The role of thromboxane A2 in the pathogenesis of airway hyperresponsiveness.

Airway hyperresponsiveness to a variety of bronchoconstrictor mediators and physical stimuli, such as exercise, is present in patients with asthma [1]. Inhalation of inflammatory stimuli such as allergens [2] or occupational sensitizing agents [3] in sensitized subjects, the atmospheric pollutant ozone [4], or the development of viral upper respiratory tract infections (5] can cause transient airway hyperresponsiveness, which can last days, weeks or occasionally months [6] and is associated with worsening symptoms of asthma [7]. Investigation of the pathogenesis of airway hyperresponsiveness has been most easily carried out in animals or humans by studying stimuli known to cause airway hyperresponsiveness. This is because administration of these stimuli can be carefully controlled in a laboratory setting. Those most extensively studied have been the inhaled allergens, toluene diisocyanate (TDI) or ozone both in humans [6, 8, 9], and in several animal models [10-13]. There are, however, several problems with this approach. For example, the mechanisms of airway hyperresponsiveness, even to the same stimulus, appear to differ between species [14, 15]. Also, the mechanisms causing acute airway hyperresponsiveness may be different to those causing persistent airway hyperresponsiveness in asthma. Thromboxane A2 (TxA;>, may be an important mediator in the pathogenesis of airway hyperresponsiveness in animal models, and allergic responses as well as transient and persistent airway hyperresponsiveness in humans. This article will review the evidence that Tx~ is involved in these responses.