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. CONCLUSION: 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.
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. CONCLUSION: 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: Bin Ouyang; David I Bernstein; Zana L Lummus; Jun Ying; Louis-Philippe Boulet; André Cartier; Denyse Gautrin; Shuk-Mei Ho Journal: Toxicol Sci Date: 2013-03-27 Impact factor: 4.849
Authors: Vanessa De Vooght; Jeroen A J Vanoirbeek; Katrien Luyts; Steven Haenen; Benoit Nemery; Peter H M Hoet Journal: PLoS One Date: 2010-09-07 Impact factor: 3.240
Authors: Lena S Jönsson; Karin Broberg; Karin Paulsson; Kerstin Kronholm Diab; Jørn Nielsen Journal: Int Arch Occup Environ Health Date: 2009-03-31 Impact factor: 3.015