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

Author

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

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2023

2. Development of a Blood-based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease

Author

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

Subjects
Pulmonary and Respiratory Medicine, COPD, Framingham Risk Score, business.industry, Pulmonary disease, Critical Care and Intensive Care Medicine, medicine.disease, Bioinformatics, Peripheral blood, respiratory tract diseases, Transcriptome, Gene expression, medicine, Polygenic risk score, business
Abstract

Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...

Published
2022

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

Author

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

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Comorbid anxiety, business.industry, Internal medicine, Post-hoc analysis, Medicine, Respiratory system, business, Depressive symptoms
Published
2022

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

Author

Christopher Bertini, Muhammad H. Arain, Richard E. Champlin, Kristofer Jennings, María M. Hernández, Eric A. Hoffman, Rick R. Layman, Rohtesh S. Mehta, Gabriela Rondon, Mario Castro, Ajay Sheshadri, David Ost, Burton F. Dickey, Stephen McEleney, Uday R. Popat, Sophie Paczesny, Diana Montanez, Jered Sieren, Laila Noor, Chitra Hosing, Amin M. Alousi, Lara Bashoura, and Myrna C. B. Godoy

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung, Hematopoietic cell, business.industry, Bronchiolitis obliterans, Deformation (meteorology), Critical Care and Intensive Care Medicine, computer.software_genre, medicine.disease, Airflow obstruction, Transplantation, medicine.anatomical_structure, Voxel, Internal medicine, medicine, Cardiology, Cardiology and Cardiovascular Medicine, business, computer
Published
2021

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

Author

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

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

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

Published
2021

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

Author

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

Subjects
Pulmonary and Respiratory Medicine
Published
2023

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

Author

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

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung, medicine.diagnostic_test, business.industry, Interstitial lung disease, Respiratory physiology, respiratory system, medicine.disease, body regions, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, Pulmonary fibrosis, Medicine, 030212 general & internal medicine, Honeycombing, Radiology, Quantitative computed tomography, skin and connective tissue diseases, business, Densitometry, Rank correlation
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.

Published
2020

9. Machine Learning Characterization of COPD Subtypes

Author

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

Subjects
Pulmonary and Respiratory Medicine, Spirometry, COPD, medicine.diagnostic_test, business.industry, Context (language use), Disease, Critical Care and Intensive Care Medicine, medicine.disease, Machine learning, computer.software_genre, Subtyping, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Genetic epidemiology, medicine, Clinical significance, 030212 general & internal medicine, Artificial intelligence, Genetic risk, Cardiology and Cardiovascular Medicine, business, computer
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

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

Author

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

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

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

Published
2021

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

Author

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

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary disease, Computed tomography, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Distribution (pharmacology), 030212 general & internal medicine, Aged, Aged, 80 and over, COPD, medicine.diagnostic_test, business.industry, Respiration, Smoking, Editorials, Middle Aged, respiratory system, medicine.disease, Respiratory Function Tests, respiratory tract diseases, Small airways disease, Pulmonary Emphysema, 030228 respiratory system, Multivariate Analysis, Female, Radiology, Tomography, X-Ray Computed, business
Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, caused by emphysema and small airways disease (SAD). Computed tomography (CT) coupled with image anal...

Published
2019

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

Author

Adel Boueiz, Betty Pham, Robert Chase, Andrew Lamb, Sool Lee, Zun Zar Chi Naing, Michael H. Cho, Margaret M. Parker, Phuwanat Sakornsakolpat, Craig P. Hersh, James D. Crapo, Andrew B. Stergachis, Ruth Tal-Singer, Dawn L. DeMeo, Edwin K. Silverman, Xiaobo Zhou, Peter J. Castaldi, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Michael Cho, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dandi Qiao, Emily S. Wan, Sungho Won, Dmitry Prokopenko, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Jessica Bon, Barry Make, Carlos Martinez, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O’Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, Y. Feschenko, V. Gavrisyuk, L. Yashina, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, Rancho Mirage, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal-Singer, J. Yates, B. Miller, Per Bakke, Amund Gulsvik, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, and MUMC+: MA Longziekten (3)

Subjects
EXPRESSION, 0301 basic medicine, Pulmonary and Respiratory Medicine, Quantitative Trait Loci, Clinical Biochemistry, Genome-wide association study, Computational biology, Biology, Polymorphism, Single Nucleotide, Proof of Concept Study, OBSTRUCTIVE PULMONARY-DISEASE, chronic obstructive pulmonary disease, Transforming Growth Factor beta1, Jurkat Cells, Pulmonary Disease, Chronic Obstructive, integrative genomics, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, Cell Line, Tumor, Humans, WIDE ASSOCIATION, GWAS, Distribution (pharmacology), Genetic Predisposition to Disease, LUNG-VOLUME-REDUCTION, Lung, Molecular Biology, Gene, ACVR1B, Original Research, ACVR1B gene, Genetic association, Emphysema, emphysema distribution, LANDSCAPE, transforming growth factor-beta signaling, Editorials, DNA, Genomics, Cell Biology, Integrative genomics, Causal gene, ACVR1B Gene, 030104 developmental biology, Pulmonary Emphysema, 030228 respiratory system, Activin Receptors, Type I, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have identified multiple associations with emphysema apicobasal distribution (EABD), but the biological functions of these variants are unknown. To characterize the functions of EABD-associated variants, we integrated GWAS results with 1) expression quantitative trait loci (eQTL) from the Genotype Tissue Expression (GTEx) project and subjects in the COPDGene (Genetic Epidemiology of COPD) study and 2) cell type epigenomic marks from the Roadmap Epigenomics project. On the basis of these analyses, we selected a variant near ACVR1B (activin A receptor type 1B) for functional validation. SNPs from 168 loci with P values less than 5 × 10(−5) in the largest GWAS meta-analysis of EABD were analyzed. Eighty-four loci overlapped eQTL, with 12 of these loci showing greater than 80% likelihood of harboring a single, shared GWAS and eQTL causal variant. Seventeen cell types were enriched for overlap between EABD loci and Roadmap Epigenomics marks (permutation P

Published
2019

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

Author

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

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

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

Published
2018

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

Author

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

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

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

Published
2020

15. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

Author

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

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Pulmonary disease, Critical Care and Intensive Care Medicine, Machine Learning, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, COPD, business.industry, Disease progression, Editorials, Original Articles, Middle Aged, Models, Theoretical, respiratory system, medicine.disease, respiratory tract diseases, 030228 respiratory system, Disease Progression, Bronchitis, Female, Ct imaging, business, Tomography, X-Ray Computed, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) 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 < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

Published
2020

16. Inter- and intra-software reproducibility of computed tomography lung density measurements

Author

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

Subjects
Reproducibility, Percentile, Imaging biomarker, business.industry, Reproducibility of Results, General Medicine, Standard deviation, Article, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Software, Pulmonary Emphysema, 030220 oncology & carcinogenesis, Hounsfield scale, Medicine, Humans, Lung volumes, business, Nuclear medicine, Tomography, X-Ray Computed, Quality assurance, Lung
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 COPDGene™ 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 (LAA(950)), 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, LAA(950) and Perc15, respectively. The RDC was 0.35 L, 1.2% and 1.8 HU for TLV, LAA(950) and Perc15, respectively. Intersoftware RDC remained unchanged following QA: 0.35 L, 1.2% and 1.8 HU for TLV, LAA(950) and Perc15, respectively. All software investigated had an intrasoftware RDC of 0. The RDC was comparable for TLV, LAA(950) 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 LAA(950) 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.

Published
2019

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

Author

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

Subjects
Pulmonary and Respiratory Medicine, COPD, medicine.medical_specialty, Exacerbation, business.industry, Respiratory disease, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, 030212 general & internal medicine, Risk factor, Respiratory system, Cardiology and Cardiovascular Medicine, business, Airway, Asthma
Abstract

Background Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Methods Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at Results Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Conclusions Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. Trial Registry ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov.

Published
2018

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

Author

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

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

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

Published
2018

19. The Modern Art of Reading Computed Tomography Images of the Lungs: Quantitative CT

Author

Jonas Herth, Maren Schuhmann, Joshua Schirm, Jered Sieren, Susan A. Wood, Miranda Kirby, and Felix J.F. Herth

Subjects
Pulmonary and Respiratory Medicine, Respiratory physician, medicine.medical_specialty, COPD, Lung, medicine.diagnostic_test, business.industry, Diagnostic algorithms, Computed tomography, Disease, respiratory system, medicine.disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, medicine, Humans, Radiology, Quantitative computed tomography, Tomography, X-Ray Computed, Lung cancer, business
Abstract

Lung diseases are increasing in prevalence and overall burden worldwide. To stem the tide, more and more national and international guidelines are recommending the use of various diagnostic algorithms that are disease specific. There is growing consensus among the respiratory community that although patient histories and lung function testing are the minimum required for clinical examinations, these tests alone are not sufficient for disease characterization. Therefore, the use of computed tomography (CT) imaging is increasing used in clinical decision making for lung diseases. Lung diseases affect various components of lung, including the small airways, lung parenchyma, the interstitial space and the pulmonary vasculature. Quantitative CT (QCT) methods are emerging and are increasingly available using commercial software to quantify the underlying disease components, and a growing body of evidence suggests that QCT is an important tool in the clinical setting to help accurately and reproducibly detect where the disease is located in the lung, and to quantify the extent and overall severity for several lung diseases. Furthermore, this growing body of evidence has promoted the use of thoracic QCT to the point that it is now considered by many as an indispensable technology for longitudinal analysis and intervention trials. Many QCT imaging measurements are available to the respiratory physician, and the aim of this review is to introduce and describe pulmonary QCT imaging measurements and methodologies.

Published
2017

20. Quantitative Computed Tomography in Systemic Sclerosis-Associated Interstitial Lung Disease: A Densitometric Assessment of Disease Severity

Author

John D. Newell, D. Castillo Saldana, Cameron J. Hague, Juerg Tschirren, Harvey O. Coxson, Miranda Kirby, Christopher J. Ryerson, Jered Sieren, and Darra T. Murphy

Subjects
medicine.medical_specialty, Disease severity, medicine.diagnostic_test, business.industry, medicine, Interstitial lung disease, Radiology, Quantitative computed tomography, medicine.disease, business
Published
2019

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

Author

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

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

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

Published
2019

22. Quantitative CT of Interstitial Lung Disease

Author

Sam Peterson, Jered Sieren, John D. Newell, Juerg Tschirren, and Madeline Beinlich

Subjects
Pathology, medicine.medical_specialty, business.industry, MEDLINE, Interstitial lung disease, medicine.disease, Evaluation Studies as Topic, Medicine, Humans, Radiology, Nuclear Medicine and imaging, business, Lung Diseases, Interstitial, Tomography, X-Ray Computed, Lung
Published
2019

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

Author

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

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

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

Published
2018

24. High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study

Author

Jason D. Christie, Robert C Basner, Matthew N. Bartels, John H.M. Austin, Russell P. Tracy, David J. Lederer, Karen Hinckley Stukovsky, Joel D. Kaufman, Hilary F. Armstrong, Eric A. Hoffman, Kayleen Williams, Sushil Sonavane, Paul L. Enright, John D. Newell, Bernadette R. Gochuico, Jubal R. Watts, Anna J. Podolanczuk, R. Graham Barr, Steven M. Kawut, Scott M. Palmer, Ganesh Raghu, Jessica L. Sell, Daniel Rabinowitz, Jered Sieren, Elizabeth C. Oelsner, and P. Hrudaya Nath

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Vital capacity, Lung injury, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Internal medicine, Hounsfield scale, medicine, Humans, 030212 general & internal medicine, Respiratory system, Exercise, Lung, Aged, Proportional Hazards Models, Inflammation, Interleukin-6, Proportional hazards model, business.industry, Smoking, Interstitial lung disease, Middle Aged, medicine.disease, Fibrosis, Extracellular Matrix, C-Reactive Protein, medicine.anatomical_structure, 030228 respiratory system, Spirometry, Matrix Metalloproteinase 7, Cardiology, Female, Radiography, Thoracic, Radiology, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business, Biomarkers
Abstract

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between −600 and −250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3–11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8–13.0), lower forced vital capacity (FVC) (mean adjusted difference −82 mL, 95% CI −119–−44), lower 6-min walk distance (mean adjusted difference −40 m, 95% CI −1–−80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43–2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39–1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Published
2016

25. 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

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

Subjects
Scanner, medicine.diagnostic_test, business.industry, Computer science, Computed tomography, General Medicine, Object detection, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, medicine, Medical imaging, Computer vision, Artificial intelligence, Nuclear medicine, business
Abstract

Purpose: A test object (phantom) is an important tool to evaluate comparability and stability of CTscanners 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. Methods: 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. Results: 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. Conclusions: 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

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

Author

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

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

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

Published
2018

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

Author

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

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

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

Published
2018

28. Topological leakage detection and freeze-and-grow propagation for improved CT-based airway segmentation

Author

Syed Ahmed Nadeem, Eric A. Hoffman, Punam K. Saha, and Jered Sieren

Subjects
Initial Seed, medicine.diagnostic_test, Airway tree, Computer science, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Computed tomography, respiratory system, Topology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Tree (data structure), 0302 clinical medicine, 030228 respiratory system, medicine, Segmentation, Airway segmentation, Digital topology, Leakage (electronics)
Abstract

Numerous large multi-center studies are incorporating the use of computed tomography (CT)-based characterization of the lung parenchyma and bronchial tree to understand chronic obstructive pulmonary disease status and progression. To the best of our knowledge, there are no fully automated airway tree segmentation methods, free of the need for user review. A failure in even a fraction of segmentation results necessitates manual revision of all segmentation masks which is laborious considering the thousands of image data sets evaluated in large studies. In this paper, we present a novel CT-based airway tree segmentation algorithm using topological leakage detection and freeze-and-grow propagation. The method is fully automated requiring no manual inputs or post-segmentation editing. It uses simple intensity-based connectivity and a freeze-and-grow propagation algorithm to iteratively grow the airway tree starting from an initial seed inside the trachea. It begins with a conservative parameter and then, gradually shifts toward more generous parameter values. The method was applied on chest CT scans of fifteen subjects at total lung capacity. Airway segmentation results were qualitatively assessed and performed comparably to established airway segmentation method with no major visual leakages.

Published
2018

29. Dependence of subject-specific parameters for a fast helical CT respiratory motion model on breathing rate: an animal study

Author

Melissa Saylor, Dylan O'Connell, James Lamb, Tai Dou, David Thomas, John H. Lewis, Jered Sieren, Eric A. Hoffman, Daniel A. Low, Christian Hofmann, and Percy Lee

Subjects
Percentile, Radiological and Ultrasound Technology, Respiratory rate, Mean squared error, Swine, Image processing, Displacement (vector), 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Amplitude, Respiratory Rate, 030220 oncology & carcinogenesis, Breathing, Errors-in-variables models, Animals, Radiology, Nuclear Medicine and imaging, Organ Motion, Algorithm, Lung, Tomography, Spiral Computed, Mathematics
Abstract

To determine if the parameters relating lung tissue displacement to a breathing surrogate signal in a previously published respiratory motion model vary with the rate of breathing during image acquisition. An anesthetized pig was imaged using multiple fast helical scans to sample the breathing cycle with simultaneous surrogate monitoring. Three datasets were collected while the animal was mechanically ventilated with different respiratory rates: 12 bpm (breaths per minute), 17 bpm, and 24 bpm. Three sets of motion model parameters describing the correspondences between surrogate signals and tissue displacements were determined. The model error was calculated individually for each dataset, as well asfor pairs of parameters and surrogate signals from different experiments. The values of one model parameter, a vector field denoted [Formula: see text] which related tissue displacement to surrogate amplitude, determined for each experiment were compared. The mean model error of the three datasets was 1.00 ± 0.36 mm with a 95th percentile value of 1.69 mm. The mean error computed from all combinations of parameters and surrogate signals from different datasets was 1.14 ± 0.42 mm with a 95th percentile of 1.95 mm. The mean difference in [Formula: see text] over all pairs of experiments was 4.7% ± 5.4%, and the 95th percentile was 16.8%. The mean angle between pairs of [Formula: see text] was 5.0 ± 4.0 degrees, with a 95th percentile of 13.2 mm. The motion model parameters were largely unaffected by changes in the breathing rate during image acquisition. The mean error associated with mismatched sets of parameters and surrogate signals was 0.14 mm greater than the error achieved when using parameters and surrogate signals acquired with the same breathing rate, while maximum respiratory motion was 23.23 mm on average.

Published
2018

30. CT imaging for evaluation of calcium crystal deposition in the knee: initial experience from the Multicenter Osteoarthritis (MOST) study

Author

Devyani Misra, Jered Sieren, James C. Torner, Tuhina Neogi, David T. Felson, John A. Lynch, and Ali Guermazi

Subjects
Male, musculoskeletal diseases, medicine.medical_specialty, Calcium crystals, Knee Joint, Radiography, Biomedical Engineering, Pilot Projects, Chondrocalcinosis, Osteoarthritis, Article, Rheumatology, Joint capsule, medicine, Humans, Knee, Orthopedics and Sports Medicine, Aged, Medial collateral ligament, Hyaline cartilage, business.industry, Cartilage, Middle Aged, medicine.disease, musculoskeletal system, medicine.anatomical_structure, CT imaging, Calcium, Female, Radiology, business, Crystallization, Tomography, X-Ray Computed, Calcification
Abstract

Summary Objective Role of intra-articular calcium crystals in osteoarthritis (OA) is unclear. Imaging modalities used to date for its evaluation have limitations in their ability to fully characterize intra-articular crystal deposition. Since Computed Tomography (CT) imaging provides excellent visualization of bones and calcified tissue, in this pilot project we evaluated the utility of CT scan in describing intra-articular calcium crystal deposition in the knees. Method We included 12 subjects with and four subjects without radiographic chondrocalcinosis in the most recent visit from the Multicenter Osteoarthritis (MOST) study, which is a longitudinal cohort of community-dwelling older adults with or at risk for knee OA. All subjects underwent CT scans of bilateral knees. Each knee was divided into 25 subregions and each subregion was read for presence of calcium crystals by a musculoskeletal radiologist. To assess reliability, readings were repeated 4 weeks later. Results CT images permitted visualization of 25 subregions with calcification within and around the tibio-femoral and patello-femoral joints in all 24 knees with radiographic chondrocalcinosis. Intra-articular calcification was seen universally including meniscal cartilage (most common site involved in 21/24 knees), hyaline cartilage, cruciate ligaments, medial collateral ligament and joint capsule. Readings showed good agreement for specific tissues involved with calcium deposition (kappa: 0.70, 95% CI 0.62–0.80). Conclusion We found CT scan to be a useful and reliable tool for describing calcium crystal deposition in the knee and therefore potentially for studying role of calcium crystals in OA. We also confirmed that "chondrocalcinosis" is a misnomer because calcification is present ubiquitously.

Published
2015
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31. Very Low-Dose (0.15 mGy) Chest CT Protocols Using the COPDGene 2 Test Object and a Third-Generation Dual-Source CT Scanner With Corresponding Third-Generation Iterative Reconstruction Software

Author

Junfeng Guo, Thomas Allmendinger, Kung-Sik Chan, Jered Sieren, John D. Newell, Eric A. Hoffman, and Matthew K. Fuld

Subjects
medicine.medical_specialty, Image quality, Radiography, Population, Iterative reconstruction, Radiation Dosage, Article, Pulmonary Disease, Chronic Obstructive, Multidetector Computed Tomography, Image Processing, Computer-Assisted, medicine, Medical imaging, Image noise, Humans, Radiology, Nuclear Medicine and imaging, education, Lung, education.field_of_study, medicine.diagnostic_test, Phantoms, Imaging, business.industry, Magnetic resonance imaging, General Medicine, Radiographic Image Enhancement, Radiographic Image Interpretation, Computer-Assisted, Radiology, Nuclear medicine, business, Software, Lung cancer screening
Abstract

The new third-generation dual-source computed tomographic (CT) scanners and third-generation iterative reconstruction software enable substantial reductions in radiation dose to the patient.1 This is of great importance to the medical imaging community because the recent increase in the use of x-ray CT has greatly increased the amount of ionizing radiation received by populations in the United States and other countries around the world.2,3 The recently published National Lung Cancer Screening Trial study showed a 20% decrease in mortality from lung cancer with the use of screening CT scans of the thorax in patients at high risk for lung cancer.4–7 The use of CT for lung cancer screening will further increase the number of x-ray CT studies performed on the thorax. Reducing the CT radiation dose to the thorax would be of great benefit to patients enrolled in lung cancer screening programs. Computed tomography is also increasingly being used to establish quantitative phenotypes to subtype lung diseases such as COPD and asthma,8–15 and reducing the CT dose in these CT studies would also be beneficial. The medical imaging community has been trying to reduce the amount of ionizing radiation to the general population using a number of approaches. These include using medical imaging studies only when they are known to be beneficial to the patient, substituting nonionizing radiation studies such as ultrasound and magnetic resonance imaging for x-ray CT studies whenever possible, lowering the radiation dose of both radiographic and x-ray CT studies as much as possible while still maintaining adequate image quality and image noise levels, and, finally, encouraging CT manufacturers to pursue advanced technological solutions for reducing the radiation exposures necessary to provide diagnostic images of the thorax and other body parts. It is very important for quantitative CT scanning of the lung to maintain the accuracy of the CT attenuation values with acceptable levels of image noise. This is accomplished using carefully designed CT protocols.16 It is also important to monitor the performance of CT scanners that are used for obtaining quantitative measurements over time. This is typically achieved using CT test objects (CT phantoms) that are made up of nonbiologic materials that simulate different in vivo tissue CT densities such as soft tissue, water, lung tissue, and air. The COPDGene 1 test object in the COPDGene phase 1 multicenter National Institutes of Health study is one of the commonly used CT test objects that is used for CT quality control.17 This CT test object has been used in a number of National Institutes of Health and privately sponsored multicenter lung research studies that use quantitative CT to phenotype lung disease including COPDGene, multi-ethnic study of atherosclerosis, severe asthma research program, and subpopulations and intermediate outcome measures in COPD study. We have recently described18 the effects of reducing dose on CT attenuation values in the COPDGene 2 test object using a second-generation dual-source CT scanner, SOMATOM Definition FLASH, and second-generation iterative reconstruction software, SAFIRE.19 In that study, we showed that the COPDGene 2 test object can be used to assess the effects of decreasing dose on the mean attenuation values of the 8 materials in the COPDGene 2 test object using weighted filtered back projection (WFBP) and using the SAFIRE iterative reconstruction method. In this study, we have sought to evaluate the quantitative stability of measures derived from the COPDGene 2 test object while lowering imaging to ultralow doses, taking advantage of advances in third-generation dual-source CT technologies including third-generation iterative reconstruction methods.

Published
2015

32. CT derived emphysema sub-lobar phenotype distribution: perspectives for endoscopic approach

Author

Amarilio Vieira de Macedo-Neto, Hugo Goulart de Oliveira, Diogo Martins de Oliveira, Feiran Jiao, Joschua Schirm, Jered Sieren, and Juerg Tschirren

Subjects
medicine.medical_specialty, business.industry, Treatment options, respiratory system, Bronchoscopic lung volume reduction, Lobe, respiratory tract diseases, Collateral ventilation, medicine.anatomical_structure, medicine, Distribution (pharmacology), Lung volumes, Radiology, Radiation treatment planning, business, Lung tissue
Abstract

Valves and Coils are two current therapeutic options available for bronchoscopic lung volume reduction procedures. Current treatment planning is based on CT derived quantitative emphysema measurements. Today’s treatment protocols utilize the amount of inter-lobar emphysema heterogeneity and collateral ventilation as key factors in deciding on treatment options. In this work, we take a step beyond current inter-lobar emphysema measurements and evaluate the intra-lobar emphysema distribution. The goal is to determine how much non-emphysematous lung tissue is being affected in today’s whole lobe based treatment protocols. We retrospectively analyzed 200 DICOM CT datasets acquired at total lung capacity from patients referred to an Emphysema Treatment Center for endoscopic valve treatment. We evaluated the sub-lobar segments in each lobe. Imaging software (VIDA Diagnostics, Coralville, IA) was used to collect emphysema distribution and heterogeneity on a sub-lobar level. Of the total 200, 164 (82%) have at least 1 possible target lobe. In intra-lobar target lobe evaluation, a considerable number of subjects (21.95%, n=36) had at least one healthy/slight disease ( Our findings show that intra-lobar emphysema heterogeneity is quite frequent in valve candidate patients in special for LUL, RLL and LLL. Further research is required to evaluate if future treatments should target individual sub-lobes instead of whole lobes in some patients.

Published
2017

33. GOLD-associated shape variations in central airway tree assessed via QCT

Author

Eugene R. Bleecker, Graham R. Barr, Stephen McEleney, Alejandro P. Comellas, Juerg Tschirren, Richard E. Kanner, Eric A. Hoffman, Fernando J. Martinez, Nadja Hansel, Jered Sieren, John D. Newell, David Couper, MeiLan K. Han, Christopher B. Cooper, Prescott G. Woodruff, and A. Motahari

Subjects
business.industry, Lumen (anatomy), Context (language use), respiratory system, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Medicine, Central airway, 030212 general & internal medicine, business, Airway, Nuclear medicine, Automated method
Abstract

Background: We seek to evaluate an automated method developed to assess central airway shape (cross-sectional and longitudinal) variations in the context of a multi-center study, SPIROMICS, seeking to evaluate phenotypes of COPD. Methods: 717 subjects (GOLD 1: 28, GOLD 2: 275, GOLD 3: 293, GOLD 4: 121) randomly selected from SPIROMICS baseline scans. Matching TLC and RV datasets were analyzed (VIDA Diagnostics) with a focus on the trachea and the left and right mainstem bronchi (LMB, RMB). Measurements included: extent of concave sections and deviation from circularity in lumen cross-sections, and straightness along the airway centerline. Results: Concavity and circularity: there is a significant increase in concavity and decrease in circularity between TLC and RV for all GOLD groups. Kruskal-Wallis test indicates significant concavity and circularity differences at RV in the trachea and LMB between GOLD groups 2 and 4, as well as 3 and 4. Straightness: statistically significant but physically small change in straightness between TLC and RV for all three major airways. Significant differences at RV in straightness across GOLD groups for trachea and LMB, but not for RMB. Conclusions: Central airway shapes change significantly across the vital capacity with distinctly different shape changes detectable across GOLD status.

Published
2017

34. Comparison of Low and Ultra-Low Dose Computed Tomography Protocols For Quantitative Lung and Airway Assessment

Author

Melissa Saylor, Jered Sieren, John D. Newell, Eric A. Hoffman, Craig Vidal, Shayna Hogue, Jessica C. Sieren, Frank A. De Stefano, Alexa Sieren, Chelsea M. Sloan, and Emily Hammond

Subjects
medicine.medical_specialty, Ultralow dose, Iterative reconstruction, Article, 030218 nuclear medicine & medical imaging, Perimeter, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Quantitative computed tomography, Lung, Protocol (science), medicine.diagnostic_test, business.industry, General Medicine, Repeatability, medicine.anatomical_structure, 030228 respiratory system, Pulmonary Emphysema, Radiology, Airway, Nuclear medicine, business, Tomography, X-Ray Computed
Abstract

Purpose Quantitative computed tomography (CT) measures are increasingly being developed and used to characterize lung disease. With recent advances in CT technologies, we sought to evaluate the quantitative accuracy of lung imaging at low and ultra-low radiation doses with the use of iterative reconstruction (IR), tube current modulation (TCM), and spectral shaping. Methods We investigated the effect of five independent CT protocols reconstructed with IR on quantitative airway measures and global lung measures using an in-vivo large animal model as a human subject surrogate. A control protocol was chosen (NIH-SPIROMICS + TCM) and five independent protocols investigating TCM, low and ultra-low radiation dose, and spectral shaping. For all scans quantitative global parenchymal measurements (mean, median and standard deviation of the parenchymal HU, along with measures of emphysema) and global airway measurements (number of segmented airways and pi10) were generated. In addition, selected individual airway measurements (minor and major inner diameter, wall thickness, inner and outer area, inner and outer perimeter, wall area fraction, and inner equivalent circle diameter) were evaluated. Comparisons were made between control and target protocols using difference and repeatability measures. Results Estimated CT volume dose index (CTDIvol) across all protocols ranged from 7.32 mGy to 0.32 mGy. Low and ultra-low dose protocols required more manual editing and resolved fewer airway branches; yet, comparable pi10 whole lung measures were observed across all protocols. Similar trends in acquired parenchymal and airway measurements were observed across all protocols, with increased measurement differences using the ultra-low dose protocols. However, for small airways (1.9 ± 0.2mm) and medium airways (5.7 ± 0.4mm) the measurement differences across all protocols were comparable to the control protocol repeatability across breath-holds. Diameters, wall thickness, wall area fraction, and equivalent diameter had smaller measurement differences, than area and perimeter measurements. Conclusions In conclusion, the use of IR with low and ultra-low dose CT protocols with CT volume dose indices down to 0.32 mGy maintains selected quantitative parenchymal and airway measurements relevant to pulmonary disease characterization. This article is protected by copyright. All rights reserved.

Published
2017

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

Author

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

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

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

Published
2017

36. Development of Quantitative Computed Tomography Lung Protocols

Author

John D. Newell, Eric A. Hoffman, and Jered Sieren

Subjects
musculoskeletal diseases, Pulmonary and Respiratory Medicine, Protocol (science), medicine.medical_specialty, Lung, medicine.diagnostic_test, business.industry, Image processing software, medicine.disease, Obstructive lung disease, respiratory tract diseases, body regions, Software, medicine.anatomical_structure, Hounsfield scale, Medicine, Radiology, Nuclear Medicine and imaging, Radiology, Tomography, Quantitative computed tomography, business
Abstract

The purpose of this review article is to review the process of developing optimal computed tomography (CT) protocols for quantitative lung CT (QCT). In this review, we discuss the following important topics: QCT-derived metrics of lung disease; QCT scanning protocols; quality control; and QCT image processing software. We will briefly discuss several QCT-derived metrics of lung disease that have been developed for the assessment of emphysema, small airway disease, and large airway disease. The CT scanning protocol is one of the most important elements in a successful QCT. We will provide a detailed description of the current move toward optimizing the QCT protocol for the assessment of chronic obstructive pulmonary disorder and asthma. Quality control of CT images is also a very important part of the QCT process. We will discuss why it is necessary to use CT scanner test objects (phantoms) to provide frequent periodic checks on the CT scanner calibration to ensure precise and accurate CT numbers. We will discuss the use of QCT image processing software to segment the lung and extract the desired QCT metrics of lung disease. We will discuss the practical issues of using this software. The data obtained from the image processing software are then combined with those from other clinical examinations, health status questionnaires, pulmonary physiology, and genomics to increase our understanding of obstructive lung disease and improve our ability to design new therapies for these diseases.

Published
2013

37. Normal human airway dimensions and branching geometry assessed via QCT for 5 standardized paths

Author

John D. Newell, Youbing Yin, Susan A. Wood, Jered Sieren, Juerg Tschirren, David P. Naidich, and Eric A. Hoffman

Subjects
education.field_of_study, business.industry, Population, Lumen (anatomy), Anatomy, Human airway, Human lung, Branching (linguistics), medicine.anatomical_structure, Monopodial, Medicine, Airway, business, Wall thickness, education
Abstract

Background: We seek to establish baseline computed tomography (CT)-based airway measures for 5 standardized paths into the lung that include segmental bronchi RB1, RB4, RB10, LB1, LB10, incl. differences between normal male (M) and female (F). Methods : 56 normal subjects (34 female, 22 male) of 100 imaged using a standardized CT protocol: std kernel, 0.5mm slice thick., 100mAs, 120kV, breath-hold at 90% vital cap. have been analyzed to date. Subjs age range: 20 - 70. Data analysis included airway segmentation, labeling (incl. sub-segmental), and measurements (Apollo® 2.0, VIDA Diagn.). All steps were automated but visually verified by human experts and edited as needed to assure data quality. Results : Common lumen diameter (D) and wall thickness (WT) were observed across the population, with segment specific differences. M and F subjects differ significantly in most but not all segments, with D in M being bigger where significant. E.g., 1.12 mm D diff. in RB1, 0.45 mm in LB1, but no significant diff. in RB4. WT are generally greater in M than in F. Unique branching patterns (lumen dimension & branching angles) common across the population were observed for sub-segmental branches in LB/RB 3, RB9, LB/RB10 (monopodal rather than bipodal, with the latter being dominant in the rest of the human airway tree). Path-based Pi10 measurements to date have not differed significantly, between individual sub-trees or between F and M. Conclusions: A common monopodial branching pattern has been identified for 3 branches. Normative measures for a standardized set of paths into the normal human lung have been established and provide a basis for evaluating changes associated with pathologic processes.

Published
2016

38. Variability in lung volume dependent changes in lobar-based pulmonary blood volume in a COPD population

Author

Eric A. Hoffman, John D. Newell, Juerg Tschieren, Jered Sieren, Youbing Yin, Susan A. Wood, and Graham Barr

Subjects
medicine.medical_specialty, education.field_of_study, Pathology, COPD, Lung, business.industry, Population, Blood volume, respiratory system, medicine.disease, Confidence interval, respiratory tract diseases, medicine.anatomical_structure, Internal medicine, Hounsfield scale, Parenchyma, medicine, Cardiology, Lung volumes, business, education
Abstract

Background: Pulmonary blood volume(PBV) changes with lung inflation and this can be measured as a change in non-air volume via quantitative CT, assuming that tissue volume remains constant. Methods: 40 subjects(20 female, 20 male) were selected across various COPD classes from SPIROMICS multicenter research study. TLC and RV pair was acquired for each subject. Lobar segmentation for TLC was obtained via Apollo lung analytics platform(VIDA Diagnostics, US) with occasional edits from expert analysts. RV lobar mask was obtained via VIDA9s automatic image registration whereby TLC lobar mask was warped into the RV domain. Lung tissue mass (parenchyma plus blood) was derived from Hounsfield units. Results: PBV is greater at TLC compared to RV: mean relative tissue mass difference of 3.5% (95% confidence interval:[2.1%, 5.0%]) for the whole lung. Relative tissue mass (thus PBV) changes between TLC and RV are similar across all lobes with a mean value of 6.0%(significantly different from whole lung, p=0.001). In addition, as seen in, there is considerable difference in distribution of PBV changes across subjects. Conclusion: Decreases in PBV with lung inflation demonstrate subject variability when a mixed COPD population is evaluated suggesting lung volume effects must be considered when reporting regional PBV, especially when using blood volume as a surrogate for regional perfusion as is done with Dual Energy CT.

Published
2016

39. SPIROMICS Protocol for Multicenter Quantitative Computed Tomography to Phenotype the Lungs

Author

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

Subjects
Pulmonary and Respiratory Medicine, musculoskeletal diseases, Lung Diseases, medicine.medical_specialty, Pulmonary Perspective, Context (language use), Critical Care and Intensive Care Medicine, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Body Mass Index, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Predictive Value of Tests, Multicenter trial, Multidetector Computed Tomography, medicine, Humans, Multicenter Studies as Topic, Lung volumes, Quantitative computed tomography, Lung, Asthma, Emphysema, COPD, medicine.diagnostic_test, business.industry, medicine.disease, respiratory tract diseases, body regions, medicine.anatomical_structure, Phenotype, 030228 respiratory system, Predictive value of tests, Radiology, business, Lung Volume Measurements
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

40. Standardizing CT lung density measure across scanner manufacturers

Author

Sean B. Fain, Antonio Possolo, David A. Lynch, Philip F. Judy, Jered Sieren, Matthew K. Fuld, Bernice E. Hoppel, Junfeng Guo, and Huaiyu H. Chen-Mayer

Subjects
Models, Anatomic, Accuracy and precision, Tomography Scanners, X-Ray Computed, computer.software_genre, Standard deviation, Imaging phantom, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Voxel, Hounsfield scale, Calibration, Humans, Lung, Mathematics, Reproducibility, business.industry, Phantoms, Imaging, Uncertainty, Reproducibility of Results, General Medicine, Models, Theoretical, 030220 oncology & carcinogenesis, Measurement uncertainty, Nuclear medicine, business, Tomography, X-Ray Computed, computer
Abstract

Purpose Computed Tomography (CT) imaging of the lung, reported in Hounsfield Units (HU), can be parameterized as a quantitative image biomarker for the diagnosis and monitoring of lung density changes due to emphysema, a type of chronic obstructive pulmonary disease (COPD). CT lung density metrics are global measurements based on lung CT number histograms, and are typically a quantity specifying either the percentage of voxels with CT numbers below a threshold, or a single CT number below which a fixed relative lung volume, nth percentile, falls. To reduce variability in the density metrics specified by CT attenuation, the Quantitative Imaging Biomarkers Alliance (QIBA) Lung Density Committee has organized efforts to conduct phantom studies in a variety of scanner models to establish a baseline for assessing the variations in patient studies that can be attributed to scanner calibration and measurement uncertainty. Methods Data were obtained from a phantom study on CT scanners from four manufacturers with several protocols at various tube potential voltage (kVp) and exposure settings. Free from biological variation, these phantom studies provide an assessment of the accuracy and precision of the density metrics across platforms solely due to machine calibration and uncertainty of the reference materials. The phantom used in this study has three foam density references in the lung density region, which, after calibration against a suite of Standard Reference Materials (SRM) foams with certified physical density, establishes a HU-electron density relationship for each machine-protocol. We devised a 5-step calibration procedure combined with a simplified physical model that enabled the standardization of the CT numbers reported across a total of 22 scanner-protocol settings to a single energy (chosen at 80 keV). A standard deviation was calculated for overall CT numbers for each density, as well as by scanner and other variables, as a measure of the variability, before and after the standardization. In addition, a linear mixed-effects model was used to assess the heterogeneity across scanners, and the 95% confidence interval of the mean CT number was evaluated before and after the standardization. Results We show that after applying the standardization procedures to the phantom data, the instrumental reproducibility of the CT density measurement of the reference foams improved by more than 65%, as measured by the standard deviation of the overall mean CT number. Using the lung foam that did not participate in the calibration as a test case, a mixed effects model analysis shows that the 95% confidence intervals are [-862.0 HU, -851.3 HU] before standardization, and [-859.0 HU, -853.7 HU] after standardization to 80 keV. This is in general agreement with the expected CT number value at 80 keV of -855.9 HU with 95% CI of [-857.4 HU, -854.5 HU] based on the calibration and the uncertainty in the SRM certified density. Conclusions This study provides a quantitative assessment of the variations expected in CT lung density measures attributed to non-biological sources such as scanner calibration and scanner x-ray spectrum and filtration. By removing scanner-protocol dependence from the measured CT numbers, higher accuracy and reproducibility of quantitative CT measures were attainable. The standardization procedures developed in study may be explored for possible application in CT lung density clinical data.

Published
2016

41. Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities

Author

Joseph E. Cavanaugh, Pradeep K. Singh, Michael J. Welsh, Jered Sieren, B. Grogan, Eric A. Hoffman, David A. Stoltz, Edward F. McKone, Katherine B. Hisert, Thomas J. Gross, Ryan J. Adam, Jonathan D. Dodd, Janel K. Barnes, Janice L. Launspach, Charles G. Gallagher, and Anthony J. Fischer

Subjects
Spirometry, medicine.medical_specialty, Pathology, congenital, hereditary, and neonatal diseases and abnormalities, 030204 cardiovascular system & hematology, Air trapping, Cystic fibrosis, Ivacaftor, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Pulse wave velocity, Lung, medicine.diagnostic_test, business.industry, General Medicine, respiratory system, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Cardiology, medicine.symptom, Clinical Medicine, Airway, business, medicine.drug
Abstract

BACKGROUND. Airflow obstruction is common in cystic fibrosis (CF), yet the underlying pathogenesis remains incompletely understood. People with CF often exhibit airway hyperresponsiveness, CF transmembrane conductance regulator (CFTR) is present in airway smooth muscle (ASM), and ASM from newborn CF pigs has increased contractile tone, suggesting that loss of CFTR causes a primary defect in ASM function. We hypothesized that restoring CFTR activity would decrease smooth muscle tone in people with CF. METHODS. To increase or potentiate CFTR function, we administered ivacaftor to 12 adults with CF with the G551D-CFTR mutation; ivacaftor stimulates G551D-CFTR function. We studied people before and immediately after initiation of ivacaftor (48 hours) to minimize secondary consequences of CFTR restoration. We tested smooth muscle function by investigating spirometry, airway distensibility, and vascular tone. RESULTS. Ivacaftor rapidly restored CFTR function, indicated by reduced sweat chloride concentration. Airflow obstruction and air trapping also improved. Airway distensibility increased in airways less than 4.5 mm but not in larger-sized airways. To assess smooth muscle function in a tissue outside the lung, we measured vascular pulse wave velocity (PWV) and augmentation index, which both decreased following CFTR potentiation. Finally, change in distensibility of

Published
2016

42. Computed Tomography and Magnetic Resonance Imaging for Longitudinal Characterization of Lung Structure Changes in a Yucatan Miniature Pig Silicosis Model

Author

David K. Meyerholz, Jered Sieren, John D. Newell, Samantha K. N. Dilger, Daniel R. Thedens, Eric A. Hoffman, Jessica C. Sieren, Nicholas Stoyles, John Morgan, and Emily Hammond

Subjects
medicine.medical_specialty, Biomedical Research, Swine, Silicosis, Computed tomography, Toxicology, Article, 030218 nuclear medicine & medical imaging, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Structured reporting, medicine, Medical imaging, Animals, Molecular Biology, Lung, medicine.diagnostic_test, business.industry, Histocytochemistry, Magnetic resonance imaging, Cell Biology, medicine.disease, Magnetic Resonance Imaging, Lung structure, Disease Models, Animal, 030220 oncology & carcinogenesis, Yucatan Miniature pig, Swine, Miniature, Female, Radiology, business, Tomography, X-Ray Computed, Preclinical imaging
Abstract

Medical imaging is a rapidly advancing field enabling the repeated, noninvasive assessment of physiological structure and function. These beneficial characteristics can supplement studies in swine by mirroring the clinical functions of detection, diagnosis, and monitoring in humans. In addition, swine may serve as a human surrogate, facilitating the development and comparison of new imaging protocols for translation to humans. This study presents methods for pulmonary imaging developed for monitoring pulmonary disease initiation and progression in a pig exposure model with computed tomography and magnetic resonance imaging. In particular, a focus was placed on systematic processes, including positioning, image acquisition, and structured reporting to monitor longitudinal change. The image-based monitoring procedure was applied to 6 Yucatan miniature pigs. A subset of animals ( n = 3) were injected with crystalline silica into the apical bronchial tree to induce silicosis. The methodology provided longitudinal monitoring and evidence of progressive lung disease while simultaneously allowing for a cross-modality comparative study highlighting the practical application of medical image data collection in swine. The integration of multimodality imaging with structured reporting allows for cross comparison of modalities, refinement of CT and MRI protocols, and consistently monitors potential areas of interest for guided biopsy and/or necropsy.

Published
2016

43. Reference standard and statistical model for intersite and temporal comparisons of CT attenuation in a multicenter quantitative lung study

Author

David A. Lynch, Eric A. Hoffman, Junfeng Guo, Kung-Sik Chan, John D. Newell, P Judy, and Jered Sieren

Subjects
Molecular Epidemiology, Accuracy and precision, Scanner, Models, Statistical, Time Factors, business.industry, Air, Attenuation, Water, Image processing, General Medicine, Iterative reconstruction, Reference Standards, Pulmonary Disease, Chronic Obstructive, Radiation Imaging Physics, Image Processing, Computer-Assisted, Medical imaging, Calibration, Humans, Tomography, Tomography, X-Ray Computed, Nuclear medicine, business, Mathematics
Abstract

Purpose: The purpose of this study was to detect and analyze anomalies between a large number of computed tomography (CT) scanners, tracked over time, utilized to collect human pulmonary CT data for a national multicenter study: chronic obstructive pulmonary disease genetic epidemiology study (COPDGene). Methods: A custom designed CT reference standard “Test Object” has been developed to evaluate the relevant differences in CT attenuation between CT scanners in COPDGene. The materials used in the Test Object to assess CT scanner accuracy and precision included lung equivalent foam (−856 HU), internal air (−1000 HU), water (0 HU), and acrylic (120 HU). Nineteen examples of the Test Object were manufactured. Initially, all Test Objects were scanned on the same CT scanner before the Test Objects were sent to the 20 specific sites and 42 individual CT scanners that were used in the study. The Test Objects were scanned over 17 months while the COPDGene study continued to recruit subjects. A mixed linear effect statistical analysis of the CT scans on the 19 Test Objects was performed. The statistical model reflected influence of reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency on CT attenuation. Results: Depending on the Test Object material, there were significant differences between reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency. The two Test Object materials of most interest were lung equivalent foam and internal air. With lung equivalent foam, there were significant (p < 0.05) differences between the Siemens B31 (−856.6, ±0.82; mean ± SE) and the GE Standard (−856.6 ± 0.83) reconstruction kernel relative to the Siemens B35 reference standard (−852.5 ± 1.4). Comparing lung equivalent foam attenuation there were also significant differences between CT scanner models (p < 0.01), tube current (p < 0.005), and in temporal consistency (p < 0.005) at individual sites. However, there were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. For internal air, significant (p < 0.005) differences were found between all reconstruction kernels (Siemens B31, GE Standard, and Phillips B) compared to the reference standard. There were significant differences between CT models (p < 0.005), and tube current (p < 0.005). There were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. Differences, across scanners, between external air and internal air measures in this simple (relative to the in vivo lung) test object varied by as much as 15 HU. Conclusions: The authors conclude that the Test Object designed for this study was able to detect significant effects regarding individual CT scanners that altered the CT attenuation measurements relevant to the study that are used to determine lung density. Through an understanding of individual scanners, the Test Object analysis can be used to detect anomalies in an individual CT scanner and to statistically model out scanner differences and individual scanner changes over time in a large multicenter trial.

Published
2012

44. Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease

Author

James Murphy, Edwin J. R. van Beek, Eugene Berkowitz, Carlos Orozco, Venkata Bandi, Robert M. Steiner, Shivam Chandan, Stephanie A. Santorico, Joel L. Weissfeld, Kalpalatha K. Guntupalli, Matthew J. Budoff, Robert H. Brown, Charles Trinh, Ya Hong Chen, Phillip M. Westgate, John D. Newell, Gloria Westney, Raúl San José Estépar, Russell P. Bowler, Geoffrey McLennan, Robert A. Wise, Ella A. Kazerooni, Nathaniel Marchetti, John H. M. Austin, Harvey O. Coxson, Douglas Everett, Joseph H. Tashjian, Antonio Anzueto, Joe Piccoli, Homayoon Farzadegan, Richard Casaburi, Michael H. Cho, Philip Alapat, Charlene McEvoy, Sandra G. Adams, Marilyn G. Foreman, R. Graham Barr, Jessica Bon, Fernando J. Martinez, Susan Murray, Nadia N. Hansel, Paul J. Friedman, Francine L. Jacobson, Ruthie Knowles, Verity McArthur, Jennifer L. Black-Shinn, Joe W. Ramsdell, Janos Porszasz, Martina Wamboldt, Chandra Dass, Terri H. Beaty, John J. Reilly, Timothy Bresnahan, Hans Fischer, Jordan A. Zach, Victor Kim, Jacqueline B. Hetmanski, Elizabeth Guy, Dzimitry Kazlouski, Stacey Meyerer, Eric A. Hoffman, Philip F. Judy, Sarah Moyle, Adam L. Friedlander, Frank C. Sciurba, Brad H. Thompson, Mark T. Dransfield, Tanda Murray, Michael E. DeBakey, Margaret Forbes, Nicola A. Hanania, Gregory L. Kinney, Barbara J. Klanderman, Mustafa A. Atik, Gerard J. Criner, Christine H. Wendt, Dwight C. Look, James D. Crapo, Elizabeth A. Regan, Hirani Kamal, Andrew Allen, Anastasia Rodionova, Amber Powell, Heather Baumhauer, Quentin Anderson, Aditi Satti, Dennis E. Niewoehner, John E. Hokanson, Marci K. Sontag, William C. Bailey, Lyrica X. Liu, Hrudaya Nath, Neil R. MacIntyre, David A. Lynch, Kathryn L. Rice, Samantha Bragan, Barry J. Make, Byron Thomashow, Douglas Stinson, Jered Sieren, Richard Rosiello, Roham Darvishi, Robert L. Jensen, Tanya Mann, Lacey Washington, Gregory B. Diette, Christoph Lange, Mario E. Ruiz, Jeffrey L. Curtis, Joyce D. Schroeder, Antara Mallampalli, Tadashi Allen, Rebecca Leek, Nan M. Laird, Craig P. Hersh, George R. Washko, H. Page McAdams, Amir Sharafkhaneh, Alex Kluiber, MeiLan K. Han, Carl R. Fuhrman, A. James Mamary, Carla Wilson, James C. Ross, Carlos H. Martinez, Edwin K. Silverman, Dawn L. DeMeo, and Maura Robinson

Subjects
Male, Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Health Status, Body Mass Index, Pulmonary Disease, Chronic Obstructive, Surveys and Questionnaires, Internal medicine, Hounsfield scale, medicine, Humans, Lung emphysema, Lung, Aged, Aged, 80 and over, Emphysema, COPD, medicine.diagnostic_test, business.industry, Middle Aged, respiratory system, medicine.disease, humanities, Obstructive lung disease, respiratory tract diseases, Dyspnea, medicine.anatomical_structure, Multivariate Analysis, Cardiology, Physical therapy, Regression Analysis, Female, Tomography, X-Ray Computed, Airway, business, Body mass index
Abstract

The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p0.001; for WA%, 1.20-fold increase, p0.001; for pi10, 1.16-fold increase, p0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p0.001).Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.

Published
2012

45. Statistical Interior Tomography

Author

Jered Sieren, Ge Wang, Hengyong Yu, Qiong Xu, Eric A. Hoffman, and Xuanqin Mou

Subjects
Mathematical optimization, Iterative reconstruction, Poisson distribution, Article, symbols.namesake, Image Processing, Computer-Assisted, Animals, Humans, Computer Simulation, Poisson Distribution, Electrical and Electronic Engineering, Mathematics, Sheep, Radiological and Ultrasound Technology, Phantoms, Imaging, Reproducibility of Results, Signal Processing, Computer-Assisted, Maximization, Computer Science Applications, Compressed sensing, symbols, A priori and a posteriori, Radiography, Thoracic, Minification, Hilbert transform, Tomography, X-Ray Computed, Algorithm, Algorithms, Software, Count data
Abstract

This paper presents a statistical interior tomography (SIT) approach making use of compressed sensing (CS) theory. With the projection data modeled by the Poisson distribution, an objective function with a total variation (TV) regularization term is formulated in the maximization of a posteriori (MAP) framework to solve the interior problem. An alternating minimization method is used to optimize the objective function with an initial image from the direct inversion of the truncated Hilbert transform. The proposed SIT approach is extensively evaluated with both numerical and real datasets. The results demonstrate that SIT is robust with respect to data noise and down-sampling, and has better resolution and less bias than its deterministic counterpart in the case of low count data.

Published
2011

46. The National Lung Screening Trial: Overview and Study Design

Author

Natalie Cunningham, Michael Khalili, John Waltz, Ralph Weiben, Deb Gurtner, Linda DeAlmeida, Sanjay Gupta, Sharon Maxfield, Crissy Kibic, Kathleen DeWitt, David DeMets, Walter Allen Bowman, Robert Epstein, Mia Burkhard, Stephen J. Swensen, Hattie Cromwell, Kianoush Rezai, Steadman Sankey, Lisa Scott Wasson, Rita Musanti, Tamim Malbari, Joy Ferola, Qimei He, Patty Trapnell, Melba Francis, Sam Quattlebaum, Joanice Thompson, Ana Birofka, Robin Griggs, Elizabeth Johnson, Margaret R. Spitz, Nicole Richardson, Yuting Liang, Lawrence G. Hutchins, Mirjana Tecmire, Lila Camara, James J. Navin, Eileen Frost, Diane Romano, Carrie Petkus, Eric J. Berns, Pei Jan P Lin, Steve D. Uttecht, Marian Acerra, Lawrence R. Ragard, Leo P. Lawler, Christopher M. Rogers, Alan Lee Goodwin, L. Ellen Martinusen, Melissa Ford, Michael T. Fisher, Beverly Powell, Cindy Lin, Jamie Downs, Brent Fodera, Bonita Wohlers, Michael Brangan, Peggy Bradley, Todd B. Burt, Susan Allen, Shiva Borgheian, Mingying Zeng, Thomas Riley, Danielle Gherardini, Steven Shiff, Olivia Campa, Wahied Gendi, Fang F. Xu, Ivana K. Kazda, Anne Chung, Briar Doi, Helen Price, Maria Vlachou, Alan Morgan, Simone Vuong, Pierre P. Massion, Darcy Watson, Debbie William, Esther Nakano, Karen Broski, David Creed, Melanie Bvorak, Lakisha Hawkins, Gladys Hino, Raymond Dauphinais, Michele Sallas, Helene Shiratori, Venus Brown, Denise Brooks, Heather Porter, Ilana F. Gareen, Tracy Lee, Melissa Cates, Kyle Turner, Tiffanie Hammond, Margaret Paquette, Lorraine Kerchum, Barbara Lewis, Douglas J. Reding, Thomas E. Hartman, Cathy Longden, Melissa Laron, Reza Abaya, Beborah Robertson, J W Semenkovich, Christine Holland, Hugh McGinley, Chani Montalbo, Karen Zubena, Vanessa Ralda, Adam C. Stein, Jennifer Ott, Lawrence M. Kotner, Jing Lee, Arnold Ssali, Michael Young, Quinn A. DeMordaunt, Linda V. White, Steve Dubinett, Pearl Chan, Roxana Phillips, Mallory Kolich, Brent B. Nelson, Phi Do, Jill Spivak, Angele LaFleur, Kesha Smith, Elayne Weslowsky, Patricia Nieters, Maurice LeBlanc, Satinder Singh, Lonna Matthews, Quentin McMullen, Karen Lappe, Sharon Longacre, Cindy Cobb, Jane A. Zehner, Michael Teepe, Pamela M. Marcus, Kathleen Bow, Wendy Francis, Mary Gemmel, Robert S. Fontana, Linda Jurjans, Barbara Ginther, Jonathan B. Clapp, Monica Richel, Scott F. Pickering, Brenda Edwards, Kendrick Looney, Randy Marshall, Roni Atkins, Danielle Wicks, Julie Peterson, Dcanna Cape, Albert J. Cook, Jerry Brekke, Louisa Turner, Larry Stoller, Mark B. Salerno, Bavid E. Midthun, Mark Delano, Minnetta Belyea, Deborah Greene, Jonathan Goldin, Terry Lewis, Virginia Fischer, Andrea Chapman, Shari Jordan, Deb Warren, Demetria Johnson, Rekha Khatri, Lisa Sirianni, Guillermo Geisse, Michael A. Fuchs, Kanya Kumbalasiri, Jeremy J. Erasmus, Vicki Shambaugh, Denise Boyles, Sarah Hallsky, Anna Nanovski, Jill Heinz, Mollie King, Kay Vydareny, Olga Soukhanova, Patricia Rueweler, Perry G. Pernicano, Regina Rendas-Baum, Phyllis Pirotte, Russell Harris, Neil Argyle, Miyoung Kim, June Krebsbach, Audrey Gallego, Sheila Wein, Mukesh F. Karwat, Karla Myra-Bloom, Pamela Byrnes, Mitchell D. Schnall, Hector Ahumada, Eric Sanchez, Donna DesMarais, Julie Maderitz, Cindy Lavergne, Lori Kirchoff, Patricia C. Sanders, Elizabeth Thielke, Michael Sullivan, Jennifer Gaegler, Janet Manual, Jennifer R. Heinz, Ray Zisumbo, Diane C. Strollo, Candace Mueller, Irene Mahon, Brenda Delfosse, Carolyn M. Johnson, William E. Grizzle, Merideth Stanley, Sylvan Green, Pamela Harvey, Lindsay Richardson, Brenda K. Brewer, Philip Costello, Deanna Zapolski, John Worrell, Jeffrey G. Schragin, David S. Alberts, Edward L. Korn, Tamara Owens, Hank Brastater, Kay Mathiesen-Viergutz, Mark Broschinsky, Paul W. Spirn, Grace Isaacs, John S. Waltz, Mitch Goodsitt, Christi Newton-Foster, Sharlene Snowden, Barbara Voight, Gail Bizer, Kathy McDonough, William Huynh, Eduard Van Stam, Robert A. Carlson, Mike Florzyk, Paula M. Jacobs, Joan Fuller, Mauren Grunenwald, Ann Bangerter, Jacksonville, Adriane Andersen, Tess Thompson, Kenneth Nowers, Stephanie Helwi, Martin J. Edelman, Emmanuel Omoba, Rubenia Flores, Kevin T. White, Patrick W. Wolfe, Michael Milacek, Sharon Gard, Brandon B. Bigby, Cynthia H. McCollough, Andrew Burnside, Sheryl L. Ogden, Maisha Pollard, Thomas K. Pilgram, Sydney Laster, Claudia J. Kasales, Bruce W. Turnbull, Cheri Haselhuhn, Laura N. Myers, Jean Jacobsen, Melissa Love, Gavin D. Watt, Cheryl Love, Gerald F. Abbott, Susanne Kozakowski, Jerry L. Montague, Cynthia Hill, Neil F. O'Donnell, Anna Sear, Thomas M. Beck, Jean Wegner, Chrispina Wray, Edward M. Brown, Louise Ledbetter, Karen Bellware, Julie Moody, Noel Bahr, Matthew T. Freedman, Thomas Hensley, John E. Madewell, Leanne Hadfield, David R. Maffitt, Lisa Cottrell, John J. Warner, Deborah Graham, Krystal Arnold, Alejandra Reyes, Kristin Lieberman, Derek Omori, Donna Garland, Mike Burek, Mel Johnson, Judith Harkins, Martha Fronheiser, M. Y. M. Chen, Dawn Simmons, Kathleen Voight, Aaron O. Bungum, Marianne Rice, Lakeshia Murray, Tami Krpata, Donna Sammons, Leslie Kmetty, Catherine Duda, Carissa Krzeczkowski, Anne Nguyen, Richard H. Lane, Cynthia Mack, Loren C. Macey, Eddy Wicklander, Kelly McDaniel, Sue Zahradka, Hassan Bourija, Cristina Farkas, Jincy George, Renae Kiffmeyer, Wendell Christie, Catherine Engartner, John Crump, Mimi Kim, Carol Steinberg, Reginald F. Munden, Deb Kirby, Jo Ann Stetz, Barbara O'Brien, Sally Tenorio, Laura Multerer, Carlotta McCalister-Cross, Jessica Silva-Gietzen, Tamara Saunders, Harvey Glazer, Cam Vashel, Maria Oh, Rodkise Estell, Steven M. Moore, Tara Riley, Grant Izmirlian, D. Claire Anderson, James Burner, Steven Peace, Phil Hoffman, Angela Del Pino, Brian Irons, Carlos Jamis-Dow, John K. Lawlor, Edward F. Patz, Jay Afiat, Amber Barrow, Bawn M. Beno, Melissa S. Fritz, Lynn Coppage, Scott J. Sheltra, Tim Swan, Jerry Bergen, Charlie Fenton, Eric Deaton, Marilyn J. Siegel, Korinna Vigeant, Kerry Engber, Sarah Merrill, Buddy Williams, Kimberly Stryker, Bradley S. Snyder, Christina Romo, Andrea Hugill, Michael J. O'Shea, Linda White, Gail Fellows, Yasmeen Hafeez, Joe Woodside, Shauna Dave Scholl, Philip C. Prorok, Sharon Carmen, Kelly Hatton, Steven V. Marx, Sooah Kim, Robert Kobistek, Dawn Thomas, Lea Momongan, Chris Steward, Kari Bohman, Holly Bradford, Bradley S. Sabloff, Phillip Peterson, William C. Black, Lisa Pineda, James G. Ravenel, Karen Taylor, Beverly Trombley, Mona N. Fouad, Amber McDonald, Lauren J. Ramsay, Lisa Harmon, Jeffrey Geiger, David L. Spizarny, Jeffrey S. Klein, Xizeng Wu, Heather Tumberlinson, Joy Espiritu, Gina Varner, Dawn Fuehrer, Eric A. Hoffman, Sheila Moesinger, Nina Wadhwa, Steve King, Patricia Lavernick, Paola Spicker, Timothy R. Church, Cheryl Whistle, Sheila Greenup, Patricia Fantuz, Stephanie Levi, Peter Balkin, Mary E. Johnson, Johanna Ziegler, Susan Hoffman, Kathy L. Clingan, Craig Kuhlka, Maria Marchese, Lawrence F Cohen, Cylen Javidan-Nejad, Wilbur A. Franklin, Kevin J. Leonard, Tim A. Parritt, Jade Quijano, Kathleen Poler, Jennifer Rosenbaum, Xiuli Zhang, Christine Brown, Terri David-Schlegel, Susan M. Peterson, James R. Jett, Kenneth W. Clark, Edward P. Gelmann, Arthur Migo, Patricia Fox, Lori Hamm, Janie McMahon, Darlene Guillette, Robert C. Young, Patty Beckmann, Jerome Jones, Nikki Jablonsky, Roberta Yoffie, Heather L. Bradley, Darlene Higgins, Francine L. Jacobson, Christine B. Berg, Mark Bramwitt, Constantine N. Petrochko, Karen Stokes, Jennifer Rowe, Kathy McKeeta-Frobeck, Brenda Sleasman, Courtney Bell, Dave Tripp, Saundra S. Buys, Susan Walsh, Jo Rean D. Sicks, Richard G. Barr, Kirk Midkiff, Tom Caldwell, Elisabeth A. Grady, Subbarao Inampudi, Marilyn Calulot, Paul A. Kvale, Alice DuChateau, Kathy Berreth, Ruth Holdener, Katie Kuenhold, Thomas E. Warfel, David P. Naidich, Mandie Leming, Fraser Wilton, Leanne Franceshelli, Kathleen McMurtrie, Elaine Bowman, Donald F. Bittner, Helen Kaemmerer, Merri Mullennix, Adelheid Lowery, Andrew Karellas, Jenny Hirschy, Kate Naughton, Ashley B. Long, Kristin M. Gerndt, Kathleen Young, Richard M. Schwartzstein, Wendy Smith, Joseph Aisner, Shane Ball, Kathleen Krach, Cathy Mueller, Virginia May, Christopher Blue, Marsha Lawrence, Ronald S. Kuzo, Colleen McGuire, Alisha Moore, Sara Cantrell, Christie Leary, Pamela Allen, Maryann Trotta, Clifford Caughman, Peggy J. Gocala, Brian Mullen, Janan Alkilidar, Maryann Duggan, Lin Mueller, Alesis Nieves, Fenghai Duan, Frederick Olson, Edwin G. Williams, Jo Ann Hall Sky, Grant Izmirilian, Peggy Joyce, Judy Preston, Cristine Juul, Julianne Falcone, Bruce Neilson, Fla Lisa Beagle, Beth Evans, Jamie Mood, Janet Bishop, Jean Tsukamoto, Vivien Gardner, Gillian Devereux, Minesh Patel, Sally Fraki, Celia Stolin, Ami Lyn Taplin, Stephenie Johnson, Saeed Matinkhah, Jenna Bradford, Sanjeev Bhalla, Charles Jackson, Julie Haglage, Darlene R. Fleming, Allie M. Bell, Paul A. Bunn, Gail Orvis, Andrew J. Bierhals, Julie Ngo, Belores K. Prudoehl, Elaine N. Daniel, Peggy Olson, Paul F. Pinsky, Glenna M. Fehrmann, Aras Acemgil, Andrea Hamilton-Foss, Leeta Grayson, Smita Patel, Scott Emerson, Carl J. Zylak, James R. Maxwell, Jennifer Fleischer, Suzanne Smith, Jacqueline R. Sheeran, Alan Williams, Scott Gaerte, John Fletcher, Sonya Clark, Nancy Gankiewicz, Stuart S. Sagel, Jason Spaulding, Nancy E. Hanson, Nicole Fields, Richard D. Nawfel, Dinakar Gopalakrishnan, Margaret Oechsli, Susan Wenmoth, Isabelle Forter, Elizabeth Morrell, Jessica Rider, Letitia Clark, Michael Woo, Cynthia A. Brown, Camille Mueller, Mark T. Dransfield, Lois M. Roberts, Anne Randall, Eduard J. Gamito, Carrie O'Brien, Carolyn Palazzolo, Julie Schach, Robert Falk, Melissa Hudson, Jennifer Garcia Livingston, Cynthia L. Andrist, Tammy Fox, Elliott Drake, Tanya Zeiger, Renee Metz, Kevin Thomas, Neha Kumar, Elizabeth Couch, Beborah Bay, Mei Hsiu Chen, Jason Bronfman, Philip Dennis, Deb Engelhard, Pamela McBride, Daniel Kimball, Amy Haas, Pamela M. Mazuerk, Marlea Osterhout, Venetia Cooke, Tina Taylor, Amy St.Claire, Joe Hughes, Becky McElsain, Beverly Brittain, Michele Adkinson, Paige Beck, Martha Maineiro, Paula R. Beerman, Jackie Seivert, Mary M. Pollock, Donald Corle, Tina Herron, Marcella Petruzzi, Natalie F. Scully, Kenneth A. Coleman, Jennifer Yang, Debra Loria, Wendy Moss, Alan Brisendine, Cheryl M. Lewis, Dalphany Blalock, Lonni Schultz, Douglas Bashford, Nora Szabo, David Shea, Amanda Devore, Karen Schleip, Judy Netzer, Barry Clot, Gerald M. Mulligan, Nancy E. Krieger Black, David Schultz, Jim Pool, Craig E. Leymaster, Kathryn Rabanal, Kay Bohn, Tara Berg, Marisol Furlong, Stacey Mitchell, Donna Biracree, Laura Jones, Cassie Olson, Robin Stewart, Jeremy Pierce, Marilyn Bruger, Valene Kennedy, Stephanie Davis, Colin O'Donnell, Glenn A. Tung, Shannon Wright, William Lake, Sharon Jones, Vincent Girardi, Brad Benjamin, Veenu Harjani, Drew A. Torigian, Kevin Edelman, Sue Frederickson, Paul E. Smart, Michelle Wann Haynes, D S Gierada, Glenn Fletcher, Rosalie Ronan, Patricia Ann Street, Eleace Eldridge-Smith, Lynly Wilcox, Cindy Lewis-Burke, La Tonja Davis, Rachel Black Thomas, Dawn Shone, Evangeline Griesemer, Tim Budd, Lindsey Dymond, Marlene Semansky, Amy Rueth, Constantine Gatsonis, Kay H. Vydareny, Usha Singh, Amy Lita Evangelista, Angelica C. Barrett, Bethany Pitino, Shirley Wachholz, Angela M. Williams, Sandra Fiarman, Karen Luttrop, David Chellini, Michael Bradley, Helen Fink, Aaron Zirbes, Roger Inatomi, Joon K. Lee, Heather Bishop Blake, Lisa Woodard, Craig Hritz, Sarah Neff, Aine Marie Kelly, Deborah Harbison, Baigalmaa Yondonsambuu, Amy Lloyd, Christine Gjertson, Erin Cunningham, Angelee Mean, June Morfit, Ping Hu, William Thomas, Jazman Brooke, Paul Marcus, Jeremy Gorelick, Erin Lange, William Stanford, Denise R. Aberle, Lena Glick, Annabelle Lee, Ian Malcomb, Deanna L. Miller, Mary Mesnard, Jacqueline Jackson, Jhenny Hernandez, Desiree E. Morgan, Howard I. Jolies, Jacquie Marietta, Teresa Lanning, Debra Rempinski, Amanda C. Davis, Karen Mathews Batton, Mahadevappa Mahesh, Erik Wilson, Deana Nelson, Sharan L. Campleman, William Manor, Julie Sears, Howard Mann, E. David Crawford, Carl Krinopol, Greg Gambill, Margo Cousins, Rex C. Yung, Sangeeta Tekchandani, Thomas Vahey, Ann D. McGinnis, Kimberly Nolan, Kaylene Crawford, Kelli P. Rockwell, Dana Roeshe, Fred W. Prior, Kari Ranae Kramer, Heidi Nordstrom, Frank Stahan, Shawn Sams, Cherie Baiton, Joy Tani, Thomas J. Watson, Angela Cosas, Diane Kowalik, Pritha Dalal, Ann Jolly, Jeanine Wade, Laura Bailey, Julie Varner, Glen K. Nyborg, Christopher Toyn, David Gemmel, Susanna N. Dyer, Laurie Amendolare, Mary Ellen Frebes, Judy Ho, Adele Perryman, John Keller, D. Sullivan, George Mahoney, Scott Cupp, Linda L. Welch, Peter Greenwald, Robert Sole, Marcello Grigolo, Caroline Chiles, Patricia Sheridan, Deborah M. Chewar, Vijayasri Narayanaswami, Susan Blackwell, Suzanne B. Lenz, Alphonso Dial, Melvin Tockman, Carolyn Hill, John Stubblefield, Catherine E. Smith, Judith Lobaugh, Rosa M. Medina, Jackie Meier, Nandita Bhattacharjee, Robert Tokarz, Lisa Clement, Nancy Caird, Cindy Masiejczyk, Patricia Shwarts, Laura Springhetti, Sandra Schornak-Curtis, Edwin F. Donnelly, Patricia Tesch, Laurie Rathmell, Pamela K. Woodard, Edward A. Sausville, David R. Pickens, Kylee Hansen, Paulette Williams, Barbara Ferris, Rachel L. McCall, Nicole M. Carmichael, Dawn Whistler, Ramachandra Chanapatna, Glynis Marsh, Mary Wiseman, Tony DeAngelis, L. Heather, Vicki Prayer, Robin Laura, Priscilla Bland, Gregory W. Gladish, Amy Garrett, Kelly McNulty, Daniel J. Pluta, Mylene T. Truong, Serelda Young, Crista Cimis, Gordon Jacob Sen, Rhonda Rosario, Anthony B. Miller, Edward Hunt, Juanita Helms, Jill K. Bronson, Jeff Yates, Ginette D. Turgeon, Bo Lu, Nancy Fredericks, Pam Senn, Ryan Pena, Hakan Sahin, Mary Lynn Steele, Jill E. Cordes, Noel Maddy, R. Adam DeBaugh, Hope Hooks, Zipporah Lewis, Robert L. Berger, Shani Harris, Natalie Gray, Jennifer Kasecamp, Elizabeth King, Jacinta Mattingly, Hrudaya Nath, Kathy Torrence, Christine Cole Johnson, Sara Mc Clellan, Kalin Albertsen, Kim Sprenger, Ryan Norton, Jody Wietharn Kristopher, Linda Warren, Byung Choi, Casey O'Quinn, Mark K. Haron, Chris J. Jennings, Karen Robinson, Joan Molton, Dorothy Hastings, Robert I. Garver, Christopher J. Cangelosi, Jeannette Lynch, Peter Ohan, Angela Campbell, Dawn Mead, Miriam Galbraith, Divine Hartwell, Natalya Portnov, Gene L. Colice, Andetta R. Hunsaker, Analisa Somoza, Todd Risa, Daniel C. Sullivan, Karthikeyan Meganathan, Tammy DeCoste, Peter Zamora, Richard M. Fagerstrom, Iiana Gareen, Phyllis J. Walters, Barbara L. Carter, Alem Mulugeta, Rob Bowman, Kavita Garg, Andrea Franco, Mary Adams Zafar Awan, Edward Reed Smith, Rachel Phillips, Michelle Aganon-Acheta, Fred R. Hirsch, Peter Jenkins, Pamela Taybus, Joy Knowles, Karen M. Horton, Cheryl Spoutz-Ryan, Sarah Landes, William G. Hocking, Laura B. Schroeder, Erini Makariou, Jered Sieren, Kaylene Evans, Erin Nekervis, Brenda Polding, Tonda Robinson, Joel L. Weissfeld, Terry J. Sackett, Michael F. McNitt-Gray, Leslie Dobson, Raymond Weatherby, Randell Kruger, Revathy B. Iyer, Mary Krisk, Anthony Levering, Susan Collins, Alison Schmidt, William M. Hanson, Patricia Schuler, Karen Glanz, Morgan Ford, Beatrice Trotman-Bickenson, Richard Guzman, Paul Koppel, Judith K. Amorosa, Meredith Slear, Dayna Love, Carol Vaughn, Kellyn Adams, Celeste Monje, Garry Morrison, Sherri Mesquita, Paul Cronin, Tony Blake, Constance Elbon-Copp, Robert A. Clark, Felix Mestas, Erich Allman, Armen Markarian, Cheryl Souza, Karen O’Toole, Elliot K. Fishman, Karen Augustine, Jane Hill, Bonnie Kwit, Ralph Drosten, Susan Foley, Stacy E. Smith, Angie Bailey, Jennifer Bishop Kaufmann, Shelly Meese, Phillip M. Boiselle, Howard Morrow, Thomas D. Hinke, Barry Edelstein, Erin Schuler, William C. Bailey, Donna Letizia, David S. Gierada, Frederick J. Larke, Robin Haverman, Sarah Baum, Sally Hurst, Richard L. Morin, Ben Dickstein, William Russell, J. Anthony Seibert, Sophia Sabina, Mary Alyce Riley, Michael A. Taylor, Katherine BeAngelis, Robert A. Hawkins, Fernando R. Gutierrez, Amie Welch, Heather Lancor, George Armah, James Blaine, Eric Henricks, Joel Dunnington, Carole Walker, Laura Motley, Melody Kolich, Bruce J. Hillman, David W. Sturges, Mindy Lofthouse, Amy Warren, Michael Black, Mark Kolich, Lisa A. Holloway, Shannon M. Pretzel, Susan Shannon, Yassminda Harts, Dallas Sorrel, Lance A. Yokochi, Diana Wisler, Arthur Sandy, Roberta Clune, Shirley Terrian, Shalonda Manning, Bradley Willcox, Thomas J. Payne, James L. Tatum, Dale Brawner, Sandy Morales, Rodolfo C. Morice, Amy Vieth, Emily Jewitt, Chelsea O'Carroll, Theresa C. McLoud, John E. Langenfeld, Chris H. Cagnon, Lisa B. Hinshaw, Gena Kucera, Helena R. Richter, Drew Torigian, June McSwain, Courtney Eysmans, Vinis Salazar, David Spizarny, Mary Kelly-Truran, Mark Whitty, Henry Albano, Connie L. Sathre, William R. Geiser, Barnett S. Kramer, Marianna Gustitis, Gordon C. Jones, Neil E. Caporaso, Timothy Welsh, Roger Tischner, Ana Maria Mendez, Dominick A. Antico, Cathy L. Bornhorst, Carla Chadwell, Stephanie Pawlak, Kelli M. West, Joe V. Selby, Randall Kruger, Jodi Hildestad, Elaine Freesmeier, Nicole Rivas, Andrew Goodman, Naima Vera-Gonzalez, Stuart Lutzker, Eric M. Hart, Melanie Yeh, Shane Sorrell, Deb Multerer, Sharon Jacoby, Debbie Gembala, Elizabeth Fleming, Myrle Johnson, Michael J. Flynn, Frank Tabrah, Martin L. Schwartz, Deanna Mandley, Brad Siga, Guillermo Marquez, Jeffrey Koford, Victoria Jenkins, Janice Pitts, Constantine A. Gatsonis, Natalie Baptiste, Edith M. Marom, Gina Sammons, Anne Burrough, Martha Ramirez, Jack Cahill, Carl Jaffe, Linda Heinrichs, Aura Cole, Paul Rust, Alon Coppens, Gregg Hamm, Lisa Conklin, Kathleen A. Robbins, Carleaner Williams, Gwen Chalom, Winston Sterling, Colleen Hudak, Lea Matous, Ella A. Kazerooni, Denise Kriescher, David A. Lynch, Liz Bolan, Jacob Wolf, Jonathan G. Goldin, Roberta Quinn, L. A. Schneider, Kathleen A. Murray, Erica Sturgeon, Jennifer Avrin, Michelle T. Biringer, Mark Hinson, Cynthia Reiners, Brian Chin, Amy Brunst, Ann M. Lambrecht, Katherine Lohmann, Jennifer Bacon, Ulander Giles, Diane Shepherd, William T. Corey, Timothy Cosgrove, Lana C. Walters, Nancy Kadish, Hilary C. Nosker, Christine D. Berg, Thomas Payne, Jackie Becker, Kanistha Sookpisal, Lyn Seguin, Todd R. Hazelton, Roy Adaniya, James Fisher, Annmarie Walsh, Shirleen Hyun, Laura Stark, Kenneth Hansen, Carolyn Nelson, Martin Tammemagi, Mary A. Wolfsberger, Barry H. Gross, Valentina Ortico, Marge Watry, Jeff Childs, Gabe Herron, Loretta Thorpe, Lisa Damon, Evanthia Papadopoulos, Denise Moline, Voula E. Christopoulos, John D. Minna, Tony Jones, Mitchell Machtay, Michael Plunkett, Melissa Laughren, Luis Zagarra, Adam Leming, Eda Ordonez, Chris Howell, Marissa Peters, Wendy Mosiman, Joanne Gerber, Alfonso Lorenzo, Barbara L. McComb, Laura Hill, Gale Christensen, Hanna Comer, Carmen Guzman, Kathy Taylor, Misty Oviatt, Malcolm King, Lily Stone, Rex Welsh, Bernadette Pennetta, Cristina Raver, Jan E. Hyder, Stephanie Clabo, Peggy Lau, Jacqueline Fearon, Patricia Pangburn, Pamela Dow, William K. Evans, Victor De Caravalho, Mike Wirth, Brooke Johnson, Meridith Blevins, Lisa H. Gren, Sharon L. Kurjan, James P. Evans, Kirk E. Smith, Donna King, John A. Worrell, Mindy S. Geisser, Philip F. Judy, Richard Barr, Sue Misko, Stanley R. Phillips, Jillian Nickel, Christine M. McKey, Joe Austin, Donna Hartfeil, Laura Young, Shovonna White, Alexis K. Potemkin, Anthony Boulos, Tawny Martin, Karen Kofka, Heather McLaughlin, Matthew K. Siemionko, Melissa Houston, Angela Lee Rowley, Adys Fernandez, Murray Backer, Jagdish Singh, Mary Weston, Nancy Payte, Charles Apgar, John K. Gohagan, Jeff Fairbanks, Wylie Burke, David Chi, Michael Nahill, Kevin DeMarco, Karen Patella, Beverly Rozanok, Carol M. Moser, Nicole Matetic Mac, Karen Boyle, Dinah Lorenzo, Elanor Adkins, Phyllis Olsson, Amanda M. Adams, Sujaya Rao, K.E. Jones, Polly Kay, D. Lynn Werner, John B. Weaver, Sally Anne Kopesec, Jennifer Frye, Victoria Chun, Cathy Francow, Cheri Whiton, Jo Ann Nevilles, Andrew Bodd, Barbara Galen, Sabrina Chen, Cindy Cyphert, Stephen M. Moore, Petra J. Lewis, Shanna Nichols, Mareie Walters, Thea Palmer Zimmerman, Warren B. Gefter, Peter Dubbs, Ann Reinert, Holly Washburn, Renee MacDonald, Boleyn R. Andrist, Dianalyn M. Evans, Marvin Flores, Tricia Adrales-Bentz, Claudine Isaacs, Regina C. MacDougall, Greg M. Silverman, Nichoie Cadez, Lynne Bradford, Rochelle Williams, Angela M. McLaughlin, Ellen Sandberg, Cheryl Crozier, Robert Mayer, Richard P. Remitz, Sheron Bube, Leroy Riley, Vish Iyer, Sophie Breer, Stephen Baylin, Anna Boyle, Shannon Williams, Kristen Keating, Martin M. Oken, Gerald L. Andriole, Bruce E. Hubler, Eric T. Goodman, David Engelhart, Bonna Au, Brianne Whittaker, Tricia Hoffa, Eng Brown, Tammy Wolfsohn, Denise L. Foster, Barry H. Cohen, Linda Galocy, Matthew T. Bee, Jacqueline Matuza, Leslie Henry, Katherine Meagher, Mona Fouad, Beth McLellan, Troy Cook, John Sheflin, Lilian Villaruz, Marcella Moore, Brandy Mack-Pipkin, Vanessa Graves, Ryan Weyls, William T. Herbick, Geoffrey McLennan, Lynn Hoese, Janise Webb, Terrie Kitchner, Michele Lee, Robert T. Greenlee, Charles C. Matthews, Nicole Spiese, Jeffrey Heffernon, Dianna D. Cody, Patricia Blair, Kathy Garrett, Michael A. Sullivan, and Loretta Granger

Subjects
Oncology, medicine.medical_specialty, business.industry, Mortality rate, medicine.disease, law.invention, Quality-adjusted life year, Randomized controlled trial, law, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, National Lung Screening Trial, Radiology, Overdiagnosis, business, Lung cancer, Lung cancer screening, Mass screening
Abstract

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.

Published
2011

47. A Process Model for Direct Correlation between Computed Tomography and Histopathology

Author

Jacqueline Thiesse, Joseph M. Reinhardt, Geoffrey McLennan, Jessica C. Sieren, Eric A. Hoffman, Jered Sieren, Jamie A. Weydert, and Eman Namati

Subjects
medicine.medical_specialty, Solitary pulmonary nodule, business.industry, Image quality, Coordinate system, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Process (computing), Image registration, Image processing, medicine.disease, ComputingMethodologies_PATTERNRECOGNITION, medicine, Radiology, Nuclear Medicine and imaging, Histopathology, Computer vision, Artificial intelligence, Lung cancer, business
Abstract

Rationale and Objectives Multimodal imaging techniques for capturing normal and diseased human anatomy and physiology are being developed to benefit patient clinical care, research, and education. In the past, the incorporation of histopathology into these multimodal datasets has been complicated by the large differences in image quality, content, and spatial association. Materials and Methods We have developed a novel system, the large-scale image microtome array (LIMA), to bridge the gap between nonstructurally destructive and destructive imaging such that reliable registration between radiological data and histopathology can be achieved. Registration algorithms have been designed to align the multimodal datasets, which include computed tomography, computed micro-tomography, LIMA, and histopathology data to a common coordinate system. Results The resulting volumetric dataset provides an abundance of valuable information relating to the tissue sample including density, anatomical structure, color, texture, and cellular information in three dimensions. An image processing pipeline has been established to register all the multimodal data to a common coordinate system. Conclusion In this study, we have chosen to use human lung cancer nodules as an example; however, the flexibility of the image acquisition and subsequent processing algorithms makes it applicable to any soft organ tissue. A novel process model has been established to generate cross registered multimodal datasets for the investigation of human lung cancer nodule content and associated image-based representation.

Published
2010

48. CT Metrics of Airway Disease and Emphysema in Severe COPD

Author

James Walter, David Godwin, Joyce Canterbury, Thomas E. Hartman, Yen Pin Chiang, Jeanne Smith, John J. Reilly, Hope Livingston, Abby M. Krichman, Mahasti Rittinger, Karma L. Kreizenbeck, Kymberley Anable, Ameena Al-Amin, Colleen Witt, Karen McVearry, Claude Deschamps, Selim M. Arcasoy, Liz Roessler, James K. Stoller, Yahya M. Berkmen, Paul J. Friedman, Enrique Fernandez, Laura Kotler-Klein, Chris Piker, Robert E. Hyatt, Mark J. Krasna, Priscilla McCreight, Jo Anna Baldwin, Jennifer M Lamb, Francisco Alvarez, Janet R. Maurer, Rodney Simcox, Gerald O'Brien, Iris Moskowitz, Marianne C. Fahs, Judd Gurney, A. Mark Fendrick, Mike Mantinaos, Sanjay Kalra, Robert M. Kaplan, Kevin R. Flaherty, Timothy Gilbert, James K. Garrett, Kathy Mieras, Kapreena Owens, Trina Limberg, Patricia Belt, Rolf D. Hubmayr, Roger Barnette, James Carter, Phillip M. Boiselle, Brian Woodcock, Anne Marie Kuzma, Brian F. Mullan, Dean Follmann, Mary Ellen Kleinhenz, Judith Harle, Ubaldo J. Martin, Bonnie Edwards, Fernando I. Martinez, Sandy Do, Alejandro A. Diaz, F.C. Sciurba, William Russell, David J. Sugarbaker, Theresa Alcorn, Susan Borosh, Patricia McDowell, Carolyn Wheeler, Blake Wood, Edwin K. Silverman, Alan J. Moskowitz, John F. Plankeel, William F. Bria, Susan Clark, Patricia Ward, Scott D. Ramsey, Barry J. Make, David H Kupferberg, Chinh T. Q. Nguyen, Stanley Aukberg, Elisabeth L. George, Steven Piantadosi, Geoffrey McLennan, Carl D. Mottram, Martin Zamora, Marvin Pomerantz, Ella A. Kazerooni, Jennifer Propst, Bessie Kachulis, Carol Fanning, Valentina Yegyan, Kenneth Silver, James P. Kiley, Sabine Duffy, David H. Harpole, Junfeng Guo, Donald C. Oxorn, Andrew L. Ries, Paramjit Gill, Bruce H. Culver, Todd M. Officer, Catherine Wood Larsen, John Hansen-Flaschen, Patrick Ross, Mindi Steiger, Lori Hanson, Rose Butanda, Paul F. Simonelli, Neil W. Brister, Amy Chong, Charles L. White, Eric A. Jensen, Cynthia Raymond, Mark K. Ferguson, Moulay Meziane, Mary Milburn-Barnes, James D. Luketich, Douglas E. Wood, A. John McSweeny, Woo Jin Kim, Kim Stavrolakes, John A. Waldhausen, Gregory L. Aughenbaugh, Chul Kwak, Sara L. Bartling, Joan Osterloh, Larry R. Kaiser, John S. Howe, Michael I. Lewis, Andrew Bowdle, Mark A. Gerhardt, Richard O'Connell, Brian R. Lawlor, Neil R. MacIntyre, David A. Lynch, Milton Joyner, Louie Boitano, James P. Utz, Everett Hood, Paul J. Smith, Joshua O. Benditt, John Apostolakis, Frances L. Brogan, Robert McKenna, Berend Mets, Phyllis Dibbern, Kevin Carney, Joan M. Lacomis, Kevin McCarthy, A. Laurie Shroyer, Mitchell K. O’Shea, Barry Make, Dora Greene, Janice Willey, Catherine Ramirez, Gwendolyn B. Vance, Philip R. Karsell, David DeMets, Angela DiMango, Peter Rising, Erik J. Kraenzler, Michael F. Keresztury, Laurie Ney Silfies, Michael Magliocca, Vivian Knieper, Betsy Ann Bozzarello, Marlene Edgar, Madelina Lorenzon, Deb Andrist, Sophia Chatziioannou, Darryl Atwell, Sally Frese, Ruth Etzioni, Stephen I. Marglin, Maria Shiau, Thomas Schroeder, Vincent J. Carey, Vladmir Formanek, Robert Levine, Cindy Chwalik, David Rittinger, Kenneth Martay, Brett A. Simon, Nancy Kurokawa, Anne L. Fuhlbrigge, Peter J. Julien, Michelle T. Toshima, Sean D. Sullivan, Joanne Deshler, Margaret Wu, Anthony Norris, David A. Lipson, Scott J. Swanson, Diane Lockhart, Omar A. Minai, Joseph l. Reeves-Viets, Raed A. Dweik, Keith S. Naunheim, Angela Delsing, Minnie Ellisor, Jane Whalen-Price, Victor F. Tapson, Leonard Rossoff, Susan M. Peterson, Deborah Nowakowski, David M. Shade, Susanne Snedeker, Susan Craemer, Anne Marie G. Sykes, Jennifer Norten, Manmohan S. Biring, Diane C. Strollo, Beth Elliot, Kedren Williams, Heather Sheaffer, Sheila Shearer, Robert P. Hoffman, Robert Quaife, J. Mendez, Donald A. Mahler, Janice Cook-Granroth, Scott Marlow, Zab Mosenifar, Malcolm M. DeCamp, Paul J. Christensen, Rosetta Jackson, Wissam Chatila, Robert Schilz, Glenda DeMercado, Peter B. O'Donovan, Kimberly Dubose, Robert J. Keenan, Satoshi Furukawa, Theodore Kopp, Gerald T. Ayres, Betty Collison, Stephen J. Swensen, Jennifer Stone-Wynne, Nicole Jenson, Stanley S. Siegelman, Tina Bees, Owen B. Wilson, R. Duane Davis, Pierre A. DeVilliers, Marcia Katz, Carolyn M. Clancy, Eddie L. Hoover, Bryan Benedict, Karen Kirsch, Philip M. Hartigan, Simon C. Body, Mark Stafford-Smith, David A. Zisman, Jeanne M. Hoffman, Fernando J. Martinez, Clarence Weir, Jeffrey D. Edelman, William Stanford, Zab Mohsenifar, Michael P. Donahoe, Michele Donithan, Catherine A. Meldrum, William A. Slivka, Lori Zaremba, Michael W. Smith, Martin D. Abel, Robert B Gerber, Sarah Hooper, Steven M. Scharf, Karen A. Hanson, Katherine P. Grichnik, J. Sanford Schwartz, Margaret L. Snyder, Charles J. Hearn, Joe Chin, Tammy Ojo, Gregory D.N. Pearson, Vera Edmonds, George R. Washko, Christine Young, Jennifer Minkoff-Rau, Ron Daniele, Chun Yip, Gregory L. Foster, Harold I. Palevsky, Joan E. Sexton, Dev Pathak, Pamela Fox, Paul E. Kazanjian, Karen King, Jacqueline Pfeffer, Imran Nizami, Judith Wagner, Catherine Wrona, John H. M. Austin, Karla Conejo-Gonzales, Sharon Bendel, Amir Sharafkhaneh, Carol Geaga, Denise Vilotijevic, Thomas H. Sisson, Steven H. Sheingold, Ryan Colvin, Elaine Baker, Karen Collins, Charles F. Emery, Mark Ginsburg, Abass Alavi, David D. Frankville, Joseph M. Reinhardt, Jan Drake, John M. Travaline, Rafael Espada, Kathy Lautensack, Leslie E. Quint, Jeffrey T. Chapman, Rosemary Lann, Steven M. Berkowitz, Alice L. Sternberg, Thurman Gillespy, Nadia Howlader, Frank J. Papatheofanis, Robert Frantz, Manuel L. Brown, Sarah Shirey, Yvonne Meli, Andra E. Ibrahim, Patricia A. Jellen, Rebecca Crouch, Warren B. Gefter, Michael J. Reardon, Jonathan B. Orens, Neal S. Kleiman, Marilyn L. Moy, Daniel L. Miller, Julie Fuller, Reuben M. Cherniack, Claudette Sikora, Lynn Bosco, Harry Handelsman, R. Edward Coleman, Judith M. Aronchick, James Tonascia, Delmar J. Gillespie, Patricia Berkoski, David P. Kapelanski, Cesar A. Keller, Amanda L. Blackford, Charles C. Miller, Kelly M. Campbell, Jill Meinert, Carl R. Fuhrman, Gordon R. Bernard, Connie Hudson, Roger Russell, Lewis Poole, Dale Williams, Magdy Younes, Shing Lee, Steven L. Sax, Martin Carlos, Diane C. Saunders, John Dodge, Matthew N. Bartels, Amy Jahn, Karen Taylor, Gregg L Ruppel, Wallace T. Miller, Mary Gilmartin, Tanisha Carino, Alfred P. Fishman, Gerene Bauldoff, Frank C. Sciurba, Gerard J. Criner, John Haddad, Mark D. Iannettoni, Terri Durr, Gordon F. Harms, Susan Golden, Norman E. Torres, Lisa Geyman, Alan Hibbit, Paul Rysso, Gilbert E. D'Alonzo, Henry E. Fessler, Mark L. Van Natta, Peter Wahl, James H. Harrell, Willard Chamberlain, Roger D. Yusen, Boleyn Hammel, Dawn E. Sassi-Dambron, Mark S. Allen, Jennifer Cutler, Shangqian Qi, Susan Rinaldo-Gallo, John D. Newell, June Hart, Raúl San José Estépar, Kerri McKeon, Staci Opelman, Eric S. Edell, Kathy Winner, Joe R. Rodarte, Mark A. King, Eric A. Hoffman, Laura A. Wilson, Phil Cagle, Jennifer Meyers, Kristin Berry, Mark P. Steele, Katherine Hale, Peter Barnard, Charles Soltoff, Melissa Weeks, Arfa Khan, Cary Stolar, Jeanine P. Wiener-Kronish, Jeannie Ricketts, Nancy Battaglia, Francine L. Jacobson, Satish G. Jhingran, Robert B. Teague, Mary Louise Dempsey, Leighton Chan, Philip T. Diaz, David Hicks, David E. Midthun, Charlene Levine, Andetta R. Hunsaker, Tomeka Simon, Jered Sieren, Susan Lubell, Scott A. Schartel, H P McAdams, Francis Cordova, Kris Bradt, Jeffery J. Johnson, Kenneth White, Mercedes True, Erin A. Sullivan, Byron Thomashow, Gail Weinmann, Robert A. Wise, Donna Tsang, Robert M. Kotloff, Atul C. Mehta, Gregory Tino, and Angela Wurster

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Critical Care and Intensive Care Medicine, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Predictive Value of Tests, Forced Expiratory Volume, Internal medicine, medicine, Humans, Lung volumes, Respiratory system, Aged, Probability, Original Research, Analysis of Variance, Univariate analysis, COPD, business.industry, Total Lung Capacity, Respiratory disease, Middle Aged, respiratory system, Airway obstruction, medicine.disease, Respiratory Function Tests, respiratory tract diseases, Airway Obstruction, Dyspnea, medicine.anatomical_structure, Pulmonary Emphysema, Multivariate Analysis, Cardiology, Female, Pulmonary Ventilation, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Airway, Respiratory tract
Abstract

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Published
2009

49. Static Versus Prospective Gated Non–breath Hold Volumetric MDCT Imaging of the Lungs1

Author

Geoffrey McLennan, Jered Sieren, Eric A. Hoffman, Kenneth C. Beck, Osama I. Saba, Joseph M. Reinhardt, and Deokiee Chon

Subjects
Reproducibility, business.industry, Dynamic imaging, Coefficient of variation, Medicine, Image acquisition, Radiology, Nuclear Medicine and imaging, Respiratory cycle, Gold standard (test), Nuclear medicine, business, Imaging phantom, Volume (compression)
Abstract

Rationale and Objectives: We seek to establish lung imaging methods which provide for the ability to image the lung under dynamic, non-breath hold conditions while providing “virtual breath hold,” quantifiable volumetric image data sets. We use static, breath hold images as the gold standard for evaluating these virtual breath hold images in both a phantom and sheep. Materials and Methods: We have developed axial methods for gating image acquisition to multiple points in the respiratory cycle interleaved with incremental table stepping during multidetector-row CT (MDCT) scanning. Datasets are generated over multiple breaths, providing volume images representative of multiple points within a respiratory cycle. To determine the reproducibility and accuracy of the methods , 6 anesthetized sheep were studied by MDCT in non-gated and airway-pressure (Pawy)-gated modes where Pawy was 0, 7 and 15 cmH2O. Results: No significant differences were found between the coefficient of variation in air volume measured from repeated static scans (1.74±1.78%), gated scans: Inspiratory gated (1.2±0.44%) or expiratory-gated (1.39±0.98%), or between static (1.74±1.78%) and gated (1.39+/-0.98%) scanning at similar Pawy (p>0.1). Measured air volumes were larger from static vs. gated scans by 5.85±3.77% at 7cmH2O and 4.45±3.6% at 15cmHL2O Pawy (p

Published
2005

50. Effect of lung inflation level on hyperpolarized 3He apparent diffusion coefficient measurements in never-smokers

Author

Daniel R. Thedens, Jered Sieren, Eric A. Hoffman, Matthew K. Fuld, Ahmed F. Halaweish, and Edwin Jacques Rudolph van Beek

Subjects
Adult, Male, medicine.medical_specialty, Vital Capacity, Hyperpolarized Helium 3, Helium, Nuclear magnetic resonance, medicine, Effective diffusion coefficient, Humans, Radiology, Nuclear Medicine and imaging, Diffusion (business), Lung, Aged, Monitoring, Physiologic, Original Research, Analysis of Variance, business.industry, respiratory system, Middle Aged, respiratory tract diseases, Never smokers, medicine.anatomical_structure, Diffusion Magnetic Resonance Imaging, Spirometry, Breathing, Female, Radiology, Lung inflation, business, Lung Volume Measurements, Regional differences
Abstract

To evaluate the effects of lung volume differences on apparent diffusion coefficient (ADC) measurements on a regional basis, with breath holds at volumes adjusted for differences in lung size across individuals according to the subject's vital capacity (VC).This study was approved by the local institutional review board and was compliant with HIPAA. Informed consent was obtained from all subjects. Imaging was performed under a physician's Investigational New Drug application from the Food and Drug Administration. ADC changes as a function of inflation levels were evaluated in 24 healthy never-smokers across three lung volumes (20%, 60%, and 100% VC) on the basis of the spirometric data collected from each subject. Response variables based on lung volume and anatomic position were assessed with multifactorial analysis of variance followed by posthoc pair-wise testing. Imaging was performed with a 1.5-T magnetic resonance (MR) unit with use of a two-dimensional gradient-echo fast low-angle shot sequence.Significant differences in ADCs between lung volumes were observed for all inflation levels (20%, 60%, and 100% VC; P.001), along with significant dependent-nondependent vertical gradients at 20% VC (P.0001) and 60% VC (P.0001, left lung only). In addition, significant differences between mean values in the left and right lungs with respect to those in the whole lung were observed at the lower lung inflation levels (20% and 60% VC, P.01), reaching more uniform expansion at 100% VC.The results confirm known anatomic differences in patterns of regional inflation and ventilation with corresponding lung volume changes, emphasizing the need for tight control over lung volume when performing hyperpolarized helium 3 ((3)He) lung studies if (3)He MR imaging is to be used to follow up small longitudinal changes in lung abnormalities.

Published
2013

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