The Investigators aim to:

1. 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,
2. Relate PVCM to airway symptoms and measurements of intra- and extra-thoracic airway hyperresponsiveness (ET-AHR),
3. Evaluate the effects of inhaled anti-cholinergic agents on PVCM induced by hyperventilation.

Hypotheses:

1. In health PVCM will not occur in response to hyperventilation,
2. In asthma PVCM will occur in response to hyperventilation,
3. Airway symptoms and ET-AHR will develop in parallel with PVCM,
4. Inhaled anticholinergic agents will prevent PVCM induced by hyperventilation.

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.

Inclusion Criteria for Healthy Controls:

• Inclusion criteria for healthy controls include:

  • age >18 to 65 years old
  • non-smokers
  • No history of chronic respiratory symptoms.

Exclusion Criteria for Healthy Controls:

• Exclusion criteria for controls include:

  • Age < 18 or > 65, smokers or smoking history >10 pack years
  • Any history of respiratory disorders such as asthma or chronic obstructive pulmonary disease (COPD)
  • Known vocal cord pathology (i.e. laryngeal cancer) or diagnosed voice condition
  • Known brain or brainstem cancer
  • Known head and neck cancer
  • Known neurological disorders (i.e. stroke)
  • Use of medications (i.e. beta-blockers or anti-cholinergic agents which may interfere with vocal cord function)
  • Singers
  • Pregnancy.

Inclusion Criterial for Asthmatics:

• The Investigators shall recruit a total of 16 patients with asthma - 8 patients with mild asthma (Group 2) and 8 patients with severe asthma (Group 3).

  • Mild asthma will be defined as patients with forced expiratory volume in 1 second (FEV1) >80% predicted.
  • Severe asthma will be defined as patients with FEV1 50-60% predicted.
  • Asthmatics will also have a forced expiratory ratio (FER) less than the lower limit of normal, indicating obstruction.

• Inclusion criteria will include:

  • age 18-65 years
  • A history of asthma defined as a bronchodilator response with increase in FEV1 >12% and 200mls or positive bronchoprovocation testing (methacholine).
  • Asthmatics will have FEV1 >50% predicted.

Exclusion Criteria for Asthmatics:

- Exclusion criteria will include:

• Age < 18 or > 65
• Smoking history > 10 pack years,
• FEV1 < 50% predicted
• Allergy to anti-cholinergics, known COPD
• Known vocal cord pathology (i.e. laryngeal cancer) or diagnosed voice condition
• Known brain or brainstem cancer
• Known head and neck cancer
• Known neurological disorders (i.e. stroke)
• Singers
• Pregnancy

Healthy controls: We shall recruit 8 normal healthy subjects (Group 1). Inclusion criteria for healthy controls include age >18 to 65 years old, non-smokers and no history of chronic respiratory symptoms. Asthmatics: We shall recruit a total of 16 patients with asthma - 8 patients with mild asthma (Group 2) and 8 patients with severe asthma (Group 3). Mild asthma will be defined as patients with forced expiratory volume in 1 second (FEV1) >80% predicted. Severe asthma will be defined as patients with FEV1 50-60% predicted. Asthmatics will also have a forced expiratory ratio (FER) less than the lower limit of normal, indicating obstruction.

Though publication

10 years

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