ABSTRACT
In order to determine whether treatment with ketotifen inhibits asthmatic reactions induced by toluene di-isocyanate (TDI), we studied six sensitized subjects with previously demonstrated dual or late asthmatic reaction after inhalation challenge with TDI. Ketotifen (1 mg b.i.d., orally) or placebo was administered for 7 days to the examined subjects, according to a double-blind, cross-over, placebo-controlled study design. When the subjects were treated with either ketotifen or placebo, FEV1 markedly decreased after exposure to TDI. These results suggest that the anti-asthmatic agent ketotifen is not effective in TDI-induced asthma and suggest that it should not be used in the prophylaxis of asthmatic reactions induced by TDI in sensitized subjects.
Subject(s)
Asthma/prevention & control , Cyanates/antagonists & inhibitors , Ketotifen/pharmacology , Toluene 2,4-Diisocyanate/antagonists & inhibitors , Asthma/chemically induced , Double-Blind Method , Forced Expiratory Volume , Humans , Hypersensitivity, Delayed , Immunization , Ketotifen/administration & dosage , Methacholine Chloride , Methacholine Compounds/immunology , Random Allocation , Toluene 2,4-Diisocyanate/adverse effectsABSTRACT
To determine whether late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI) are linked to airway inflammation, we investigated whether they are inhibited by prednisone. Ten "sensitized" subjects were studied in 2 sets of experiments. In the first set, each subject was given no treatment and was studied before and for 8 h after exposure to TDI. In the second set, 2 to 4 wk later, each subject was studied before treatment and then during treatment with prednisone (50 mg once a day for 3 days, orally), both before and after exposure to TDI. To assess late asthmatic reactions to TDI, we measured FEV1 immediately before and after exposure, then hourly for 8 h. To assess changes in airway responsiveness, we measured the provocation dose (mg) of methacholine causing a 20% decrease in FEV1 (PD20FEV1) before and 8 h after exposure to TDI. When the subjects received no prednisone treatment, TDI caused late asthmatic reactions and increased airway responsiveness. By contrast, when the subjects received prednisone, TDI caused no late asthmatic reaction or increased airway responsiveness. Prednisone did not change baseline airway caliber or airway responsiveness. These results suggest that late asthmatic reactions and the associated increase in airway responsiveness induced by TDI in "sensitized" subjects may depend on the development of a steroid-responsive acute inflammatory reaction within the airways.
Subject(s)
Asthma/physiopathology , Cyanates/toxicity , Prednisone/pharmacology , Respiratory System/drug effects , Toluene 2,4-Diisocyanate/toxicity , Adult , Female , Forced Expiratory Volume , Humans , Male , Methacholine Chloride , Methacholine Compounds/pharmacology , Middle AgedABSTRACT
Exposure to toluene was studied in a group of 14 subjects working in a printing industry, who were exposed to this solvent only. Environmental monitoring was carried out using personal samplers for the whole workshift over three consecutive days. Toluene TWA concentrations ranged from 37 to 229 mg/m3. At the end of the workshift on each day of investigation, urine samples were collected for the determination of hippuric acid and ortho-cresol. Hippuric acid was also determined for urine before the workshift and on the Saturday and Monday mornings after the end of exposure; hippuric acid was also determined in 16 controls over the same five-day period. At the end of the workshift, hippuricuria levels in exposed workers always turned out to be statistically different from pre-workshift levels and those of the controls. The end-of-workshift hippuricuria levels of exposed workers were significantly correlated with the mean daily environmental concentration (TWA): in the three days of comparative study, we found r = 0.63 (P less than 0.05) on Day 1, r = 0.90 (P less than 0.001) on Day 2, and r = 0.87 (P less than 0.001) on Day 3. Ortho-cresol turned out to be correlated with daily exposure less significantly than hippuric acid: r = 0.49 (n.s.) on Day 1; r = 0.78 (P less than 0.001) on Day 2, and r = 0.65 (P less than 0.05) on Day 3. Using all available data (41 observations), a very significant correlation (P less than 0.001) was found between the TWA and both metabolites (r = 0.80 for hippuric acid; r = 0.68 for o-cresol). The values of the two metabolites in the end-of-workshift urine samples (41 observations) also turned out to be well correlated (r = 0.70; P less than 0.001). The authors conclude that hippuric acid is a valid test for evaluating even low exposures to toluene.
