title: Is the analysis of histamine and/or interleukin-4 release after isocyanate challenge useful in the identification of patients with IgE-mediated isocyanate asthma?
abstract: Isocyanates are a well-known and frequent cause of occupational asthma. The implementation of specific inhalation challenges (SICs) is the gold standard in asthma diagnosis supporting occupational case history, lung function testing, specific skin prick tests and the detection of specific IgE. However, the diagnosis is not always definitive. An interesting new approach, analyses of individual genetic susceptibilities, requires discrimination between a positive SIC reaction arising from IgE-mediated immune responses and one from other pathophysiological mechanisms. Hence, additional refinement tools would be helpful in defining sub-classes of occupational asthma and diagnosis. We used total IgE levels, specific IgE and SIC results for sub-classification of 27 symptomatic isocyanate workers studied. Some mutations in glutathione S-transferases (GSTs) are suspected either to enhance or to decrease the individual risk in the development of isocyanate asthma. Our patient groups were assessed for the point mutations GSTP1*I105V and GSTP1*A114V as well as deletions (null mutations) of GSTM1 and GSTT1. There seems to be a higher risk in developing IgE-mediated reactions when GSTM1 is deleted, while GSTT1 deletions were found more frequently in the SIC positive group. Blood samples taken before SIC, 30-60 min and 24h after SIC, were analyzed for histamine and IL-4, classical markers for the IgE-mediated antigen-specific activation of basophils or mast cells. We suggest that the utility of histamine measurements might provide an additional useful marker reflecting isocyanate-induced cellular reactions (although the sampling times require optimization). The promising measurement of IL-4 is not feasible at present due to the lack of a reliable, validated assay.
authors: Division of Occupational Toxicology and Immunology, Institute for Occupational and Maritime Medicine (ZfAM), University Medical Center Hamburg-Eppendorf, Germany.
authors: Silke
authors: S
authors: Blindow
authors: Division of Clinical Occupational Medicine, Institute for Occupational and Maritime Medicine (ZfAM), University Medical Center Hamburg-Eppendorf, Germany.
authors: Alexandra M
authors: AM
authors: Preisser
authors: Division of Occupational Lung Diseases and Allergy, Institute for Occupational Medicine, Charite-University Medicine Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Xaver
authors: X
authors: Baur
authors: Division of Occupational Toxicology and Immunology, Institute for Occupational and Maritime Medicine (ZfAM), University Medical Center Hamburg-Eppendorf, Germany. Electronic address: L.Budnik@uke.de.
authors: Lygia T
authors: LT
authors: Budnik
mesh_terms: D059366:Asthma, Occupational / Q000175:diagnosis* / Q000276:immunology; D001985:Bronchial Provocation Tests; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006632:Histamine / Q000097:blood; D006636:Histamine Release; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood / Q000378:metabolism*; D017953:Isocyanates / Q000276:immunology; D016273:Occupational Exposure; D012882:Skin Tests
chemical_list: D005982:Glutathione Transferase; D006632:Histamine; D007073:Immunoglobulin E; D015847:Interleukin-4; D017953:Isocyanates; C508598:IL4 protein, human; C413545:glutathione S-transferase T1
keywords: Diisocyanates MDI, TDI, and HDI; Glutathione S-transferase (GSTP1, GSTT1, and GSTM1); Histamine; IgE; Interleukin-4 (IL-4); Isocyanate asthma; Specific inhalation challenge (SIC)