Bronchodilating and Bronchoprotective Effects of Deep Inspirations

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01659476
• Other study ID #: 2012-01
• Status: Completed
• Phase: N/A
• First received: July 30, 2012
• Last updated: April 4, 2018
• Start date: October 2012
• Est. completion date: August 2017

Study information

• Verified date: April 2018
• Source: Queen's University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Cough
• Respiratory Aspiration

Intervention

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.
• 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:

Locations

Country	Name	City	State
Canada	Kingston General Hospital at Queen's University	Kingston	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Queen's University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mid expiratory flows	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.	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.
Secondary	percent fall in FEV1	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)	After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Secondary	respiratory system reactance (X5)	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.	After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Secondary	peripheral resistance (R5-R20)	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.	After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Secondary	Central airway resistance	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.	After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Secondary	Forced vital capacity (FVC)	As an index of airway closure.	After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Secondary	FEV1/FVC	As an index of airway narrowing (obstruction)	After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.