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Am. J. Respir. Crit. Care Med., Volume 159, Number 3, March 1999, 702-709

Acute Inflammatory Responses in the Airways and Peripheral Blood After Short-Term Exposure to Diesel Exhaust in Healthy Human Volunteers

SUNDEEP SALVI, ANDERS BLOMBERG, BERTIL RUDELL, FRANK KELLY, THOMAS SANDSTRÖM, STEPHEN T. HOLGATE, and ANTHONY FREW

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

Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.




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