Occupational Asthma Caused by Diisocyanates: Mechanisms of Etiopathogenesis

Overview

Highly reactive low-molecular compounds diisocyanates represent a significant cause of occupational asthma. Besides formaldehydeand latex, diisocyanates become a significant cause of occupational bronchial asthma (AB) in industrial countries, estimatedprevalence of AB caused by diisocyanates is 5–15% of all exposed workers. Diisocyanates (DI) are highly reactive aromatic andaliphatic compounds reacting with compounds rich in hydroxyl groups by polyaddition reaction resulting in polyurethanes. Themost commonly used forms of DI are toluendiisocyanate (TDI), methylendiphenyldiisocyanate (MDI), hexamethylendiisocyanate(HDI). They are irreplaceable in furniture-making, motor-car, electronic, clothing and refrigeration industry. Immunopathogenesisof AB caused by DI is studied from many points of view. AB caused by diisocyanates shows some clinical features typical for atopicAB – development of considerable bronchial hyperreactivity to DI in subirritative concentrations, latent period of months to yearsunder continuous exposure, occurence of an early and late phase of bronchial response. At the same time, it differs from atopic ABwith some characteristics – absence of eye and nasal allergic symptoms, absence of specific IgE (DI-conjugate) in majority ofworkers with confirmed AB, frequent occurence of an isolated late phase of bronchial response. Research on bronchial asthmainduced by DI is currently focused on several topics: genetic factors which determine susceptibility to the disease, the role ofepithelial barrier in sensibilization of organism, identification of DI – protein conjugates in their role of antigens, characteristics ofimmunological response in AB caused by DI and the role of neurogenic mechanisms in pathogenesis of the disease. Studiesconcerned with presented topics support the concept that AB caused by diisocyanates is presented by mixed type of the TH1/TH2response, influx and regulatory role of CD4+ and CD8+ T lymphocytes. The increased frequency of the DQA1*0104 andDQB1*0503 alleles was proved in patients with diagnosed disease compared to exposed individuals without symptoms but confirmedincreased frequency of the DQA1* 0101 and DQB1*0501 alleles. Knowledge of the pathogenesis of AB caused by diisocyanatesmay accelerate the development of diagnostic tests and consequent treatment intervention.

Key words:
occupational bronchial asthma, diisocyanates, immunopathogenesis