Prepolymers of hexamethylene diisocyanate as a cause of occupational asthma

Background: Occupational asthma (OA) caused by products that contain hexamethylene diisocyanate (HDI) has been ascribed to the highly volatile monomer of HDI. Most two-component paints are now made up primarily of nonvolatile prepolymers of HDI (30% to 60%) with only trace amounts (<0.1%) of the monomer. The respective role of the two chemical forms of HDI in causing OA has never been investigated. Methods: Twenty workers who were consecutively referred for possible OA that resulted from exposure to spray paints underwent inhalation challenges on separate days with pure HDI monomer and the commercial formulation of HDI prepolymers to which they had been exposed at work. Results: Specific inhalation challenges elicited a positive asthmatic reaction in 10 of the 20 subjects. Among these subjects, four had positive bronchial reactions (two early, one late, and one dual) to both the monomer and the prepolymers. Four other subjects had asthmatic reactions (two early, one late, and one dual) after exposure to the prepolymers but not after exposure to the monomer. The discordance in bronchial response elicited by the monomer and the prepolymers could not be due to differences in the level of baseline nonspecific bronchial reactivity or in HDI concentrations during the tests. One subject showed an atypical progressive reaction after exposure to the monomer but not after exposure to the prepolymer. In this case, the discordant response could be explained by differences in HDI concentration. Conclusion: These observations show that, although they are nonvolatile, the prepolymers of HDI can induce OA and that asthmatic reactions as a result of exposure to prepolymers but not the monomer is not a rare occurrence.