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 pathogenesis of isocyanate-induced asthma remains controversial. In particular, 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 referred for evaluation of respiratory symptoms thought to be related to TDI 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 FEV1 (PD20)) was determined. A PD20 of 1.4 mg or more was considered normal. Subjects were challenged by exposure to 5 to 10 ppb TDI for up to 30 min in a 9 m3 exposure chamber. A positive response was a 20% or more decrease in FEV1 within 1 h (early) 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 remainder had dual responses. Thirty-two individuals (51%) had a positive response 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 mean IgE, 143 versus 69 IU/ml; p = 0.09) and those with isolated late-onset responses (30 IU/ml; p < 0.05). Neither skin test positivity nor TDI-specific IgE was associated with response to TDI provocation challenge. 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 TDI provocation challenge.