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Plasma metabolomic signatures of COPD

ABSTRACT: The NIH sponsored multicenter Genetic Epidemiology of COPD (COPDGene (ClinicalTrials.gov Identifier: NCT01969344) study was approved and reviewed by the institutional review board at all participating centers (1). All study participants provided written informed consent. This study enrolled 10,198 non-Hispanic white (NHW) and African American (AA) individuals from January 2008 until April 2011 (Phase 1) who were aged 45-80 with ≥10 pack-year smoking history and no exacerbations for >30 days. In addition, 465 age and gender matched healthy individuals with no history of smoking were enrolled as controls (mostly at Phase 2). From July 2013 to July 2017, 5,697 subjects returned for an in-person 5-year visit. Each in-person visit included spirometry before and after albuterol, quantitative CT imaging of the chest, and blood sampling. From two clinical centers (National Jewish Health and University of Iowa) 162 subjects at Phase 1 (all NHW) and 1,136 subjects (1,040 NHW, 96 AA) participated in an ancillary study in which they provided fresh frozen plasma collected using an 8.5 ml p100 tube (Becton Dickinson) at Phase 2.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Copd

SUBMITTER: Russell Bowler

PROVIDER: ST001443 | MetabolomicsWorkbench | Thu Mar 19 00:00:00 GMT 2020

REPOSITORIES: MetabolomicsWorkbench

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Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells and uncover the complex dynamics of host response to ARIs such as pandemic H1N1. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N=133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. Healthy adults were invited to enroll to be followed for acute respiratory illness (ARI) through two consecutive influenza seasons 2009-2010 and 2010-2011. After subjects provided consent, baseline blood specimens were obtained during enrollment. Subjects were given thermometers and instructions to call and report for evaluation within 48 hours of ARI onset. Those persons who had a new ARI were seen within 48 hours of onset (day 0) and 2, 4, and 6 days later for repeat evaluation, blood specimen collections, and medical care (including the antiviral zanamivir if indicated) and 21 days later for collection of convalescent specimens. Nasal wash samples were collected for virus detection by RT-PCR on day 0 and day 2. Surveillance for influenza was terminated after 5.5 months; all subjects were asked to return for specimen collection and to provide a medical and ARI history in spring of next year. Serum specimens obtained at baseline, day 0 and day 21 visits for illnesses, and the terminal visit were tested simultaneously using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains. Peripheral blood RNA (PaxGene) obtained from blood specimens at each visit were analyzed using Illumina Human HT-12 v4. The study was repeated 2010-2011. A total of 880 arrays, corresponding to 133 individuals, passed quality control and are included in this data set.

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Plasma metabolomic signatures of COPD

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