Systemic Markers of Lung Function and Forced Expiratory Volume in 1 Second Decline across Diverse Cohorts.

Autor:	Ngo D; Cardiovascular Research Institute.; Division of Pulmonary, Critical Care, and Sleep Medicine, and., Pratte KA; National Jewish Health, Denver, Colorado., Flexeder C; Institute of Epidemiology and.; Comprehensive Pneumology Center Munich (CPC-M) as member of the German Center for Lung Research (DZL), Munich, Germany.; Institute and Clinic for Occupational, Social, and Environmental Medicine, University Hospital, Ludwig-Maximilians-University, Munich, Germany., Petersen H; Lovelace Respiratory Research Institute, Albuquerque, New Mexico., Dang H; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Ma Y; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia., Keyes MJ; Cardiovascular Research Institute., Gao Y; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; and.; Institute and Clinic for Occupational, Social, and Environmental Medicine, University Hospital, Ludwig-Maximilians-University, Munich, Germany., Deng S; Cardiovascular Research Institute., Peterson BD; Cardiovascular Research Institute., Farrell LA; Cardiovascular Research Institute., Bhambhani VM; Cardiovascular Research Institute., Palacios C; Cardiovascular Research Institute., Quadir J; Cardiovascular Research Institute., Gillenwater L; National Jewish Health, Denver, Colorado., Xu H; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts., Emson C; Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland., Gieger C; Institute of Epidemiology and.; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany., Suhre K; Department of Physiology and Biophysics, Weill Cornell Medicine Qatar, Education City, Doha, Qatar., Graumann J; Philipps-Universität, Marburg, Germany., Jain D; Department of Biostatistics, University of Washington, Seattle, Washington., Conomos MP; Department of Biostatistics, University of Washington, Seattle, Washington., Tracy RP; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont., Guo X; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA (University of California, Los Angeles) Medical Center, Torrance, California., Liu Y; Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina., Johnson WC; Department of Biostatistics, University of Washington, Seattle, Washington., Cornell E; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont., Durda P; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont., Taylor KD; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA (University of California, Los Angeles) Medical Center, Torrance, California., Papanicolaou GJ; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia., Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA (University of California, Los Angeles) Medical Center, Torrance, California., Rennard SI; Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California., Curtis JL; University of Michigan, Ann Arbor, Michigan., Woodruff PG; Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California., Comellas AP; University of Iowa, Iowa City, Iowa., Silverman EK; Channing Division of Network Medicine, and., Crapo JD; National Jewish Health, Denver, Colorado., Larson MG; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.; The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts., Vasan RS; The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.; Division of Preventive Medicine and.; Division of Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Wang TJ; Department of Medicine, UT (University of Texas) Southwestern Medical Center, Dallas, Texas.; Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Correa A; Jackson Heart Study, Department of Medicine, and.; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; and., Sims M; Jackson Heart Study, Department of Medicine, and.; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; and., Wilson JG; Cardiovascular Research Institute.; Jackson Heart Study, Department of Medicine, and., Gerszten RE; Cardiovascular Research Institute.; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts., O'Connor GT; The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.; Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts., Barr RG; Department of Medicine and.; Department of Epidemiology, Columbia University, New York, New York., Couper D; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Dupuis J; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts., Manichaikul A; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia., O'Neal WK; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Tesfaigzi Y; Lovelace Respiratory Research Institute, Albuquerque, New Mexico.; Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Schulz H; Institute of Epidemiology and.; Comprehensive Pneumology Center Munich (CPC-M) as member of the German Center for Lung Research (DZL), Munich, Germany., Bowler RP; National Jewish Health, Denver, Colorado.
Jazyk:	angličtina
Zdroj:	Annals of the American Thoracic Society [Ann Am Thorac Soc] 2023 Aug; Vol. 20 (8), pp. 1124-1135.
DOI:	10.1513/AnnalsATS.202210-857OC
Abstrakt:	Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. Objectives: To determine what proteins and pathways are associated with impaired pulmonary function in a diverse population. Methods: We studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analysis and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline forced expiratory volume in 1 second (FEV 1 ) and FEV 1 /forced vital capacity (FVC). In linear mixed effects models, we investigated the associations of baseline protein levels with rate of FEV 1 decline (ml/yr) in 2,777 participants with up to 7 years of follow-up spirometry. Results: We identified 254 proteins associated with FEV 1 in our discovery analyses, with 80 proteins validated in the Jackson Heart Study. Novel validated protein associations include kallistatin serine protease inhibitor, growth differentiation factor 2, and tumor necrosis factor-like weak inducer of apoptosis (discovery β = 0.0561, Q  = 4.05 × 10 -10 ; β  = 0.0421, Q  = 1.12 × 10 -3 ; and β = 0.0358, Q  = 1.67 × 10 -3 , respectively). In longitudinal analyses within cohorts with follow-up spirometry, we identified 15 proteins associated with FEV 1 decline ( Q  < 0.05), including elafin leukocyte elastase inhibitor and mucin-associated TFF2 (trefoil factor 2; β = -4.3 ml/yr, Q  = 0.049; β = -6.1 ml/yr, Q  = 0.032, respectively). Pathways and processes highlighted by our study include aberrant extracellular matrix remodeling, enhanced innate immune response, dysregulation of angiogenesis, and coagulation. Conclusions: In this study, we identify and validate novel biomarkers and pathways associated with lung function traits in a racially diverse population. In addition, we identify novel protein markers associated with FEV 1 decline. Several protein findings are supported by previously reported genetic signals, highlighting the plausibility of certain biologic pathways. These novel proteins might represent markers for risk stratification, as well as novel molecular targets for treatment of COPD.
Databáze:	MEDLINE
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