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154. Pathological Comparisons of Paraseptal and Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease.

Author

Naoya Tanabe, Vasilescu, Dragoş M., Hague, Cameron J., Ikezoe, Kohei, Murphy, Darra T., Kirby, Miranda, Stevenson, Christopher S., Verleden, Stijn E., Vanaudenaerde, Bart M., Gayan-Ramirez, Ghislaine, Janssens, Wim, Coxson, Harvey O., Paré, Peter D., Hogg, James C., and Tanabe, Naoya

Subjects
OBSTRUCTIVE lung diseases, PULMONARY emphysema, MULTIDETECTOR computed tomography, LUNG transplantation, BRONCHIOLES, RESEARCH, CROSS-sectional method, RESEARCH methodology, EVALUATION research, MEDICAL cooperation, COMPARATIVE studies, RESEARCH funding, DISEASE complications
Abstract

Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE.Objectives: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD).Methods: Air-inflated frozen lung specimens (n = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n = 8) and peripheral (n = 8) regions of each lung, scanned with micro-computed tomography (microCT), and processed for histology. The core locations were registered to the MDCT, and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Furthermore, microCT-based volume fractions of CLE and PSE allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant.Measurements and Main Results: The percentages of PSE measured on MDCT and microCT were positively associated (P = 0.015). The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with mild emphysema and PSE-dominant regions (all P < 0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all P > 0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (P = 0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared with CLE regions.Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD. [ABSTRACT FROM AUTHOR]

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

Author

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

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

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

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

Author

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

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

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

Published
2020
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157. Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults.

Author

Smith, Benjamin M., Kirby, Miranda, Hoffman, Eric A., Kronmal, Richard A., Aaron, Shawn D., Allen, Norrina B., Bertoni, Alain, Coxson, Harvey O., Cooper, Chris, Couper, David J., Criner, Gerard, Dransfield, Mark T., Han, MeiLan K., Hansel, Nadia N., Jacobs, David R., Kaufman, Joel D., Lin, Ching-Long, Manichaikul, Ani, Martinez, Fernando J., and Michos, Erin D.

Abstract

Importance: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained.Objective: To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD.Design, Setting, and Participants: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016).Exposures: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio).Main Outcomes and Measures: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma).Results: In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P = .30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y ]; difference, -17 mL/y; 95% CI, -32 to -3; P = .004).Conclusions and Relevance: Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD. [ABSTRACT FROM AUTHOR]

Published
2020
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158. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Author

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

Published
2018
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160. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

Author

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

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

Author

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

Published
2018
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164. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Author

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

Abstract

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

Published
2016
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166. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

Author

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

Published
2017
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168. Free-breathing Pulmonary (1)H and Hyperpolarized (3)He MRI: Comparison in COPD and Bronchiectasis

Author

Capaldi, Dante P I, Sheikh, Khadija, Guo, Fumin, Svenningsen, Sarah, Etemad-Rezai, Roya, Coxson, Harvey O, Leipsic, Jonathon A, McCormack, David G, and Parraga, Grace

Subjects
Medical Biophysics, Fourier decomposition, bronchiectasis, chronic obstructive pulmonary disease, magnetic resonance imaging
Abstract

RATIONALE AND OBJECTIVES: In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing (1)H magnetic resonance imaging (FDMRI) to hyperpolarized (3)He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. MATERIALS AND METHODS: All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and (3)He MRI, and these were compared using analysis of variance and Pearson correlations. RESULTS: Twenty-six subjects were evaluated including 12 COPD subjects (67 ± 9 years) and 14 bronchiectasis subjects (70 ± 11 years). For COPD subjects, FDMRI and (3)He MRI ventilation defect percent (VDP) was 7 ± 6% and 24 ± 14%, respectively (P < .001; bias = -16 ± 9%). In COPD subjects, FDMRI was significantly correlated with (3)He MRI VDP (r = .88; P = .0001), (3)He MRI apparent diffusion coefficient (r = .71; P < .05), airways resistance (r = .60; P < .05), and RA950 (r = .80; P < .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and (3)He MRI VDP (18 ± 9%) were significantly different (P < .001) and not correlated (P > .05). The Dice similarity coefficient (DSC) for FDMRI and (3)He MRI ventilation was 86 ± 7% for COPD and 86 ± 4% for bronchiectasis subjects (P > .05); the DSC for FDMRI ventilation defects and CT RA950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects (P < .01). CONCLUSIONS: FDMRI and (3)He MRI VDP were strongly related in COPD but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with (3)He ventilation defects and emphysema.

Published
2014

169. Longitudinal computed tomography and magnetic resonance imaging of COPD: Thoracic imaging network of Canada (TINCan) study objectives

Author

Kirby, Miranda, Pike, Damien, McCormack, David G, Lam, Stephen, Coxson, Harvey O, and Parraga, Grace

Subjects
Medical Biophysics, CT, MRI, airways disease, emphysema, imaging phenotypes, respiratory tract diseases
Abstract

Although the human and societal burden and cost of COPD is staggering, there are few clinical tools that provide earlier diagnoses or a means to regionally monitor disease in a way that might lead to improved therapies and outcomes. In acknowledgement of the current gaps in COPD therapy, the objective of the Thoracic Imaging Network of Canada (TINCan) is to improve COPD patient phenotyping through imaging, to provide methods and imaging-based intermediate endpoints for the development of new treatments, and to evaluate disease progression and patient-based outcomes in COPD patients and those at risk of COPD. Here we summarize and outline the TINCan study protocol and describe our objectives. TINCan is a prospective study that aims to identify and quantify novel COPD phenotypes from thoracic computed tomography (CT) and thoracic hyperpolarized noble gas magnetic resonance imaging (MRI) in 200 ex-smokers, 50 years of age or greater, including asymptomatic ex-smokers with normal pulmonary function and Global initiative for chronic Obstructive Lung Disease (GOLD) Unclassified (U) , and GOLD stages I-IV patients. Baseline and 2-year follow-up measurements will be acquired using spirometry, plethysmography, diffusing capacity of the lung for carbon monoxide (DL

Published
2014

172. Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency

Author

Beiko, Tatsiana, primary, Janech, Michael G., additional, Alekseyenko, Alexander V., additional, Atkinson, Carl, additional, Coxson, Harvey O., additional, Barth, Jeremy L., additional, Stephenson, Sarah E., additional, Wilson, Carole L., additional, Schnapp, Lynn M., additional, Barker, Alan, additional, Brantly, Mark, additional, Sandhaus, Robert A., additional, Silverman, Edwin K., additional, Stoller, James K., additional, Trapnell, Bruce, additional, and Strange, Charlie, additional

Published
2017
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173. Functional respiratory imaging, regional strain, and expiratory time constants at three levels of positive end expiratory pressure in an ex vivo pig model

Author

Henderson, William R., primary, Molgat-Seon, Yannick, additional, Vos, Wim, additional, Lipson, Rachel, additional, Ferreira, Francisca, additional, Kirby, Miranda, additional, Holsbeke, Cedric Van, additional, Dominelli, Paolo B., additional, Griesdale, Donald E. G., additional, Sekhon, Mypinder, additional, Coxson, Harvey O., additional, Mayo, John, additional, and William Sheel, A., additional

Published
2016
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175. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry

Author

Leung, Janice M., primary, Chen, Virginia, additional, Hollander, Zsuzsanna, additional, Dai, Darlene, additional, Tebbutt, Scott J., additional, Aaron, Shawn D., additional, Vandemheen, Kathy L., additional, Rennard, Stephen I., additional, FitzGerald, J. Mark, additional, Woodruff, Prescott G., additional, Lazarus, Stephen C., additional, Connett, John E., additional, Coxson, Harvey O., additional, Miller, Bruce, additional, Borchers, Christoph, additional, McManus, Bruce M., additional, Ng, Raymond T., additional, and Sin, Don D., additional

Published
2016
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176. Chronic Hypoxia Accentuates Dysanaptic Lung Growth

Author

Llapur, Conrado J., primary, Martínez, Myriam R., additional, Grassino, Pedro T., additional, Stok, Ana, additional, Altieri, Héctor H., additional, Bonilla, Federico, additional, Caram, María M., additional, Krowchuk, Natasha M., additional, Kirby, Miranda, additional, Coxson, Harvey O., additional, and Tepper, Robert S., additional

Published
2016
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177. Non-emphysematous chronic obstructive pulmonary disease is associated with diabetes mellitus

Author

Hersh, Craig P, Make, Barry J, Lynch, David A, Barr, R Graham, Bowler, Russell P, Calverley, Peter M A, Castaldi, Peter J, Cho, Michael H, Coxson, Harvey O, DeMeo, Dawn L, Foreman, Marilyn G, Han, MeiLan K, Harshfield, Benjamin J, Hokanson, John E, Lutz, Sharon, Ramsdell, Joe W, Regan, Elizabeth A, Rennard, Stephen I, Schroeder, Joyce D, Sciurba, Frank C, Steiner, Robert M, Tal-Singer, Ruth, van Beek, Edwin, Silverman, Edwin K, Crapo, James D, and Mattheisen, Manuel

Subjects
Thorax, Male, humanos, Comorbidity, Severity of Illness Index, enfisema pulmonar, volumen espiratorio forzado, Pulmonary Disease, Chronic Obstructive, Diabetes mellitus, Quality of life, Forced Expiratory Volume, Epidemiology, Tomography, mediana edad, anciano, COPD, Exercise Tolerance, medicine.diagnostic_test, Age Factors, Middle Aged, respiratory system, 3. Good health, Pulmonary Emphysema, Female, Research Article, Spirometry, CT scan, Pulmonary and Respiratory Medicine, medicine.medical_specialty, tolerancia al ejercicio, tomografía, Internal medicine, Severity of illness, Airway disease, medicine, Humans, índice de gravedad de la enfermedad, Intensive care medicine, Aged, Emphysema, business.industry, medicine.disease, United States, respiratory tract diseases, calidad de vida, Quality of Life, business, Tomography, X-Ray Computed
Abstract

Background: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients. Methods: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA(-950)) >= 10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA(-950) < 5%). Results: Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA(-950) between 5-10% and were not categorized. Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St. George's Respiratory Questionnaire score 43 vs 31, p < 0.0001). Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use. The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study. Conclusions: Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes. COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa., Supported by U.S. National Institutes of Health grants R01HL094635 (CPH), R01NR013377 (CPH), R01HL089856 (EKS), R01HL089897 (JDC), P01HL105339 (EKS). COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Pfizer, Novartis, Boehringer-Ingelheim, Siemens, Sunovion, and GlaxoSmithKline. ECLIPSE is supported by GlaxoSmithKline. The sponsors had no role in study design; collection, analysis, and interpretation of the data; preparation of the manuscript; and decision to submit the manuscript for publication.

Published
2014
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178. Quantitative pulmonary imaging using computed tomography and magnetic resonance imaging

Author

Washko, George R, Parraga, Grace, and Coxson, Harvey O

Subjects
Emphysema, Lung Diseases, Male, Chronic Obstructive, Cystic Fibrosis, respiratory system, Magnetic Resonance Imaging, Asthma, respiratory tract diseases, X-Ray Computed, Pulmonary Disease, Pulmonary Disease, Chronic Obstructive, Medical Biophysics, Airway Remodeling, Humans, Female, Interstitial, Lung Diseases, Interstitial, Tomography, X-Ray Computed, Lung, Tomography
Abstract

Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image-based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy and function. In this review, we will focus on two of them; X-ray computed tomography and magnetic resonance imaging. Following a brief introduction of each method, we detail some of the most recent work being done to characterize smoking-related lung disease and the clinical applications of such knowledge.

Published
2012

180. Characterisation of COPD heterogeneity in the ECLIPSE cohort

Author

Agusti, Alvar, Calverley, Peter MA, Celli, Bartolome, Coxson, Harvey O, Edwards, Lisa D, Lomas, David A, MacNee, William, Miller, Bruce E, Rennard, Steve, Silverman, Edwin K, Tal-Singer, Ruth, Wouters, Emiel, Yates, Julie C, Vestbo, Jørgen, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators, and Apollo - University of Cambridge Repository

Subjects
Adult, Cohort Studies, Male, Pulmonary Disease, Chronic Obstructive, Cross-Sectional Studies, Smoking, Humans, Female, Longitudinal Studies, Middle Aged, respiratory tract diseases, Aged, Respiratory Function Tests
Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE). METHODS: We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography. RESULTS: COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage. The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study. The distribution of these variables within each GOLD stage was wide. Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation. The amount of emphysema increased with GOLD severity. The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage. Some gender differences were also identified. CONCLUSIONS: The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

Published
2010

181. Reproducibility of optical coherence tomography airway imaging

Author

Kirby, Miranda, primary, Ohtani, Keishi, additional, Nickens, Taylor, additional, Lisbona, Rosa Maria Lopez, additional, Lee, Anthony M. D., additional, Shaipanich, Tawimas, additional, Lane, Pierre, additional, MacAulay, Calum, additional, Lam, Stephen, additional, and Coxson, Harvey O., additional

Published
2015
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182. CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

Author

Lynch, David A., primary, Austin, John H. M., additional, Hogg, James C., additional, Grenier, Philippe A., additional, Kauczor, Hans-Ulrich, additional, Bankier, Alexander A., additional, Barr, R. Graham, additional, Colby, Thomas V., additional, Galvin, Jeffrey R., additional, Gevenois, Pierre Alain, additional, Coxson, Harvey O., additional, Hoffman, Eric A., additional, Newell, John D., additional, Pistolesi, Massimo, additional, Silverman, Edwin K., additional, and Crapo, James D., additional

Published
2015
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184. An official American Thoracic Society/European Respiratory Society statement: research questions in COPD

Author

Celli, Bartolome R., primary, Decramer, Marc, additional, Wedzicha, Jadwiga A., additional, Wilson, Kevin C., additional, Agustí, Alvar A., additional, Criner, Gerard J., additional, MacNee, William, additional, Make, Barry J., additional, Rennard, Stephen I., additional, Stockley, Robert A., additional, Vogelmeier, Claus, additional, Anzueto, Antonio, additional, Au, David H., additional, Barnes, Peter J., additional, Burgel, Pierre-Regis, additional, Calverley, Peter M., additional, Casanova, Ciro, additional, Clini, Enrico M., additional, Cooper, Christopher B., additional, Coxson, Harvey O., additional, Dusser, Daniel J., additional, Fabbri, Leonardo M., additional, Fahy, Bonnie, additional, Ferguson, Gary T., additional, Fisher, Andrew, additional, Fletcher, Monica J., additional, Hayot, Maurice, additional, Hurst, John R., additional, Jones, Paul W., additional, Mahler, Donald A., additional, Maltais, François, additional, Mannino, David M., additional, Martinez, Fernando J., additional, Miravitlles, Marc, additional, Meek, Paula M., additional, Papi, Alberto, additional, Rabe, Klaus F., additional, Roche, Nicolas, additional, Sciurba, Frank C., additional, Sethi, Sanjay, additional, Siafakas, Nikos, additional, Sin, Don D., additional, Soriano, Joan B., additional, Stoller, James K., additional, Tashkin, Donald P., additional, Troosters, Thierry, additional, Verleden, Geert M., additional, Verschakelen, Johny, additional, Vestbo, Jorgen, additional, Walsh, John W., additional, Washko, George R., additional, Wise, Robert A., additional, Wouters, Emiel F.M., additional, and ZuWallack, Richard L., additional

Published
2015
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185. Bronchial thermoplasty in asthma: 2-year follow-up using optical coherence tomography

Author

Kirby, Miranda, primary, Ohtani, Keishi, additional, Lopez Lisbona, Rosa Maria, additional, Lee, Anthony M.D., additional, Zhang, Wei, additional, Lane, Pierre, additional, Varfolomeva, Nina, additional, Hui, Linda, additional, Ionescu, Diana, additional, Coxson, Harvey O., additional, MacAulay, Calum, additional, FitzGerald, J. Mark, additional, and Lam, Stephen, additional

Published
2015
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186. A Comparison of Pain, Fatigue, Dyspnea and their Impact on Quality of Life in Pulmonary Rehabilitation Participants with Chronic Obstructive Pulmonary Disease.

Author

Chen, Yi-Wen, Camp, Pat G., Coxson, Harvey O., Road, Jeremy D., Guenette, Jordan A., Hunt, Michael A., and Reid, W. Darlene

Subjects
OBSTRUCTIVE lung diseases, FATIGUE (Physiology), DYSPNEA, BRIEF Pain Inventory, QUALITY of life, SYMPTOMS
Abstract

In addition to dyspnea and fatigue, pain is a prevalent symptom in chronic obstructive pulmonary disease (COPD). Understanding the relative prevalence, magnitude, and interference with aspects of daily living of these symptoms can improve COPD management. Therefore, the purposes of this study were to: (1) compare the prevalence and magnitude of dyspnea, fatigue, and pain and how each limits aspects of daily living; (2) determine the association between pain and the other two symptoms; and (3) assess the impact of these symptoms on quality of life in COPD. Participants were recruited from pulmonary rehabilitation programs. Pain, dyspnea, and fatigue were measured using the Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), and Dyspnea Inventory (DI), respectively. Quality of life was measured using the Clinical COPD Questionnaire (CCQ). The prevalence of dyspnea, fatigue, and pain were 93%, 77%, and 74%, respectively. Individuals with COPD reported similar severity scores of the three symptoms. Dyspnea interfered with general activity more than pain (F1.7,79.9= 3.1,p< 0.05), whilst pain interfered with mood (F1.8, 82.7= 3.6,p< 0.05) and sleep (F1,46= 7.4,p< 0.01) more than dyspnea and fatigue. These three symptoms were moderately-to-highly correlated with each other (ρ = 0.49–0.78,p< 0.01) and all individually impacted quality of life. In summary, pain is a common symptom in addition to dyspnea and fatigue in COPD; all three interfere similarly among aspects of daily living with some exceptions. Accordingly, management of COPD should include a multifaceted approach that addresses pain as well as dyspnea and fatigue. [ABSTRACT FROM AUTHOR]

Published
2018
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187. A Novel Method of Estimating Small Airway Disease Using Inspiratory-to-Expiratory Computed Tomography.

Author

Kirby, Miranda, Yin, Youbing, Tschirren, Juerg, Tan, Wan C., Leipsic, Jonathon, Hague, Cameron J., Bourbeau, Jean, Sin, Don D., Hogg, James C., and Coxson, Harvey O.

Subjects
OBSTRUCTIVE lung disease diagnosis, TREATMENT of respiratory obstructions, AIRWAY (Anatomy), COMPUTED tomography, DIFFUSION of innovations, PROBABILITY theory, RESPIRATION, PULMONARY function tests, PATIENT selection, DATA analysis software, DESCRIPTIVE statistics
Abstract

Background: Disease accumulates in the small airways without being detected by conventional measurements. Objectives: To quantify small airway disease using a novel computed tomography (CT) inspiratory-to-expiratory approach called the disease probability measure (DPM) and to investigate the association with pulmonary function measurements. Methods: Participants from the population-based CanCOLD study were evaluated using full-inspiration/full-expiration CT and pulmonary function measurements. Full-inspiration and full-expiration CT images were registered, and each voxel was classified as emphysema, gas trapping (GasTrap) related to functional small airway disease, or normal using two classification approaches: parametric response map (PRM) and DPM (VIDA Diagnostics, Inc., Coralville, IA, USA). Results: The participants included never-smokers (n = 135), at risk (n = 97), Global Initiative for Chronic Obstructive Lung Disease I (GOLD I) (n = 140), and GOLD II chronic obstructive pulmonary disease (n = 96). PRMGasTrap and DPMGasTrap measurements were significantly elevated in GOLD II compared to never-smokers (p < 0.01) and at risk (p < 0.01), and for GOLD I compared to at risk (p < 0.05). Gas trapping measurements were significantly elevated in GOLD II compared to GOLD I (p < 0.0001) using the DPM classification only. Overall, DPM classified significantly more voxels as gas trapping than PRM (p < 0.0001); a spatial comparison revealed that the expiratory CT Hounsfield units (HU) for voxels classified as DPMGasTrap but PRMNormal (PRMNormal- DPMGasTrap = -785 ± 72 HU) were significantly reduced compared to voxels classified normal by both approaches (PRMNormal-DPMNormal = --722 ± 89 HU; p < 0.0001). DPM and PRM GasTrap measurements showed similar, significantly associations with forced expiratory volume in 1 s (FEV1) (p < 0.01), FEV1/forced vital capacity (p < 0.0001), residual volume/total lung capacity (p < 0.0001), bronchodilator response (p < 0.0001), and dyspnea (p < 0.05). Conclusion: CT inspiratory-to-expiratory gas trapping measurements are significantly associated with pulmonary function and symptoms. There are quantitative and spatial differences between PRM and DPM classification that need pathological investigation. [ABSTRACT FROM AUTHOR]

Published
2017
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188. One-year change in health status and subsequent outcomes in COPD

Author

Wilke, Sarah, primary, Jones, Paul W, additional, Müllerova, H, additional, Vestbo, Jørgen, additional, Tal-Singer, Ruth, additional, Franssen, Frits ME, additional, Agusti, Alvar, additional, Bakke, Per, additional, Calverley, Peter M, additional, Coxson, Harvey O, additional, Crim, Courtney, additional, Edwards, Lisa D, additional, Lomas, David A, additional, MacNee, William, additional, Rennard, Stephen I, additional, Yates, Julie C, additional, Wouters, Emiel FM, additional, and Spruit, Martijn A, additional

Published
2015
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190. Quantitative computed tomography measures of pectoralis muscle area and disease severity in chronic obstructive pulmonary disease. A cross-sectional study.

Author

McDonald, Merry-Lynn N, McDonald, Merry-Lynn N, Diaz, Alejandro A, Ross, James C, San Jose Estepar, Raul, Zhou, Linfu, Regan, Elizabeth A, Eckbo, Eric, Muralidhar, Nina, Come, Carolyn E, Cho, Michael H, Hersh, Craig P, Lange, Christoph, Wouters, Emiel, Casaburi, Richard H, Coxson, Harvey O, Macnee, William, Rennard, Stephen I, Lomas, David A, Agusti, Alvar, Celli, Bartolome R, Black-Shinn, Jennifer L, Kinney, Greg L, Lutz, Sharon M, Hokanson, John E, Silverman, Edwin K, Washko, George R, McDonald, Merry-Lynn N, McDonald, Merry-Lynn N, Diaz, Alejandro A, Ross, James C, San Jose Estepar, Raul, Zhou, Linfu, Regan, Elizabeth A, Eckbo, Eric, Muralidhar, Nina, Come, Carolyn E, Cho, Michael H, Hersh, Craig P, Lange, Christoph, Wouters, Emiel, Casaburi, Richard H, Coxson, Harvey O, Macnee, William, Rennard, Stephen I, Lomas, David A, Agusti, Alvar, Celli, Bartolome R, Black-Shinn, Jennifer L, Kinney, Greg L, Lutz, Sharon M, Hokanson, John E, Silverman, Edwin K, and Washko, George R

Abstract

RationaleMuscle wasting in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis and is not readily assessed by measures of body mass index (BMI). BMI does not discriminate between relative proportions of adipose tissue and lean muscle and may be insensitive to early pathologic changes in body composition. Computed tomography (CT)-based assessments of the pectoralis muscles may provide insight into the clinical significance of skeletal muscles in smokers.ObjectivesWe hypothesized that objective assessment of the pectoralis muscle area on chest CT scans provides information that is clinically relevant and independent of BMI.MethodsData from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) Study (n = 73) were used to assess the relationship between pectoralis muscle area and fat-free mass. We then used data in a subset (n = 966) of a larger cohort, the COPDGene (COPD Genetic Epidemiology) Study, to explore the relationship between pectoralis muscle area and COPD-related traits.Measurements and main resultsWe first investigated the correlation between pectoralis muscle area and fat-free mass, using data from a subset of participants in the ECLIPSE Study. We then further investigated pectoralis muscle area in COPDGene Study participants and found that higher pectoralis muscle area values were associated with greater height, male sex, and younger age. On subsequent clinical correlation, compared with BMI, pectoralis muscle area was more significantly associated with COPD-related traits, including spirometric measures, dyspnea, and 6-minute-walk distance (6MWD). For example, on average, each 10-cm(2) increase in pectoralis muscle area was associated with a 0.8-unit decrease in the BODE (Body mass index, Obstruction, Dyspnea, Exercise) index (95% confidence interval, -1.0 to -0.6; P < 0.001). Furthermore, statistically significant associations between pectoralis muscle area and COPD-related traits rema

Published
2014

194. Common Genetic Variants Associated with Resting Oxygenation in Chronic Obstructive Pulmonary Disease

Author

McDonald, Merry-Lynn N., primary, Cho, Michael H., additional, Sørheim, Inga-Cecilie, additional, Lutz, Sharon M., additional, Castaldi, Peter J., additional, Lomas, David A., additional, Coxson, Harvey O., additional, Edwards, Lisa D., additional, MacNee, William, additional, Vestbo, Jørgen, additional, Yates, Julie C., additional, Agusti, Alvar, additional, Calverley, Peter M. A., additional, Celli, Bartolome, additional, Crim, Courtney, additional, Rennard, Stephen I., additional, Wouters, Emiel F. M., additional, Bakke, Per, additional, Tal-Singer, Ruth, additional, Miller, Bruce E., additional, Gulsvik, Amund, additional, Casaburi, Richard, additional, Wells, J. Michael, additional, Regan, Elizabeth A., additional, Make, Barry J., additional, Hokanson, John E., additional, Lange, Christoph, additional, Crapo, James D., additional, Beaty, Terri H., additional, Silverman, Edwin K., additional, and Hersh, Craig P., additional

Published
2014
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195. The IBV Valve Trial

Author

Wood, Douglas E., primary, Nader, Daniel A., additional, Springmeyer, Steven C., additional, Elstad, Mark R., additional, Coxson, Harvey O., additional, Chan, Andrew, additional, Rai, Navdeep S., additional, Mularski, Richard A., additional, Cooper, Christopher B., additional, Wise, Robert A., additional, Jones, Paul W., additional, Mehta, Atul C., additional, Gonzalez, Xavier, additional, and Sterman, Daniel H., additional

Published
2014
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198. DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Author

Lee, Jin Hwa, primary, McDonald, Merry-Lynn N, additional, Cho, Michael H, additional, Wan, Emily S, additional, Castaldi, Peter J, additional, Hunninghake, Gary M, additional, Marchetti, Nathaniel, additional, Lynch, David A, additional, Crapo, James D, additional, Lomas, David A, additional, Coxson, Harvey O, additional, Bakke, Per S, additional, Silverman, Edwin K, additional, and Hersh, Craig P, additional

Published
2014
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