PREDICTIVE VALUE OF AIRWAYS HYPERRESPONSIVENESS AND CIRCULATING IGE FOR IDENTIFYING TYPES OF RESPONSES TO TOLUENE DIISOCYANATE INHALATION CHALLENGE

Development of asthma after exposure to toluene diisocyanate (TDI) has been recognized in a variety of occupational settings. However, the p athogenesis of isocyanate-induced asthma remains controversial. In par ticular, the role of IgE in the development of TDI-induced asthma has remained uncertain. To investigate predictive factors for response to inhalation challenge with TDI, we analyzed data from 63 subjects refer red for evaluation of respiratory symptoms thought to be related to TD I sensitization. All subjects underwent interview, routine phlebotomy, spirometry, methacholine challenge, and allergy skin testing prior to TDI challenge. Spirometry and methacholine challenge were repeated 1 day after TDI challenge. The cumulative dose of methacholine needed to produce a 20% decrease in FEV(1) (PD20) was determined. A PD20 of 1.4 mg or more was considered normal. Subjects were challenged by exposur e to 5 to 10 ppb TDI for up to 30 min in a 9 m(3) exposure chamber. A positive response was a 20% or more decrease in FEV(1) within 1 h (ear ly) or beyond 1 h (late) after TDI exposure. Thirty-four subjects (54% ) had a positive response, of whom 12 (35% of responders) had isolated early responses, 13 (38%) had isolated late responses, and the remain der had dual responses. Thirty-two individuals (51%) had a positive re sponse to methacholine (AR+) prior to TDI challenge. AR+ was strongly associated with a positive TDI challenge: 23 AR+ subjects (72%) had a positive TDI challenge, compared with only 11 AR- subjects (35%) (p < 0.01). AR positivity did not predict the time of onset of TDI response . The serum IgE level was higher in subjects demonstrating an isolated early response to TDI than in those without any response (geometric m ean IgE, 143 versus 69 IU/ml; p = 0.09) and those with isolated late-o nset responses (30 IU/ml; p < 0.05). Neither skin test positivity nor TDI-specific IgE was associated with response to TDI provocation chall enge. These data suggest that airways hyperresponsiveness is a strong predictor of response to TDI challenge, independent of atopy and serum IgE, and that serum IgE is associated with early-onset responses to T DI provocation challenge.