Journal article
Systemic Markers of Lung Function and FEV1 Decline across Diverse Cohorts
Annals of the American Thoracic Society, Vol.20(8), pp.1124-1135
08/2023
DOI: 10.1513/AnnalsATS.202210-857OC
PMCID: PMC10405603
PMID: 37351609
Abstract
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? METHODSWe studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analyses and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline FEV1 and FEV1/FVC. In linear mixed effects models we investigated the associations of baseline protein levels with rate of FEV1 decline (mL/year) in 2,777 participants with up to 7 years of follow-up spirometry. RESULTS We identified 254 proteins associated with FEV1 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, β=0.0358, Q=1.67×10-3, respectively). In longitudinal analyses within cohorts with follow up spirometry, we identified 15 proteins associated with FEV1 decline (Q<0.05), including elafin leukocyte elastase inhibitor and mucin-associated trefoil factor 2 (β=-4.3 mL/year, Q=0.049; β=-6.1 mL/year, 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. CONCLUSION In this study, we identify and validate novel biomarkers and pathways associated with lung function traits in a racially diverse population. Additionally, we identify novel protein markers associated with FEV1 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 endophenotyping and risk stratification, as well novel molecular targets for treatment of COPD.
Details
- Title: Subtitle
- Systemic Markers of Lung Function and FEV1 Decline across Diverse Cohorts
- Creators
- Debby Ngo - Beth Israel Deaconess Medical CenterKatherine A Pratte - National Jewish HealthClaudia Flexeder - Ludwig-Maximilians-Universität MünchenHans Petersen - Lovelace Respiratory Research InstituteHong Dang - Lung InstituteYanlin Ma - Office of Public Health GenomicsMichelle J Keyes - Beth Israel Deaconess Medical CenterYan Gao - University of Mississippi Medical CenterShuliang Deng - Beth Israel Deaconess Medical CenterBennet D Peterson - Beth Israel Deaconess Medical CenterLaurie A Farrell - Beth Israel Deaconess Medical CenterVictoria M Bhambhani - Beth Israel Deaconess Medical CenterCesar Palacios - Beth Israel Deaconess Medical CenterJuweria Quadir - Beth Israel Deaconess Medical CenterLucas Gillenwater - University of Colorado Anschutz Medical CampusHanfei Xu - Boston UniversityClaire Emson - AstraZeneca (United Kingdom)Christian Gieger - Helmholtz Zentrum MünchenKarsten Suhre - Weill Cornell Medical College in QatarJohannes Graumann - Philipps University of MarburgDeepti Jain - University of WashingtonMatthew P Conomos - University of WashingtonRussell P Tracy - University of VermontXiuqing Guo - Ronald Reagan UCLA Medical CenterYongmei Liu - Duke UniversityW Craig Johnson - University of WashingtonElaine Cornell - University of VermontPeter Durda - University of Vermont Medical CenterKent D Taylor - Harbor–UCLA Medical CenterGeorge J Papanicolaou - National Heart Lung and Blood InstituteStephen S Rich - University of VirginiaJerome I Rotter - Ronald Reagan UCLA Medical CenterStephen I Rennard - University of Nebraska at OmahaJeffrey L Curtis - University of MichiganPrescott Woodruff - University of California, San FranciscoAlejandro P Comellas - University of IowaEdwin K Silverman - Brigham and Women's HospitalJames D Crapo - National Jewish HealthMartin G Larson - Boston UniversityRamachandran S Vasan - Boston UniversityThomas J Wang - Southwestern Medical CenterAdolfo Correa - University of Mississippi Medical CenterMario Sims - University of Mississippi Medical CenterJames G Wilson - University of Mississippi Medical CenterRobert E Gerszten - Beth Israel Deaconess Healthcare Jamaica Plain, 50975, Cardiology, Jamaica Plain, Massachusetts, United States.George T O'Connor - Boston UniversityR Graham Barr - Columbia UniversityDavid Couper - University of North Carolina at Chapel HillJosée Dupuis - Boston UniversityAni Manichaikul - University of VirginiaWanda O'Neal - University of North Carolina at Chapel HillYohannes Tesfaigzi - Brigham and Women's HospitalHolger Schulz - Helmholtz Zentrum MünchenRussell Bowler - National Jewish Health
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.20(8), pp.1124-1135
- DOI
- 10.1513/AnnalsATS.202210-857OC
- PMID
- 37351609
- PMCID
- PMC10405603
- NLM abbreviation
- Ann Am Thorac Soc
- ISSN
- 2329-6933
- eISSN
- 2325-6621
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL089856, R01HL089897, R01HL132320, R01HL133870, R01HL137995, RO1 HL068111, RO1 HL068111; name: State of New Mexico; name: German Federal Ministry of Education and Research; DOI: 10.13039/100000002, name: Novartis
- Language
- English
- Electronic publication date
- 06/23/2023
- Date published
- 08/2023
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; ICTS; Internal Medicine
- Record Identifier
- 9984438759702771
Metrics
13 Record Views