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

NCT01064245 | Completed

• 1 other identifier: 2010-01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Cough Variant Asthma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• %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)

Study Arms (2)

Cough Variant Asthma

EXPERIMENTAL

Those diagnosed with cough variant asthma.

Drug: high-dose methacholine challenge test; Other: mannitol challenge test

Asthma

EXPERIMENTAL

Those with diagnosed asthma.

Drug: high-dose methacholine challenge test; Other: mannitol challenge test

Interventions

high-dose methacholine challenge test DRUG

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

Also known as: Provocholine

Asthma; Cough Variant Asthma

mannitol challenge test OTHER

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

Also known as: Aridol

Asthma; Cough Variant Asthma

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Diane Lougheed: lead
• The Ontario Thoracic Society of the Ontario Lung Association: collaborator
• Queen's University (William M Spear / Start Memorial Fund): collaborator

Study Sites (1)

Kingston General Hospital

Kingston, Ontario, K7L2V7, Canada

Location

MeSH Terms

Conditions

Asthma; Cough-Variant Asthma; Cough; Hypersensitivity

Interventions

Methacholine Chloride; Mannitol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methacholine Compounds; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Sugar Alcohols; Alcohols; Carbohydrates

Study Officials

• Diane Lougheed, MD

  Queen's University

  PRINCIPAL INVESTIGATOR

• Scott Turcotte

  Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 1, 2010
• First Posted: February 8, 2010
• Study Start: February 1, 2010
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 28, 2022

Record last verified: 2022-02

Locations

CA (1)