Physician-Scientist Pilot Projects 2006
The following proposals were approved for funding in 2006:
Project 1: Effects of Diesel Exhaust Particles on Influenza-induced Nasal Inflammation in Allergic Rhinitics
PI:Terry L. Noah, MD; Associate Professor and Division Chief, UNC Pediatric Pulmonology
Project 2: Metals and Biomarkers of Joint Metabolism in a Community-based Cohort: The Johnston County Osteoarthritis Project
PI: Joanne M. Jordan, MD MPH; Associate Professor, Medicine and Orthopaedics, and Adjunct Associate Professor, Epidemiology
Phys-Sci Project 1-2006:
Effects of Diesel Exhaust Particles on Influenza-induced Nasal Inflammation in Allergic Rhinitics
Principal Investigator: Terry L. Noah, MD; Associate Professor and Division Chief, UNC Pediatric Pulmonology
Abstract
Asthma is exacerbated commonly by viruses and pollutants, but little is currently known about the effects of interaction of these factors on allergic or asthmatic inflammation. Our preliminary data suggest that exposure of human respiratory epithelium to DEP causes increased infectivity for influenza virus and increased expression of inflammatory factors in vitro and in mice in vivo. We propose a clinical/translational study testing the hypothesis that allergic rhinitics (AR) have enhanced inflammatory responses to live attenuated influenza virus (LAIV) following diesel DEP exposures, through a randomized, prospective comparison study between cohorts of AR subjects receiving DEP/placebo, followed by LAIV. Primary outcomes will be production of IL-13 and ECP, two markers of allergic inflammation, at the mucosal surface. A large number of secondary outcomes will be assessed including inflammatory cells, other cytokines and mediators, expression profiles for Phase II network genes in biopsied nasal epithelium, and the effect of genotype for the antioxidant gene GTSM1. The relevance of this work to public health is the possibility of identifying novel antioxidant strategies for reducing the impact of inhaled oxidant pollutants on virus-induced asthma exacerbations. This project would generate preliminary data for an NIH application extending our initial findings and testing potential therapeutic interventions.
Phys-Sci Project 2-2006:
Metals and Biomarkers of Joint Metabolism in a Community-based Cohort: The Johnston County Osteoarthritis Project
Principal Investigator: Joanne M. Jordan, MD MPH; Associate Professor, Medicine and Orthopaedics, and Adjunct Associate Professor, Epidemiology
Abstract
Accumulating toxicological data suggest that exposure to metals results in skeletal and joint toxicity. Yet, little attention has been directed to metals in relationship to osteoarthritis (OA), the most common cause of arthritis, characterized by profound bone and cartilage disruption. The primary objective is to understand how toxic metals (lead [Pb] and mercury [Hg]) affect OA. This proposal leverages bio-specimens and data from The Johnston County Osteoarthritis Project, a population-based prospective cohort of OA in African-American and White adults, in which associations between Pb, Hg, and selenium (Se) and OA were seen. Using linear regression and analysis of covariance, we will investigate associations between whole blood Pb and toenail Hg and 5 biomarkers of joint tissue metabolism related to OA pathophysiology in 376 men. Together with extant data on 375 women, we will examine factors likely to interfere with mechanisms of metal-associated OA (age, sex, and race) and identify factors (e.g., Se) that may counteract adverse responses to metal exposures. Further, this proposal will provide preliminary data for planned NIH proposals to examine additional metals in OA.
