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

Completed

• Conditions: Hyperventilation; Larynx; Asthma
• Interventions: Other: Acute Hyperventilation; Other: Chronic hyperventilation; Drug: Effects of anticholinergic medication

• Registration Number: NCT05565430
• Lead Sponsor: Monash Medical Centre

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2016-05-31
• Study Start: 2018-06-01
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-04
• Status Verified: 2024-10
• Primary Completion: 2025-02-10
• Study Completion: 2025-02-10
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Control	Chronic hyperventilation	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Healthy Control	Effects of anticholinergic medication	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Mild Asthmatics	Acute Hyperventilation	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Mild Asthmatics	Chronic hyperventilation	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Mild Asthmatics	Effects of anticholinergic medication	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Severe Asthmatics	Acute Hyperventilation	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Healthy Control	Acute Hyperventilation	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Severe Asthmatics	Chronic hyperventilation	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.
Severe Asthmatics	Effects of anticholinergic medication	1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement.

Primary Outcome Measures

Name	Time	Method
Vocal cord aperture measured using continuous laryngoscopy after hyperventilation in normal subjects and asthmatics	6 years	For each experiment, the subject will sit in a comfortable armchair and breathe though a rubber mouthpiece and turbine pneumotachometer (Oxycon Delta, Jaeger, Wurzburg, Germany). The airflow and volume signals and that from the carbon dioxide (CO2) analyser will be displayed on a monitor and recorded. Subjects will breath through the spirometer during endoscopy to record respiratory phase for later correlation with laryngeal recording.; Laryngeal movement analysis - Image stills will be taken from the continuous laryngoscopy recording, at end inspiration and end expiration. Measurement of narrowing of the laryngeal structures in relative terms during one breathing cycle, which is independent of the distance between the laryngoscope and the glottis.

Secondary Outcome Measures

Name	Time	Method
Vocal cord changes after anti-cholinergic inhalers and/or exercise.	6 years	Vocal cord changes after anti-cholinergic inhalers and/or exercise. Subjects will inhale 4 puffs of ipratropium bromide (20 mcg/actuation inhalation) or placebo using normal tidal breathing. Subjects will then be exercised on an ergometer (Cateye Ergociser) at 75% to 85% of their predicted maximal heart rate (maximal heart rate equals 220 minus subjects age) for 8 minutes while breathing dry air at 10oC. Laryngoscopy will be conducted in situ as detailed in Project 1.; Exercise will be discontinued and PVCM will be assessed. Final lung function testing will be performed to assess the degree of respiratory obstruction produced.
Role of the extra-thoracic airway hyper-responsiveness measured using bronchial provocation test to identify asthma like symptoms.	6 years	Role of the extra-thoracic airway hyper-responsiveness to asthma like symptoms using Mannitol bronchial provocation testing
Lung function indices after hyperventilation in normal and asthmatic patients.	6 years	Spirometry indices after hyperventilation. Baseline spirometry will be recorded. Forced vital capacity (FVC) and forced expiratory volume (FEV1) will be calculated. Both are measurements of volume of air expired after maximum inspiration, measured in litres.

Trial Locations

Locations (1)

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia