A Phase 4 interventional study of Methacholine (MCh) Challenge Testing and Eucapneic Voluntary Hyperventilation (EVH) in Asthma, Cough and Cough Variant Asthma, sponsored by Dr. Diane Lougheed. Completed at 1 site in Canada. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-12.
Sponsored by Dr. Diane Lougheed · Phase 4, Interventional, and Basic science
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.
3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.
This study's enrollment of 45 is below the median of 83 across 2,752 interventional studies indexed under Asthma.
Browse Asthma studies →Dr. Diane Lougheed is the lead sponsor of 2 studies on the registry; none are open to participants now.
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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:
Exclusion Criteria:
Individuals diagnosed with Cough variant asthma
Drug: Methacholine (MCh) Challenge Testing · Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) · Drug: Mannitol Inhalation Kit
Individuals with chronic cough and negative methacholine challenge
Drug: Methacholine (MCh) Challenge Testing · Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) · Drug: Mannitol Inhalation Kit
Individuals with no history of asthma or chronic cough
Drug: Methacholine (MCh) Challenge Testing · Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) · Drug: Mannitol Inhalation Kit
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
Also known as: MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)], Provocholine
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Also known as: Mannitol Challenge Test
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: 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
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.
Time frame: After dose administration; will occur 2-5 minutes after dose
Peripheral Resistance (R5-R20)
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.
Time frame: 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.
Time frame: After dose administration; will occur 2-5 minutes after dose
Forced Vital Capacity (FVC)
As an index of airway closure.
Time frame: After dose administration; will occur 2-5 minutes after dose
FEV1/FVC
As an index of airway obstruction.
Time frame: After dose administration; will occur 2-5 minutes after dose
Plan to share: No
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Dr. Diane Lougheed