Am. J. Respir. Crit. Care Med., Volume 159, Number 2, February 1999, 536-543

Persistent Airway Inflammation but Accommodated Antioxidant and Lung Function Responses after Repeated Daily Exposure to Nitrogen Dioxide

ANDERS BLOMBERG, MAMIDIPUDI T. KRISHNA, RAGNBERTH HELLEDAY, MARGARETA SÖDERBERG, MAJ-CARI LEDIN, FRANK J. KELLY, ANTHONY J. FREW, STEPHEN T. HOLGATE, and THOMAS SANDSTRÖM

Department of Respiratory Medicine and Allergy, University Hospital, and National Institute for Occupational Health/Working Life, Medical Division, Umeå, Sweden; Air Pollution Group/Immunopharmacology Group, University Medicine, Southampton General Hospital, Southampton; and Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom

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.

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