Bronchodilating and Bronchoprotective Effects of Deep Inspirations

NCT01659476 | Completed

• 1 other identifier: 2012-01
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma; Cough

Keywords

methacholine; deep inspiration; bronchoprotective effect; bronchodilating effect

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• percent fall in FEV1

  After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.

• respiratory system reactance (X5)

  After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.

• peripheral resistance (R5-R20)

  After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.

• Central airway resistance

  After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.

• Forced vital capacity (FVC)

  After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.

Study Arms (4)

Asthma

EXPERIMENTAL

Individuals diagnosed with asthma.

Other: Methacholine(MCh) Challenge Testing

Cough Variant Asthma

EXPERIMENTAL

Individuals diagnosed with cough variant asthma.

Other: Methacholine(MCh) Challenge Testing

Mch-induced cough w/normal airway sensitivity

EXPERIMENTAL

Individuals with chronic cough normal PC20 MCh(\>16 mg/mL) \& who cough during Mch challenge testing.

Other: Methacholine(MCh) Challenge Testing

Normal

EXPERIMENTAL

Individuals with no history of asthma or chronic cough

Other: Methacholine(MCh) Challenge Testing

Interventions

Methacholine(MCh) Challenge Testing OTHER

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.

Also known as: Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)], Other names: Provocholine

Asthma; Cough Variant Asthma; Mch-induced cough w/normal airway sensitivity

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• asthma: episodic respiratory symptoms occurring in association with variable airflow obstruction (Canadian Asthma Consensus Report definition);
• 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);
• 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.

You may not qualify if:

• 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
• 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) is a relative contraindication;
• 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

Sponsors & Collaborators

• Queen's University: lead

Study Sites (1)

Kingston General Hospital at Queen's University

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Asthma; Cough

Condition Hierarchy (Ancestors)

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; Pathological Conditions, Signs and Symptoms

Study Officials

• M. Diane Lougheed, MD MSc

  Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 30, 2012
• First Posted: August 7, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: April 6, 2018

Record last verified: 2018-04

Locations

CA (1)