title: Occupational asthma caused by isocyanates: patterns of asthmatic reactions to increasing day-to-day doses.
abstract: Inhalation challenges to isocyanates are conducted in specialized centers to confirm occupational asthma. The pattern of asthmatic reactions due to consecutively increasing daily doses of isocyanates is unknown. We conducted a study involving 24 subjects who had undergone specific inhalation challenges to isocyanates (toluene diisocyanate [TDI], n = 8; hexamethylene diisocyanate [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 the total inhaled dose (concentration x duration). The pattern of asthmatic reactions was described. In addition, dose-response curves were analyzed and tested for their linear and quadratic trends. Four patterns of response were observed: (1) linear (n = 10); (2) minimal effect followed by a brisk change (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]). Subjects 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 covering 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 analysis was done on subjects with four or more days of challenge (n = 10), we found both linear and quadratic significant components. This analysis shows that the most common pattern of asthmatic reactions to inhaled isocyanates generated on consecutive days is linear; however, other patterns are also observed. In some individuals, particularly those in whom more days of challenge are required, we observed in addition to a strong linear component a quadratic component manifested by a brisk change on the last day of exposure.
authors.affiliation: Department of Chest Medicine, Sacré-Coeur Hospital, Montreal, Canada. malojl@alize.ere.umontreal.ca
authors.forename: J L
authors.initials: JL
authors.lastname: Malo
authors.forename: H
authors.initials: H
authors.lastname: Ghezzo
authors.forename: R
authors.initials: R
authors.lastname: Elie
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D017953:Isocyanates / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced*
chemical_list: D017953:Isocyanates