title: Is specific IgE antibody analysis feasible for the diagnosis of methylenediphenyl diisocyanate-induced occupational asthma?
abstract: OBJECTIVE
  Early recognition improves the prognosis of isocyanate asthma. A major unanswered question is whether IgE-dependent mechanisms are of diagnostic value? Our objective was to appraise serological methods using various methylenediphenyl diisocyanate (MDI)-albumin conjugates and weigh up the data versus the outcome of standardized comprehensive clinical diagnostics to evaluate the viability of immunological analysis in supportive MDI-asthma diagnosis (OAI).
  
  
  METHODS
  Specific IgE (sIgE) and IgG (sIgG) binding was measured with fluorescence enzyme immunoassay in 43 study subjects (using conjugates prepared in-vapor, in-solution and commercial preparations). The differential clinical diagnosis included standardized measurement of pulmonary function, non-specific bronchial hyper-responsiveness, specific MDI-prick test (MDI-SPT) and specific inhalation challenge (MDI-SIC).
  
  
  RESULTS
  Detailed diagnostic scheme allows the differential OAI and MDI-induced hypersensitivity pneumonitis (PI). The presumed OAI diagnoses were confirmed in 84 % (45 % cases having demonstrable sIgE antibodies) with RR 5.7, P > 0.001, when OAI diagnosis is correlated with MDI-SIC/MDI-SPT (RR 1.28 for MDI-SIC alone); sIgG antibodies were clinically relevant for PI and not for the OA diagnosis. MDI-specific IgE data generated with commercial ImmunoCAP preparations show high correlation with our in-vapor generated MDI conjugates.
  
  
  CONCLUSIONS
  Isocyanate-specific IgE antibodies are not always detectable but their presence is strongly predictive of OAI and supportive for the diagnosis. MDI-SPT can be a valuable parameter differentiating OAI and PI. We have confirmed and extended published data showing that isocyanate-albumin conjugates perform better in specific antibody assays when prepared with volatile phase formulations and would like to stress additionally the necessity for further refinements and standardization in clinical diagnostics procedures.
authors.affiliation: Division of Occupational Toxicology and Immunology, Department of Occupational Medicine, Faculty of Medicine, Institute for Occupational and Maritime Medicine (ZfAM), University of Hamburg, Marckmannstrasse 129 b, Bld. 3, 20539, Hamburg, Germany. LBudnik@uke.uni-hamburg.de
authors.forename: Lygia Therese
authors.initials: LT
authors.lastname: Budnik
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Preisser
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Permentier
authors.forename: Xaver
authors.initials: X
authors.lastname: Baur
mesh_terms: D000328:Adult; D000368:Aged; D059366:Asthma, Occupational / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology*; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D017953:Isocyanates / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D012709:Serum Albumin / Q000276:immunology; D012882:Skin Tests; D014797:Vital Capacity; D001559:Benzhydryl Compounds
chemical_list: D007073:Immunoglobulin E; D007074:Immunoglobulin G; D017953:Isocyanates; D012709:Serum Albumin; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds