title: Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects.
abstract: BACKGROUND
  Allergen exposure and air pollution are two risk factors for asthma development and airway inflammation that have been examined extensively in isolation. The impact of combined allergen and diesel exhaust exposure has received considerably less attention. Diesel exhaust (DE) is a major contributor to ambient particulate matter (PM) air pollution, which can act as an adjuvant to immune responses and augment allergic inflammation. We aimed to clarify whether DE increases allergen-induced inflammation and cellular immune response in the airways of atopic human subjects.
  
  
  METHODS
  Twelve atopic subjects were exposed to DE 300 μg.m(-3) or filtered air for 2 h in a blinded crossover study design with a four-week washout period between arms. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline (vehicle control) via segmental challenge. Forty-eight hours post-allergen or control exposure, bronchial biopsies were collected. The study design generated 4 different conditions: filtered air + saline (FAS), DE + saline (DES), filtered air + allergen (FAA) and DE + allergen (DEA). Biopsies sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa.
  
  
  RESULTS
  The percent positivity for tryptase expression and ECP expression remained unchanged in the bronchial submucosa in all conditions. CD4 % positive staining in DEA (0.311 ± 0.060) was elevated relative to FAS (0.087 ± 0.018; p = 0.035). IL-4% positive staining in DEA (0.548 ± 0.143) was elevated relative to FAS (0.127 ± 0.062; p = 0.034). CD138 % positive staining in DEA (0.120 ± 0.031) was elevated relative to FAS (0.017 ± 0.006; p = 0.015), DES (0.044 ± 0.024; p = 0.040), and FAA (0.044 ± 0.008; p = 0.037). CD138% positive staining in FAA (0.044 ± 0.008) was elevated relative to FAS (0.017 ± 0.006; p = 0.049). NE percent positive staining in DEA (0.224 ± 0.047) was elevated relative to FAS (0.045 ± 0.014; p = 0.031).
  
  
  CONCLUSIONS
  In vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01792232.
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. ali.hosseini@alumni.ubc.ca.|Institute for Heart and Lung Health, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada. ali.hosseini@alumni.ubc.ca.|The Lung Center, Vancouver General Hospital (VGH) - Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, 7th floor, Vancouver, BC, V5Z 1M9, Canada. ali.hosseini@alumni.ubc.ca.
authors.forename: Ali
authors.initials: A
authors.lastname: Hosseini
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. jhirota@mail.ubc.ca.|Institute for Heart and Lung Health, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada. jhirota@mail.ubc.ca.|The Lung Center, Vancouver General Hospital (VGH) - Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, 7th floor, Vancouver, BC, V5Z 1M9, Canada. jhirota@mail.ubc.ca.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Hirota
authors.affiliation: Institute for Heart and Lung Health, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada. tillie.hackett@hli.ubc.ca.
authors.forename: Tillie L
authors.initials: TL
authors.lastname: Hackett
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. kelly@brc.ubc.ca.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: Histochemistry Research Unit, Faculty of Medicine, University of Southampton, Southampton, S016 6YD, UK. s.j.wilson@soton.ac.uk.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wilson
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Chan-Yeung Centre for Occupational and Environmental Respiratory Disease, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. carlsten@mail.ubc.ca.|Institute for Heart and Lung Health, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada. carlsten@mail.ubc.ca.|The Lung Center, Vancouver General Hospital (VGH) - Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, 7th floor, Vancouver, BC, V5Z 1M9, Canada. carlsten@mail.ubc.ca.
authors.forename: Chris
authors.initials: C
authors.lastname: Carlsten
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects* / Q000276:immunology; D000485:Allergens; D000818:Animals; D029662:Betula / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000009:adverse effects* / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism; D013997:Time Factors; D001335:Vehicle Emissions; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D000485:Allergens; D015415:Biomarkers; C508598:IL4 protein, human; D018836:Inflammation Mediators; D052638:Particulate Matter; C508241:SDC1 protein, human; D053668:Syndecan-1; D001335:Vehicle Emissions; D015847:Interleukin-4; D019272:Leukocyte Elastase