Persistent Asthma Due to Isocyanates: A Follow-up Study of Subjects with Occupational Asthma Due to Toluene Diisocyanate (TDI)

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Abstract
Thirty-five subjects with occupational asthma due to toluene diisocyanate (TDI) exposure were examined. All the subjects were studied with inhalation challenges with TDI and with methacholine. TDI asthma was documented by a positive inhalation challenge to low levels of TDI. Airway responsiveness to methacholine was in the range of asthmatic patients at the time of diagnosis. After an average follow-up interval of 10 months, all the subjects were re-examined. Of the 35 subjects examined, 30 subjects (85.7%) left the workplace, and 5 remained in the same job. Twenty-seven subjects (77.1%) continued to have asthmatic attacks requiring medication for relief of symptoms. At follow-up examination, TDI asthma was documented by a positive inhalation challenge to TDI in 27 subjects. Of these 27 TDI reactors, 22 subjects were removed from occuptional exposure to TDI. The TDI reactors had persistent respiratory symptoms and airway hyperresponsiveness to methacholine. At follow-up visit, 8 subjects (22.9%) lost sensitization to TDI; 5 subjects (62.5%) in this group had also normal airway responsiveness to methacholine after removal from exposure. Only 1 subject among the TDI nonreactors complained of mild respiratory symptoms. At diagnosis, there were no significant differences between subjects who recovered and those who did not with regard to age, smoking habits, atopy, duration of exposure to isocyanates, duration of symptoms, baseline FEV1 (% pred), and baseline airway responsiveness to methacholine. At followup examination, there was a significant difference between the 3 groups with regard to FEV1 (% pred): the nonreactors showed an improvement in their spirometric measurement, and the reactors showed a deterioration in their FEV1 (% pred). Methacholine PD20 at follow-up examination was higher among the group of 8 nonreactors than in the group of the 22 reactors removed from exposure and in the group of the group of the 5 reactors exposed to isocyanates (Gmean and GSEM: 1.239 (1.41) mg versus 0.333 (1.26) mg and 0.391 (1.65) mg, respectively). The subjects who recovered were younger and had a shorter duration of exposure and of symptoms compared with subjects who did not recover. The differences, however, failed to reach the level of statistical significance. The subjects who showed improvement also tended to have immediate or dual asthmatic reactions rather than late asthmatic reactions to inhalation challenge with TDI at the time of diagnosis. We conclude that respiratory symptoms, isocyanate sensitization, and airway hyperresponsiveness to methacholine may persist after removal from occupational exposure to TDI. The type of asthmatic reaction and the severity of the reaction may be important factors for the persistence or the remission of the disease.