title: Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium - an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects.
abstract: BACKGROUND
  Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms.
  
  
  METHODS
  Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 μg/m(3)) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis.
  
  
  RESULTS
  No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge.
  
  
  CONCLUSIONS
  In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden. annelie.behndig@umu.se.
authors: Annelie F
authors: AF
authors: Behndig
authors: Histochemistry Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. karthika.shan718@gmail.com.
authors: Karthika
authors: K
authors: Shanmuganathan
authors: Histochemistry Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. laurawhitmarsh@hotmail.co.uk.
authors: Laura
authors: L
authors: Whitmarsh
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden. nikolai.stenfors@umu.se.
authors: Nikolai
authors: N
authors: Stenfors
authors: Histochemistry Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. joanna.brown@imperial.nhs.uk.
authors: Joanna L
authors: JL
authors: Brown
authors: Histochemistry Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. anthony.frew@bsuh.nhs.uk.
authors: Anthony J
authors: AJ
authors: Frew
authors: MRC - PHE Centre for Environment and Health, Franklin-Wilkins Building, King's College London, London, UK. frank.kelly@kcl.ac.uk.
authors: Frank J
authors: FJ
authors: Kelly
authors: MRC - PHE Centre for Environment and Health, Franklin-Wilkins Building, King's College London, London, UK. ian.mudway@kcl.ac.uk.
authors: Ian S
authors: IS
authors: Mudway
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden. thomas.sandstrom@umu.se.
authors: Thomas
authors: T
authors: Sandström
authors: Histochemistry Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. S.J.Wilson@southampton.ac.uk.|Histochemistry Research Unit, Sir Henry Wellcome Laboratories, Mailpoint 894, Level B, South Block, Southampton General Hospital, Tremona Road, Southampton, UK. S.J.Wilson@southampton.ac.uk.
authors: Susan J
authors: SJ
authors: Wilson
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D017209:Apoptosis; D001249:Asthma / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000473:pathology*; D001999:Bronchoscopy; D016022:Case-Control Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D020545:Respiratory Mucosa / Q000378:metabolism*; D001335:Vehicle Emissions; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D001335:Vehicle Emissions