Chronic asthmatic responses

In 1981, Chinese Restaurant Asthma was reported following capsule administration of MSG to several asthmatics (37). However, the researchers failed to account for other allergens to which the subjects could have been exposed and did not utilize the scientific practice of a "control" substance which would have helped to determine if glutamate triggered this response. In a double-blind crossover study, chronic asthmatics were challenged with MSG or a placebo. No decrease in pulmonary function was observed (39). 

Chronic exposure to fumes of heated glacial acetic acid in a canning factory has been associated with a late airway response resulting in chronic inflammation and severe bronchial asthma. Inhalation challenge induced a late asthmatic response, confirming sensitization. ... 

One of the most striking pathological features of chronic asthma is an increase in the smooth muscle mass of the airways (DunniU etal., 1969 Heard and Hossain, 1973 Hossain, 1973 Ebina etal., 1990). Hyperplasia (increase in cell number) rather than hypertrophy (increase in cell size) predominantly produces this increase in mass, and the associated reduction in airway luminal diameter. This fixed increase in muscle mass contributes to the component of airways obstruction observed in chronic asthmatics which is irreversible with bronchodilators. It also leads to an exaggerated response to bronchoconstrictor stimuli, equivalent to the characteristic bronchial hyperresponsiveness of asthmatics (James et al., 1989 Pare et al., 1991 Pare, 1993). 

Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

Bronchial asthma is defined as a chronic inflammatory disease of the lungs it affects an estimated 9 to 12 million individuals in the U.S. Furthermore, its prevalence has been increasing in recent years. Asthma is characterized by reversible airway obstruction (in particular, bronchospasm), airway inflammation, and increased airway responsiveness to a variety of bronchoactive stimuli. Many factors may induce an asthmatic attack, including allergens respiratory infections hyperventilation cold air exercise various drugs and chemicals emotional upset and airborne pollutants (smog, cigarette smoke). 

The database for HFC-134a is extensive it contains studies with both human subjects and animal models. Potentially sensitive populations, including patients with COPD and adult and pediatric asthmatic patients, were tested with direct inhalation of HFC-134a from metered-dose inhalers. The response of these groups was no different than that of healthy adults. The animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The metabolism of HFC-134a is well understood, and the relationship of exposure con... 

Th2 cytokine IL-10 is an antiinflammatory cytokine that suppresses the secretion of proinflammatory cytokines (Dll), allergen-induced airway inflammation, and nonspecific airway responsiveness (T9). IL-13 shares a receptor component, signaling pathways, and many biological activities with IL-4. In fact, IL-13 is also an antiinflammatory cytokine and plays a unique role in the optimal induction and maintenance of IgE production and IgE-mediated allergic responses when IL-4 production is low or absent (DIO, W12). Moreover, IL-13 or IL-4 shows a synergistic effect with TNF-a or IL-5 on eosinophil activation (L20). Recently, IL-11 was found to be involved in the chronic remodeling seen in asthmatic airways and is associated with increasing severity of the disease (Ml6). 

The NAC/AEGL Committee estimates the range in variability of response to specific chemical exposures primarily on the basis of quantitative human data. Acceptable experimental data are more likely to be available for AEGL-1 and AEGL-2 endpoints than for AEGL-3 endpoints. For example, numerous studies have considered induction of bronchospasm after controlled exposmes to sulfur dioxide (SO2) in asthmatic and nonasthmatic individuals (see references below). There is marked individual variability in the severity of reaction to inhalation of low concentrations of SO2. Asthmatics, individuals with hyper-reactive airways, smokers, and those with chronic respiratory or cardiac disease respond at relatively lower concentrations (Aleksieva 1983 Simon 1986). Susceptibility may also be increased in people over 60 years of age, but reports have not been consistent (Rondinelli et al. 1987 Koenig et al. 1993). By contrast, comparable human data for AEGL-3 tier concentrations are limited to anecdotal case reports. 

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