lung disease (GOLD) grade (GOLD 0–IV). Academic‐based groups (n = 4) and commercial vendors (n = 4) participated anonymously to generate CT lung density measurements using their software tools. Computed tomography total lung volume (TLV), percentage of the low attenuation areas in the lung with Hounsfield unit (HU) values below −950HU (LAA950), and the HU value corresponding to the 15th percentile on the parenchymal density histogram (Perc15) were included in the analysis. The intersoftware bias and reproducibility coefficient (RDC) was generated with and without quality assurance (QA) for manual correction of the lung segmentation; intrasoftware bias and RDC was also generated by repeated measurements on the same images. Results: Intersoftware mean bias was within ±0.22 mL, ±0.46%, and ±0.97 HU for TLV, LAA950 and Perc15, respectively. The RDC was 0.35 L, 1.2% and 1.8 HU for TLV, LAA950 and Perc15, respectively. Intersoftware RDC remained unchanged following QA: 0.35 L, 1.2% and 1.8 HU for TLV, LAA950 and Perc15, respectively. All software investigated had an intrasoftware RDC of 0. The RDC was comparable for TLV, LAA950 and Perc15 measurements, respectively, for academic‐based groups/commercial vendor‐based software tools: 0.39 L/0.32 L, 1.2%/1.2%, and 1.7 HU/1.6 HU. Multivariable regression analysis showed that academic‐based software tools had greater within‐subject standard deviation of TLV than commercial vendors, but no significant differences between academic and commercial groups were found for LAA950 or Perc15 measurements. Conclusions: Computed tomography total lung volume and lung density measurement bias and reproducibility was reported across eight different software tools. Bias was negligible across vendors, reproducibility was comparable for software tools generated by academic‐based groups and commercial vendors, and segmentation QA had negligible impact on measurement variability between software tools. In summary, results from this study report the amount of additional measurement variability that should be accounted for when using different software tools to measure lung density longitudinally with well‐standardized image acquisition protocols. However, intrasoftware reproducibility was deterministic for all cases so use of the same software tool to reduce variability for serial studies is highly recommended. [ABSTRACT FROM AUTHOR]

Published
2020
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36. Association of computed tomography densitometry with disease severity, functional decline, and survival in SSc-ILD.

Author

Saldana, Daniela Castillo, Hague, Cameron J., Murphy, Darra, Coxson, Harvey O., Tschirren, Juerg, Peterson, Sam, Sieren, Jered P., Kirby, Miranda, and Ryerson, Christopher J.

Subjects
COMPUTED tomography, SYSTEMIC scleroderma, INTERSTITIAL lung diseases, DENSITOMETRY, KURTOSIS, FIBROSIS
Abstract

A data supplement to the article "Association of Computed Tomography Densitometry With Disease Severity, Functional Decline and Survival in SSc-ILD" by Daniela Castillo Saldan, Cameron J. Hague, Darra Murphy and colleagues, that was published within the issue is presented. It shows baseline associations among quantitative computed tomography (qCT) variables such as skewness, kurtosis, and mean lung attenuation, visual fibrosis scores with pulmonary function, and unadjusted hazard ratios.

Published
2020
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37. Association of Computed Tomography Densitometry with Disease Severity, Functional Decline, and Survival in Systemic Sclerosis-associated Interstitial Lung Disease.

Author

Castillo Saldana, Daniela, Hague, Cameron J., Murphy, Darra, Coxson, Harvey O., Tschirren, Juerg, Peterson, Sam, Sieren, Jered P., Kirby, Miranda, Ryerson, Christopher J., and Saldana, Daniela Castillo

Subjects
SYSTEMIC scleroderma, INTERSTITIAL lung diseases, PULMONARY fibrosis, COMPUTED tomography, DENSITOMETRY, SURVIVAL, RESEARCH, RESEARCH methodology, REGRESSION analysis, RETROSPECTIVE studies, MEDICAL cooperation, EVALUATION research, SEVERITY of illness index, COMPARATIVE studies, PULMONARY function tests
Abstract

Rationale: Measuring disease extent and progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is challenging, with recent studies suggesting potential utility of quantitative measurements from computed tomography (CT) scans.Objectives: To determine the associations of quantitative computed tomography (qCT) density-based measures with physiological parameters, visual CT scores, and survival in patients with SSc-ILD.Methods: Patients with SSc-ILD and volumetric high-resolution CT images with ≤1.25-mm slice thickness were retrospectively identified. Cardiothoracic radiologists produced visual CT scores of ground glass, reticulation, and honeycombing, with visual fibrosis score equaling the sum of reticulation and honeycombing. qCT measurements included high-attenuation areas (HAA), skewness, kurtosis, and mean lung attenuation (MLA). Associations of qCT measures with pulmonary physiology, visual CT scores, and mortality were analyzed using Spearman's rank correlation and Cox regression.Results: A total of 503 CT scans from 170 patients with SSc-ILD were included. qCT HAA, skewness, kurtosis, and MLA were associated with lung function and visual fibrosis scores, independent of age, sex, and pack-years, using both baseline and change data. Baseline and changes in qCT measures (except ∆skewness) were associated with mortality on unadjusted analysis. Changes in all qCT variables remained associated with survival after adjustment for baseline age, sex, pack-years, and lung function, but not when adjusting for changes in lung function. ∆HAA and ∆MLA were associated with survival after adjustment for age, sex, pack-years, and change in visual CT scores.Conclusions: CT density measurements correlate with physiologic impairment and visual CT scores in patients with SSc-ILD; however, they were not associated with survival independent of changes in pulmonary physiology. The clinical utility of more sophisticated qCT measures should be explored. [ABSTRACT FROM AUTHOR]

Published
2020
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38. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

Author

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

Published
2018
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41. Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline

Author

Hayden, Lystra P., primary, Hardin, Megan E., additional, Qiu, Weiliang, additional, Lynch, David A., additional, Strand, Matthew J., additional, van Beek, Edwin J., additional, Crapo, James D., additional, Silverman, Edwin K., additional, Hersh, Craig P., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Boueiz, Adel R., additional, Busch, Robert, additional, Castaldi, Peter J., additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hansel, Nadia N., additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Qiao, Dandi, additional, Santorico, Stephanie, additional, Wan, Emily S., additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Newell, John D., additional, Ross, James C., additional, Estepar, Raul San Jose, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Crooks, Jim, additional, Everett, Douglas, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, and Young, Kendra A., additional

Published
2018
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42. A controlled statistical study to assess measurement variability as a function of test object position and configuration for automated surveillance in a multicenter longitudinal COPD study (SPIROMICS)

Author

Guo, Junfeng, Wang, Chao, Chan, Kung-Sik, Jin, Dakai, Saha, Punam K., Sieren, Jered P., Barr, R. G., Han, MeiLan K., Kazerooni, Ella, Cooper, Christopher B., Couper, David, Newell, John D., and Hoffman, Eric A.

Subjects
Models, Anatomic, Quality Control, Phantoms, Imaging, Air, Data Interpretation, Statistical, QUANTITATIVE IMAGING AND IMAGE PROCESSING, Multidetector Computed Tomography, Water, Longitudinal Studies, Pattern Recognition, Automated
Abstract

A test object (phantom) is an important tool to evaluate comparability and stability of CT scanners used in multicenter and longitudinal studies. However, there are many sources of error that can interfere with the test object-derived quantitative measurements. Here the authors investigated three major possible sources of operator error in the use of a test object employed to assess pulmonary density-related as well as airway-related metrics.Two kinds of experiments were carried out to assess measurement variability caused by imperfect scanning status. The first one consisted of three experiments. A COPDGene test object was scanned using a dual source multidetector computed tomographic scanner (Siemens Somatom Flash) with the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) inspiration protocol (120 kV, 110 mAs, pitch = 1, slice thickness = 0.75 mm, slice spacing = 0.5 mm) to evaluate the effects of tilt angle, water bottle offset, and air bubble size. After analysis of these results, a guideline was reached in order to achieve more reliable results for this test object. Next the authors applied the above findings to 2272 test object scans collected over 4 years as part of the SPIROMICS study. The authors compared changes of the data consistency before and after excluding the scans that failed to pass the guideline.This study established the following limits for the test object: tilt index ≤0.3, water bottle offset limits of [-6.6 mm, 7.4 mm], and no air bubble within the water bottle, where tilt index is a measure incorporating two tilt angles around x- and y-axis. With 95% confidence, the density measurement variation for all five interested materials in the test object (acrylic, water, lung, inside air, and outside air) resulting from all three error sources can be limited to ±0.9 HU (summed in quadrature), when all the requirements are satisfied. The authors applied these criteria to 2272 SPIROMICS scans and demonstrated a significant reduction in measurement variation associated with the test object.Three operator errors were identified which significantly affected the usability of the acquired scan images of the test object used for monitoring scanner stability in a multicenter study. The authors' results demonstrated that at the time of test object scan receipt at a radiology core laboratory, quality control procedures should include an assessment of tilt index, water bottle offset, and air bubble size within the water bottle. Application of this methodology to 2272 SPIROMICS scans indicated that their findings were not limited to the scanner make and model used for the initial test but was generalizable to both Siemens and GE scanners which comprise the scanner types used within the SPIROMICS study.

Published
2016

43. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Author

Adams, Sandra, Swift, Irene, El-Bouiez, Adel, Weissfeld, Joel, Guy, Elizabeth, Mann, Tanya, Qiao, Dandi, Maselli-Caceres, Diego, Hokanson, John E., McEvoy, Charlene, LaVange, Lisa M., O’Neal, Wanda K., Ruiz, Mario E., Kanner, Richard E., Ross, James C, Jacobson, Francine, Tschirren, Juerg, Fuhrman, Carl, Thompson, Brad, Kelsen, Steven, Chen, Ting-Huei, Humphries, Stephen, Bell, Brian, Al Qaisi, Mustafa, Jacobs, Michael, San Jose Estepar, Raul, Bowler, Russell, Dransfield, Mark, Alexis, Neil E., Cho, Michael, Newell, John, Crapo, James, Wilson, Carla, Curtis, Jeffrey L., Tashjian, Joseph, Rosiello, Richard, Rossiter, Harry, Swift, Alex, Washko, George, Peters, Stephen P., Fischer, Hans, Hardin, Megan, Stinson, Douglas, Adami, Alessandra, Lazarus, Stephen C., Cooper, Christopher B., Duca, Lindsey, Berkowitz, Eugene, Han, MeiLan K., Busch, Robert, Hoffman, Eric A., Anzueto, Antonio, Ciccolella, David, Han, MeiLan, Hansel, Nadia, Washington, Lacey, Castaldi, Peter, Desai, Parag, Wise, Robert A., Begum, Ferdouse, Parulekar, Amit, Sun, Wei, Cho, Michael H., Budoff, Matthew, Beaty, Terri, Strand, Matt, Kluiber, Alex, Judy, Philip F, Bailey, William, Soler, Xavier, Dransfield, Mark T., Regan, Elizabeth, Carretta, Elizabeth E., Parker, Margaret, Lynch, David A., Bhatt, Surya, Friedman, Paul, Everett, Douglas, Hawkins, Gregory A., Kechris, Katerina, Sieren, Jered, Lutz, Sharon, Sciurba, Frank, Wise, Robert, Hersh, Craig P., Schroeder, Joyce, Chandra, Divay, Kazerooni, Ella A, Wendt, Christine, Won, Sungho, Nachiappan, Arun, Stoel, Berend C, Bandi, Venkata, Hanania, Nicola A., Dass, Chandra, Horton, Karen, Wan, Emily, James Mamary, Paine, Robert, Pace, David, Freeman, Christine M., Brown, Robert, Newell, John D., McDonald, Merry-Lynn, Boucher, Richard C., Alapat, Philip, Pratte, Katherine, Bon, Jessica, Vega-Sanchez, Maria Elena, Steiner, Robert M., Austin, John, Martinez, Carlos H., Nath, Hrudaya, Allen, Tadashi, Yang, Jenny, Billings, Joanne, Kleerup, Eric C., van Ginneken, Bram, Lan, Charlie, D'Souza, Belinda, Atik, Mustafa, Hobbs, Brian, Michael Wells, Woodruff, Prescott G., Pearson, Gregory D.N., Comellas, Alejandro, Faino, Anna, Halper-Stromberg, Eitan, Laird, Nan, Sharafkhaneh, Amir, Drummond, M. Bradley, Thomashow, Byron, Comellas, Alejandro P., Foreman, Marilyn, Hersh, Craig, D'Alonzo, Gilbert, Criner, Gerard, Cornellas, Alejandro, Meyers, Deborah A., Jensen, Robert, Couper, David J., Silverman, Edwin K., McAdams, H. Page, Kazerooni, Ella, Jacobson, Francine L, Martinez, Carlos, Casaburi, Richard, Silverman, Edwin, Kim, Victor, Shenoy, Kartik, Yen, Andrew, Putcha, Nirupama, Doerschuk, Claire M., Demeo, Dawn, Gray, Teresa, MacIntyre, Neil, Crapo, James D., Lynch, David, Bleecker, Eugene R., Satti, Aditi, Barr, R. Graham, Gouskova, Natalia A., Boriek, Aladin, Oelsner, Elizabeth C., Tashkin, Donald P., Crystal, Ronald G., Wilson, Carla G, Kaner, Robert J., Jacobson, Sean, Regan, Elizabeth A., De, Dawn, Santorico, Stephanie, Hastie, Annette T., Van Beek, Edwin, Kinney, Gregory, Rennard, Stephen I., Scholand, Mary Beth, Martinez, Fernando J., Hokanson, John, Coxson, Harvey O., Marchetti, Nathaniel, Ramsdell, Joe, Quibrera, Pedro Miguel, Lange, Christoph, Pernicano, Perry G., van Rikxoort, Eva, Young, Kendra, Anderson, Wayne, Hansel, Nadia N., Wells, J. Michael, Hetmanski, Jacqueline, Criner, Gerard J., Porszasz, Janos, Rozenshtein, Anna, Christenson, Stephanie A., Krishnan, Jerry A., Westney, Gloria, Make, Barry, Guntupalli, Kalpatha, Basta, Patricia V., and Cordova, Francis

Abstract

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

Published
2016
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46. GOLD-associated shape variations in central airway tree assessed via QCT

Author

Tschirren, Juerg, primary, McEleney, Stephen, additional, Sieren, Jered, additional, Motahari, Amin, additional, Han, Meilan, additional, Barr, Graham, additional, Bleecker, Eugene, additional, Comellas, Alejandro, additional, Cooper, Christopher, additional, Couper, David, additional, Hansel, Nadja, additional, Kanner, Richard, additional, Martinez, Fernando, additional, Newell, John, additional, Woodruff, Prescott, additional, and Hoffman, Eric, additional

Published
2017
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47. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

Author

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

Published
2017
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