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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cough Variant Asthma | Experimental | Individuals diagnosed with Cough variant asthma |
|
| Methacholine-induced cough | Experimental | Individuals with chronic cough and negative methacholine challenge |
|
| Control | Experimental | Individuals with no history of asthma or chronic cough |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methacholine (MCh) Challenge Testing | Drug | Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops. |
| Measure | Description | Time Frame |
|---|---|---|
| Mid expiratory flows | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Respiratory System Reactance (X5) | 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. | After dose administration; will occur 2-5 minutes after dose |
| Peripheral Resistance (R5-R20) |
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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:
Individuals aged 18-65 years of age with no history of asthma or chronic cough.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| M. Diane Lougheed, MD, MSc | Contact | 613-548-2348 | diane.lougheed@kingstonhsc.ca | |
| Taylar Wall, RRT | Contact | 613-549-6666 | 2798 | taylar.wall@kingstonhsc.ca |
| Name | Affiliation | Role |
|---|---|---|
| M. Diane Lougheed, MD, MSc | Department of Medicine, Queen's University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kingston Health Sciences Centre | Recruiting | Kingston | Ontario | K7L 2V7 | Canada |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| D003371 | Cough |
| D000096823 | Cough-Variant Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D016210 | Methacholine Chloride |
| ID | Term |
|---|---|
| D008688 | Methacholine Compounds |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
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|
| Eucapneic Voluntary Hyperventilation (EVH) | Diagnostic Test | Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit. |
|
| Mannitol Inhalation Kit | Drug | Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit. |
|
|
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. |
| After dose administration; will occur 2-5 minutes after dose |
| Central Airway Resistance | 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. | After dose administration; will occur 2-5 minutes after dose |
| Forced Vital Capacity (FVC) | As an index of airway closure. | After dose administration; will occur 2-5 minutes after dose |
| FEV1/FVC | As an index of airway obstruction. | After dose administration; will occur 2-5 minutes after dose |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D012120 | Respiration Disorders |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 | Organic Chemicals |
| D009861 | Onium Compounds |