Occupational asthma caused by isocyanates - Patterns of asthmatic reactions to increasing day-to-day doses

Inhalation challenges to isocyanates are conducted in specialized centers t o confirm occupational asthma. The pattern of asthmatic reactions due to co nsecutively increasing daily doses of isocyanates is unknown. We conducted a study involving 24 subjects who had undergone specific inhalation challen ges to isocyanates (toluene diisocyanate [TDI], n = 8; hexamethylene diisoc yanate [HDI], n = 10; and methylene diisocyanate [MDI], n = 6) on three or more consecutive days. Challenge tests were given through a closed-circuit apparatus (n = 12) or in small cubicles (n = 12), allowing assessment of th e total inhaled dose (concentration x duration). The pattern of asthmatic r eactions was described. In addition, dose-response curves were analyzed and tested for their linear and quadratic trends. Four patterns of response we re observed: (1) linear (n = 10); (2) minimal effect followed by a brisk ch ange (n = 7); (3) significant change followed by tachyphylaxis or a plateau (n = 4); (4) biphasic (i.e., significant change followed by a reduction in the effect and significant change on the last day of exposure [n = 3]). Su bjects with a linear dose-response pattern had been exposed to isocyanates at work for a significantly shorter interval (7.2 +/- 6.7 yr) than subjects with a nonlinear pattern (20.0 +/- 13.1 yr). An analysis of variance cover ing a 3-d period for all subjects showed a significant linear model for the response (p < 0.0001); there was no quadratic trend. However, when the ana lysis was done on subjects with four or more days of challenge (n = 10), we found both linear and quadratic significant components. This analysis show s that the most common pattern of asthmatic reactions to inhaled isocyanate s generated on consecutive days is linear; however, other patterns are also observed. In some individuals, particularly those in whom more days of cha llenge are required, we observed in addition to a strong linear component a quadratic component manifested by a brisk change on the last day of exposu re.