Air Pollution, Inflammation, and New Onset Asthma
Condition: Asthma; Lung Diseases
MeSH terms: Asthma; Lung Diseases
Study type: Observational

Summary: 
      To examine air pollution, inflammation and new onset asthma in a large cohort of children in
      southern California.
    

Detailed description: 
      BACKGROUND:

      Ambient air pollution is well accepted as a cause of asthma exacerbations, but its role in
      the etiology of new onset asthma is less clear. Evidence for an etiologic role of ambient air
      pollutants is emerging from epidemiologic studies; however, the ecologic patterns of
      increasing asthma prevalence concurrent with decreasing levels of some pollutants have raised
      questions about the validity of these associations. A better understanding of the biological
      processes that mediate the effects of ambient air pollution on asthma occurrence is likely to
      contribute to answering these questions. Chronic oxidative/nitrosative stress and airway
      inflammation are probably critical processes in asthma etiology and these inter-related
      processes may mediate the increased asthma risk from air pollution.

      This study builds on the existing Asthma Incidence Risk (AIR) study which is an ongoing
      cohort study consisting of 6000 children with new onset asthma. The children live in 12
      communities in Southern California. The communities were chosen to give a range of the key
      ambient air pollutants of ozone, small particulates, NOx, acid vapors and tailpipe emissions.

      DESIGN NARRATIVE:

      The study will use exhaled nitric oxide (eNO) to investigate the role of inflammation and
      oxidative/nitrosative stress in the pathobiology of new onset asthma, with a focus on ambient
      air pollution and genetic susceptibility. The investigators choose ambient pollutants based
      on potential contribution to oxidative/nitrosative stress (O3; particulates (PM10 and PM2.5
      and their chemical constituents, particle counts, NOx (NO and NO2), acid vapors; and fresh
      tailpipe emissions). The primary hypotheses to be assessed in the program of research are: 1)
      children with high ambient air pollution exposures have chronic airway inflammation as
      indicated by elevated eNO. 2) susceptibility to airway inflammation and oxidative/nitrosative
      stress from ambient air pollution varies by NOS1, NOS2. NOS3. GSTM1. GSTP1. NQO1, and HO-1
      haplotypes and functional variants, and 3) children with chronic airway inflammation as
      indicated by elevated eNO are at increased risk for new onset asthma. To test these
      hypotheses, the study builds on the population resource of the Asthma Incidence Risk (AIR)
      study, an ongoing prospective cohort study of the determinants of new onset asthma in 6000
      children in 13 southern California communities, and an extensive program of ambient air
      pollution exposure characterization in these communities. The investigators will measure eNO
      using off-line techniques and genotype 3000 children from the AIR cohort. A number of
      resources will enhance the study, including the Children's Environmental Health Center, the
      Molecular Biology Core of Southern California Environmental Health Sciences Center, and
      expertise from the Southern California Particle Center and Supersite.