JR Balmes, LL Chen, C Scannell, I Tager, D Christian, PQ Hearne, T Kelly and RM Aris
Center for Occupational and Environmental Health, Cardiovascular Research Institute, University of California, San Francisco 94143-0854, USA.

In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least- sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most- sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.

This article has been cited by other articles:

				M. C. Liu, R. J. Riese, K. Van Gundy, P. Norwood, B. E. Sullivan, P. F. Schwartz, and J. G. Teeter Effects of inhaled human insulin on airway lining fluid composition in adults with diabetes Eur. Respir. J., July 1, 2008; 32(1): 180 - 188. [Abstract] [Full Text] [PDF]

				J. Bosson, S. Barath, J. Pourazar, A. F. Behndig, T. Sandstrom, A. Blomberg, and E. Adelroth Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans Eur. Respir. J., June 1, 2008; 31(6): 1234 - 1240. [Abstract] [Full Text] [PDF]

				S. E. Alexeeff, A. A. Litonjua, H. Suh, D. Sparrow, P. S. Vokonas, and J. Schwartz Ozone Exposure and Lung Function: Effect Modified by Obesity and Airways Hyperresponsiveness in the VA Normative Aging Study Chest, December 1, 2007; 132(6): 1890 - 1897. [Abstract] [Full Text] [PDF]

				T. Islam, W J. Gauderman, K. Berhane, R. McConnell, E. Avol, J. M Peters, and F. D Gilliland Relationship between air pollution, lung function and asthma in adolescents Thorax, November 1, 2007; 62(11): 957 - 963. [Abstract] [Full Text] [PDF]

				C. Chen, M. Arjomandi, I. B. Tager, N. Holland, and J. R. Balmes Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes Eur. Respir. J., October 1, 2007; 30(4): 677 - 683. [Abstract] [Full Text] [PDF]

				J. W. Hollingsworth, S. R. Kleeberger, and W. M. Foster Ozone and Pulmonary Innate Immunity Proceedings of the ATS, July 1, 2007; 4(3): 240 - 246. [Abstract] [Full Text] [PDF]

				A. J. Ghio, J. L. Turi, M. C. Madden, L. A. Dailey, J. D. Richards, J. G. Stonehuerner, D. L. Morgan, S. Singleton, L. M. Garrick, and M. D. Garrick Lung injury after ozone exposure is iron dependent Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L134 - L143. [Abstract] [Full Text] [PDF]

				M. Arjomandi, A. Witten, E. Abbritti, K. Reintjes, I. Schmidlin, W. Zhai, C. Solomon, and J. Balmes Repeated Exposure to Ozone Increases Alveolar Macrophage Recruitment into Asthmatic Airways Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 427 - 432. [Abstract] [Full Text] [PDF]

				O. Holz, R. Tal-Singer, F. Kanniess, K. J. Simpson, A. Gibson, R. S. J. Vessey, S. Janicki, H. Magnussen, R. A. Jorres, and K. Richter Validation of the Human Ozone Challenge Model as a Tool for Assessing Anti-Inflammatory Drugs in Early Development J. Clin. Pharmacol., May 1, 2005; 45(5): 498 - 503. [Abstract] [Full Text] [PDF]

				J. W. Hollingsworth, B. J. Chen, D. M. Brass, K. Berman, M. D. Gunn, D. N. Cook, and D. A. Schwartz The Critical Role of Hematopoietic Cells in Lipopolysaccharide-induced Airway Inflammation Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 806 - 813. [Abstract] [Full Text] [PDF]

				J. Schwartz How Sensitive Is the Association between Ozone and Daily Deaths to Control for Temperature? Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 627 - 631. [Abstract] [Full Text] [PDF]

				R. A. Johnston, J. P. Mizgerd, and S. A. Shore CXCR2 is essential for maximal neutrophil recruitment and methacholine responsiveness after ozone exposure Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L61 - L67. [Abstract] [Full Text] [PDF]

				A. Gryparis, B. Forsberg, K. Katsouyanni, A. Analitis, G. Touloumi, J. Schwartz, E. Samoli, S. Medina, H. R. Anderson, E. M. Niciu, et al. Acute Effects of Ozone on Mortality from the "Air Pollution and Health: A European Approach" Project Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1080 - 1087. [Abstract] [Full Text] [PDF]

				J. W. Hollingsworth II, D. N. Cook, D. M. Brass, J. K. L. Walker, D. L. Morgan, W. M. Foster, and D. A. Schwartz The Role of Toll-like Receptor 4 in Environmental Airway Injury in Mice Am. J. Respir. Crit. Care Med., July 15, 2004; 170(2): 126 - 132. [Abstract] [Full Text] [PDF]

				M. K. Pulfer and R. C. Murphy Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant J. Biol. Chem., June 18, 2004; 279(25): 26331 - 26338. [Abstract] [Full Text] [PDF]

				L. L. Chen, I. B. Tager, D. B. Peden, D. L. Christian, R. E. Ferrando, B. S. Welch, and J. R. Balmes Effect of Ozone Exposure on Airway Responses to Inhaled Allergen in Asthmatic Subjects Chest, June 1, 2004; 125(6): 2328 - 2335. [Abstract] [Full Text] [PDF]

				I. S. Mudway and F. J. Kelly An Investigation of Inhaled Ozone Dose and the Magnitude of Airway Inflammation in Healthy Adults Am. J. Respir. Crit. Care Med., May 15, 2004; 169(10): 1089 - 1095. [Full Text] [PDF]

				A. Blomberg, I. Mudway, M. Svensson, A. Hagenbjork-Gustafsson, L. Thomasson, R. Helleday, X. Dumont, B. Forsberg, G. Nordberg, and A. Bernard Clara cell protein as a biomarker for ozone-induced lung injury in humans Eur. Respir. J., December 1, 2003; 22(6): 883 - 888. [Abstract] [Full Text] [PDF]

				M. Nickmilder, S. Carbonnelle, C. de Burbure, and A. Bernard Relationship Between Ambient Ozone and Exhaled Nitric Oxide in Children JAMA, November 19, 2003; 290(19): 2546 - 2547. [Full Text] [PDF]

				M. J. Hazucha, L. J. Folinsbee, and P. A. Bromberg Distribution and reproducibility of spirometric response to ozone by gender and age J Appl Physiol, November 1, 2003; 95(5): 1917 - 1925. [Abstract] [Full Text] [PDF]

				B. Vagaggini, M. Taccola, S. Cianchetti, S. Carnevali, M. L. Bartoli, E. Bacci, F. L. Dente, A. Di Franco, D. Giannini, and P. L. Paggiaro Ozone Exposure Increases Eosinophilic Airway Response Induced by Previous Allergen Challenge Am. J. Respir. Crit. Care Med., October 15, 2002; 166(8): 1073 - 1077. [Abstract] [Full Text] [PDF]

				B. VAGAGGINI, M. TACCOLA, I. CONTI, S. CARNEVALI, S. CIANCHETTI, M. L. BARTOLI, E. BACCI, F. L. DENTE, A. DI FRANCO, D. GIANNINI, et al. Budesonide Reduces Neutrophilic but Not Functional Airway Response to Ozone in Mild Asthmatics Am. J. Respir. Crit. Care Med., December 15, 2001; 164(12): 2172 - 2176. [Abstract] [Full Text] [PDF]

				J. M. SAMET, G. E. HATCH, D. HORSTMAN, S. STECK-SCOTT, L. ARAB, P. A. BROMBERG, M. LEVINE, W. F. MCDONNELL, and R. B. DEVLIN Effect of Antioxidant Supplementation on Ozone-Induced Lung Injury in Human Subjects Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 819 - 825. [Abstract] [Full Text] [PDF]

				H.-Y. Cho, L.-Y. Zhang, and S. R. Kleeberger Ozone-induced lung inflammation and hyperreactivity are mediated via tumor necrosis factor-{alpha} receptors Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L537 - L546. [Abstract] [Full Text] [PDF]

				W. M. Foster, R. H. Brown, K. Macri, and C. S. Mitchell Bronchial reactivity of healthy subjects: 18-20 h postexposure to ozone J Appl Physiol, November 1, 2000; 89(5): 1804 - 1810. [Abstract] [Full Text] [PDF]

				R. A. JÖRRES, O. HOLZ, W. ZACHGO, P. TIMM, S. KOSCHYK, B. MÜLLER, F. GRIMMINGER, W. SEEGER, F. J. KELLY, C. DUNSTER, et al. The Effect of Repeated Ozone Exposures on Inflammatory Markers in Bronchoalveolar Lavage Fluid and Mucosal Biopsies Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1855 - 1861. [Abstract] [Full Text]

				S. R. Kleeberger, S. Reddy, L.-Y. Zhang, and A. E. Jedlicka Genetic Susceptibility to Ozone-Induced Lung Hyperpermeability . Role of Toll-Like Receptor 4 Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 620 - 627. [Abstract] [Full Text]

				J. A. NIGHTINGALE, D. F. ROGERS, K. FAN CHUNG, and P. J. BARNES No Effect of Inhaled Budesonide on the Response to Inhaled Ozone in Normal Subjects Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 479 - 486. [Abstract] [Full Text]

				R. M. KAFOURY, W. A. PRYOR, G. L. SQUADRITO, M. G. SALGO, X. ZOU, and M. FRIEDMAN Induction of Inflammatory Mediators in Human Airway Epithelial Cells by Lipid Ozonation Products Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 1934 - 1942. [Abstract] [Full Text]

				J. A Nightingale, D. F Rogers, and P. J Barnes Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects Thorax, December 1, 1999; 54(12): 1061 - 1069. [Abstract] [Full Text]

				I. Jaspers, J. M. Samet, and W. Reed Arsenite Exposure of Cultured Airway Epithelial Cells Activates kappa B-dependent Interleukin-8 Gene Expression in the Absence of Nuclear Factor-kappa B Nuclear Translocation J. Biol. Chem., October 22, 1999; 274(43): 31025 - 31033. [Abstract] [Full Text] [PDF]

				H. S. JENKINS, J. L. DEVALIA, R. L. MISTER, A. M. BEVAN, C. RUSZNAK, and R. J. DAVIES The Effect of Exposure to Ozone and Nitrogen Dioxide on the Airway Response of Atopic Asthmatics to Inhaled Allergen . Dose- and Time-dependent Effects Am. J. Respir. Crit. Care Med., July 1, 1999; 160(1): 33 - 39. [Abstract] [Full Text]

				O. HOLZ, R. A. JÖRRES, P. TIMM, M. MÜCKE, K. RICHTER, S. KOSCHYK, and H. MAGNUSSEN Ozone-induced Airway Inflammatory Changes Differ between Individuals and Are Reproducible Am. J. Respir. Crit. Care Med., March 1, 1999; 159(3): 776 - 784. [Abstract] [Full Text]

				N. Noviski, J. P. Brewer, W. A. Skornik, S. J. Galli, J. M. Drazen, and T. R. Martin Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice J Appl Physiol, January 1, 1999; 86(1): 202 - 210. [Abstract] [Full Text] [PDF]

				D. L. CHRISTIAN, L. L. CHEN, C. H. SCANNELL, R. E. FERRANDO, B. S. WELCH, and J. R. BALMES Ozone-induced Inflammation Is Attenuated with Multiday Exposure Am. J. Respir. Crit. Care Med., August 1, 1998; 158(2): 532 - 537. [Abstract] [Full Text] [PDF]

				L. LIU, J. A. LEECH, R. B. URCH, and F. S. SILVERMAN In Vivo Salicylate Hydroxylation: A Potential Biomarker for Assessing Acute Ozone Exposure and Effects in Humans Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1405 - 1412. [Abstract] [Full Text]

				A. TORRES, M. J. UTELL, P. E. MOROW, K. Z. VOTER, J. C. WHITIN, C. COX, R. JOHN LOONEY, D. M. SPEERS, Y. TSAI, and M. W. FRAMPTON Airway Inflammation in Smokers and Nonsmokers with Varying Responsiveness to Ozone Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 728 - 736. [Abstract] [Full Text] [PDF]

				M. T. KRISHNA, D. SPRINGALL, Q.-H. MENG, N. WITHERS, D. MACLEOD, G. BISCIONE, A. FREW, J. POLAK, and S. HOLGATE Effects of Ozone on Epithelium and Sensory Nerves in the Bronchial Mucosa of Healthy Humans Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 943 - 950. [Abstract] [Full Text] [PDF]