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.
The Investigators aim to:~Study the effect of hyperventilation on the development of paradoxical vocal cord movement (PVCM) in healthy individuals and in patients with mild and severe asthma,~Relate PVCM to airway symptoms and measurements of intra- and extra-thoracic airway hyperresponsiveness (ET-AHR),~Evaluate the effects of inhaled anti-cholinergic agents on PVCM induced by hyperventilation.~Hypotheses:~In health PVCM will not occur in response to hyperventilation,~In asthma PVCM will occur in response to hyperventilation,~Airway symptoms and ET-AHR will develop in parallel with PVCM,~Inhaled anticholinergic agents will prevent PVCM induced by hyperventilation.