Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests

• ClinicalTrials.gov Identifier: NCT01064245
• Recruitment Status: Completed
• First Posted: February 8, 2010
• Last Update Posted: February 28, 2022
• Sponsor: Dr. Diane Lougheed
• Collaborators: The Ontario Thoracic Society of the Ontario Lung Association; Queen's University (William M Spear / Start Memorial Fund)
• Information provided by (Responsible Party): Dr. Diane Lougheed, Queen's University

Study Description

Brief Summary:

Cough is a common, disruptive and at times disabling symptom which often prompts patients to seek medical attention. Determining the cause(s) of chronic cough can be challenging, and costly. Asthma and other airway disorders are among the most common causes of chronic cough; and cough can be the sole symptom of asthma. Little is known about why some patients with asthma primarily cough and do not develop the other symptoms of asthma such as shortness of breath or wheeze. Improved understanding of the reasons for these different manifestations may lead to new and more effective treatment strategies. We have notices differences in pressure measurements inside the chest in patients who mostly cough during induced bronchoconstriction, which might be part of the explanation for varying symptoms. This study will compare lung mechanical responses during methacholine and mannitol-induced induced airway narrowing between typical asthma, cough variant asthma (CVA) and an airway inflammatory disorder that is not asthma.The purpose of this research is to explore the pathophysiology and sensory-mechanics of cough in individuals with asthma, CVA and methacholine-induced cough but normal airway sensitivity using mannitol and high-dose methacholine bronchoprovocation testing.

Condition or disease	Intervention/treatment	Phase
Asthma; Cough Variant Asthma	Drug: high-dose methacholine challenge test; Other: mannitol challenge test	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests
• Actual Study Start Date: February 1, 2010
• Actual Primary Completion Date: December 31, 2021
• Actual Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cough Variant Asthma; Those diagnosed with cough variant asthma.	Drug: high-dose methacholine challenge test; nebulized liquid inhalation, 0.0625 - 256 mg/mL, doubling doses; Other Name: Provocholine; Other: mannitol challenge test; inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg; Other Name: Aridol
Experimental: Asthma; Those with diagnosed asthma.	Drug: high-dose methacholine challenge test; nebulized liquid inhalation, 0.0625 - 256 mg/mL, doubling doses; Other Name: Provocholine; Other: mannitol challenge test; inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg; Other Name: Aridol

Outcome Measures

Primary Outcome Measures :

1. PD15 (15% fall in forced expiratory volume in one second (FEV1) from baseline during challenge test visits) [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]

Secondary Outcome Measures :

1. %ΔFEV1 (percentage change in forced expiratory volume in one second) [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
2. Plateau response [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
3. Dose-response slope [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
4. Expiratory Flow Limitation (EFL) [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects with asthma or suspected CVA who have previously participated in or who have expressed interest in participating in studies will be invited to participate in the study. Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion, but medication use will be recorded and examined in the analysis.

Exclusion Criteria:

1. An exacerbation necessitating any alteration in medication, emergency department visit or hospitalizations within the previous 4 weeks;
2. Inability to perform acceptable quality spirometry;

3. Medical contraindications to methacholine challenge testing 35, including:

   1. Severe airflow limitation (FEV1 <50% predicted or <1.0 L);
   2. Heart attack or stroke in last 3 months;
   3. Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100;
   4. Known aortic aneurysm;
   5. Moderate airflow limitation < 60% predicted or <1.5 L);
   6. Inability to perform acceptable quality spirometry;
   7. Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
   8. Pregnant or nursing mothers.
4. Smoking history in excess of 10 pack years;

5. Medical contraindications to mannitol challenge testing, including:

   1. Aortic or cerebral aneurysm;
   2. Uncontrolled hypertension; and
   3. Myocardial infarction or a cerebral vascular accident in the previous six months).
6. Women who are pregnant or breastfeeding because the effects of a possible hyperresponsiveness reaction to mannitol in mothers and/or fetuses are unknown and many compounds are excreted in human milk therefore caution should be taken.

Contacts and Locations

Locations

Canada, Ontario

Kingston General Hospital

Kingston, Ontario, Canada, K7L2V7

Sponsors and Collaborators

Dr. Diane Lougheed

The Ontario Thoracic Society of the Ontario Lung Association

Queen's University (William M Spear / Start Memorial Fund)

Investigators

• Principal Investigator: Diane Lougheed, MD; Queen's University
• Principal Investigator: Scott Turcotte; Queen's University

More Information

• Responsible Party: Dr. Diane Lougheed, Professor of Medicine, Queen's University
• ClinicalTrials.gov Identifier: NCT01064245
• Other Study ID Numbers: 2010-01
• First Posted: February 8, 2010
• Last Update Posted: February 28, 2022
• Last Verified: February 2022

Keywords provided by Dr. Diane Lougheed, Queen's University:

Asthma; Cough Variant Asthma; Mannitol; Methacholine; Cough; Hypersensitivity

Additional relevant MeSH terms:

Asthma; Cough; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Mannitol; Methacholine Chloride; Diuretics, Osmotic; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Miotics; Autonomic Agents; Peripheral Nervous System Agents; Parasympathomimetics; Bronchoconstrictor Agents; Respiratory System Agents; Muscarinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action