Bronchodilating and Bronchoprotective Effects of Deep Inspirations
Condition: Asthma; Cough
MeSH terms: Asthma; Cough; Respiratory Aspiration
Study type: Interventional

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.
    

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.
    

Intervention name(s): Methacholine(MCh) Challenge Testing; Methacholine(MCh) Challenge Testing
Intervention type(s): Other; Other
Intervention description(s): 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.; 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 intervention name(s): Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)]; Other names: Provocholine; Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)]; Other names: Provocholine
Intervention MeSH terms: Methacholine Chloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: methacholine; deep inspiration; bronchoprotective effect; bronchodilating effect