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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. 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

3. 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

4. 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

5. 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

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

Author

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

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chronic Obstructive, Clinical Sciences, Respiratory System, Critical Care and Intensive Care Medicine, COPD: Original Research, Body Mass Index, Pectoralis Muscles, Pulmonary Disease, sarcopenia, Pulmonary Disease, Chronic Obstructive, Interquartile range, Clinical Research, Internal medicine, medicine, Tobacco Smoking, COPD, 2.1 Biological and endogenous factors, Humans, Longitudinal Studies, Aetiology, Pectoralis Muscle, Lung, Nutrition, Smokers, COPDGene Investigators, Proportional hazards model, business.industry, Prevention, Smoking, muscle wasting, medicine.disease, mortality, Confidence interval, Good Health and Well Being, Sarcopenia, Cardiology, Body Composition, Cardiology and Cardiovascular Medicine, business, Body mass index, Bioelectrical impedance analysis, Biomarkers
Abstract

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

Published
2021

7. 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

8. 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

9. Incidence of venous thromboembolism in coronavirus disease 2019: An experience from a single large academic center

Author

Parth Rali, Oisin O'Corragain, Lawrence Oresanya, Daohai Yu, Omar Sheriff, Robert Weiss, Catherine Myers, Parag Desai, Nadia Ali, Anthony Stack, Michael Bromberg, Andrea L. Lubitz, Joseph Panaro, Riyaz Bashir, Vladimir Lakhter, Roberto Caricchio, Rohit Gupta, Chandra Dass, Kumaran Maruti, Xiaoning Lu, A. Koneti Rao, Gary Cohen, Gerard J. Criner, Eric T. Choi, Aaron Mishkin, Abbas Abba, Abhijit S. Pathak, Abhinav Rastogi, Adam Diamond, Aditi Satti, Adria Simon, Ahmed Soliman, Alan Braveman, Albert J. Mamary, Aloknath Pandya, Amy Goldberg, Amy Kambo, Andrew Gangemi, Anjali Vaidya, Ann Davison, Anuj Basil, Beata Kosmider, Charles T. Bakhos, Bill Cornwell, Brianna Sanguily, Brittany Corso, Carla Grabianowski, Carly Sedlock, Charles Bakhos, Chenna Kesava Reddy Mandapati, Cherie Erkmen, Chethan Gangireddy, Chih-ru Lin, Christopher T. Burks, Claire Raab, Deborah Crabbe, Crystal Chen, Daniel Edmundowicz, Daniel Sacher, Daniel Salerno, Daniele Simon, David Ambrose, David Ciccolella, Debra Gillman, Dolores Fehrle, Dominic Morano, Donnalynn Bassler, Edmund Cronin, Eduardo Dominguez, Ekam Randhawa, Ekamjeet Randhawa, Eman Hamad, Eneida Male, Erin Narewski, Francis Cordova, Frederic Jaffe, Frederich Kueppers, Fusun Dikengil, Jonathan Galli, Jamie Garfield, Gayle Jones, Gennaro Calendo, Gerard Criner, Gilbert D'Alonzo, Ginny Marmolejos, Matthew Gordon, Gregory Millio, Fernandez Gustavo, Hannah Simborio, Harwood Scott, Heidi Shore-Brown, Hernan Alvarado, Ho-Man Yeung, Ibraheem Yousef, Ifeoma Oriaku, Iris Jung-won Lee, Isaac Whitman, James Brown, Jamie L. Garfield, Janpreet Mokha, Jason Gallagher, Jeffrey Stewart, Jenna Murray, Jessica Tang, Jeyssa Gonzalez, Jichuan Wu, Jiji Thomas, Jim Murrett, Joanna Beros, John M. Travaline, Jolly Varghese, Jordan Senchak, Joseph Lambert, Joseph Ramzy, Joshua Cooper, Jun Song, Junad Chowdhury, Kaitlin Kennedy, Karim Bahmed, Karim Loukmane, Karthik Shenoy, Kathleen Brennan, Keith Johnson, Kevin Carney, Kraftin Schreyer, Kristin Criner, Maruti Kumaran, Lauren Miller, Laurie Jameson, Laurie Johnson, Laurie Kilpatrick, Lii-Yoong Criner, Lily Zhang, Lindsay K. McGann, Llera A. Samuels, Marc Diamon, Margaret Kerper, Maria Vega Sanchez, Mariola Marcinkienwicz, Maritza Pedlar, Mark Aksoy, Mark Weir, Marla R. Wolfson, Marla Wolfson, Robert Marron, Martin Keane, Massa Zantah, Mathew Zheng, Matthew Delfiner, Maulin Patel, Megan Healy, Melinda Darnell, Melissa Navaro, Meredith A. Brisco-Bacik, Michael Gannon, Michael Jacobs, Mira Mandal, Nanzhou Gou, Nathaniel Marchetti, Nathaniel Xander, Navjot Kaur, Neil Nadpara, Nicole Desai, Nicole Mills, Norihisa Shigemura, Ohoud Rehbini, Oneida Arosarena, Osheen Abramian, Paige Stanley, Patrick Mulhall, Pravin Patil, Priju Varghe, Puja Dubal, Puja Patel, Rachael Blair, Rajagopalan Rengan, Rami Alashram, Randol Hooper, Rebecca A. Armbruster, Regina Sheriden, Rogers Thomas, Rohit Soans, Roman Petrov, Roman Prosniak, Romulo Fajardo, Ruchi Bhutani, Ryan Townsend, Sabrina Islam, Samantha Pettigrew, Samantha Wallace, Sameep Sehgal, Samuel Krachman, Santosh Dhungana, Sarah Hoang, Sean Duffy, Seema Rani, Shapiro William, Sheila Weaver, Shelu Benny, Sheril George, Shuang Sun, Shubhra Srivastava-Malhotra, Stephanie Brictson, Stephanie Spivack, Stephanie Tittaferrante, Stephanie Yerkes, Stephen Priest, Steve Codella, Steven G. Kelsen, Steven Houser, Steven Verga, Sudhir Bolla, Sudhir Kotnala, Sunil Karhadkar, Sylvia Johnson, Tahseen Shariff, Tammy Jacobs, Thomas Hooper, Tom Rogers, Tony S. Reed, Tse-Shuen Ku, Uma Sajjan, Victor Kim, Whitney Cabey, Wissam Chatila, Wuyan Li, Zach Dorey-Stein, Zachariah Dorey-Stein, and Zachary D. Repanshek

Subjects
Male, medicine.medical_specialty, Computed Tomography Angiography, Deep vein, Hypercoagulable state in COVID-19, 030204 cardiovascular system & hematology, COVID-19 VTE, Article, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, COVID-19 coagulopathy, medicine, Humans, Thrombophilia, 030212 general & internal medicine, cardiovascular diseases, Prospective cohort study, Retrospective Studies, Philadelphia, Venous Thrombosis, Ultrasonography, Doppler, Duplex, business.industry, SARS-CoV-2, Incidence (epidemiology), Incidence, COVID-19, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Prognosis, equipment and supplies, Respiration, Artificial, Confidence interval, Pulmonary embolism, medicine.anatomical_structure, Cohort, Surgery, Female, Cardiology and Cardiovascular Medicine, business, Pulmonary Embolism
Abstract

Background Infection with the novel severe acute respiratory syndrome coronavirus 2 has been associated with a hypercoagulable state. Emerging data from China and Europe have consistently shown an increased incidence of venous thromboembolism (VTE). We aimed to identify the VTE incidence and early predictors of VTE at our high-volume tertiary care center. Methods We performed a retrospective cohort study of 147 patients who had been admitted to Temple University Hospital with coronavirus disease 2019 (COVID-19) from April 1, 2020 to April 27, 2020. We first identified the VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]) incidence in our cohort. The VTE and no-VTE groups were compared by univariable analysis for demographics, comorbidities, laboratory data, and treatment outcomes. Subsequently, multivariable logistic regression analysis was performed to identify the early predictors of VTE. Results The 147 patients (20.9% of all admissions) admitted to a designated COVID-19 unit at Temple University Hospital with a high clinical suspicion of acute VTE had undergone testing for VTE using computed tomography pulmonary angiography and/or extremity venous duplex ultrasonography. The overall incidence of VTE was 17% (25 of 147). Of the 25 patients, 16 had had acute PE, 14 had had acute DVT, and 5 had had both PE and DVT. The need for invasive mechanical ventilation (adjusted odds ratio, 3.19; 95% confidence interval, 1.07-9.55) and the admission D-dimer level ≥1500 ng/mL (adjusted odds ratio, 3.55; 95% confidence interval, 1.29-9.78) were independent markers associated with VTE. The all-cause mortality in the VTE group was greater than that in the non-VTE group (48% vs 22%; P = .007). Conclusions Our study represents one of the earliest reported from the United States on the incidence rate of VTE in patients with COVID-19. Patients with a high clinical suspicion and the identified risk factors (invasive mechanical ventilation, admission D-dimer level ≥1500 ng/mL) should be considered for early VTE testing. We did not screen all patients admitted for VTE; therefore, the true incidence of VTE could have been underestimated. Our findings require confirmation in future prospective studies.

Published
2020

10. 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

11. 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

12. 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

13. 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

14. A Telemedicine-Based Intervention Reduces the Frequency and Severity of COPD Exacerbation Symptoms: A Randomized, Controlled Trial

Author

Michael R. Jacobs, Kathleen Brennan, John P. Gaughan, David Ciccolella, Carla Grabianowski, Francis Cordova, Frederick J. Goldstein, and Gerard J. Criner

Subjects
medicine.medical_specialty, Telemedicine, 020205 medical informatics, State of health, Health Informatics, 02 engineering and technology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Health Information Management, Randomized controlled trial, law, Intervention (counseling), 0202 electrical engineering, electronic engineering, information engineering, medicine, 030212 general & internal medicine, Disease management (health), Original Research, COPD, business.industry, General Medicine, medicine.disease, Computer algorithm, Copd exacerbation, Physical therapy, business
Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) may not recognize worsening symptoms that require intensification of therapy. They may also be reluctant to contact a healthcare provider for minor worsening of symptoms. A telemedicine application for daily symptom reporting may reduce these barriers and improve patient outcomes. Materials and Methods: Patients hospitalized for a COPD exacerbation within the past year or using supplemental O2 were approached for participation. Patients received optimal COPD care and were given a telecommunication device for symptom reporting. Initial symptom scores were obtained while patients were in their usual state of health. Patients were randomly assigned to an intervention group or a control group (usual medical care). The control group patients were instructed to seek medical care if their condition worsened. The intervention group symptom scores were assessed by a computer algorithm and compared with initial values. Scores 1 or more points above the initial score generated an “alert,” and patients were reviewed by a nurse and referred to a physician who prescribed treatment. Results: Eighty-six patients were screened; 79 met entry criteria and were randomized (intervention group, n=39; control group, n=40). Twelve patients submitted five or fewer symptom reports (5 intervention; 7 control) and were excluded from the analysis. Daily peak flow and dyspnea scores improved only in the intervention group. There were no differences in hospitalization and mortality rates between groups. No serious adverse events were reported. Conclusions: A telemedicine-based symptom reporting program facilitated early treatment of symptoms and improved lung function and functional status.

Published
2016

15. 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

16. 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

17. 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

18. Hospitalized Acute Exacerbation of COPD Impairs Flow and Nitroglycerin-Mediated Peripheral Vascular Dilation

Author

Mohammed A. Kashem, John P. Gaughan, Alfred A. Bove, Aaron Crookshank, David Ciccolella, Gerard J. Criner, Nathaniel Marchetti, and Michael R. Jacobs

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Brachial Artery, Exacerbation, Copd patients, Vasodilator Agents, Flow mediated dilation, Disease, Muscle, Smooth, Vascular, Nitroglycerin, Pulmonary Disease, Chronic Obstructive, Vascular dilation, Forced Expiratory Volume, Internal medicine, medicine, Humans, Aged, Aged, 80 and over, Peripheral Vascular Diseases, COPD, business.industry, Middle Aged, medicine.disease, Peripheral, Hospitalization, Vasodilation, Disease Progression, Cardiology, Physical therapy, Female, Vascular function, business
Abstract

Vascular function, as measured by flow mediated dilation (FMD) and nitroglycerin mediated dilation (NMD), is impaired in COPD. Increases in systemic inflammatory mediators during acute exacerbations of COPD (AECOPD) may further impair vascular function and may account for the increased prevalence of cardiovascular disease in COPD patients. Similarly it may account for the increased morbidity and mortality in COPD patients hospitalized with acute exacerbations. We hypothesized that FMD and NMD would be impaired during AECOPD requiring hospitalization and that vascular function would improve upon AECOPD resolution. We used FMD and NMD to evaluate vascular function in 19 patients hospitalized with AECOPD. FMD and NMD were repeated approximately three months later in 8 of these patients. In these eight patients significant improvements were observed in FMD (2.6 ± 1.5% vs 5.1 ± 2.4%, p = 0.04) and NMD (5.0 ± 2.6% vs 13.3 ± 4.5, p = 0.02) after resolution of their exacerbation. We conclude that endothelial and vascular smooth muscle function is markedly impaired during AECOPD requiring hospitalization and improves following resolution. The systemic vascular impairment that occurs during AECOPD may partially explain the observed increased in cardiac morbidity and mortality that occur in this population.

Published
2011

19. Isolation of Laceyella sp. from the Blood of a Patient with Interstitial Lung Disease

Author

Shobha Parajuli, Allan L. Truant, Raghava Potula, and David Ciccolella

Subjects
Microbiology (medical), Genetics, Endospore formation, food.ingredient, Thermoflavimicrobium, biology, Phylogenetic tree, Thermoactinomycetaceae, 16S ribosomal RNA, biology.organism_classification, medicine.disease_cause, Thermoactinomyces, Infectious Diseases, food, Seinonella, medicine, Laceyella sacchari
Abstract

Introduction The genus Laceyella within the family Bacillaceae was proposed by Yoon et al. (1) in 2005 and was placed in the family Thermoactinomycetaceae by Matsuo et al. (2) in 2006. Members of the genus Laceyella were initially considered to belong in the genus Thermoactinomyces (also known as actinomycetes). When Yoon and colleagues (1) first proposed the genus Laceyella, only two species were known: Laceyella sacchari and Laceyella putidus, which were previously named Thermoactinomyces sacchari (Thermoactinomyces thalpophilus) and Thermoactinomyces putidus, respectively (1,3). Because of the characteristics of endospore formation, DNA G+C content, and phylogenetic data, the genus Thermoactinomyces was placed within the family Bacillaceae in 2005 by Yoon et al (1), and the family was divided into four genera: Thermoactinomyces, Laceyella, Thermoflavimicrobium, and Seinonella. This classification was made on the basis of unique profiles of menaquinone and fatty acid composition, together with phenotypic comparisons and phylogenic analyses of 16S rRNA gene sequences (1,4,5). Subsequently, two more genera were added, and a new family, Thermoactinomycetaceae, was proposed by Matsuo et al. and others (2,6-8) on the basis of polyphasic taxonomic studies. Since then, more genera have been added to the family (4,5,7).

Published
2014

20. Chronic Cough and Dyspnea in Ice Hockey Players After an Acute Exposure to Combustion Products of a Faulty Ice Resurfacer

Author

Erika S. Kahan, Steve Spungen, Gerard J. Criner, David Ciccolella, and Ubaldo J. Martin

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.drug_class, Nitrogen Dioxide, Chest pain, Statistics, Nonparametric, Pulmonary function testing, Cohort Studies, Ice hockey, Airway resistance, Bronchodilator, Humans, Medicine, Exertion, Vehicle Emissions, Carbon Monoxide, business.industry, Respiratory Function Tests, Surgery, Chronic cough, Dyspnea, Treatment Outcome, Impulse Oscillometry, Cough, Hockey, Air Pollution, Indoor, Anesthesia, Exercise Test, medicine.symptom, business, Follow-Up Studies
Abstract

The aim of this study was to characterize pulmonary function and radiologic testing in ice hockey players after exposure to combustion products of a faulty ice resurfacer. Our patients were 16 previously healthy hockey players who developed chronic cough and dyspnea after exposure. Symptom questionnaires, pulmonary function tests (PFTs), bronchoprovocation testing, cardiopulmonary exercise testing, high-resolution computed tomography (CT) imaging, and impulse oscillometry (IOS) were all used. A normal group was used for PFTs and IOS controls. Patients had onset of cough within 72 h of exposure. Ninety-two percent complained of dyspnea, 75% chest pain, and 33% hemoptysis. Eight percent were initially hospitalized for their symptoms. Eighty-five percent were treated with systemic steroids and 39% with inhaled bronchodilators. Six months postexposure, 54% complained of cough and 46% complained of dyspnea on exertion. All patients had normal PFTs; 8.3% had a significant bronchodilator response. All had normal exercise tests (mean VO2max = 90 ± 3% predicted) and chest CTs. With IOS, 80% had a significant bronchodilator response (decreased resistance > 12% and SD score > 1; mean change = 21.1 ± 9.9%, mean SD score = 3.1 ± 2.5). No correlation existed between changes in resistance or reactance and spirometric values. Patient symptoms correlated significantly with bronchodilator response on IOS resistance (R = 0.61, p = 0.03). More than 50% of patients exposed to the combustion products of a faulty ice resurfacer remained symptomatic six months after exposure. Despite persistence of symptoms, conventional pulmonary function tests and radiologic evaluation did not reveal airway abnormalities. IOS showed evidence of increased airway resistance and small-airway disease, which correlated with patient symptoms.

Published
2007

21. Risk Factors for Venous Thromboembolism in Chronic Obstructive Pulmonary Disease

Author

Victor Kim, Nishant Goel, Jinal Gangar, Huaqing Zhao, David Ciccolella, Edwin Silverman, James Crapo, and Gerard Criner

Subjects
Pulmonary and Respiratory Medicine, education, cardiovascular diseases, equipment and supplies, humanities, respiratory tract diseases, Original Research
Abstract

COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear.Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology (COPDGene) study were divided into 2 groups: VTE+, those who reported a history of VTE by questionnaire, and VTE-, those who did not. We compared variables in these 2 groups with either t-test or chi-squared test for continuous and categorical variables, respectively. We performed a univariate logistic regression for VTE, and then a multivariate logistic regression using the significant predictors of interest in the univariate analysis to ascertain the determinants of VTE.The VTE+ group was older, more likely to be Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had a lower 6-minute walk distance, worse quality of life scores, and more dyspnea and respiratory exacerbations than the VTE- group. Lung function was not different between groups. A greater percentage of the VTE+ group described multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk distance, pneumothorax, peripheral vascular disease, and congestive heart failure significantly increased the odds for VTE by history.BMI, exercise capacity, and medical comorbidities were significantly associated with VTE in moderate to severe COPD. Clinicians should suspect VTE in patients who present with dyspnea and should consider possibilities other than infection as causes of COPD exacerbation.

Published
2015

22. Air Current Applied to the Face Improves Exercise Performance in Patients with COPD

Author

Matthew R. Lammi, Brian Civic, Nathaniel Marchetti, Gerard J. Criner, John M. Travaline, and David Ciccolella

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Time Factors, Copd patients, Blood Pressure, Respiratory physiology, Article, Pulmonary Disease, Chronic Obstructive, Physical medicine and rehabilitation, Heart Rate, Forced Expiratory Volume, Exercise performance, Heart rate, Medicine, Humans, In patient, Exercise physiology, Dynamic hyperinflation, Exercise, Aged, Air Movements, COPD, Cross-Over Studies, Exercise Tolerance, business.industry, Middle Aged, medicine.disease, respiratory tract diseases, Exercise Therapy, Dyspnea, Face, Physical therapy, Respiratory Mechanics, Female, business, Inspiratory Capacity
Abstract

Improving dyspnea and exercise performance are goals of COPD therapy. We tested the hypothesis that air current applied to the face would lessen dyspnea and improve exercise performance in moderate-severe COPD patients.We recruited 10 COPD patients (5 men, age 62 ± 6 years, FEV1 0.93 ± 0.11 L (34 ± 3% predicted), TLC 107 ± 6%, RV 172 ± 18%) naïve to the study hypothesis. Each patient was randomized in a crossover fashion to lower extremity ergometry at constant submaximal workload with a 12-diameter fan directed at the patients face or exposed leg. Each patients' studies were separated by at least 1 week. Inspiratory capacity and Borg dyspnea score were measured every 2 min and at maximal exercise.Total exercise time was longer when the fan was directed to the face (14.3 ± 12 vs. 9.4 ± 7.6 min, face vs. leg, respectively, p = 0.03). Inspiratory capacity tended to be greater with the fan directed to the face (1.4 (0.6-3.25) vs. 1.26 (0.56-2.89) L, p = 0.06). There was a reduction in dynamic hyperinflation, as reflected by higher IRV area in the fan on face group (553 ± 562 a.u. vs. 328 ± 319 a.u., p = 0.047). There was a significant improvement in the Borg dyspnea score at maximal exercise (5.0 (0-10) vs. 6.5 (0-10), p = 0.03), despite exercising for 34 % longer with the fan directed to the face.Air current applied to the face improves exercise performance in COPD. Possible mechanisms include an alteration in breathing pattern that diminishes development of dynamic hyperinflation or to a change in perception of breathlessness.

Published
2015

23. Dose-Response Characteristics of Nebulized Albuterol in the Treatment of Acutely Ill, Hospitalized Asthmatics

Author

Kathleen Brennan, Steven G. Kelsen, Gerard J. Criner, and David Ciccolella

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Spirometry, medicine.drug_class, Methylprednisolone, Drug Administration Schedule, immune system diseases, Forced Expiratory Volume, Bronchodilator, Administration, Inhalation, Bronchodilation, Humans, Immunology and Allergy, Medicine, Albuterol, Asthma, Aerosols, Dose-Response Relationship, Drug, medicine.diagnostic_test, Inhalation, business.industry, Cumulative dose, Respiratory disease, Signal Processing, Computer-Assisted, medicine.disease, Bronchodilator Agents, respiratory tract diseases, Hospitalization, Anesthesia, Acute Disease, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Salbutamol, Drug Therapy, Combination, Female, Emergency Service, Hospital, business, medicine.drug
Abstract

We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age41 years old and12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean +/- SE) forced expiratory volume in 1 sec (FEV1) of 1.26 +/- 0.14 L (42 +/- 4.0% predicted), which increased significantly (p0.05) during albuterol titration to a maximum FEV1 of 1.70 +/- 0.19 L (57 +/- 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bronchodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1 response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The bronchodilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.

Published
1999

24. Exercise-induced Bronchospasm in High School Athletes via a Free Running Test

Author

Marcia Polansky, Gilbert E. D'Alonzo, Scott Porter, David Ciccolella, David S. Kukafka, James Rogers, and David M. Lang

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, biology, Sports medicine, Athletes, business.industry, Incidence (epidemiology), Critical Care and Intensive Care Medicine, Placebo, medicine.disease, biology.organism_classification, respiratory tract diseases, Epidemiology, Heart rate, Physical therapy, medicine, Risk factor, Cardiology and Cardiovascular Medicine, business, human activities, Asthma
Abstract

Background Exercise-induced bronchospasm (EIB) affects up to 35% of athletes and up to 90% of asthmatics. Asthma morbidity and mortality have increased over the past several decades among residents of Philadelphia, PA. It is possible that a simple free running test for EIB may serve as a tool to study the factors contributing to recent trends in asthma, and to screen for asthma in athletes in the urban setting. Objectives The purposes of this study were to (1) assess a free running test to screen for EIB, and (2) examine prevalence of and epidemiologic factors associated with EIB in high school athletes. Design Cross-sectional observational study on the incidence and risk factors for EIB. To validate our method and criteria for the diagnosis of EIB, a repeat test was performed on a portion of the athletes. In a randomized single-blinded fashion, 15 athletes who had demonstrated EIB initially received albuterol or placebo prior to a repeat exercise test. Setting Community high school athletic facilities. Participants We studied 238 male high school varsity football players. Intervention All athletes underwent an acquaintance session with a questionnaire, followed by a 1-mile outdoor run (6 to 8 mins). Measurements Peak expiratory flow (PEF) measurements were determined prior to and 5, 15, and 30 min after exercise. Heart rates (HRs) and dyspnea scores were measured. EIB was defined as a decrease of 15% in PEF at any time point after exercise. Associations of EIB with demographic factors were assessed by univariate and multivariate analyses. Results Two hundred thirty-eight athletes participated: 92 European-Americans (EA), 140 African-Americans (AA), 5 Hispanics, and 1 Native American. Mean age was 16 ± 1 years. Average HR postexercise was 156 ± 24 beats/min. Twenty-four (10%) reported a history of treated asthma. The prevalence of EIB among the remaining 214 athletes was 19 of 214 (9%). The rate of EIB among AA athletes was higher than among EA athletes: (17/126 [13%] AA vs 2/82 [2%] EA, p = 0.01). During the validation portion of the study, the placebo-treated group (n = 7) demonstrated a consistent drop in PEF after exercise on repeat testing, with a 16 ± 5% fall in PEF on initial testing and a 14 ± 13 drop with placebo. In contrast, the fall in airflow in the albuterol-treated athletes (n = 8) following exercise reversed with albuterol treatment, from a 15 ± 6% fall in PEF at initial testing to an increase in PEF of 6 ± 9% from baseline following albuterol administration. A history of wheezing (p Conclusions Our findings indicate a substantial rate of unrecognized EIB exists among urban varsity athletes, and suggest that active screening for EIB, especially for students residing in poverty areas, may be indicated to identify individuals at risk for EIB and asthma.

Published
1998

25. Asthma

Author

David Ciccolella and Gilbert D’Alonzo

Published
2013

26. Reverse halo sign on chest imaging in a renal transplant recipient

Author

Gilbert E. D'Alonzo, Heather Clauss, Namrata Patel, David Ciccolella, Jeffrey I. Stewart, and Heba Y Durra Md

Subjects
Graft Rejection, medicine.medical_specialty, Radiography, Context (language use), Chest pain, Tacrolimus, Immunocompromised Host, Prednisone, medicine, Humans, Mucormycosis, Halo sign, Kidney transplantation, Transplantation, Lung Diseases, Fungal, business.industry, Middle Aged, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Surgery, Pneumonia, Infectious Diseases, Female, medicine.symptom, business, Tomography, X-Ray Computed, Immunosuppressive Agents, medicine.drug
Abstract

Without proper treatment, the mortality of pulmonary mucormycosis is nearly 100%. Although the diagnosis is often made histologically, it can be suspected when patients have a reverse halo sign on computed tomography (CT) of the chest, along with the right clinical findings. We describe the case of a woman 7 months post renal transplant who presented with fevers, malaise, and chest pain. Her chest CT revealed a round, focal area of ground-glass attenuation surrounded by a complete rim of consolidation in the left upper lobe, consistent with the reverse halo sign. Pulmonary mucormycosis was diagnosed by transbronchial lung biopsy. She was successfully treated with combined medical and surgical therapies. In the context of this case, we provide a brief review of the diagnosis of pulmonary mucormycosis, with a focus on radiographic and pathologic findings.

Published
2012

28. Increased oxygen pulse after lung volume reduction surgery is associated with reduced dynamic hyperinflation

Author

Malcolm Kohler, Nathaniel Marchetti, Gerard J. Criner, David Ciccolella, and Matthew R. Lammi

Subjects
Pulmonary and Respiratory Medicine, Male, Partial Pressure, Oxygen pulse, Blood Pressure, Lung volume reduction surgery, Pulmonary Disease, Chronic Obstructive, Functional residual capacity, Capnography, Medicine, Humans, Lung volumes, Dynamic hyperinflation, Pneumonectomy, Lung, Aged, Retrospective Studies, business.industry, Total Lung Capacity, Heart, Stroke Volume, Stroke volume, Middle Aged, Pulse pressure, Oxygen, Preload, Treatment Outcome, Breath Tests, Pulmonary Emphysema, Spirometry, Anesthesia, Exercise Test, Female, business
Abstract

Stroke volume augmentation during exercise is limited in chronic obstructive pulmonary disease patients because of decreased preload from dynamic hyperinflation (DH). We hypothesised that oxygen pulse and pulse pressure (PP) improve following lung volume reduction surgery (LVRS), and the magnitude of improvement correlates with reduction in DH. We compared 16 emphysema patients undergoing LVRS with six emphysema patients not undergoing LVRS. Oxygen pulse and PP were calculated from maximal cardiopulmonary exercise tests at baseline and 6 months. End-expiratory lung volume (EELV)/total lung capacity (TLC) represented DH. Comparisons were made between baseline and 6 months at metabolic isotimes (per cent maximal carbon dioxide production (V'(CO(2),max))). At baseline, the LVRS group was older with higher forced expiratory volume in 1 s, but had similar hyperinflation to the non-LVRS group. At 6 months, oxygen pulse (50%, 75%, and 100% V'(CO(2),max)) and PP (50% and 75% V'(CO(2),max)) increased in the LVRS, but not in the non-LVRS group. Baseline functional residual capacity/TLC inversely correlated with resting oxygen pulse (r= -0.449, p=0.04). Decreased EELV/TLC correlated with increased oxygen pulse at 75% (r= -0.487, p=0.02) and 100% V'(CO(2),max) (r= -0.548, p=0.008). LVRS led to increased oxygen pulse and PP during exercise at metabolic isotimes 6 months following surgery. Reductions in DH correlated with increases in oxygen pulse during exercise. Reducing lung volume may improve stroke volume response to exercise by decreasing DH.

Published
2012

31. Physiologic correlates of sleep quality in severe emphysema

Author

Ubaldo J. Martin, John P. Gaughan, Wissam Chatila, Alice L. Sternberg, Irene Permut, Gerard J. Criner, Samuel L. Krachman, Gilbert E. D'Alonzo, and David Ciccolella

Subjects
Pulmonary and Respiratory Medicine, Spirometry, Male, Sleep Wake Disorders, medicine.medical_specialty, Polysomnography, Polysomnogram, Diaphragm, FEV1/FVC ratio, Internal medicine, medicine, Humans, Lung volumes, Aged, Ultrasonography, COPD, medicine.diagnostic_test, Sleep quality, business.industry, respiratory system, Middle Aged, medicine.disease, respiratory tract diseases, Respiratory Function Tests, Oxygen, Pulmonary Emphysema, Anesthesia, Cardiology, Arterial blood, Female, Blood Gas Analysis, business, circulatory and respiratory physiology
Abstract

Sleep quality is poor in severe emphysema. We hypothesized that in addition to nocturnal oxygen desaturation, the severity of airflow obstruction and degree of thoracic hyperinflation are responsible.Twenty-five patients (14 males, 64 ± 6 [ ± SD] yrs, BMI 24.7 ± 4.2 kg/m(2)) with severe emphysema (FEV(1) = 28 ± 8% predicted, TLC = 125 ± 14% predicted) were studied. Measurements included spirometry, lung volumes, arterial blood gas, length of the diaphragm's zone of apposition (LZAP) and a polysomnogram.Total sleep time (TST) was 227 ± 93 minutes with a sleep efficiency (SE) of 56 ± 21%. The mean SaO(2), lowest SaO(2), and% TST with a SaO(2)90% were 90 ± 5%, 83 ± 8% and 29 ± 40%, respectively. TST correlated with FEV(1)% (r = 0.5, p = 0.02), FVC% (r = 0.4, p = 0.03) and LZAP (r = 0.5, p = 0.01). SE correlated with FEV(1)% (r = 0.5, p = 0.02) and LZAP (r = 0.5, p = 0.01), but not with FVC% (r = 0.4, p = 0.07). Additionally, TST and SE correlated negatively with residual volume% (r = -0.4, p = 0.046, and r = -0.4, p = 0.03, respectively). There was no correlation between TST and SE and measures of nocturnal oxygenation. Multiple linear regression was used to predict TST, with 50% (r(2) = 0.49) explained by a combination of LZAP (27%), mean SaO(2) (23%), and the lowest SaO(2) (1%). To predict SE, 44% (r(2) = 0.43) was explained by a combination of LZAP (29%), mean SaO(2) (14%), and the lowest SaO(2) (1%).Although parameters of respiratory function and mechanics correlate with sleep quality, both nocturnal oxygenation and measurements of respiratory function/mechanics predict sleep quality in severe emphysema.

Published
2011

32. Outcomes of COPD Exacerbations Treated with Corticosteroids, Antibiotics, or Both

Author

Christopher B. Remakus, John P. Gaughan, David Ciccolella, Gerard J. Criner, Francis Cordova, Matthew R. Lammi, Kartik Shenoy, Carla Grabianowski, and A. James Mamary

Subjects
medicine.medical_specialty, Treatment response, COPD, Article Subject, medicine.drug_class, business.industry, Standard treatment, Antibiotics, medicine.disease, Treatment failure, Surgery, respiratory tract diseases, Refractory, Internal medicine, medicine, Corticosteroid, Sputum, medicine.symptom, business
Abstract

Background. The outcomes for outpatient treatment of acute exacerbations of COPD (AECOPD) are poorly described. Design. The results of a daily diary recording symptoms and peak flows were compiled into a severity score to trigger algorithm-based treatments and a symptom index to follow treatment response. Treatment failure (symptom index failing to return to baseline for 2 consecutive days or hospitalization within 21 days) was the main outcome. Results. Twenty-two patients (FEV1 0.81 ± 0.26 L) were treated for 115 AECOPDs (corticosteroids = 36, antibiotics = 41, corticosteroids/antibiotics = 38). Treatment failure was 50% for the corticosteroid/antibiotic compared to 28% () for the corticosteroid and 34% () for the antibiotic group. Patients suffering from AECOPDs treated with corticosteroids had dyspnea, wheezing, and decreased peak flow; those treated with antibiotics had sputum symptoms; those treated with corticosteroids/antibiotics had dyspnea, wheezing, sputum symptoms, and decreased peak flows. Conclusions. AECOPDs with both dyspnea and sputum symptoms are more refractory to standard treatment and likely require closer monitoring.

Published
2011
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34. Enteral Feeding Tubes

Author

David Ciccolella

Subjects
medicine.medical_specialty, Parenteral nutrition, Feeding tube insertion, business.industry, Percutaneous endoscopic gastrostomy, medicine.medical_treatment, Tube placement, Medicine, business, Feeding tube, Enteral administration, Surgery
Abstract

After studying this chapter, you should be able to do the following: Be familiar with the various methods of delivering enteral feeding. Know the indications and contraindications for using enteral feeding tubes. Know the complications associated with enteral feeding tube insertion.

Published
2010

35. Pharmacologic Hemodynamic Therapy of Shock

Author

Christina Rose, David Ciccolella, and Neil W. Brister

Subjects
Cardiac output, medicine.medical_specialty, Septic shock, business.industry, Central venous pressure, Hemodynamics, medicine.disease, Shock (circulatory), Internal medicine, medicine, Cardiology, medicine.symptom, business, Spinal cord injury, Hemodynamic effects
Abstract

Know the indications and contraindications for each medication. Know the clinical hemodynamic effects of each medication. Know the potential complications associated with each medication. Know the use of these agents in specific shock states.

Published
2010

39. Efficacy of Corticosteroids and Antibiotics in AECOPD

Author

Christopher B. Remakus, G.J. Criner, John P. Gaughan, David Ciccolella, Francis Cordova, and Carla Grabianowski

Subjects
medicine.medical_specialty, medicine.drug_class, business.industry, Internal medicine, Antibiotics, medicine, business
Published
2009

41. Risk Factors for Airway Stenosis in Lung Transplant Recipients

Author

Nishant Goel, J Thacker, Namrata Patel, G.J. Criner, R Steiner, V Coca, N Ferrer, and David Ciccolella

Subjects
medicine.medical_specialty, Stenosis, Lung, medicine.anatomical_structure, business.industry, Internal medicine, Cardiology, Medicine, business, Airway, medicine.disease
Published
2009

42. Evaluation of an Electronic Diary for Daily COPD Symptom Reporting:<u>P</u>ennsylvani<u>A</u><u>S</u>tudy of<u>C</u>hronic<u>O</u>bstructive<u>P</u>ulmonary<u>E</u>xacerbations (PA-SCOPE)

Author

Francis Cordova, Kathleen Brennan, PC Fiehler, Ann Marie Kuzma, David Ciccolella, G.J. Criner, Carla Grabianowski, Heidi S. Smith, and DA Fiehler

Subjects
COPD, medicine.medical_specialty, Scope (project management), business.industry, medicine, Symptom reporting, Physical therapy, medicine.disease, business, Electronic diary
Published
2009

44. Altered Immune Competence of Peripheral Blood Leukocytes during AECOPD

Author

Lara Chensny, Wissam Chatila, G.J. Criner, AD Crookshank, Thomas J. Richards, Naftali Kaminski, David Ciccolella, A.J. Mamary, Cunanan, Frank C. Sciurba, Thomas J. Rogers, John P. Gaughan, and Carla Grabianowski

Subjects
Immune system, business.industry, Immunology, Medicine, business, Competence (human resources), Peripheral blood
Published
2009

45. African Americans and men with severe COPD have a high prevalence of osteoporosis

Author

Kathleen Brennan, Gerard J. Criner, Lihua Li, John P. Gaughan, David Ciccolella, and Anne Marie Kuzma

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Bone density, Fractures, Stress, Osteoporosis, Comorbidity, Pulmonary function testing, Cohort Studies, FEV1/FVC ratio, Pulmonary Disease, Chronic Obstructive, Sex Factors, Prednisone, Bone Density, Risk Factors, Internal medicine, medicine, Prevalence, Humans, Retrospective Studies, Philadelphia, Univariate analysis, COPD, business.industry, Middle Aged, medicine.disease, Respiratory Function Tests, Osteopenia, Black or African American, Multivariate Analysis, Physical therapy, Female, business, medicine.drug
Abstract

Osteoporosis is a non-pulmonary manifestation whose true prevalence is uncertain in severe chronic obstructive pulmonary disease (COPD). We describe the prevalence and risk factors for osteoporosis in a large, well characterized COPD cohort. Dual energy x-ray absorptiometry of the lumbar spine and hip, full pulmonary function testing, cardiopulmonary exercise test, 6 minute walk distance and demographics were performed in 179 non-selected COPD patients. Patients were 59 +/- 7 years old, smoked 53 +/- 32 pack years, FEV(1) 26% +/- 9.8, and 45% were currently taking prednisone. Bone mineral density measurements were abnormal in 97%; 66% had dual energy X-ray absorptiometry defined osteoporosis, while 31% had osteopenia. The prevalence of osteoporosis in males versus females was 70% versus 62% (p = 0.33); both groups had similar fracture rates. The prevalence of osteoporosis in African Americans versus Caucasians was 69% versus 65% (p = 0.78). Caucasians had a significantly lower Ward's Triangle T score than African Americans (-2.52 +/- -0.96 vs. -2.16 +/- -0.91, p = 0.04). Those with bone fractures took higher doses of prednisone than those without fractures. Univariate analysis identified BMI and FVC% as predictors for osteoporosis (p = 0.03 OR 0.934 p = 0.006 OR 0.974). Multivariate analysis revealed only FVC% as a significant predictor (p = 0.006, OR 0.974). Osteoporosis is highly prevalent in severe COPD, and affects males and African Americans to a similar degree as females and Whites. Osteoporosis should be considered in severe COPD regardless of race or gender.

Published
2008

46. Enteral Nutrition in Acute Pulmonary Disease

Author

David Ciccolella

Subjects
medicine.medical_specialty, Parenteral nutrition, business.industry, Medicine, Pulmonary disease, business, Intensive care medicine
Published
2005

47. Brush Biopsy and Culture of Airway Epithelial Cells: β -Adrenoceptor System Function

Author

Kathleen Brennan, David Ciccolella, and Steven G. Kelsen

Subjects
Adenylyl cyclase, chemistry.chemical_compound, Chemistry, Second messenger system, Catecholamine, medicine, Cyclic adenosine monophosphate, Secretion, Stimulation, Airway, Mucus, Cell biology, medicine.drug
Abstract

Stimulation by catecholamine agonists of the β-adrenergic coupled adenylyl cyclase (βAR-AC) system, expressed on human tracheobronchial epithelial cells (ECs), elicits a variety of cellular responses that favorably affect airway function, the intensity of the inflammatory reaction, and even the integrity of the epithelial lining (1-6). For example, β-agonist-stimulated production of second messenger, cyclic adenosine monophosphate (cAMP), enhances salt and water exchange (2), ciliary beating (3), mucus secretion by goblet cells (1,4), proliferation of airway ECs (5), and protection against free radical induced injury (6).

Published
2003

48. Chronic effects of inhaled albuterol on beta-adrenoceptor system function in human respiratory cells

Author

Steven G. Kelsen, David Ciccolella, Mark O. Aksoy, Kathleen Brennan, and Bernard Borbely

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Down-Regulation, Respiratory Mucosa, Downregulation and upregulation, Double-Blind Method, In vivo, Internal medicine, Administration, Inhalation, Macrophages, Alveolar, Receptors, Adrenergic, beta, medicine, Cyclic AMP, Immunology and Allergy, Humans, Albuterol, Respiratory system, Receptor, Asthma, Cross-Over Studies, business.industry, Inhaler, Adrenergic beta-Agonists, medicine.disease, Adenosine, Endocrinology, Pediatrics, Perinatology and Child Health, Female, Airway, business, medicine.drug
Abstract

The in vivo effects of beta-adrenergic receptor (betaAR) agonists given chronically by metered-dose inhaler (MDI) on the molecular components of the beta-adrenoceptor system expressed by human respiratory cells are poorly understood. This study examined the effects of inhaled albuterol (180 microg four times daily for 7 days) on betaAR function of airway epithelial cells (AECs) and alveolar macrophages (AMs) freshly isolated from 10 normal subjects. Responses were related to beta2AR genotype in codons 16 and 27, regions which affect chronic responses to beta2-agonists. In AEC, betaAR density and adenosine cyclic 3',5'-phosphate (cAMP) production in response to isoproterenol (ISO) were significantly lower in the albuterol versus placebo treatment arm (p0.01 for both). Moreover, in AEC, albuterol treatment increased betaAR-kinase (betaARK) protein immunoreactivity. In contrast, in AM, albuterol tended to decrease betaAR density and cAMP production but changes did not achieve statistical significance (p0.20 for both) and had no effect on betaARK immunoreactivity. Changes in betaAR density occurred in all subjects but tended to be greater in subjects with the glycine 16 genotype. In cultured cells exposed to equal concentrations of beta-agonist in vitro, the magnitude of betaAR down-regulation (p0.05) and cAMP densensitization (p0.05) was greater in AEC than AM. These results indicate that albuterol taken by inhalation in a therapeutically relevant dose for 1 week produces betaAR down-regulation, densensitizes the cAMP response of airway epithelial cells to a beta2-adrenergic agonist, and increases betaARK immunoreactivity. Greater densensitization of AEC than AM in response to chronic albuterol inhalation likely reflects cell type-specific responses.

Published
2000

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