1,721,047 research outputs found
Late asthmatic reactions, airway inflammation and chronic asthma in TDI sensitized subjects.
No full textSensitized subjects may develop symptoms of asthma after exposure to isocyanates in their place of work. After challenge with isocyanates in the laboratory, sensitized subjects develop immediate, late and dual asthmatic reactions. We speculated that toluene diisocyanate (TDI) might cause late asthmatic reactions and increase bronchial responsiveness by causing an acute inflammatory reaction in the airways, and that airway inflammation may be responsible for persistence of occupational asthma induced by isocyanates. To test these hypotheses, we examined sensitized subjects during asthmatic reactions induced by exposure to toluene diisocyanate in the laboratory. We observed that late and dual, but not early, asthmatic reactions are associated with a transient increase of bronchial responsiveness which is associated with an acute inflammatory reaction of the airways characterized by an increase of neutrophils followed by eosinophils, by an increase of leukotriene B4 and albumin in bronchoalveolar lavage fluid, and that all these effects are inhibited by steroids. Longitudinal studies suggest that the majority of subjects with occupational asthma continue to have persistent asthma months and years after the cessation of exposure, and the results of our studies combined with the results of studies performed by others suggest that the persistence of asthma may be related to the persistence of airway inflammation
Human leukocyte antigen associations in occupational asthma induced by isocyanates.
No full textExposure to diisocyanates is recognized as a leading cause of occupational asthma. Occupational asthma induced by isocyanates shares many characteristics with immunoglobulin E (IgE)-mediated asthma: in both, the responsible agent is known, and the clinical presentation, response to inhalation challenge in the laboratory, and response to antiasthma drugs are similar. Although asthma mediated by an IgE mechanism occurs in atopic subjects, occupational asthma induced by isocyanates occurs mostly in nonatopic asthmatics, and an IgE-mediated mechanism has not been consistently demonstrated. However, activated T lymphocytes, methacromatic cells, and eosinophils are increased in the bronchial mucosa of allergic and nonallergic asthmatics and subjects with occupational asthma induced by isocyanates, suggesting similar, probably immunologically mediated mechanisms for both nonoccupational and occupational asthma. Occupational asthma occurs in up to 5-10% of the exposed subjects. Evaluation of major histocompatibility complex (MHC) class II genes in exposed subjects who develop toluene diisocyanate (TDI) asthma has shown a negative association with HLA-DQB1*0501 and a positive association with HLA-DQB1*0503 alleles. In addition, a high proportion of TDI asthmatics express the HLA-DQB1*0503-associated aspartic acid at residue 57, suggesting that HLA-DQ may have a key role in conferring susceptibility. Thus, asthma induced by the low-molecular-weight agent TDI may result from an immunologic reaction due to the interaction of genetic susceptibility with exposure in the workplace. Mapp CE, Balboni A, Baricordi R, Fabbri LM. Human leukocyte antigen associations in occupational asthma induced by isocyanates
Combined asthma and alveolitis due to diphenylmethane diisocyanate (MDI) with demonstration of no crossed respiratory reactivity to toluene diisocyanate (TDI).
No full textTwo workers, who developed asthmatic symptoms, were studied with inhalation provocation tests using diphenylmethane diisocyanate (MDI) and toluene diisocyanate (TDI). The subjects showed specific asthmatic reactions to MDI challenge (more than 20% fall in FEV1), and one also had an alveolar response. Alveolitis was suggested by fever, basal crackles, increased neutrophil counts in venous blood and in bronchoalveolar lavage. The asthmatic reaction to MDI challenge was associated with an increase in airway responsiveness to methacholine in both subjects. We conclude that MDI is a cause of asthma and/or hypersensitivity pneumonitis in workers exposed to diphenylmethane diisocyanate
Mechanisms of occupational asthma
No full textInhalation of agents in the workplace can induce asthma in a relatively small proportion of exposed workers. Like nonoccupational asthma, occupational asthma is probably the result of multiple genetic, environmental, and behavioral influences. It is important that occupational asthma be recognized clinically because it has serious medical and socioeconomic consequences. Environmental factors that can affect the initiation of occupational asthma include the intrinsic characteristics of causative agents as well as the influence of the level and route of exposure at the workplace. The identification of host factors, polymorphisms, and candidate genes associated with occupational asthma may improve our understanding of mechanisms involved in asthma. High-molecular-weight compounds from biological sources and low-molecular-weight chemicals cause occupational asthma after a latent period of exposure. Although the clinical, functional, and pathologic features of occupational asthma caused by low-molecular-weight agents resemble those of allergic asthma, the failure to detect specific IgE antibodies against most low-molecular-weight agents has resulted in a search for alternative or complementary physiopathologic mechanisms leading to airway sensitization. Recent advances have been made in the characterization of the immune response to low-molecular-weight agents. In contrast, the mechanism of the type of occupational asthma that occurs without latency after high-level exposure to irritants remains undetermined
Effect of cromolyn on carbachol-induced bronchoconstriction.
No full textThe effect of premedication with cromolyn 40 mg on the bronchial response to inhaled carbachol was investigated in four atopic and four non-atopic subjects with mild asthma. Paired carbachol inhalation tests were carried out on consecutive days in a double-blind fashion following randomized premedication with cromolyn or placebo. Bronchial sensitivity was expressed as the log dose of carbachol provoking a 15% decrease in FEV1 (log PD15 FEV1) or a 30% decrease in FEF25-75 (log PD30 FEF25-75). The mean log PD15 FEV1 was significantly greater following cromolyn compared to placebo (2.34 +/- .22 vs 1.87 +/- .10; mean +/- SE; p less than 0.05) as was log PD30 FEF25-75 (2.30 +/- .16 vs 1.72 +/- .08; p less than 0.005). These results indicate that cromolyn interferes with cholinergic induced bronchoconstriction and support the suggestion that it has an effect at a more fundamental level than the inhibition of antigen induced mediator release from mast cells
Late asthmatic reactions, airway inflammation and chronic asthma in toluene-diisocyanate-sensitized subjects.
No full textTo determine the importance of airway inflammation for exacerbation and prognosis of asthma induced by toluene diisocyanate (TDI), we first examined sensitized subjects during asthmatic reactions induced by exposure to TDI in the laboratory. We observed that late and dual, but not early, asthmatic reactions induced by TDI are accompanied by a transient increase of airway responsiveness, bronchoalveolar neutrophilia followed by eosinophilia and by an increase of LTB4 and albumin in bronchoalveolar lavage fluid. All these effects were prevented by pretreatment with prednisone. In addition, we examined the lung pathology of 1 sensitized subject who died after exposure at work. The pathologic features of fatal asthma induced by TDI and of chronic asthma induced by TDI suggest the importance of inflammation for the exacerbation and prognosis of the disease
Neutrophils and asthma.
No full textThe importance of inflammation in asthma has been recognized for a long time and recently proved in man and animal models. All inflammatory cells are probably involved in exacerbations of asthma. Neutrophils in particular are present in the airways during and after the spontaneous asthma attacks in man and during asthmatic reactions and airway hyperresponsiveness induced experimentally in man and animals. Depletion of neutrophils prevents these effects and repletion with neutrophils reconstitutes them. Moreover, the supernatant from stimulated human neutrophils causes transient hyperresponsiveness. However, neutrophils are not increased in stable asthmatics with hyperreactive airways and are not involved in airway hyperresponsiveness induced experimentally in some animals (e.g. guinea-pigs). The studies reviewed suggest that neutrophils may be involved in the transient increases of airway responsiveness associated with exacerbations of asthma, but not in the long-lasting hyperresponsiveness of stable asthmatics
Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research.
No full textIn the present paper, we have reviewed experimental animal studies on the effects of the two most important oxidant airborne pollutants, nitrogen dioxide and ozone, on the respiratory system. The toxic effects depend on concentration and length of exposure, and are generally similar for both oxidants, with ozone operative at lower concentrations. High doses of both oxidants cause death due to lung oedema. Exposure to sublethal levels causes functional alterations such as airflow limitation and airway hyperresponsiveness to bronchoconstrictor stimuli. These effects, which are generally reversible, are associated with epithelial injury, oedema and airway and parenchymal infiltration by inflammatory cells. Loss of cilia of airway epithelium and necrosis of type I alveolar epithelial cells are the most prominent consequences at the epithelial level. Inflammation is characterized by early neutrophilic infiltration, followed by an increased number of mononuclear cells, predominantly alveolar macrophages. After long-term exposure, whilst nitrogen dioxide causes predominantly emphysema, ozone produces mainly pulmonary fibrosis. Biochemical effects include lipid peroxidation, increased antioxidant metabolism, and alteration of enzyme activity. Nitrogen dioxide and ozone may also alter the immunological response and reduce the defence against infections, increasing the susceptibility of exposed animals to infections
Comparison of ultrasonically nebulized distilled water and hyperventilation with cold air in asthma.
No full textTo assess the potential value of brief non-pharmacologic challenge tests in the measurement of bronchial responsiveness and to investigate whether the responses are induced by similar mechanisms, we carried out comparative five-minute inhalation challenges with ultrasonically nebulized distilled water and cold air hyperventilation in nine asthmatic subjects. Decrements in FEV1 following both challenges were closely correlated (r = 0.885) and ranged from 8% to 59% of baseline following challenge with the former and from 6% to 59% following the latter. Each method was therefore equally effective in demonstrating bronchial hyperresponsiveness. Moreover, the strong correlation between the responses to both challenges coupled with previous observations suggests that the two stimuli may act by similar mechanisms
Non-allergic factors of bronchial asthma
No full textThe functional characteristic of all forms of asthma is the airway hyperresponsiveness to several stimuli. Airway hyperresponsiveness is always present in current asthmatics and can be also documented in some subjects during the symptom-free periods. The mechanisms of the spontaneous or induced increases of airway hyperresponsiveness are probably different from those responsible for stable airway hyperresponsiveness. The transitory increases in airway hyperresponsiveness are associated with an acute inflammatory response of the bronchial mucosa, whereas airway inflammation is not a constant finding in subjects with stable airway hyperresponsiveness. The mechanisms involved in the latter condition might be a functional and/or structural derangement of bronchial epithelium, a functional or structural alteration of airway smooth muscle or alteration in the function of the autonomic nervous system
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