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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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A. Nemmar, M. F. Hoylaerts, P. H. M. Hoet, D. Dinsdale, T. Smith, H. Xu, J. Vermylen, and B. Nemery
Ultrafine Particles Affect Experimental Thrombosis in an In Vivo Hamster Model
Am. J. Respir. Crit. Care Med., October 1, 2002; 166(7): 998 - 1004.
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 ThoraxHome page
J Douwes, P Gibson, J Pekkanen, and N Pearce
Non-eosinophilic asthma: importance and possible mechanisms
Thorax, July 1, 2002; 57(7): 643 - 648.
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 Eur Respir JHome page
O.S. von Ehrenstein, E. von Mutius, E. Maier, T. Hirsch, D. Carr, W. Schaal, A.A. Roscher, B. Olgemoller, T. Nicolai, and S.K. Weiland
Lung function of school children with low levels of {alpha}1-antitrypsin and tobacco smoke exposure
Eur. Respir. J., June 1, 2002; 19(6): 1099 - 1106.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. A. Jimenez, E. M. Drost, P. S. Gilmour, I. Rahman, F. Antonicelli, H. Ritchie, W. MacNee, and K. Donaldson
PM10-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha
Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L237 - L248.
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H. FUJIMAKI, N. UI, and T. ENDO
Induction of Inflammatory Response of Mice Exposed to Diesel Exhaust Is Modulated by CD4+ and CD8+ T Cells
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1867 - 1873.
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A. J. GHIO, J. G. GILBEY, V. L. ROGGLI, J. H. RICHARDS, J. K. MCGEE, J. L. CARSON, R. B. DEVLIN, and W. E. CASCIO
Diffuse Alveolar Damage after Exposure to an Oil Fly Ash
Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1514 - 1518.
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 Am. J. Respir. Cell Mol. Bio.Home page
V. Bonvallot, A. Baeza-Squiban, A. Baulig, S. Brulant, S. Boland, F. Muzeau, R. Barouki, and F. Marano
Organic Compounds from Diesel Exhaust Particles Elicit a Proinflammatory Response in Human Airway Epithelial Cells and Induce Cytochrome p450 1A1 Expression
Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 515 - 521.
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A. ZANOBETTI and J. SCHWARTZ
Are Diabetics More Susceptible to the Health Effects of Airborne Particles?
Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 831 - 833.
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 Eur Respir JHome page
C. Nordenhall, J. Pourazar, M-C. Ledin, J-O. Levin, T. Sandstrom, and E. Adelroth
Diesel exhaust enhances airway responsiveness in asthmatic subjects
Eur. Respir. J., May 1, 2001; 17(5): 909 - 915.
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A. Sydbom, A. Blomberg, S. Parnia, N. Stenfors, T. Sandstrom, and S-E. Dahlen
Health effects of diesel exhaust emissions
Eur. Respir. J., April 1, 2001; 17(4): 733 - 746.
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S. Kawasaki, H. Takizawa, K. Takami, M. Desaki, H. Okazaki, T. Kasama, K. Kobayashi, K. Yamamoto, K. Nakahara, M. Tanaka, et al.
Benzene-Extracted Components Are Important for the Major Activity of Diesel Exhaust Particles . Effect on Interleukin-8 Gene Expression in Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 419 - 426.
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R. A. PAUWELS, A. S. BUIST, P. M. A. CALVERLEY, C. R. JENKINS, and S. S. HURD
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease . NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary
Am. J. Respir. Crit. Care Med., April 1, 2001; 163(5): 1256 - 1276.
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 Am. J. Respir. Crit. Care Med.Home page
A. J. GHIO, C. KIM, and R. B. DEVLIN
Concentrated Ambient Air Particles Induce Mild Pulmonary Inflammation in Healthy Human Volunteers
Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 981 - 988.
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O. Fahy, H. Hammad, S. Sénéchal, J. Pestel, A.-B. Tonnel, B. Wallaert, and A. Tsicopoulos
Synergistic Effect of Diesel Organic Extracts and Allergen Der p 1 on the Release of Chemokines by Peripheral Blood Mononuclear Cells from Allergic Subjects . Involvement of the MAP Kinase Pathway
Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 247 - 254.
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J. A. NIGHTINGALE, R. MAGGS, P. CULLINAN, L. E. DONNELLY, D. F. ROGERS, R. KINNERSLEY, K. FAN CHUNG, P. J. BARNES, M. ASHMORE, and A. NEWMAN-TAYLOR
Airway Inflammation after Controlled Exposure to Diesel Exhaust Particulates
Am. J. Respir. Crit. Care Med., July 1, 2000; 162(1): 161 - 166.
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S. S. SALVI, C. NORDENHALL, A. BLOMBERG, B. RUDELL, J. POURAZAR, F. J. KELLY, S. WILSON, T. SANDSTRÖM, S. T. HOLGATE, and A. J. FREW
Acute Exposure to Diesel Exhaust Increases IL-8 and GRO-alpha Production in Healthy Human Airways
Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 550 - 557.
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S. HASHIMOTO, Y. GON, I. TAKESHITA, K. MATSUMOTO, I. JIBIKI, H. TAKIZAWA, S. KUDOH, and T. HORIE
Diesel Exhaust Particles Activate p38 MAP Kinase to Produce Interleukin 8 and RANTES by Human Bronchial Epithelial Cells and N-Acetylcysteine Attenuates p38 MAP Kinase Activation
Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 280 - 285.
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A. Seaton, A. Soutar, V. Crawford, R. Elton, S. McNerlan, J. Cherrie, M. Watt, R. Agius, and R. Stout
Particulate air pollution and the blood
Thorax, November 1, 1999; 54(11): 1027 - 1032.
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 CirculationHome page
R. D. Brook, J. R. Brook, B. Urch, R. Vincent, S. Rajagopalan, and F. Silverman
Inhalation of Fine Particulate Air Pollution and Ozone Causes Acute Arterial Vasoconstriction in Healthy Adults
Circulation, April 2, 2002; 105(13): 1534 - 1536.
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