title: Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses.
abstract: This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise following ozone challenge. Thirteen healthy nonsmoking subjects were exposed in a single blinded, crossover control fashion to 0.2 parts per million (ppm) O3 and filtered air for 2 h, using a standard intermittent exercise and rest protocol. Lung function was assessed pre- and immediately post-exposure. Bronchoscopy was performed with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range of antioxidants and oxidative damage markers in BW and BAL fluid samples. There was a significant upregulation after O3 exposure in the expression of vascular endothelial P-selectin (p<0.005) and intercellular adhesion molecule-1 (p<0.005). This was associated with a 2-fold increase in submucosal mast cells (p<0.005) in biopsy samples, without evidence of neutrophilic inflammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p<0.005), with an activation of the remaining macrophage subset (2.5-fold increase in % human leukocyte antigen (HLA)-DR+ cells, p<0.005). In addition, exposure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) concentrations, in BW and BAL fluid respectively (p<0.05), with alterations in urate and alpha-tocopherol plasma/RTLF partitioning ratios (p<0.05). Spirometry showed reductions in forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.01), with evidence of small airway narrowing using forced expiratory flow values (p<0.005). Evidence was found of O3-induced early adhesion molecule upregulation, increased submucosal mast cell numbers and alterations to the respiratory tract lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed. The results therefore indicate that the initial lung function decrements are not predictive of, or causally related to the O3-induced inflammatory events in normal human subjects.
authors.affiliation: Dept. of Respiratory Medicine and Allergy, University Hospital, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Blomberg
authors.forename: I S
authors.initials: IS
authors.lastname: Mudway
authors.forename: C
authors.initials: C
authors.lastname: Nordenhäll
authors.forename: H
authors.initials: H
authors.lastname: Hedenström
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: A J
authors.initials: AJ
authors.lastname: Frew
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: T
authors.initials: T
authors.lastname: Sandström
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001999:Bronchoscopy; D002452:Cell Count; D018592:Cross-Over Studies; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume; D005978:Glutathione / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D018836:Inflammation Mediators / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008450:Maximal Midexpiratory Flow Rate; D010083:Oxidants, Photochemical / Q000009:adverse effects*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010126:Ozone / Q000009:adverse effects*; D015656:Respiratory Mechanics / Q000187:drug effects*; D016037:Single-Blind Method; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood; D014797:Vital Capacity; D014810:Vitamin E / Q000097:blood
chemical_list: D000975:Antioxidants; D019040:E-Selectin; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D010083:Oxidants, Photochemical; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; D014527:Uric Acid; D010126:Ozone; D005978:Glutathione