Mediators, airway responsiveness, and asthma

There appears to be a close interrelationship among airway responsiveness to mediators and to natural stimuli, the presence and severity of asthma, and endogenous mediator release in the airways. Histamine and methacholine have been most commonly used to measure airway responsiveness. Airway responsiveness to the two drugs is increased in patients with current symptoms of asthma, and the degree of increase relates closely to the degree of variable airflow obstruction and the therapy to control symptoms. The degree of airway responsiveness to histamine also correlates closely with the degree of responsiveness to methacholine and less closely with responsiveness to PGF2 alpha and to natural stimuli such as exercise and allergens. The less close correlations with responsiveness to exercise and allergens is probably because of variations in the ease and type of endogenous mediator release in the airways by these stimuli. Endogenous mediator release from a number of stimuli including allergens and ozone causes inflammation in the airways, asthma, and airway hyperresponsiveness. These various interrelationships indicate that the treatment of asthma should be directed to reduce airway responsiveness, prevent mediator release, and prevent or reverse inflammation.