Am. J. Respir. Crit. Care Med., Volume 159, Number 6, June 1999, 1879-1883

Occupational Asthma Caused by Isocyanates
Patterns of Asthmatic Reactions to Increasing Day-to-Day Doses

JEAN-LUC MALO, HEBERTO GHEZZO, and ROBERT ÉLIE

Department of Chest Medicine, Sacré-Coeur Hospital, Montreal; and Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada

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 × 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.

This article has been cited by other articles:

				R Castano, D Gautrin, G Theriault, C Trudeau, H Ghezzo, and J-L Malo Occupational rhinitis in workers investigated for occupational asthma Thorax, January 1, 2009; 64(1): 50 - 54. [Abstract] [Full Text] [PDF]

				J. Pauluhn Brown Norway Rat Asthma Model of Diphenylmethane-4,4'-Diisocyanate (MDI): Analysis of the Elicitation Dose-Response Relationship Toxicol. Sci., August 1, 2008; 104(2): 320 - 331. [Abstract] [Full Text] [PDF]

				S. Austin Biological monitoring of TDI-derived amines in polyurethane foam production Occup. Med., September 1, 2007; 57(6): 444 - 448. [Abstract] [Full Text] [PDF]

				A. V. WISNEWSKI, R. SRIVASTAVA, C. HERICK, L. XU, R. LEMUS, H. CAIN, N. M. MAGOSKI, M. H. KAROL, K. BOTTOMLY, and C. A. REDLICH Identification of Human Lung and Skin Proteins Conjugated with Hexamethylene Diisocyanate In Vitro and In Vivo Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2330 - 2336. [Abstract] [Full Text]