Models and mechanisms of exercise-induced asthma

Abstract

Airflow-induced bronchoconstriction (AIB) in mammals can be broadly categorized as either vagal-dependent or vagal-independent. Among mammals, rabbits and cats belong to the former and guinea-pigs belong to the latter categories. Although insufficient data are available to classify monkeys, dogs and man appear to occupy the middle ground in which a small but significant parasympathetic component modulates airflow-induced bronchoconstriction. The fact that vagal activity can only partially account for airflow-induced bronchoconstriction in some asthmatic subjects suggests that vagal-dependent models may be of limited value in studying the human condition, but should prove valuable in elucidating the parasympathetic component of this mechanism. Although airflow-induced bronchoconstriction appears to be remarkably similar in guinea-pigs, dogs and humans, there are important differences concerning the potential role of specific mediators in producing airflow limitation. Concordant data from animal models and man suggest that: 1) airflow-induced bronchoconstriction is a basic mammalian response to airway desiccation; 2) airway drying stimulates and cooling inhibits this response; 3) hyperpnoea with dry air may damage the bronchial mucosa and contribute to this response; 4) biochemical mediators contribute to the development of this response; 5) vascular engorgement and airway oedema do not appear to be the primary effectors of this response, and in fact may antagonize it; 6) airway smooth muscle constriction is involved in the production of airflow-induced bronchoconstriction, and airway oedema may enhance its effect; and 7) airway and vascular responses to dehydration may protect against acute dry air-induced mucosal injury. Finally, although one must be cautious in extrapolating results from animals to humans, the similarities that do exist suggest that the investigation of airflow-induced bronchoconstriction in carefully selected animal models will continue to provide new insights concerning its development in humans.