Persistent airway inflammation but accommodated antioxidant and lung function responses after repeated daily exposure to nitrogen dioxide

Am J Respir Crit Care Med. 1999 Feb;159(2):536-43. doi: 10.1164/ajrccm.159.2.9711068.


Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant that may induce deterioration of respiratory health. In this study the effects of repeated daily exposure to NO2 on airway antioxidant status, inflammatory cell and mediator responses, and lung function were examined. Healthy nonsmoking subjects were exposed under controlled conditions to air (once) and to 2 ppm of NO2 for 4 h on four consecutive days. Lung function measurements were made before and immediately after the end of each exposure. Bronchoscopy with endobronchial biopsies, bronchial wash (BW), and bronchoalveolar lavage (BAL) was carried out 1.5 h after the air exposure and after the last exposure to NO2. Repeated NO2 exposure resulted in a decrease in neutrophil numbers in the bronchial epithelium. The BW revealed a twofold increase in content of neutrophils (p < 0.05) and a 1.5-fold increase in myeloperoxidase (MPO) (p < 0.01) indicative of both migration and activation of neutrophils in the airways. After the fourth NO2 exposure, antioxidant status of the airway fluid was unchanged. Significant decrements in FEV1 and FVC were found after the first exposure to NO2, but these attenuated with repeated exposures. Together, these data indicate that four sequential exposures to NO2 result in a persistent neutrophilic inflammation in the airways, whereas changes in pulmonary function and airway antioxidants are resolved. We conclude that NO2 is a proinflammatory air pollutant under conditions of repeated exposure.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Air Pollutants / adverse effects*
  • Antioxidants / metabolism*
  • Biopsy
  • Bronchitis / chemically induced
  • Bronchitis / diagnosis
  • Bronchitis / metabolism*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoconstriction / drug effects
  • Bronchoscopy
  • Chromatography, High Pressure Liquid
  • Cytokines / metabolism
  • Epithelium / immunology
  • Epithelium / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Inhalation Exposure / adverse effects*
  • Macrophages, Alveolar / immunology
  • Male
  • Neutrophils / pathology
  • Nitrogen Dioxide / adverse effects*
  • Oxidants, Photochemical / adverse effects*
  • Respiratory Function Tests
  • T-Lymphocytes / immunology


  • Air Pollutants
  • Antioxidants
  • Cytokines
  • Oxidants, Photochemical
  • Nitrogen Dioxide