b Serum sIgE antibody levels for one MDI-asthma patient (pat#1, Tables 3, 4) in a longitudinal study during MDI exposure and subsequent follow-up for 4.5 years who developed isocyanate asthma with dermatitis during the exposure period (sIgE values are shown as solid white columns). After change in workplace and no exposure to isocyanates for the last 5 years, his lung function improved but he continued to exhibit MDI-specific IgE antibodies, but no specific IgG antibodies (shown as solid gray DMXAA Trichostatin A columns; note that all measured IgG

values were below the reference value <3 mg/L); n.d. = not determined Correlation with other diagnostic parameters and the antibody data Presumed MDI-asthma cases (group A) The specific IgE-/IgG-binding data were compared with other diagnostic parameter (see Tables 1, 2 for diagnostic parameter and supplementary

Fig. 1 for the diagnostic flow chart). Interestingly, all patients with high specific IgE binding gave also a positive MDI-skin-prick test result. All patients in this group EPZ004777 also exhibited a positive SIC response when challenged with MDI. In the patient group without MDI-sIgE antibodies, all but one had negative MDI-skin-prick results; NSBHR was both present and absent, the SIC results were positive and negative, and all had IgG antibodies at low levels. When looking closer at individual patients, the presumed MDI-asthma diagnosis could be confirmed by clinical findings, symptoms and cross-shift course of lung function or SIC in 7 out of 12 patients, although only 4 patients in this group had specific IgE antibodies. However, the combination of positive MDI-SIC, MDI-SPT and specific IgE antibodies correlated with asthma diagnosis (with RR of

5.7, P < 0.001, n = 12), whereas MDI-HSA-specific IgE alone showed RR of 1.28, P < 0.50 (when correlated with the clinical OAI diagnosis) given the limitation of the small patient group. There was no significant correlation between the presence of IgG antibodies and asthma diagnosis (RR 0.4, P > 0.5). Interestingly, patients out Amrubicin of the IgE-negative group were diagnosed with MDI-induced hypersensitivity pneumonitis, with typical systemic and pulmonary symptoms and respective MDI-provoked SIC responses. The IgG binding (in combination with the positive SIC data) could be positively correlated (RR 1.2, P < 0.50) with the clinical diagnosis of PI. Control groups (B, C, D) Table 4 also provide data from a field study including a small group of 6 industrial workers with exposure to MDI (~5 ppb). The subjects were diagnosed directly in the workplace (only serum and urine samples were taken to the laboratory). None of the workers had asthmatic symptoms, as defined by the questionnaire, and had no evidence of airway obstruction, with all having FEV1 > 80 % predicted and FEV1/FVC higher than predicted-1 SD.