title: Effect of GST variants on lung function following diesel exhaust and allergen co-exposure in a controlled human crossover study.
abstract: Isolated exposure to diesel exhaust (DE) or allergen can cause decrements in lung function that are impacted by the presence of genetic variants in the glutathione-S-transferase (GST) family but the effect of GST interactions with DE-allergen co-exposure on lung function is unknown. We aimed to assess the impact of DE and allergen co-exposure on lung function and the influence of GSTM1 or GSTT1 variation
  
  
  
  We used a blinded crossover study design with 17 atopic subjects exposed to filtered air (FA; the control for DE) or DE for 2h. One hour following each exposure to DE or FA, bronchoscopy was performed to deliver a diluent-controlled segmental allergen challenge (SAC). Methacholine challenge and forced expiratory volume in 1s (FEV1) was performed pre-exposure (baseline airway responsiveness) and 24h post-exposure (effect of co-exposure). Additionally, FEV1 was performed hourly after DE/FA exposure and protein carbonyl content was measured in plasma as an oxidative stress marker.
  
  
  
  Changes in FEV1 from baseline were dependent on time following allergen exposure. DE, as opposed to FA, led to a significant change in FEV1 at 2h post-allergen exposure in GSTT1 variants only (24.5±19.6% reduction in GSTT1 null individuals vs. 9.2±7.3% reduction in GSTT1 present individuals). Moreover, plasma protein carbonyl level 4h after co-exposure was higher in the individuals who have the GSTT1 null genotype.
  
  
  
  This suggests a gene-environment interaction that endangers susceptible populations co-exposed to DE and allergen.
authors.affiliation: Institute of Environmental Science, Shanxi University, Taiyuan, China; Department of Medicine, Division of Respiratory Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, Canada; Institute for Heart and Lung Health, University of British Columbia, Vancouver, Canada.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Hirota
authors.affiliation: Center for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, Canada; Institute for Heart and Lung Health, University of British Columbia, Vancouver, Canada. Electronic address: carlsten@mail.ubc.ca.
authors.forename: Chris
authors.initials: C
authors.lastname: Carlsten
mesh_terms: D000328:Adult; D000485:Allergens / Q000633:toxicity; D001985:Bronchial Provocation Tests; D001999:Bronchoscopy; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D059647:Gene-Environment Interaction; D005838:Genotype; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001335:Vehicle Emissions / Q000633:toxicity; D055815:Young Adult
chemical_list: D000485:Allergens; D005982:Glutathione Transferase; D001335:Vehicle Emissions; C413545:glutathione S-transferase T1
keywords: Air pollution; Airway hyperresponsiveness; Atopy; Diesel exhaust; GSTM1; GSTT1