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

المصدر: CHEST Journal. 160(4)

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

الوصف: BackgroundAttenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers.Research questionIs use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema?MethodsFormer and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume

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الوصول الحر: https://escholarship.org/uc/item/4w5477zqTest

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

المصدر: CHEST Journal. 160(3)

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

الوصف: BackgroundSmokers manifest varied phenotypes of pulmonary impairment.Research questionWhich pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers?Study design and methodsWe analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV1 to FVC ratio, < 0.70).ResultsPulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV1 and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts.InterpretationLung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV1 and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

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الوصول الحر: https://escholarship.org/uc/item/7x06z7jhTest

المؤلفون: Wilson, Ava C, Kumar, Preeti L, Lee, Sool, Parker, Margaret M, Arora, Itika, Morrow, Jarrett D, Wouters, Emiel FM, Casaburi, Richard, Rennard, Stephen I, Lomas, David A, Agusti, Alvar, Tal-Singer, Ruth, Dransfield, Mark T, Wells, J Michael, Bhatt, Surya P, Washko, George, Thannickal, Victor J, Tiwari, Hemant K, Hersh, Craig P, Castaldi, Peter J, Silverman, Edwin K, McDonald, Merry-Lynn N

المصدر: Respiratory Research. 21(1)

مصطلحات موضوعية: Hematology, Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, Genetics, Nutrition, Respiratory, Aged, Aged, 80 and over, Cachexia, Cohort Studies, Down-Regulation, Female, Follow-Up Studies, Genome-Wide Association Study, Heme, Humans, Longitudinal Studies, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Chronic obstructive pulmonary disease, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Respiratory System

الوصف: IntroductionCachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.MethodsWe analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) ( 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB.ResultsThe prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR

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الوصول الحر: https://escholarship.org/uc/item/3kw8v9gmTest

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

المصدر: CHEST Journal. 157(5)

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

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

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الوصول الحر: https://escholarship.org/uc/item/6wq8n7z4Test

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

المصدر: American Journal of Respiratory and Critical Care Medicine. 201(3)

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

الوصف: 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

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الوصول الحر: https://escholarship.org/uc/item/5gn6w804Test

المؤلفون: Bartlett, Robert H., Carlet, Jean, Cook, Deborah, Gattinoni, Luciano, Harvey, Maurene, Jacobi, Judith, Parker, Margaret M., Sprung, Charles L., Suter, Peter, Thompson, Ann, Vincent, Jean-Louis

المساهمون: Bartlett, Robert H., Carlet, Jean, Cook, Deborah, Gattinoni, Luciano, Harvey, Maurene, Jacobi, Judith, Parker, Margaret M., Sprung, Charles L., Suter, Peter, Thompson, Ann, Vincent, Jean-Louis

الوصف: On the 50th anniversary of the Society of Critical Care Medicine’s journal Critical Care Medicine , critical care pioneers reflect on the importance of the journal to their careers and to the development of the field of adult and pediatric critical care.

العلاقة: https://resolver.sub.uni-goettingen.de/purl?gro-2/134731Test

الإتاحة: https://doi.org/10.1097/CCM.0000000000005728Test
https://resolver.sub.uni-goettingen.de/purl?gro-2/134731Test

المؤلفون: Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, Gharib, Sina A

المصدر: Nature communications. 9(1)

مصطلحات موضوعية: Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive

الوصف: Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

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الوصول الحر: https://escholarship.org/uc/item/4cx2v3pkTest

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

المصدر: Journal of Allergy and Clinical Immunology. 141(6)

مصطلحات موضوعية: Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, Respiratory, Aged, Disease Progression, Eosinophils, Female, Humans, Leukocyte Count, Longitudinal Studies, Male, Middle Aged, Observational Studies as Topic, Pulmonary Disease, Chronic Obstructive, Chronic obstructive pulmonary disease, asthma, eosinophil, exacerbation, COPDGene and ECLIPSE Investigators, Immunology, Allergy

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

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9sq60742Test

المؤلفون: Shrine, Nick, Guyatt, Anna L, Erzurumluoglu, A Mesut, Jackson, Victoria E., Hobbs, Brian D, Melbourne, Carl A, Batini, Chiara, Fawcett, Katherine A, Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F, Obeidat, Ma'en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A, Cook, James P, Sun, Benjamin B, Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E, Marten, Jonathan, Enroth, Stefan, Kerr, Shona M, Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J, Bakke, Per S, Beaty, Terri H, Bleecker, Eugene R, Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D, Danesh, John, DeMeo, Dawn L, Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L, Hao, Ke, Hoffman, Joshua D, Hokanson, John E, Homuth, Georg, Joshi, Peter K., Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian'an, Mahajan, Anubha, Maranville, Joseph C., Murray, Alison D., Nickle, David C., Packer, Richard, Parker, Margaret M., Paynton, Megan L., Porteous, David J., Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Smith, Blair H, Sin, Don D., Artigas, María Soler, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul R.H.J., Van den Berge, Maarten, Whittaker, John C., Woodruff, Prescott G., Yerges-Armstrong, Laura M., Troyanskaya, Olga G., Raitakari, Olli T., Kähönen, Mika, Polasek, Ozren, Gyllensten, Ulf B., Rudan, Igor, Deary, Ian J., Probst-Hensch, Nicole M., Schulz, Holger, James, Alan L., Wilson, James F., Stubbe, Beate, Zeggini, Eleftheria, Järvelin, Marjo-Riitta, Wareham, Nick, Silverman, Edwin K., Hayward, Caroline, Morris, Andrew P., Butterworth, Adam S., Scott, Robert A., Walters, Robin G, Meyers, Deborah A., Cho, Michael H., Strachan, David P., Hall, Ian P., Tobin, Martin D., Wain, Louise V.

المصدر: Shrine , N , Guyatt , A L , Erzurumluoglu , A M , Jackson , V E , Hobbs , B D , Melbourne , C A , Batini , C , Fawcett , K A , Song , K , Sakornsakolpat , P , Li , X , Boxall , R , Reeve , N F , Obeidat , M , Zhao , J H , Wielscher , M , Understanding Society Scientific Group , Weiss , S , Kentistou , K A , Cook , J P , Sun , B B , Zhou , J ....

الوصف: Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0321-7Test, published online 25 February 2019.

العلاقة: https://discovery.dundee.ac.uk/en/publications/6bb400f7-ac03-47b3-9d00-5bb5eda9dbd0Test

الإتاحة: https://doi.org/10.1038/s41588-024-01752-4Test
https://discovery.dundee.ac.uk/en/publications/6bb400f7-ac03-47b3-9d00-5bb5eda9dbd0Test

المؤلفون: Ghosh, Auyon J., Hobbs, Brian D., Yun, Jeong H., Saferali, Aabida, Moll, Matthew, Xu, Zhonghui, Chase, Robert P., Morrow, Jarrett, Ziniti, John, Sciurba, Frank, Barwick, Lucas, Limper, Andrew H., Flaherty, Kevin, Criner, Gerard, Brown, Kevin K., Wise, Robert, Martinez, Fernando J., McGoldrick, Daniel, Cho, Michael H., DeMeo, Dawn L., Silverman, Edwin K., Castaldi, Peter J., Crapo, James D., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Cho, Michael, Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S., Won, Sungho, Centeno, Juan Pablo

المساهمون: National Institutes of Health

المصدر: Respiratory Research ; volume 23, issue 1 ; ISSN 1465-993X

الوصف: Background Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF. Methods We performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets. Results We found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts. Conclusions We identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.

الإتاحة: https://doi.org/10.1186/s12931-022-02013-wTest