New mechanistic model for organic diisocyanate-induced respiratory disease

The pathophysiological mechanisms of organic diisocyanate-induced respirato ry disease remain largely unknown. Some 20% of patients have specific antib odies towards diisocyanate monomers whereas even in this circumstance their presence does not correlate very well with results in clinical provocation tests. The formation of diisocyanate haptens is the trigger for the immuno logical reactions, However, it is known that the reactions with protein and other macromolecules may be slow and hydrolysis of the isocyanate moities to corresponding amines as catalyzed by bicarbonate is more rapid. The libe rated amines, or their intermediates, probably have an important role in th e activation of tissue thromboplastin activator, loss of serum antitrypsin activity, and, finally, in neurogenic inflammation. Hypothetically, suscept ible individuals probably include those which are slow acetylators of exoge nous aminies and carries of heterozygous antitrypsin phenotypes.