The Effect of Deep Inhalation on Mannitol Responsiveness

Study Overview
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Brief Summary
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The study will assess how the inhalation technique used (deep inhalations versus tidal breathing) influences the results of a mannitol challenge test and a methacholine challenge test, if at all.

Detailed Description
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This study will look at airway responsiveness to inhaled methacholine and mannitol administered with and without deep inhalation. This study will also investigate the role of airway inflammation on these responses, using sputum differential cell counts and fractional exhaled nitric oxide. This is a single center, open label, randomized study. Individuals with stable asthma will be eligible for enrollment. The study will consist of two parts, screening and testing. Part 1: Screening Participants will undergo consent procedures and assessments of fractional exhaled nitric oxide levels, airway responsiveness to methacholine and sputum induction. If participants show airway responsiveness to methacholine (i.e. methacholine PC20 16mg/mL), they will be scheduled to undergo the testing part of the study. Part 2: Testing Participants will be randomized to undergo two methacholine or two mannitol challenges. Further randomization will occur with respect to whether the standard challenge method or the modified challenge method is performed first.

Official Title
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The Effect of Deep Inhalation on Mannitol Responsiveness

Conditions
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Asthma

Intervention / Treatment
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* Procedure: Deep inhalation technique
* Procedure: Tidal breathing technique
* Drug: Methacholine
* Drug: Mannitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent men and women between 18 and 75 years of age FEV1 at first measurement of greater than or equal to 65% predicted methacholine provocative concentration causing a 20% in FEV1 at screening that is less than or equal to 16mg/ml generally good health stable asthma Exclusion Criteria: respiratory infection within 4 weeks of screening visit worsening of asthma within 4 weeks of screening visit lung disease other than asthma significant medical comorbidity current smoker or ex-smoker with significant smoking history currently pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mannitol challenge<br>Mannitol challenge performed per standard mannitol challenge procedure with deep inhalation technique | Procedure: Deep inhalation technique<br>* Use of deep inhalations for administration of inhalant<br>Drug: Mannitol<br>* Mannitol indirect bronchoconstrictor used for bronchoprovocation challenge<br>* Other names: Aridol;|
| Experimental: Mannitol challenge w/ TBI<br>Mannitol challenge performed per standard mannitol challenge procedure except with tidal breathing technique | Procedure: Tidal breathing technique<br>* Use of tidal breathing for administration of inhalant<br>Drug: Mannitol<br>* Mannitol indirect bronchoconstrictor used for bronchoprovocation challenge<br>* Other names: Aridol;|
| Experimental: Methacholine challenge w/ DI<br>Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure except with deep inhalation technique | Procedure: Deep inhalation technique<br>* Use of deep inhalations for administration of inhalant<br>Drug: Methacholine<br>* Methacholine direct bronchoconstrictor used for bronchoprovocation challenge<br>* Other names: Provocholine;|
| Experimental: Methacholine challenge<br>Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure (tidal breathing technique) | Procedure: Tidal breathing technique<br>* Use of tidal breathing for administration of inhalant<br>Drug: Methacholine<br>* Methacholine direct bronchoconstrictor used for bronchoprovocation challenge<br>* Other names: Provocholine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of deep inhalation (versus tidal breathing) on mannitol provocative dose causing a 15% fall in forced expiratory volume in one second (FEV1) | Shift in mannitol provocative dose causing a 15% fall in forced expiratory volume | 24 hours between mannitol challenges | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of airway inflammation on methacholine and mannitol challenge results-fractional exhaled nitric oxide | Collection of fractional exhaled nitric oxide at screening - analysis of resulting measurement indicative of degree of baseline airway inflammation | up to 2 weeks, from baseline to end of study | 
| Effect of airway inflammation on methacholine and mannitol challenge results-sputum | Collection of sputum at screening - analysis for differential cell counts indicative of degree of baseline airway inflammation | up to 2 weeks, from baseline to end of study | 
| Effect of deep inhalation (versus tidal breathing) on methacholine provocative | Shift in methacholine provocative dose causing a 20% fall in forced expiratory volume | 24 hours between methacholine challenges | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mannitol, Methacholine, Deep inhalation, Tidal breathing