Environmental isocyanate-induced asthma: morphologic and pathogenetic aspects of an increasing occupational disease

Abstract

Occupational diseases affect more and more people every year. According to the International Labour Organization (ILO), in 2000 an estimated amount of at least 160 million people became ill as a result of occupational-related hazards or injuries. Globally, occupational deaths, diseases and injuries account for an estimated loss of 4% of the Gross Domestic Product. Important substances that are related to occupational diseases are isocyanates and their products. These substances, which are used in a lot of different industrial processes, are not only toxic and irritant, but also allergenic. Although the exposure to higher concentrations could be monitored and restricted by technical means, very low concentrations are difficult to monitor and may, over time, lead to allergic reactions in some workers, ending in an occupational disease. In order to prevent the people from sickening, the mechanisms underlying the disease, by patho-physiological and genetical means, have to be known and understood so that high risk groups and early signs in the development of an allergic reaction could be detected before the exposure to isocyanates leads to an occupational disease. Therefore, this paper reviews the so far known facts concerning the patho-physiologic appearance and mechanisms of isocyanate-associated toxic reactions and possible genetic involvement that might trigger the allergic reactions.

Keywords: clinical findings; genetic predisposition; isocyanate; occupational asthma; occupational disease; pathological findings.

Figure 1

Predicted mechanism for the effects of isocyanate in the development of isocyanate induced asthma. The inhaled isocyanate or its derivates are absorbed by the bronchial epithelia cells, i.e., by binding to tubulin. This results in a local disturbance and impairment of cilia function or a detachment of bronchial epithelia cells. Glutathione S transferase mediates the detoxification process. If the capacity of GSH is exhausted, the free isocyanate can bind to e.g., albumin. This isocyanate-albumin-complex acts as a neo-epitope, that is recognized by the immune system, and is leading to an induction of an immunological process by activation of CD4+ cells. The following inflammation process and, under certain circumstances, an additional induction of IgE antibodies induce the hypersensitivity reaction.