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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mannitol challenge | Experimental | Mannitol challenge performed per standard mannitol challenge procedure with deep inhalation technique |
|
| Mannitol challenge w/ TBI | Experimental | Mannitol challenge performed per standard mannitol challenge procedure except with tidal breathing technique |
|
| Methacholine challenge w/ DI | Experimental | Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure except with deep inhalation technique |
|
| Methacholine challenge | Experimental | Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure (tidal breathing technique) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deep inhalation technique | Procedure | Use of deep inhalations for administration of inhalant |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dr. Don Cockcroft, MD | University of Saskatchewan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asthma Research Lab - University of Saskatchewan | Saskatoon | Saskatchewan | S7N 0W8 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31785175 | Derived | Blais CM, Davis BE, Cockcroft DW. The effect of deep inhalation on mannitol responsiveness. Clin Exp Allergy. 2020 Mar;50(3):308-314. doi: 10.1111/cea.13543. Epub 2019 Dec 14. | |
| 31542451 | Derived | Blais CM, Davis BE, Graham BL, Cockcroft DW. Respiratory Duty Cycles in Individuals With and Without Airway Hyperresponsiveness. Chest. 2020 Feb;157(2):356-362. doi: 10.1016/j.chest.2019.09.005. Epub 2019 Sep 19. |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D016210 | Methacholine Chloride |
| D008353 | Mannitol |
| ID | Term |
|---|---|
| D008688 | Methacholine Compounds |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
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| Tidal breathing technique | Procedure | Use of tidal breathing for administration of inhalant |
|
| Methacholine | Drug | Methacholine direct bronchoconstrictor used for bronchoprovocation challenge |
|
|
| Mannitol | Drug | Mannitol indirect bronchoconstrictor used for bronchoprovocation challenge |
|
|
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 |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D009930 | Organic Chemicals |
| D009861 | Onium Compounds |
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
| D002241 | Carbohydrates |