Schelegle et al26 observed that ozone-induced decreases in pulmonary function, but not changes in hyper responsiveness, could be inhibited by a prostaglandin synthetase inhibitor such as indomethacin in a small group of healthy human subjects. However, indomethacin inhibits the airway hyperresponsiveness but not the neutrophil influx induced by ozone in dogs, suggesting that the mediator linked to hyperresponsiveness may be related to products of arachidonic acid that are sensitive to inhibition by indomethacin.
Some studies have shown a relationship between the use of antileukotrienes and partial inhibition of bronchoconstriction in exercise-induced asthma, suggesting that this mediator may be of particular relevance. However, bronchoalveolar lavage studies after ozone have failed to reveal an increased concentration of known chemotactic agents like leuko-triene (LTB4) or 15-hydroxyeicosatetraenoic acid (15-HETE). It should be noted that products formed in the lung from eicosanoid metabolism depend on cell type, animal species, and on the activation stimulus; thus, the prediction of the net result on physiologic parameters would be difficult and highly speculative. ventolin inhaler
The hyper responsiveness associated with ozone is linked to the development of an airway inflammatory response involving epithelial cells and neutrophils. The exact mechanism by which airway hyperresponsiveness and inflammation are linked is uncertain, but it could be explained by changes in epithelial permeability and ion transport as was shown by Bromberg et al. They found that guinea pigs exposed to 1 ppm ozone for 3 h showed a marked increase in the rate of appearance in blood of various water-soluble compounds instilled onto the surface of the trachea, indicating increased permeability of airway epithelium. A possible hypothesis to explain the interaction between ozone exposure and allergens could be related to an increased absorption of allergens across the mucosal surface and more efficient contact between antigen and antigen presenting cells.
The production of oxygen radicals may also be important in the pathogenesis of ozone-induced airway hyperresponsiveness. The oxidant effects of ozone may play a critical role in its deleterious effect; ozone contains two unpaired electrons and can oxidize target molecules or generate free radicals. Matsui et al showed that pretreatment with the antioxidants, allopurinol and desferoxamine, significantly inhibited ozone-induced airway responsiveness in dogs. However, this postulated mechanism of action remains entirely speculative. Of note, the hyperresponsiveness consequent to ovalbumin can also be inhibited by blocking the production of oxygen radicals in guinea pigs.