Asthma, Cough, Cough Variant Asthma
Conditions
Keywords
Asthma, Cough, Eucapneic Voluntary Hyperventilation, Hypertonic Saline
Brief summary
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).
Detailed 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.
Interventions
DRUGMethacholine (MCh) Challenge Testing
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
DIAGNOSTIC_TESTEucapneic Voluntary Hyperventilation (EVH)
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
DRUGMannitol Inhalation Kit
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Sponsors
Dr. Diane Lougheed
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mid expiratory flows | Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test | The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory System Reactance (X5) | After dose administration; will occur 2-5 minutes after dose | Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing. |
| Peripheral Resistance (R5-R20) | After dose administration; will occur 2-5 minutes after dose | Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing. |
| Central Airway Resistance | After dose administration; will occur 2-5 minutes after dose | Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing. |
| Forced Vital Capacity (FVC) | After dose administration; will occur 2-5 minutes after dose | As an index of airway closure. |
| FEV1/FVC | After dose administration; will occur 2-5 minutes after dose | As an index of airway obstruction. |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORM. Diane Lougheed, MD, MSc
Department of Medicine, Queen's University
Outcome results
None listed