Rationale and design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis study. Alpha-1 protocol

Details

• Personal Author:
  Adonteng-Boateng P ; Argula R ; Arnold D ; Atnes G ; Balasubramani GK ; Barbosa E ; Barkes B ; Becich M ; Becich MJ ; Beiko T ; Berry C ; Bhakta N ; Boes R ; Bowler R ; Breslin L ; Brooks M ; Brown K ; Bruno S ; Bushman F ; Carrano D ; Casanova N ; Chen E ; Collman R ; Dawod Y ; Drake W ; Elliott J ; Fitzgerald A ; Garcia J ; Gardo L ; Ghedin E ; Gibson K ; Gillespie M ; Gulati M ; Hamzeh N ; Herzog E ; Ho M ; Hochheiser HS ; Imai I ; Kaminski N ; Kanukala S ; Knepler J Jr. ; Knox K ; Koth LL ; Kreider M ; Leader JK ; Li L ; MacPhail K ; Maier L ; Methe B ; Methé BA ; Moller D ; Morris A ; Mroz P ; Navarrete J ; Oliva I ; O'Neal S ; Paoletti L ; Patterson K ; Ramstein J ; Riggs T ; Rissmiller R ; Robinson R ; Rossman M ; Sandhaus R ; Sandhaus RA ; Schnapp L ; Sciurba F ; Senior RM ; Silveira L ; Song Z ; Strange C ; Sun S ; Sweiss N ; Walker D ; Wisniewski SR ; Woodford D ; Woodruff P ; Zhang Y
• Corporate Authors:
  Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis
• Description:
  Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis A1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01832220). [Description provided by NIOSH]
• Subjects:
  Genetics Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Lung Bronchoalveolar Lavage COPD Emphysema Genes Humans Microbiome Phenotype Pulmonary System Disorders Respiratory System Disorders Statistical Analysis

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• ISSN:
  2329-6933
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; Connecticut ; Maryland ; Missouri ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 7 ; OSHA Region 8 ; Pennsylvania ; South Carolina
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  12
• Issue:
  10
• NIOSHTIC Number:
  nn:20047489
• Citation:
  Ann Am Thorac Soc 2015 Oct; 12(10):1551-1560
• Contact Point Address:
  Charlie Strange, M.D., Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, MSC 630, Charleston, SC 29401
• Email:
  strangec@musc.edu
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Construction ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Annals of the American Thoracic Society
• End Date:
  20260831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:29f36bf0f52de78d0efd51b003e1be589621387e33420bd893afdd6b55eb3f83a493b8b752e0f3c85137927d495a5df405a023020b847504f29fa471fc2bb162
• Download URL:
  https://stacks.cdc.gov/view/cdc/202543/cdc_202543_DS1.pdf
• File Type:
  [PDF - 592.61 KB ]