The goal is to investigate the mechanisms through which increased airflow alters the collateral system resistance (Rcs) in the canine lung periphery. The central hypothesis is that the collateral system response to increased airflow is a direct function of evaporative water loss. The underlying mechanism may involve either airway cooling or airway drying (i.e., changes in the osmotic environment of the pulmonary mucosa). These changes could trigger a cascade of events that lead to a number of alternative pathways that affect Rcs. Each pathway could act simultaneously and synergistically to stimulate mediator release, trigger muscarinic or adrenergic activity, or directly affect airway smooth muscle and epithelium. Experiments are described in which an animal model is used to examine various mechanisms that may be involved in exercise, cold air, and hyperventilation induced bronchospasm. The specific objectives are: 1) To determine the relationship between the osmotic condition of bronchial mucosa and peripheral lung responses to increased airflow; 2) To examine the relationship between changes in bronchial mucosa temperature (Taw) and changes in peripheral tone; and 3) To modify collateral system responses to elevated rates of airflow with various agents in an attempt to understand the underlying mechanism(s) responsible for airflow-induced bronchospasm. Experiments will utilize 1) the wedged bronchoscope technique to monitor Rcs, deliver aerosols, and challenge the lung periphery with increased rates of airflow; 2) specially designed thermisters to monitor Taw; 3) filter paper discs placed directly on the bronchial mucosa to determine the osmolarity of airway fluids in wedged sublobar segments; 4) bronchoalveolar lavage to examine the effect of high flow on cell profiles and mediator release; and 5) various pharmacologic and nonpharmacologic agents in an attempt to alter the response to increased airflow. The response of the peripheral lung to increased airflow is of particular interest considering the fact that many asthmatics exhibit small airways obstruction following a period of exercise. The results of this study should provide a more complete understanding of the underlying mechanisms responsible for airflow-induced responses of the airways.
| Wang, D; Adkinson Jr, N F; Menkes, H A et al. (1988) Aminophylline reduces air-flow-induced constriction in the canine lung periphery. Am Rev Respir Dis 137:31-7 |
| Freed, A N; Kelly, L J; Menkes, H A (1987) Airflow-induced bronchospasm. Imbalance between airway cooling and airway drying? Am Rev Respir Dis 136:595-9 |
| Freed, A N; Wang, D; Menkes, H A (1987) Dry air-induced constriction: effects of pharmacological intervention and temperature. J Appl Physiol 62:1794-800 |
