MULTIDAY EXPOSURE TO O3 IN ASTHMA

点击翻译按钮获取中文摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) Recent data from the applicant's laboratory suggest that persons with asthma have an enhanced inflammatory response to short-term inhalation of ozone. It is not known, however, whether there is progression of the inflammatory response in asthmatic persons with repeated short-term exposures (as would occur during many smog episodes). Progression of ozone-induced inflammation in persons with asthma is likely to increase the risk of acute exacerbation of the disease. Most of the data demonstrating that ozone induces respiratory tract inflammation in healthy and asthmatic subjects has been generated from studies involving bronchoscopy and analysis of bronchoalveolar lavage (BAL) fluid. While analysis if induced sputum has been validated for the investigation of effects of inhaled allergen, it has not been adequately validated for use in air pollution studies. In fact, early reports of the use of the technique in ozone exposure studies suggest that analysis for sputum (which samples the proximal airways) may yield results that conflict with analysis of BAL fluid (which samples the distal lung). In order to validate the use of sputum induction (SI) in the investigation of ozone-induced respiratory tract inflammation and to asses the effects of repeated short-term ozone exposures in asthmatic subjects, three studies are proposed. Study 1 is designed to directly compare analysis of induced sputum to that of BAL fluid after short-term ozone exposure in asthmatic subjects. Study 2 is designed to compare the results obtained from sputum induction and bronchoscopy after repeated short-term exposures to determine whether inflammatory effects are different in proximal airways and distal lung. Study 3 will test the hypothesis that there is a progression of ozone-induced respiratory tract inflammation in asthmatic subjects with repeated short-term exposure using either sputum induction alone or both sputum induction and bronchoscopy, depending on the results of the first two studies. It is anticipated that proposed research will help to validate the issue of sputum induction in air pollution studies and address whether the increased emergency department and hospital utilization of asthmatic persons exposed to ozone is due to acute exacerbation related to enhanced airway inflammation.