Bronchodilating and Bronchoprotective Effects of Deep Inspirations

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

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.