Chapter 81 Experimental Models of Airway Hyperresponsiveness

Airway hyperresponsiveness is an increased sensitivity of the airways to constrictor agonists. It is measured by subjects inhaling increasing concentrations of a stimulus ranging from bronchoconstrictor mediators, such as histamine and methacholine, to physical stimuli, such as cold air, or hypertonic or hypotonic solutions. The degree of airway responsiveness correlates with the severity of asthma and the treatment required to control symptoms. The identification of stimuli that can cause asthma proves to be important in studies of the pathogenesis of airway hyperresponsiveness in asthma. These stimuli include—environmental allergens, occupational sensitizing agents, certain viruses, and the atmospheric pollutant ozone. Each of these stimuli is known to induce airway hyperresponsiveness in experimental models. Studies of the mechanisms of airway hyperresponsiveness in animal models have identified temporal associations between the presence of inflammatory cells in the airways and airway hyperresponsiveness. These studies have led to the hypothesis that activated inflammatory cells, and the mediators released from these cells, are responsible for the development of airway hyperresponsiveness after inhalation of various stimuli in human subjects.