PMID- 10445622
OWN - NLM
STAT- MEDLINE
DCOM- 19990917
LR  - 20190822
IS  - 0903-1936 (Print)
IS  - 0903-1936 (Linking)
VI  - 13
IP  - 6
DP  - 1999 Jun
TI  - Ozone-induced lung function decrements do not correlate with early airway 
      inflammatory or antioxidant responses.
PG  - 1418-28
AB  - 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.
FAU - Blomberg, A
AU  - Blomberg A
AD  - Dept. of Respiratory Medicine and Allergy, University Hospital, Umea, Sweden.
FAU - Mudway, I S
AU  - Mudway IS
FAU - Nordenhall, C
AU  - Nordenhall C
FAU - Hedenstrom, H
AU  - Hedenstrom H
FAU - Kelly, F J
AU  - Kelly FJ
FAU - Frew, A J
AU  - Frew AJ
FAU - Holgate, S T
AU  - Holgate ST
FAU - Sandstrom, T
AU  - Sandstrom T
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur Respir J
JT  - The European respiratory journal
JID - 8803460
RN  - 0 (Antioxidants)
RN  - 0 (E-Selectin)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Oxidants, Photochemical)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 1406-18-4 (Vitamin E)
RN  - 268B43MJ25 (Uric Acid)
RN  - 66H7ZZK23N (Ozone)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Adult
MH  - Antioxidants/*metabolism
MH  - Biopsy
MH  - Bronchi/metabolism/*pathology
MH  - Bronchoalveolar Lavage Fluid/chemistry/cytology
MH  - Bronchoscopy
MH  - Cell Count
MH  - Cross-Over Studies
MH  - E-Selectin/metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Exercise Test
MH  - Female
MH  - Forced Expiratory Volume
MH  - Glutathione/analysis
MH  - HLA-DR Antigens/analysis
MH  - Humans
MH  - Immunohistochemistry
MH  - Inflammation
MH  - Inflammation Mediators/analysis
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Male
MH  - Mast Cells/pathology
MH  - Maximal Midexpiratory Flow Rate
MH  - Oxidants, Photochemical/*adverse effects
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Ozone/*adverse effects
MH  - Respiratory Mechanics/*drug effects
MH  - Single-Blind Method
MH  - Up-Regulation
MH  - Uric Acid/blood
MH  - Vital Capacity
MH  - Vitamin E/blood
EDAT- 1999/08/13 00:00
MHDA- 1999/08/13 00:01
CRDT- 1999/08/13 00:00
PHST- 1999/08/13 00:00 [pubmed]
PHST- 1999/08/13 00:01 [medline]
PHST- 1999/08/13 00:00 [entrez]
AID - 10.1183/09031936.99.13614299 [doi]
PST - ppublish
SO  - Eur Respir J. 1999 Jun;13(6):1418-28. doi: 10.1183/09031936.99.13614299.