title: Is occupational asthma to diisocyanates a non-IgE-mediated disease?
abstract: BACKGROUND
  Exposure to diisocyanates in the workplace is an important cause of occupational asthma. The majority of patients with diisocyanate-induced asthma have no detectable diisocyanate-specific IgE antibodies in serum. There has been much debate as to whether this is due to diisocyanate-induced asthma being mediated by non-IgE mechanisms or whether it is the result of using inappropriate conjugates.
  
  
  OBJECTIVE
  We sought to determine whether RNA message for Cepsilon, IL-4, and other associated inflammatory markers could be detected locally within the bronchial mucosa after diisocyanate challenge.
  
  
  METHODS
  Fiberoptic bronchoscopic bronchial biopsy specimens were obtained at 24 hours after both a control and an active challenge in 5 patients with positive and 7 patients with negative inhalation test responses to diisocyanates. Using both immunohistochemistry and in situ hybridization, we determined mRNA for Cepsilon, IL-4, IL-5, and other associated inflammatory markers.
  
  
  RESULTS
  There was a striking absence of Cepsilon and IL-4 mRNA-positive cells in bronchial biopsy specimens from patients challenged with diisocyanate (Cepsilon median of 0 and interquartile range of 0-1.85; IL-4 median of 0 and interquartile range of 0-0.85). In contrast, there were increased numbers of IL-5-, CD25-, and CD4-positive cells and a trend toward an increase in eosinophils after active challenge with diisocyanate.
  
  
  CONCLUSIONS
  We found a striking absence of both bronchial Cepsilon and IL-4 RNA message after inhalation challenge with diisocyanates, irrespective of whether the challenge test response was positive or negative. We propose that diisocyanate-induced asthma is a non-IgE-mediated disease, at least in patients in whom specific IgE antibodies to diisocyanates are undetectable.
authors.affiliation: Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK. meinir.jones@imperial.ac.uk
authors.forename: Meinir G
authors.initials: MG
authors.lastname: Jones
authors.forename: Alison
authors.initials: A
authors.lastname: Floyd
authors.forename: Kayhan T
authors.initials: KT
authors.lastname: Nouri-Aria
authors.forename: Mikila R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
authors.forename: Anthony Newman
authors.initials: AN
authors.lastname: Taylor
authors.forename: Paul
authors.initials: P
authors.lastname: Cullinan
mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology*; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D001985:Bronchial Provocation Tests; D001999:Bronchoscopy; D015704:CD4 Antigens; D004804:Eosinophils; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D017953:Isocyanates / Q000009:adverse effects*; D008297:Male; D009784:Occupational Diseases / Q000139:chemically induced* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2
chemical_list: D015704:CD4 Antigens; D015848:Interleukin-5; D017953:Isocyanates; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E