Bronchodilating and Bronchoprotective Effects of Deep Inspirations
Bronchodilating and Bronchoprotective Effects of Deep Inspirations
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.
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.
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.