title: Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.
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.
authors.affiliation: 1 Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: David R
authors.initials: DR
authors.lastname: Moller
authors.affiliation: 2 Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Koth
authors.affiliation: 3 National Jewish Health, School of Medicine, Denver, Colorado; University of Colorado, Aurora, Colorado.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
authors.affiliation: 4 School of Medicine and.
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
authors.affiliation: 5 Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Wonder
authors.initials: W
authors.lastname: Drake
authors.affiliation: 6 University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Milton
authors.initials: M
authors.lastname: Rossman
authors.affiliation: 4 School of Medicine and.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Leader
authors.affiliation: 6 University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Collman
authors.affiliation: 3 National Jewish Health, School of Medicine, Denver, Colorado; University of Colorado, Aurora, Colorado.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Hamzeh
authors.affiliation: 7 University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
authors.forename: Nadera J
authors.initials: NJ
authors.lastname: Sweiss
authors.affiliation: 4 School of Medicine and.
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 9 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Scott
authors.initials: S
authors.lastname: O'Neal
authors.affiliation: 10 Barnes-Jewish Hospital/Washington University, St. Louis, Missouri.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Senior
authors.affiliation: 4 School of Medicine and.
authors.forename: Michael
authors.initials: M
authors.lastname: Becich
authors.affiliation: 4 School of Medicine and.
authors.forename: Harry S
authors.initials: HS
authors.lastname: Hochheiser
authors.affiliation: 8 Yale School of Medicine, New Haven, Connecticut; and.
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.affiliation: 9 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.affiliation: 4 School of Medicine and.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Gibson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D015331:Cohort Studies; D005260:Female; D023281:Genomics; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D012107:Research Design; D012129:Respiratory Function Tests; D012507:Sarcoidosis / Q000145:classification* / Q000175:diagnosis*; D057566:Self Report; D014057:Tomography, X-Ray Computed; D055815:Young Adult; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis*
chemical_list: D015415:Biomarkers
keywords: bronchoalveolar lavage; lung; microbiome; phenotype; transcriptome