Immunologic and nonimmunologic mechanisms in asthma due to western red cedar ( Thuja plicata)

Abstract

Occupational asthma due to western red cedar ( Thuja plicata) is the most common form of occupational asthma in British Columbia, occurring in about 5% of the exposed workers. Plicatic acid, uniquely present in western red cedar, was found to be the agent responsible for the asthmatic reactions. Inhalation provocation tests with an extract of western red cedar or plicatic acid induced late asthmatic reactions alone in 44%, dual (immediate and late) reactions in 49%, and immediate reactions alone in 7% of the 185 patients. Of the 75 patients who left the industry and were no longer exposed to the wood, only 50% recovered completely after an average period of 3 yr; the remaining half continued to have recurrent attacks of asthma. Specific IgE antibodies to crude red cedar extract or plicatic acid-human serum albumin conjugate were found in less than 40% of the patients by the RAST, while IgG antibodies were not detected. There was no correlation between the presence and absence of specific IgE antibodies and the type of asthmatic reaction induced during inhalation challenge. IgE antibodies were not found in exposed subjects with no asthmatic reaction on inhalation challenge. There was significant correlation between the degree of nonspecific bronchial hyperreactivity and the degree of bronchial reactivity to plicatic acid during immediate or late asthnatic reactions. The degree of nonspecific bronchial hyperreactivity was increased after late asthmatic reactions induced by plicatic acid. On the other hand, the degree of nonspecific bronchial hyperreactivity was reduced and gradually returned to normal among patients who became asymptomatic after exposure was discontinued. These findings suggest that nonspecific bronchial hyperreactivity plays an important role in the pathogenesis of red cedar asthma. The mechanism of bronchial hyperreactivity induced by red cedar exposure is unknown; an immunologic mechanism may be important. Direct release of histamine from human basophils and mast cells and direct activation of the complement system by plicatic acid are unlikely pathogenetic mechanisms.