title: Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.
abstract: BACKGROUND
  Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood.
  
  
  OBJECTIVE
  To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects.
  
  
  METHODS
  18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points.
  
  
  RESULTS
  Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells.
  
  
  CONCLUSIONS
  Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.
  
  
  BACKGROUND
  NCT01792232.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, British Columbia, Canada Centre for Heart Lung Innovation, Institute for Heart and Lung Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Carlsten
authors.affiliation: Division of Medicine/Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mandy
authors.initials: M
authors.lastname: Pui
authors.affiliation: Division of Medicine/Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandstrom
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sze Wing
authors.initials: SW
authors.lastname: Wong
authors.affiliation: Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Alexis
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, British Columbia, Canada Centre for Heart Lung Innovation, Institute for Heart and Lung Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hirota
mesh_terms: D000328:Adult; D000485:Allergens / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D018932:Chemokine CCL2 / Q000276:immunology; D047150:Eosinophil Cationic Protein / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D019570:Inhalation Exposure / Q000009:adverse effects*; D015848:Interleukin-5 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000485:Allergens; D015415:Biomarkers; D018932:Chemokine CCL2; D005742:Gasoline; D015848:Interleukin-5; D016209:Interleukin-8; D001335:Vehicle Emissions; D007073:Immunoglobulin E; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D047150:Eosinophil Cationic Protein
keywords: Allergic lung disease; Occupational Lung Disease