Journal article
Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol
Annals of the American Thoracic Society, Vol.12(10), pp.1561-1571
10/2015
DOI: 10.1513/AnnalsATS.201503-172OT
PMCID: PMC4627423
PMID: 26193069
Abstract
Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.
Details
- Title: Subtitle
- Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol
- Creators
- David R Moller - 1 Johns Hopkins University School of Medicine, Baltimore, MarylandLaura L Koth - 2 Department of Medicine, University of California, San Francisco, San Francisco, CaliforniaLisa A Maier - 3 National Jewish Health, School of Medicine, Denver, Colorado; University of Colorado, Aurora, ColoradoAlison Morris - 4 School of Medicine andWonder Drake - 5 Vanderbilt University School of Medicine, Nashville, TennesseeMilton Rossman - 6 University of Pennsylvania Perelman School of Medicine, Philadelphia, PennsylvaniaJoseph K Leader - 4 School of Medicine andRonald G Collman - 6 University of Pennsylvania Perelman School of Medicine, Philadelphia, PennsylvaniaNabeel Hamzeh - 3 National Jewish Health, School of Medicine, Denver, Colorado; University of Colorado, Aurora, ColoradoNadera J Sweiss - 7 University of Illinois Hospital and Health Sciences System, Chicago, IllinoisYingze Zhang - 4 School of Medicine andScott O'Neal - 9 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaRobert M Senior - 10 Barnes-Jewish Hospital/Washington University, St. Louis, MissouriMichael Becich - 4 School of Medicine andHarry S Hochheiser - 4 School of Medicine andNaftali Kaminski - 8 Yale School of Medicine, New Haven, Connecticut; andStephen R Wisniewski - 9 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaKevin F Gibson - 4 School of Medicine andGRADS Sarcoidosis Study Group
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.12(10), pp.1561-1571
- DOI
- 10.1513/AnnalsATS.201503-172OT
- PMID
- 26193069
- PMCID
- PMC4627423
- NLM abbreviation
- Ann Am Thorac Soc
- ISSN
- 2325-6621
- eISSN
- 2325-6621
- Publisher
- American Thoracic Society
- Grant note
- U01 HL112711 / NHLBI NIH HHS U01 HL112707 / NHLBI NIH HHS U01 HL112702 / NHLBI NIH HHS 5 U24 OH009077 / NIOSH CDC HHS UL1 RR025780 / NCRR NIH HHS U24 OH009077 / NIOSH CDC HHS R01 HL114587 / NHLBI NIH HHS U01 HL112694 / NHLBI NIH HHS UL1 TR000005 / NCATS NIH HHS UL1 TR001082 / NCATS NIH HHS R01 HL110883 / NHLBI NIH HHS U01 HL112695 / NHLBI NIH HHS U01 HL112712 / NHLBI NIH HHS U54 9 UL1 TR000005 / NCATS NIH HHS U01 HL112708 / NHLBI NIH HHS UL1 RR029882 / NCRR NIH HHS UL1 TR000371 / NCATS NIH HHS U01 HL112696 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/2015
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094540202771
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