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Am. J. Respir. Crit. Care Med., Volume 156, Number 2, August 1997, 418-424

The Inflammatory Effects of 2 ppm NO2 on the Airways of Healthy Subjects

ANDERS BLOMBERG, MAMIDIPUDI T. KRISHNA, VINCENZO BOCCHINO, GIAN LUCA BISCIONE, JANIS K. SHUTE, FRANK J. KELLY, ANTHONY J. FREW, STEPHEN T. HOLGATE, and THOMAS SANDSTRÖM

Department of Pulmonary Medicine and Allergology, University Hospital of Northern Sweden and National Institute for Working Life, Medical Division, Umeå, Sweden; University Medicine, Southampton General Hospital; Southampton; and Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom

Nitrogen dioxide (NO2) is a free radical and a common oxidant in polluted air. Here we present data on the time course of inflammation after NO2 exposure, as reflected in bronchial biopsy and airway lavage specimens. Healthy, nonsmoking subjects were exposed to air or 2 ppm NO2 for 4 h in random order on separate occasions. Endobronchial biopsies, bronchial washing (BW), and bronchoalveolar lavage (BAL) were done at 1.5 h (n = 15) or 6 h (n = 15) after exposure. In BW, exposure to NO2 induced a 1.5-fold increase in interleukin-8 (IL-8) (p < 0.05) at 1.5 h and a 2.5-fold increase in neutrophils (p < 0.01) at 6 h. In BAL fluid (BALF), small increases were observed in CD45RO+ lymphocytes, B-cells, and natural killer (NK) cells only. Immunohistologic examination of bronchial biopsy specimens showed no signs of upregulation of adhesion molecules, and failed to reveal any significant changes in inflammatory cells at either time point after NO2 exposure. In summary, NO2 induced a neutrophilic inflammation in the airways that was detectable in BW at 6 h after NO2 exposure. The increase in neutrophils could be related to the enhanced IL-8 secretion observed at 1.5 h after exposure. The absence of adhesion-molecule upregulation or cellular inflammation in mucosal biopsy specimens indicates that the major site of inflammation following exposure to NO2 may be in the smaller airways and not in the alveoli.




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