Vocal Cord Responses During Hyperventilation in Normal Individuals and in Mild and Severe Asthmatics.

Specific aims: Project 1 - 'Acute' hyperventilation in normal subjects and asthmatics. Aim 1.1: To measure PVCM by endoscopy in response to a single period of hyperventilation in normal subjects and asthmatics. Aim 1.2: To relate PVCM to symptoms in both groups. Aim 1.3: To relate PVCM to bronchial and ET-AHR before and after acute hyperventilation. Project 2 - 'Chronic' hyperventilation and the effect on vocal cord movements in asthmatic subjects. Aim 2.1: To measure PVCM by endoscopy in response to multiple periods of hyperventilation (twice daily over 2 weeks) in normal subjects and asthmatics. Aim2.2: To relate PVCM to symptoms in both groups. Aim 2.1: To relate PVCM to bronchial and ET-AHR before and after chronic hyperventilation. Project 3 (a) - Effects of anticholinergic medication on PVCM. Aim 3.1: Determine the effect of anti-cholinergic inhaled medications on PVCM induced by hyperventilation. Project 3 (b) - PVCM during exercise and the effects of anticholinergic medication on PVCM If no PVCM is detected in project 1 and 2, as an alternative strategy the Investigators will examine PVCM that has been shown to occur in severe asthma in response to exercise. The effect of anti-cholinergic inhaled medications will then be examined in this model. Significance: Dysfunctional breathing may be a mechanism whereby symptomatic PVCM develops in asthma but not in health. The proposed studies will enhance the Investigators understanding of the role played by dysfunctional breathing in the pathogenesis of this distressing condition and may provide a rationale for targeted therapies.