title: Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation.
abstract: BACKGROUND
  Ozone concentrations are predicted to increase over the next 50 years due to global warming and the increased release of precursor chemicals. It is therefore urgent that good, reliable biomarkers are available to quantify the toxicity of this pollutant gas at the population level. Such a biomarker would need to be easily performed, reproducible, economically viable, and reflective of ongoing pathological processes occurring within the lung.
  
  
  METHODS
  We examined whether blood neutrophilia occurred following a controlled ozone challenge and addressed whether this could serve as a biomarker for ozone-induced airway inflammation. Three separate groups of healthy subjects were exposed to ozone (0.2 ppm, 2h) and filtered air (FA) on two separate occasions. Peripheral blood samples were collected and bronchoscopy with biopsy sampling and lavages was performed at 1.5h post exposures in group 1 (n=13), at 6h in group 2 (n=15) and at 18h in group 3 (n=15). Total and differential cell counts were assessed in blood, bronchial tissue and airway lavages.
  
  
  RESULTS
  In peripheral blood, we observed fewer neutrophils 1.5h after ozone compared with the parallel air exposure (-1.1±1.0x10(9) cells/L, p<0.01), at 6h neutrophil numbers were increased compared to FA (+1.2±1.3x10(9) cells/L, p<0.01), and at 18h this response had fully attenuated. Ozone induced a peak in neutrophil numbers at 6h post exposure in all compartments examined, with a positive correlation between the response in blood and bronchial biopsies.
  
  
  CONCLUSIONS
  These data demonstrate a systemic neutrophilia in healthy subjects following an acute ozone exposure, which mirrors the inflammatory response in the lung mucosa and lumen. This relationship suggests that blood neutrophilia could be used as a relatively simple functional biomarker for the effect of ozone on the lung.
authors.affiliation: Division of Medicine/Respiratory Medicine and Allergy, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Bosson
authors.affiliation: Division of Medicine/Respiratory Medicine and Allergy, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.affiliation: Division of Medicine/Respiratory Medicine and Allergy, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden ; Division of Respiratory Medicine and Allergy, Department of Medicine, Ostersund, Sweden.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Stenfors
authors.affiliation: Division of Medicine/Respiratory Medicine and Allergy, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Ragnberth
authors.initials: R
authors.lastname: Helleday
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King's College London, United Kingdom.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kelly
authors.affiliation: Division of Medicine/Respiratory Medicine and Allergy, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Annelie F
authors.initials: AF
authors.lastname: Behndig
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King's College London, United Kingdom.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Mudway
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007964:Leukocytosis / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000473:pathology; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D011014:Pneumonia / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D010126:Ozone