المؤلفون: Bradford, Eric, Jacobson, Sean, Varasteh, Jason, Comellas, Alejandro P., Woodruff, Prescott, O’Neal, Wanda, DeMeo, Dawn L., Li, Xingnan, Kim, Victor, Cho, Michael, Castaldi, Peter J., Hersh, Craig, Silverman, Edwin K., Crapo, James D., Kechris, Katerina, Bowler, Russell P.

مرشدي الرسالة: Univ Arizona, Coll Med, Dept Med

الوصف: Background: Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers. Methods: We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS. These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17. Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD exacerbations, and emphysema. Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs). Results: Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3-5% of the measurement variance on top of clinical variables. IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years. None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations. We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements. Conclusion: When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone.

العلاقة: http://respiratory-research.biomedcentral.com/articles/10.1186/s12931-017-0662-2Test

الإتاحة: http://hdl.handle.net/10150/626086Test
http://arizona.openrepository.com/arizona/handle/10150/626086Test

المؤلفون: Buckner, Teresa, Johnson, Randi K, Vanderlinden, Lauren A, Carry, Patrick M, Romero, Alex, Onengut-Gumuscu, Suna, Chen, Wei-Min, Kim, Soojeong, Fiehn, Oliver, Frohnert, Brigitte I, Crume, Tessa, Perng, Wei, Kechris, Katerina, Rewers, Marian, Norris, Jill M

مصطلحات موضوعية: Biomedical and Clinical Sciences, Nutrition and Dietetics, Genetics, Human Genome, Prevention, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Good Health and Well Being, oxylipin, inflammation, pediatric, genome-wide association study, polyunsaturated fatty acids, lipid mediators, Agricultural Biotechnology, Nutrition and dietetics

الوصف: BackgroundOxylipins are inflammatory biomarkers derived from omega-3 and-6 fatty acids implicated in inflammatory diseases but have not been studied in a genome-wide association study (GWAS). The aim of this study was to identify genetic loci associated with oxylipins and oxylipin profiles to identify biologic pathways and therapeutic targets for oxylipins.MethodsWe conducted a GWAS of plasma oxylipins in 316 participants in the Diabetes Autoimmunity Study in the Young (DAISY). DNA samples were genotyped using the TEDDY-T1D Exome array, and additional variants were imputed using the Trans-Omics for Precision Medicine (TOPMed) multi-ancestry reference panel. Principal components analysis of 36 plasma oxylipins was used to capture oxylipin profiles. PC1 represented linoleic acid (LA)- and alpha-linolenic acid (ALA)-related oxylipins, and PC2 represented arachidonic acid (ARA)-related oxylipins. Oxylipin PC1, PC2, and the top five loading oxylipins from each PC were used as outcomes in the GWAS (genome-wide significance: p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2j4094vmTest

المؤلفون: Hill, Andrew C, Guo, Claire, Litkowski, Elizabeth M, Manichaikul, Ani W, Yu, Bing, Konigsberg, Iain R, Gorbet, Betty A, Lange, Leslie A, Pratte, Katherine A, Kechris, Katerina J, DeCamp, Matthew, Coors, Marilyn, Ortega, Victor E, Rich, Stephen S, Rotter, Jerome I, Gerzsten, Robert E, Clish, Clary B, Curtis, Jeffrey L, Hu, Xiaowei, Obeidat, Ma-en, Morris, Melody, Loureiro, Joseph, Ngo, Debby, O’Neal, Wanda K, Meyers, Deborah A, Bleecker, Eugene R, Hobbs, Brian D, Cho, Michael H, Banaei-Kashani, Farnoush, Bowler, Russell P

المصدر: Scientific Reports. 13(1)

مصطلحات موضوعية: Epidemiology, Biological Sciences, Health Sciences, Genetics, Biotechnology, Human Genome, Cardiovascular, Atherosclerosis, Generic health relevance, Humans, Proteome, Bayes Theorem, Privacy, Genome-Wide Association Study, Polymorphism, Single Nucleotide

الوصف: Privacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level genotype probabilities, and then applied a naïve Bayesian approach to link SomaScan 1.3K proteomes to genomes for 2812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA). We correctly linked 90-95% of proteomes to their correct genome and for 95-99% we identify the 1% most likely links. The linking accuracy in subjects with African ancestry was lower (~ 60%) unless training included diverse subjects. With larger profiling (SomaScan 5K) in the Atherosclerosis Risk Communities (ARIC) correct identification was > 99% even in mixed ancestry populations. We also linked proteomes-to-proteomes and used the proteome only to determine features such as sex, ancestry, and first-degree relatives. When serial proteomes are available, the linking algorithm can be used to identify and correct mislabeled samples. This work also demonstrates the importance of including diverse populations in omics research and that large proteomic datasets (> 1000 proteins) can be accurately linked to a specific genome through pQTL knowledge and should not be considered unidentifiable.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6jt046f6Test

المؤلفون: Buckner, Teresa, Johnson, Randi K, Vanderlinden, Lauren A, Carry, Patrick M, Romero, Alex, Onengut-Gumuscu, Suna, Chen, Wei-Min, Fiehn, Oliver, Frohnert, Brigitte I, Crume, Tessa, Perng, Wei, Kechris, Katerina, Rewers, Marian, Norris, Jill M

المصدر: Nutrients. 15(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Nutrition and Dietetics, Pediatric, Nutrition, Prevention, Autoimmune Disease, Clinical Research, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Child, Adolescent, Humans, Diabetes Mellitus, Type 1, Oxylipins, Autoimmunity, Islets of Langerhans, Risk Factors, Case-Control Studies, Nutrients, oxylipin, nutrient pattern, type 1 diabetes, reduced rank regression, Food Sciences, Clinical sciences, Nutrition and dietetics, Public health

الوصف: Oxylipins, pro-inflammatory and pro-resolving lipid mediators, are associated with the risk of type 1 diabetes (T1D) and may be influenced by diet. This study aimed to develop a nutrient pattern related to oxylipin profiles and test their associations with the risk of T1D among youth. The nutrient patterns were developed with a reduced rank regression in a nested case-control study (n = 335) within the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal cohort of children at risk of T1D. The oxylipin profiles (adjusted for genetic predictors) were the response variables. The nutrient patterns were tested in the case-control study (n = 69 T1D cases, 69 controls), then validated in the DAISY cohort using a joint Cox proportional hazards model (n = 1933, including 81 T1D cases). The first nutrient pattern (NP1) was characterized by low beta cryptoxanthin, flavanone, vitamin C, total sugars and iron, and high lycopene, anthocyanidins, linoleic acid and sodium. After adjusting for T1D family history, the HLA genotype, sex and race/ethnicity, NP1 was associated with a lower risk of T1D in the nested case-control study (OR: 0.44, p = 0.0126). NP1 was not associated with the risk of T1D (HR: 0.54, p-value = 0.1829) in the full DAISY cohort. Future studies are needed to confirm the nested case-control findings and investigate the modifiable factors for oxylipins.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/98v5v5nkTest

المؤلفون: Godbole, Suneeta, Labaki, Wassim, Pratte, Katherine, Hill, Andrew, Moll, Matthew, Hastie, Annette, Peters, Stephen, Gregory, Andrew, Ortega, Victor, DeMeo, Dawn, Cho, Michael, Bhatt, Surya, Wells, J, Barjaktarevic, Igor, Stringer, Kathleen, Comellas, Alejandro, ONeal, Wanda, Kechris, Katerina, Bowler, Russell

المصدر: Metabolites. 12(5)

مصطلحات موضوعية: COPD, adaptive LASSO, lung density, metabolomics

الوصف: Chronic obstructive pulmonary disease (COPD) is a disease with marked metabolic disturbance. Previous studies have shown the association between single metabolites and lung function for COPD, but whether a combination of metabolites could predict phenotype is unknown. We developed metabolomic severity scores using plasma metabolomics from the Metabolon platform from two US cohorts of ever-smokers: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (n = 648; training/testing cohort; 72% non-Hispanic, white; average age 63 years) and the COPDGene Study (n = 1120; validation cohort; 92% non-Hispanic, white; average age 67 years). Separate adaptive LASSO (adaLASSO) models were used to model forced expiratory volume at one second (FEV1) and MESA-adjusted lung density using 762 metabolites common between studies. Metabolite coefficients selected by the adaLASSO procedure were used to create a metabolomic severity score (metSS) for each outcome. A total of 132 metabolites were selected to create a metSS for FEV1. The metSS-only models explained 64.8% and 31.7% of the variability in FEV1 in the training and validation cohorts, respectively. For MESA-adjusted lung density, 129 metabolites were selected, and metSS-only models explained 59.0% of the variability in the training cohort and 17.4% in the validation cohort. Regression models including both clinical covariates and the metSS explained more variability than either the clinical covariate or metSS-only models (53.4% vs. 46.4% and 31.6%) in the validation dataset. The metabolomic pathways for arginine biosynthesis; aminoacyl-tRNA biosynthesis; and glycine, serine, and threonine pathway were enriched by adaLASSO metabolites for FEV1. This is the first demonstration of a respiratory metabolomic severity score, which shows how a metSS can add explanation of variance to clinical predictors of FEV1 and MESA-adjusted lung density. The advantage of a comprehensive metSS is that it explains more disease than individual metabolites and can account for substantial collinearity among classes of metabolites. Future studies should be performed to determine whether metSSs are similar in younger, and more racially and ethnically diverse populations as well as whether a metabolomic severity score can predict disease development in individuals who do not yet have COPD.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9wb6w0vgTest

المؤلفون: Mason, Stefanie E, Moreta-Martinez, Rafael, Labaki, Wassim W, Strand, Matthew J, Regan, Elizabeth A, Bon, Jessica, San Jose Estepar, Ruben, Casaburi, Richard, McDonald, Merry-Lynn, Rossiter, Harry B, Make, Barry, Dransfield, Mark T, Han, MeiLan K, Young, Kendra, Curtis, Jeffrey L, Stringer, Kathleen, Kinney, Greg, Hokanson, John E, San Jose Estepar, Raul, Washko, George R, Crapo, James D, Silverman, Edwin K, Cummings, Sara, Madden, Kelley, Make, Barry J, Nabbosa, Juliet, Port, Emily, Rashdi, Serine, Stepp, Lori, Watts, Shandi, Weaver, Michael, Beaty, Terri, Bowler, Russell P, Lynch, David A, Regan, Elizabeth, Anderson, Gary, Bleecker, Eugene R, Coxson, Harvey O, Crystal, Ronald G, Hogg, James C, Province, Michael A, Rennard, Stephen I, Croxton, Thomas, Gan, Weiniu, Postow, Lisa A, Viviano, Lisa M, Costa-Davis, Corinne, Malanga, Elisha, Prieto, Delia, Tal-Singer, Ruth, Farzadegan, Homayoon, Hadji, Akila, Sathe, Leena, Baraghoshi, David, Chen, Grace, Crooks, James, Knowles, Ruthie, Pratte, Katherine, Wilson, Carla, Zelarney, Pearlanne T, Kechris, Katerina J, Leach, Sonia, Hokanson, Co-Chair John E, Austin, Erin E, Czizik, Annika, Kinney, Gregory, Li, Yisha, Lutz, Sharon M, Ragland, Margaret F, Richmond, Nicole, Young, Kendra A, Cho, Michael, Castaldi, Peter J, Glass, Kimberly, Hersh, Craig, Kim, Wonji, Liu, Yang-Yu, Hersh, Craig P, Bidinger, Jacqueline, Cho, Michael H, Conrad, Douglas, DeMeo, Dawn L

المصدر: CHEST Journal. 161(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Nutrition, Prevention, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Body Composition, Body Mass Index, Humans, Longitudinal Studies, Lung, Pectoralis Muscles, Pulmonary Disease, Chronic Obstructive, Smokers, COPD, mortality, muscle wasting, sarcopenia, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences

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

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1k42q3kxTest
https://escholarship.org/content/qt1k42q3kx/qt1k42q3kx.pdfTest

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

المصدر: American Journal of Respiratory and Critical Care Medicine. 205(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Chronic Obstructive Pulmonary Disease, Lung, Emphysema, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Markers, Genotype, Heterozygote, Humans, Longitudinal Studies, Male, Middle Aged, Phenotype, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Survival Analysis, Whole Genome Sequencing, alpha 1-Antitrypsin, COPDGene Investigators, RNA sequencing, alpha-1 antitrypsin, chronic obstructive pulmonary disease, meta-analysis, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences

الوصف: Rationale: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. Objectives: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. Methods: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. Measurements and Main Results: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV1% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV1 was 3.9% lower (95% confidence interval [CI], -6.55% to -1.26%) and emphysema (the percentage of lung attenuation areas

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2721g2jkTest

المؤلفون: Wieder, Cecilia, Cooke, Juliette, Frainay, Clement, Poupin, Nathalie, Bowler, Russell, Jourdan, Fabien, Kechris, Katerina J., Lai, Rachel PJ, Ebbels, Timothy

المساهمون: Ouzounis, Christos A., Wellcome Trust, Biotechnology and Biological Sciences Research Council, Medical Research Council, Foundation for the National Institutes of Health, Agence Nationale de la Recherche, National Heart, Lung, and Blood Institute, NIH, COPD Foundation

المصدر: PLOS Computational Biology ; volume 20, issue 3, page e1011814 ; ISSN 1553-7358

الوصف: As terabytes of multi-omics data are being generated, there is an ever-increasing need for methods facilitating the integration and interpretation of such data. Current multi-omics integration methods typically output lists, clusters, or subnetworks of molecules related to an outcome. Even with expert domain knowledge, discerning the biological processes involved is a time-consuming activity. Here we propose PathIntegrate, a method for integrating multi-omics datasets based on pathways, designed to exploit knowledge of biological systems and thus provide interpretable models for such studies. PathIntegrate employs single-sample pathway analysis to transform multi-omics datasets from the molecular to the pathway-level, and applies a predictive single-view or multi-view model to integrate the data. Model outputs include multi-omics pathways ranked by their contribution to the outcome prediction, the contribution of each omics layer, and the importance of each molecule in a pathway. Using semi-synthetic data we demonstrate the benefit of grouping molecules into pathways to detect signals in low signal-to-noise scenarios, as well as the ability of PathIntegrate to precisely identify important pathways at low effect sizes. Finally, using COPD and COVID-19 data we showcase how PathIntegrate enables convenient integration and interpretation of complex high-dimensional multi-omics datasets. PathIntegrate is available as an open-source Python package.

الإتاحة: https://doi.org/10.1371/journal.pcbi.1011814Test

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

وصف الملف: application/pdf

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.

وصف الملف: application/pdf

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