Air pollution interacts with past episodes of bronchiolitis in the development of asthma.

BACKGROUND: Exposure to ambient air pollution and bronchiolitis are risk factors for asthma. The aim of this study was to investigate the effect of air pollution on the development of asthma in children with past episodes of bronchiolitis. METHODS: A prospective 2-year follow-up survey consisting of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and allergy evaluations were conducted in 1743 children with a mean age of 6.8 years. Recent 5-year exposure to air pollution was estimated using a geographic information system. RESULTS: Higher exposure to ozone was associated with airway hyper-responsiveness (PC20  ≤ 16 mg/ml) at enrollment (odds ratio [OR] = 1.60, 95% CI [confidence interval] = 1.13-2.27) and with new episodes of wheezing during the 2-year period (OR = 1.92, 95% CI = 0.96-3.83). Past episodes of bronchiolitis were associated with both current wheezing and physician-diagnosed asthma. When the two factors were combined, the prevalence of bronchial hyper-reactivity (OR = 2.96, 95% CI = 1.41-6.24) and new wheezing (OR = 4.17, 95% CI = 0.89-19.66) as well as current wheezing and physician-diagnosed asthma was even greater (P for trend <0.05 for all). In children with both risk factors, lung function was significantly decreased, with atopic children being particularly vulnerable. CONCLUSION: In children, the interaction between air pollution and past episodes of bronchiolitis resulted in a greater prevalence of asthma and pointed to an association with bronchial hyper-reactivity and decreased lung function. These results suggest mechanisms underlying the development of asthma.

Vanadate-sensitive microsomal ATPases and microsomal 45Ca2+ uptake in tracheal epithelial cells.

Cytosolic free Ca2+ plays important roles in the regulation of physiological processes in tracheal epithelial cells and is probably regulated by many ion-transporting ATPases in these cells. Therefore, the effect of vanadate was investigated to characterize microsomal ion-transporting ATPases. Dose response experiments showed that vanadate had a biphasic effect on the microsomal ATPase activity: a decrease at the vanadate concentration below 100 microM, and a steep decrease at the concentration above 100 microM. The dose response data were fitted to two sigmoidal functions, corresponding to a low-affinity vanadate-sensitive (LAVS) ATPase and a high-affinity vanadate-sensitive (HAVS) ATPase. In 45Ca2+ uptake experiments, both LAVS and HAVS ATPases mediated microsomal 45Ca2+ uptake. The LAVS ATPase was selectively sensitive to thapsigargin in both ATPase activity and 45Ca2+ uptake, suggesting that it is an ER/SR-type intracellular Ca2+-ATPase. Although the HAVS ATPase mediated one-fourth of microsomal 45Ca2+ uptake, its activity was not sensitive to thapsigargin. These results indicate that the activities of these two vanadate-sensitive ATPases are mediated by different enzymes, since thapsigargin only blocks the activity of LAVS ATPase. In conclusion, there are two types of vanadate-sensitive microsomal ATPases, and these ATPases mediate microsomal 45Ca2+ uptake in airway epithelial cells.

Inhibition of microsomal ATPases by high concentration of Mg2+ in tracheal epithelial cells.

Previous work in our laboratory established the presence of two types of microsomal ATPases, a low-affinity vanadate-sensitive (LAVS) and a high-affinity vanadate-sensitive (HAVS) ATPases, in tracheal epithelial cells. These ATPases were identified as Ca2+-ATPases by specific inhibitors and microsomal Ca2+ uptakes. Since the regulatory roles of Mg2+ on both cellular Ca2+-signaling and epithelial transports were demonstrated, the effects of Mg2+ on these ATPases were investigated. Mg2+-dependence of ATPase activity appeared bell-shaped with a maximal activity at 1-2 mM Mg2+ and Mg2+ at higher than 2 mM inhibited these enzymes. In a kinetic analysis of the LAVS ATPase inhibition, high concentration of Mg2+ appeared to inhibit the binding of ATP to a substrate-binding site. The microsomal 45Ca2+ uptakes mediated by both ATPases were also inhibited by high concentration of Mg2+. In order to test whether high concentration of Mg2+ directly inhibits these enzymes, microsomes were made leaky by the treatment of Triton X-100 and the microsomal ATPases were solubilized with CHAPS. The leaky microsomal ATPases and CHAPS-solubilized ATPases were similarly inhibited by high concentration of Mg2+, suggesting that Mg2+ directly inhibit these enzymes. In conclusion, Mg2+ has two types of modulatory effects on these enzymes, a catalytic effect at low concentration and an inhibitory effect at high concentration.