Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol

Dr. Diane Lougheed

Status and phase: Enrolling; Phase 4

Conditions: Cough Variant Asthma; Asthma; Cough

Treatments: Drug: Mannitol Inhalation Kit; Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH)

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT03105843

2023-17

Details and patient eligibility

About

The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy individuals without asthma or chronic cough.

We hypothesize:

1. EVH and Mannitol cause dyspnea, cough, small airway obstruction with resultant dynamic hyperinflation, gas trapping and autoPEEP in individuals with CVA and COUGH, but not healthy controls.
2. The sensory-mechanical responses to both hyperosmolar challenges (EVH and Mannitol) are comparable within groups (CVA, COUGH and healthy controls).

Full description

Asthma is a chronic respiratory condition characterized by eosinophilic airway inflammation. Individuals with classic asthma experience paroxysmal symptoms including cough, wheeze, shortness of breath and chest tightness. Cough variant asthma (CVA) is asthma in which chronic cough (cough lasting eight weeks or more) is the sole or predominant symptom of asthma. The pathophysiologic mechanisms which differentiate asthma, CVA, and eosinophilic bronchitis without asthma are not fully understood. We have recently identified individuals with chronic cough who cough during methacholine but have normal airway sensitivity (ie. do not have asthma or CVA) (COUGH) and may or may not have eosinophilic bronchitis. The purpose of this research is to further explore the pathophysiologic basis for cough in these conditions using two 'indirect' inhalation challenge tests: eucapneic voluntary hyperventilation (EVH) and Mannitol), which induce osmotic and/or temperature changes in airway. Specifically, this study will collect preliminary data on the sensory-mechanical responses of individuals with CVA, COUGH and healthy controls to EVH and Mannitol Challenges.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:

  1. CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
  2. Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 > 16 mg/mL).

• Individuals aged 18-65 years of age with no history of asthma or chronic cough.

Exclusion criteria

• an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
• inability to perform acceptable spirometry
• medical contraindications to methacholine challenge testing
• smoking history in excess of 10 pack years Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Cough Variant Asthma

Experimental group

Description:

Individuals diagnosed with Cough variant asthma

Treatment:

Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH)

Drug: Methacholine (MCh) Challenge Testing

Drug: Mannitol Inhalation Kit

Methacholine-induced cough

Experimental group

Description:

Individuals with chronic cough and negative methacholine challenge

Treatment:

Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH)

Drug: Methacholine (MCh) Challenge Testing

Drug: Mannitol Inhalation Kit

Control

Experimental group

Description:

Individuals with no history of asthma or chronic cough

Treatment:

Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH)

Drug: Methacholine (MCh) Challenge Testing

Drug: Mannitol Inhalation Kit