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

Sponsor

Dr. Diane Lougheed (Other)

Overall Status

Completed

CT.gov ID

NCT01064245

Collaborator

The Ontario Thoracic Society of the Ontario Lung Association (Other), Queen's University (William M Spear / Start Memorial Fund) (Other)

Enrollment

Location

Arms

142.9

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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	N/A

Study Design

Study Type:

Interventional

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 :

Feb 1, 2010

Actual Primary Completion Date :

Dec 31, 2021

Actual Study Completion Date :

Dec 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 Names: Provocholine Other: mannitol challenge test inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg Other Names: Aridol
Experimental: Asthma Those with diagnosed asthma.	Drug: high-dose methacholine challenge test nebulized liquid inhalation, 0.0625 - 256 mg/mL, doubling doses Other Names: Provocholine Other: mannitol challenge test inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg Other Names: Aridol

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 Names:

Provocholine

Other: mannitol challenge test

inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg

Other Names:

Aridol

Experimental: Asthma

Those with diagnosed asthma.

Drug: high-dose methacholine challenge test

nebulized liquid inhalation, 0.0625 - 256 mg/mL, doubling doses

Other Names:

Provocholine

Other: mannitol challenge test

inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg

Other Names:

Aridol

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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:

An exacerbation necessitating any alteration in medication, emergency department visit or hospitalizations within the previous 4 weeks;
Inability to perform acceptable quality spirometry;
Medical contraindications to methacholine challenge testing 35, including:
Severe airflow limitation (FEV1 <50% predicted or <1.0 L);
Heart attack or stroke in last 3 months;
Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100;
Known aortic aneurysm;
Moderate airflow limitation < 60% predicted or <1.5 L);
Inability to perform acceptable quality spirometry;
Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
Pregnant or nursing mothers.
Smoking history in excess of 10 pack years;
Medical contraindications to mannitol challenge testing, including:
Aortic or cerebral aneurysm;
Uncontrolled hypertension; and
Myocardial infarction or a cerebral vascular accident in the previous six months).
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.