[A fatal case of asthma induced by toluene diisocyanate].
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Adult↗
Biomedical subjects
C E Mapp
Publications and source records attributed to C E Mapp.
Pathogenesis of late asthmatic reactions induced by exposure to isocyanates.
The importance of airways inflammation for the development of bronchial hyperresponsiveness and for exacerbation of asthma was investigated in subjects with occupational asthma. We examined subjects sensitized to isocyanates, a small molecular weight compound that causes occupational asthma. Studies in asthmatic subjects sensitized to toluene diisocyanate (TDI) demonstrated that late, but not early, asthmatic reactions induced by TDI were associated with an acute increase in bronchial responsiveness, and with a marked infiltration of neutrophils and a slight infiltration of eosinophils into the airways, both prevented by steroids. As the late asthmatic reactions and the increase in responsiveness induced by TDI were prevented by steroids, but not by indomethacin, we speculated that cell membrane phospholipid metabolites, which are inhibited by steroids but not by indomethacin, may be involved in TDI induced hyperresponsiveness. The results of these studies suggest that bronchial hyperresponsiveness and exacerbation of asthma may be related to inflammation of the airways and that cell membrane phospholipid metabolites may be involved.
Anti-Inflammatory Agents↗
Prednisone, indomethacin and airway responsiveness in toluene diisocyanate sensitized subjects.
We investigated whether late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI) in sensitized subjects are inhibited by indomethacin and/or prednisone. Four sets of experiments were conducted in five subjects sensitized to TDI. To assess late asthmatic reactions to TDI, FEV1 was measured immediately before and after exposure to TDI and then hourly for 8 h. To assess change in airway responsiveness, the provocative dose (mg) of methacholine that caused a decrease in FEV1 of 20% (PD20FEV1) before treatment, and then before and after exposure to TDI was measured. In the first set of experiments, each subject was given no treatment and was studied before and 8 h after exposure to TDI; in the other two sets, each subject was studied before treatment, then during treatment with indomethacin (50 mg q.i.d. for 3 days, orally) or prednisone (50 mg once a day, for 3 days, orally), both before and 8 h after TDI exposure. In a fourth series of experiments, each subject was again given no treatment and studied before and 8 h after TDI. When the subjects were given no treatment or indomethacin, TDI caused late asthmatic reactions and increased airway responsiveness to inhaled methacholine. In contrast, when the subjects were given prednisone, TDI caused neither late asthmatic reactions nor increased airway responsiveness. Treatment with indomethacin and prednisone did not change baseline FEV1 and airway responsiveness. These results suggest that release of prostaglandins does not contribute to late asthmatic reactions and the associated increase in airway responsiveness induced by TDI. Inflammatory mediators inhibited by prednisone but not by indomethacin may be involved.
Adult↗
[Occupational asthma: interactions between genetic factors and adverse environment?].
Bronchial asthma is very likely caused by the interaction of genetic susceptibility with an adverse environment. The mechanisms involved in asthma induced by toluene diisocyanate (TDI), a low molecular weight compound, are still unknown, but increasing interest has been expressed in the genetic component of this disease. In two collaborative studies on the role of genetic factors in isocyanate-induced asthma, a significant positive association with HLA class II DQB1*0503 allele and a negative association with HLA class II DQB1*0501 were observed. In the second study we also observed a single amino acid difference at position 57, with Aspartic Acid in DQB1*0503 allele and Valine in DQB1 allele, and we concluded that the presence of a DQB1 allele with the charged residue Aspartic Acid at position 57 has a role in creating susceptibility for isocyanate-induced asthma. These findings suggest a direct involvement of HLA class II antigens in the pathogenesis of isocyanate-induced asthma. Efforts must continue to improve the possibility of early diagnosis of isocyanate-induced asthma, and at the same time the social and ethical implications of a genetic screening at the workplace must be taken into consideration.
Alleles↗
[Leukotriene antagonists in the treatment of asthma].
Bronchial asthma is a chronic inflammatory disease of the airways. Several mediators are involved in the inflammatory process, including leukotrienes B4, C4, D4 and E4. These compounds promote bronchoconstriction, mucus hypersecretion, eosinophil infiltration, monocyte/macrophage activation, and smooth muscle proliferation. Two different approaches have been taken to interfere with activity: 1) blocking of the specific cysteinyl leukotriene receptor, and 2) inhibition of leukotriene biosynthesis (either by inhibition of the primary enzyme, 5-lipoxygenase, or its required cofactor 5-lipoxygenase-activating-protein). Available data suggest that leukotriene modifier therapy is effective in several experimental models of bronchial asthma. These agents also have demonstrable efficacy in aspirin-induced asthma and against exercise and cold-air-induced bronchoconstriction. The recent 1997 NHLBI Expert Panel Report II Guidelines suggest that leukotriene modifiers may be used as an alternative to low dose inhaled corticosteroids in mild persistent asthma. They may also be useful in more severe asthma, as supplements to inhaled corticosteroids and long-acting bronchodilators. The clinical benefit of leukotriene modifier therapy occurs early in treatment. However, the response rate for leukotriene modifiers approximates 70 to 80% suggesting that there are "responders" as well as "non-responders" for whom leukotrienes, as inflammatory mediators, may be less important. A 2 to 4-week therapeutic trial, with objective monitoring of response, may be a reasonable approach to initiating leukotriene modifier therapy. Additional controlled trials will be required to define more fully the role of these new drugs for long-term control and treatment of asthma.
Asthma↗