Bronchodilating and Bronchoprotective Effects of Deep Inspirations

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Queen's University
Sponsor:
Information provided by (Responsible Party):
Dr. Diane Lougheed, Queen's University
ClinicalTrials.gov Identifier:
NCT01659476
First received: July 30, 2012
Last updated: February 9, 2016
Last verified: February 2016
  Purpose

The objectives of this research are to compare (i) the bronchodilating and (ii) the bronchoprotective effects of deep inspirations (DIs) in individuals with: (a) asthma, (b) CVA, (c) methacholine-induced cough but normal airway sensitivity and .

(d) in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).

Hypotheses:

i. The bronchodilating effect of a DI will be: (a) absent or impaired in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in individuals with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).

ii. The bronchoprotective effect of a DI will be: (a) absent in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in those with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).

iii. Healthy individuals without asthma, chronic cough, or asymptomatic airway hyperresponsiveness, will not cough, or develop significant dyspnea, small airways obstruction or dynamic hyperinflation during high-dose methacholine bronchoprovocation.


Condition Intervention
Asthma
Cough
Other: Methacholine(MCh) Challenge Testing

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Bronchodilating and Bronchoprotective Effects of Deep Inspirations in Asthma, Cough Variant Asthma and Chronic Cough With Normal Airway Sensitivity and Sensory-Mechanical Responses to High-Dose Methacholine in Healthy Normal Subjects

Resource links provided by NLM:


Further study details as provided by Queen's University:

Primary Outcome Measures:
  • Mid expiratory flows [ Time Frame: Time frame of the methacholine challenge varies between individuals. At provocative concentration of methacholine causing a 20% and 50% decline in FEV1 (PC20 and PC50 respectively). On average, these occur about 15-25 minutes into the challenge test. ] [ Designated as safety issue: No ]
    The bronchodilating effect of a DI will be examined using responses to high-dose methacholine challenge testing (Visit 1) 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 PC20 and PC50 with that recorded at baseline.


Secondary Outcome Measures:
  • percent fall in FEV1 [ Time Frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine. ] [ Designated as safety issue: No ]
    The bronchoprotective effect of a deep inspiration will be measured by the difference between the percent fall in FEV1 following administration of methacholine using modified single-dose methacholine challenge tests on Visits 2 and 3 (with or without preceding deep inspirations)

  • respiratory system reactance (X5) [ Time Frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine. ] [ Designated as safety issue: No ]
    The bronchoprotective effect of a DI will be also examined by comparing mechanical responses to methacholine using impulse oscillometry (IOS). 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.

  • peripheral resistance (R5-R20) [ Time Frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine. ] [ Designated as safety issue: No ]
    The bronchoprotective effect of a DI will be also examined by comparing mechanical responses to methacholine using impulse oscillometry (IOS). 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.

  • Central airway resistance [ Time Frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine. ] [ Designated as safety issue: No ]
    The bronchoprotective effect of a DI will be also examined by comparing mechanical responses to methacholine using impulse oscillometry (IOS). 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.

  • Forced vital capacity (FVC) [ Time Frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine. ] [ Designated as safety issue: No ]
    As an index of airway closure.

  • FEV1/FVC [ Time Frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine. ] [ Designated as safety issue: No ]
    As an index of airway narrowing (obstruction)


Estimated Enrollment: 36
Study Start Date: October 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asthma
Individuals diagnosed with asthma.
Other: Methacholine(MCh) Challenge Testing

Visit 1: High-dose methacholine challenge test

Visit 2 or 3: Will be conducted in random order and subjects will perform one of two modified single-dose methacholine challenge tests at either visit. During these modified challenges, subjects will (a) perform five DIs from functional residual capacity (FRC) to total lung capacity (TLC) back to FRC, or (b) refrain from taking DIs prior to inhaling the previously measured single PC20 dose of methacholine.

Other Names:
  • Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)]
  • Other names: Provocholine
Experimental: Cough Variant Asthma
Individuals diagnosed with cough variant asthma.
Other: Methacholine(MCh) Challenge Testing

Visit 1: High-dose methacholine challenge test

Visit 2 or 3: Will be conducted in random order and subjects will perform one of two modified single-dose methacholine challenge tests at either visit. During these modified challenges, subjects will (a) perform five DIs from functional residual capacity (FRC) to total lung capacity (TLC) back to FRC, or (b) refrain from taking DIs prior to inhaling the previously measured single PC20 dose of methacholine.

Other Names:
  • Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)]
  • Other names: Provocholine
Experimental: Mch-induced cough w/normal airway sensitivity
Individuals with chronic cough normal PC20 MCh(>16 mg/mL) & who cough during Mch challenge testing.
Other: Methacholine(MCh) Challenge Testing

Visit 1: High-dose methacholine challenge test

Visit 2 or 3: Will be conducted in random order and subjects will perform one of two modified single-dose methacholine challenge tests at either visit. During these modified challenges, subjects will (a) perform five DIs from functional residual capacity (FRC) to total lung capacity (TLC) back to FRC, or (b) refrain from taking DIs prior to inhaling the previously measured single PC20 dose of methacholine.

Other Names:
  • Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)]
  • Other names: Provocholine
Experimental: Normal
Individuals with no history of asthma or chronic cough
Other: Methacholine(MCh) Challenge Testing

Visit 1: Baseline tests, and subjects will be randomized to complete either a high-dose methacholine using maximal expiratory flow-volume loop (MEFV), or a high-dose methacholine challenge with impulse oscillometry (IOS) and partial expiratory flow-volume loop (PEFV) and MEFV at each dose step.

Visit 2: Subjects will perform the opposite protocol, based on their first visit:

Other Names:
  • Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)]
  • Other names: Provocholine

Detailed Description:
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) and may or may not have eosinophilic bronchitis. The purpose of this research is to examine the pathophysiologic differences between three causes of chronic cough: asthma, cough variant asthma and methacholine-induced cough with normal airway sensitivity. The responses in healthy normal subjects are crucial to understand the clinical relevance of methacholine-induced cough with normal airway sensitivity.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Individuals aged 18-65 years of age with asthma, CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:

    1. asthma: episodic respiratory symptoms occurring in association with variable airflow obstruction (Canadian Asthma Consensus Report definition);
    2. CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
    3. Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 > 16 mg/mL).
  • Individuals aged 18-65 years of age with no history of asthma or chronic cough.

Exclusion Criteria:

  • an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
  • inability to perform acceptable spirometry
  • medical contraindications to methacholine challenge testing

    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) is a relative contraindication;
    6. Inability to perform acceptable quality spirometry;
    7. Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
    8. Pregnant or nursing mothers.
  • smoking history in excess of 10 pack years

Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01659476

Contacts
Contact: M. Diane Lougheed, MD MSc 613-548-2348 lougheed@kgh.kari.net
Contact: Thomas Fisher, RRT 613-549-6666 ext 2798 fishert@kgh.kari.net

Locations
Canada, Ontario
Kingston General Hospital at Queen's University Recruiting
Kingston, Ontario, Canada, K7L 2V7
Principal Investigator: M Diane Lougheed, MD MSc         
Sponsors and Collaborators
Queen's University
Investigators
Principal Investigator: M. Diane Lougheed, MD MSc Queen's University
  More Information

Responsible Party: Dr. Diane Lougheed, MD, Queen's University
ClinicalTrials.gov Identifier: NCT01659476     History of Changes
Other Study ID Numbers: 2012-01 
Study First Received: July 30, 2012
Last Updated: February 9, 2016
Health Authority: Canada: Health Canada

Keywords provided by Queen's University:
methacholine
deep inspiration
bronchoprotective effect
bronchodilating effect

Additional relevant MeSH terms:
Asthma
Cough
Respiratory Aspiration
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Pathologic Processes
Methacholine Chloride
Miotics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Parasympathomimetics
Bronchoconstrictor Agents
Respiratory System Agents
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2016