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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 66 (1994), S. 141-152 
    ISSN: 1432-1246
    Keywords: Isocyanates ; Occupational asthma ; Bronchial hyperreactivity ; Extrinsic allergic alveolitis ; Hypersensitivity pneumonitis ; Genotoxicity ; Neuropeptides ; IgE antibodies ; IgG antibodies ; Inhalative challenge test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main causes of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m3) and 20 ppb (0.14 mg/m3), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1 % of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1750
    Keywords: Asthma ; Inflammation ; Airway hyperresponsivenessEosinophils ; Leukotrienes ; Prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Toluene diisocyanate (TDI) is a volatile, highly reactive chemical widely used as a polymerizing agent in the production of polyurethane foams, lacquers, adhesives, and other items. Repeated airway exposures in the workplace to TDI may cause a concentration-dependent risk of developing chronic airway disorders. Different pathomechanisms are involved. IgE-mediated sensitization and irritative effects were clearly demonstrated in exposed subjects as well as in animals. In this study we examined the cellular and mediator composition in bronchoalveolar lavage fluid (BALF) of guinea pigs (eight in each group) exposed to TDI (10, 20, or 30 ppb) on 5 consecutive days for 2 hours each. Increased numbers of eosinophils and significantly elevated levels of LTB4 and LTC4/LTD4/LTE4 were obtained in BALF of all exposed animals when compared to nonexposed control animals. PGD2 and TXB2 remained unaltered in BALF. Stimulation of BALF cells of exposed and control animals with Ca-ionophore A23187 and arachidonic acid induced an increased generation of LTB4. Furthermore, BALF cells of the exposed animal groups generated immunoreactive LTC4/LTD4/LTE4, whereas controls did not show peptido-leukotriene formation in the presence and absence of stimuli. Our data clearly demonstrate an influx of eosinophils into the airways associated with mediator release and higher cellular responsiveness after TDI exposure.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1750
    Keywords: Rabbit model of occupational lung disease ; Isocyanates ; Neuropeptides ; Substance P ; Neurokinin A ; Acetylcholine ; Airway hyperresponsiveness ; Rabbits ; Tachykinin receptor antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine the role of neuropeptides, especially substance P (SP) and neurokinin A (NKA), in toluene diisocyanate (TDI)-induced airway hyperresponsiveness (AHR) to acetylcholine aerosols. Thirty parts per billion of TDI in air administered over 4 hours caused a significant increase in the airway constrictive response to acetylcholine (ACH) aerosols in rabbits (ΔRI: 245 ± 30%, p 〈 0.005) without altering basic values of respiratory, cardiovascular or blood gas parameters. Inhalation of the aerosolized neuropeptides SP and NKA resulted in a similar increase in airway responsiveness (AR) to ACH as exposure to 30 ppb TDI. To determine whether neuropeptides contribute to TDI-induced AHR, we studied their effects after systemic treatment with capsaicin as well as after infusion of specific synthetic antagonists for SP and NK2 (NKA) receptors. CAPS treatment performed on 4 consecutive days as well as antagonists' infusion only moderately (p 〉 0.05) decreased airway responses to ACH. CAPS application prevented the TDI-induced increase in AR to ACH in all rabbits. The increase in airway resistance to ACH did not significantly change after TDI exposure (98 ± 22% of the control response before TDI, p 〉 0.05). Simultaneous infusion of specific synthetic SP and NK2 receptor antagonists also abolished the TDI-induced increase in airway responses to ACH in all animals investigated (P 〉 0.05). The results of this study demonstrate that neuropeptides, especially the tachykinins SP and NKA, are important mediators in TDI-induced AHR in rabbits.
    Type of Medium: Electronic Resource
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