Ozone Exposure and Dose Delivered to Human Lungs
Condition: Lung Disease
MeSH terms: Lung Diseases
Study type: Observational

Summary: 
      Ozone is an air pollutant formed in at ground level by the chemical reaction between oxygen
      and automobile emissions in the presence of sunlight. The objective of this research is to
      determine how lung size, chemical composition, and normal functioning of the respiratory
      system affect the amount of inhaled ozone that reaches internal sites of tissue irritation
      and damage. To infer the distribution of inhaled ozone within the respiratory system,
      measurements of ozone concentration and air flow are made just outside the nose and mouth of
      healthy subjects who breathe laboratory-generated, ozonated air for about one hour.
      Biochemical composition of respiratory mucus is then inferred from nasal washings made with
      salt water. The amount of ozone that a subject retains in one of these experiments is less
      than the daily exposure in a large city such as New York or Los Angeles.
    

Detailed description: 
      Ozone is a ground-level air pollutant generated primarily by the photochemical reaction of
      automobile emissions. The primary objective of this research is to determine the mechanism by
      which anatomical, physiological, and biochemical factors influence the longitudinal
      distribution of respiratory ozone dose that is delivered to respiratory tissue during a
      particular exposure condition. The specific aims are: 1) test the hypothesis that an increase
      in respiratory flow increases the sensitivity of ozone dose to antioxidant levels in the
      epithelial lining fluid. Ozone absorption will be measured in the nose of healthy nonsmokers
      at different nasal flows while antioxidant levels are measured in nasal liquid; 2) test the
      hypothesis that the continuous inhalation of ozone and co-pollutant gases affects antioxidant
      levels in the epithelial lining fluid, thereby modulating the ozone dose. Ozone absorption
      and antioxidant levels in nasal lavage will be intermittently measured in the nose of healthy
      nonsmokers while these subjects are continuously exposed to clean air, ozone, nitrogen
      dioxide or sulfur dioxide during quiet nasal breathing for two hours; 3) test the hypothesis
      that antioxidant concentrations in epithelial lining fluid are directly related to plasma
      concentrations so that ozone absorption are modulated by the appropriate pharmacological or
      dietary interventions. The longitudinal distribution of ozone absorption will be measured
      throughout the conducting airways of healthy nonsmokers during quiet nasal breathing.
      Measurements will be repeated at baseline conditions, after using probenecid to
      pharmacologically reduce systemic urate, and after vitamin C supplementation to increase
      systemic ascorbate; 4) quantify the reaction kinetics between ozone and antioxidants in
      epithelial lining fluid. Samples of nasal liquid will be reacted with a controlled flow of
      ozone in a miniature bioreactor to determine the reaction rate constant and reaction order of
      ozone consumption; and 5) further develop a single-path diffusion model. Respiratory
      absorption as well as in vitro reaction kinetics data will be used to validate a mathematical
      ozone dosimetry model that can predict the longitudinal distribution of ozone dose to airway
      tissue.
    

Observational model: Natural History
Time perspective: Other
Keywords: ozone uptake; inhalation toxicology; nasal cavities; antioxidants