The Correlation Between Airway Inflammation and Loss of Deep Inhalation Bronchoprotection in Asthmatics

Study Overview
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Brief Summary
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The loss of deep inhalation bronchoprotection in asthmatic individuals has been shown to be related to the degree of airway hyperresponsiveness, a hallmark of asthma. In several studies, asthmatic individuals with mild airway hyperresponsiveness (AHR) (methacholine PC20 > 2 mg/mL) had a difference in methacholine PC20 with and without deep inhalations that averaged 1.8 doubling methacholine concentrations (p=0.0003). Conversely, asthmatic individuals with moderate to severe AHR (methacholine PC20 ≤ 2 mg/mL) had a non-significant difference in methacholine PC20 with and without deep inhalations (p=0.09). This loss of deep inhalation bronchoprotection is also now believed to play an important role in the pathogenesis of asthma. Airway inflammation is another of the key features of asthma and information on airway inflammation is increasingly being used in the diagnosis and treatment of asthma. The level of airway inflammation (as measured by fraction of exhaled nitric oxide and sputum eosinophilia) has also been shown to be correlated to the level of airway hyperresponsiveness (as measured by methacholine PC20). In addition, glucocorticoids have been shown to decrease airway hyperresponsiveness, further suggesting that these two phenomena, airway inflammation and airway hyperresponsiveness, are related. We therefore suggest that the degree of airway inflammation is related to the loss of deep inhalation bronchoprotection and expect there to be a negative correlation between the degree of deep inhalation bronchoprotection and airway inflammation.

Official Title
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The Correlation Between Airway Inflammation and Loss of Deep Inhalation Bronchoprotection in Asthmatics

Conditions
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Asthma

Intervention / Treatment
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* Other: deep inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of asthma Exclusion Criteria: other lung disease(s) smoking

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard<br>Methacholine challenges are performed using the standardized two minute tidal breathing method | Other: deep inhalation<br>* deep inhalation is comprised of an inhalation manoeuver from FRC to TLC<br>|
| Active Comparator: Modified<br>Five deep inhalation maneouvers are incorporated into the standardized methacholine challenge | Other: deep inhalation<br>* deep inhalation is comprised of an inhalation manoeuver from FRC to TLC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fraction of exhaled nitric oxide, sputum eosinophils and methacholine PC20 |  | freaction of exhaled nitric oxide data collected prior to methacholine challenges; sputum collected after the first methacholine challenge |