Determining Baseline Respiratory Duty Cycles in Subjects With and Without Airway Hyperresponsiveness

Study Overview
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Brief Summary
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The study investigates the inspiratory duty cycle in subjects with and without airway hyper-responsiveness both at rest and during a bronchoprovocation challenge. The primary goal is to determine an average inspiratory duty cycle for standard use in the calculation of bronchoprovocation test results.

Detailed Description
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At least fifteen subjects with airway hyper-responsiveness and fifteen without airway hyper-responsiveness will be recruited to participate in this randomized, crossover study. Subjects will complete 2 methacholine challenges at least 24 hours apart. One methacholine challenge will entail the volumetric method using a vibrating mesh nebulizer. The second methacholine challenge will be performed identically except that the nebulizer will be fitted onto an ultrasonic nebulizer so as to measure the inspiratory duty cycle throughout the bronchoprovocation challenge.

Official Title
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Determining Baseline Respiratory Duty Cycles in Subjects With and Without Airway Hyperresponsiveness

Conditions
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Airway Hyper Responsiveness

Intervention / Treatment
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* Procedure: Volumetric methacholine challenge unmodified
* Procedure: Modified volumetric methacholine challenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be 18 years of age or older Participants with airway hyper-responsiveness must have a positive methacholine challenge Forced expiratory volume (FEV1) of at least 65% of predicted (based on age, height, and gender) Participants without airway hyper-responsiveness must have a negative methacholine challenge All participants must avoid strenuous exercise on test days No short-acting beta-2 agonist use within 6 hours of study visit Exclusion Criteria: Participants without known airway hyper-responsiveness cannot have a current or historical respiratory condition (e.g. asthma, allergic rhinitis) Participants cannot be taking long-acting bronchodilators Participants cannot be pregnant or lactating Participants cannot have cardiovascular problems

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Volumetric methacholine challenge<br>Methacholine challenge performed per the volumetric method using an Aerogen Solo vibrating mesh nebulizer | Procedure: Volumetric methacholine challenge unmodified<br>* Bronchoprovocation challenge performed per volumetric method<br>|
| Active Comparator: Methacholine challenge with spirometer<br>Methacholine challenge performed per the volumetric method using an Aerogen Solo vibrating mesh nebulizer fitted with an ultrasonic spirometer | Procedure: Modified volumetric methacholine challenge<br>* Bronchoprovocation challenge performed per volumetric method modified to include use of ultrasonic spirometer fitted with vibrating mesh nebulizer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average inspiratory duty cycle in subjects with airway hyper-responsiveness measured using ultrasonic spirometer and tidal breathing | The inspiratory duty cycles measured for each participant (in duplicate over at least 24 hours) will be averaged for all participants with airway hyper-responsiveness and for all participants without airway-hyperresponsiveness | 24 hours | 
| Average inspiratory duty cycle in subjects without airway hyper-responsiveness | The inspiratory duty cycles measured for each participant (in duplicate over at least 24 hours) will be averaged for all participants without airway hyper-responsiveness | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within-subject variability in inspiratory duty cycle measured using ultrasonic spirometer and tidal breathing during room air inhalation | Repeat measurements of inspiratory duty cycle during tidal breathing of room air collected at least 24 hours apart | 24 hours | 
| Between-subject variability within subject group (i.e. airway hyper-responsiveness group) | Investigation of whether subjects differ in their inspiratory duty cycles (within their respective study group) | 1 hour | 
| Variability in inspiratory duty cycle within subjects when inhaling room air versus an aerosol while using tidal breathing through an ultrasonic spirometer | Investigation of whether participants differ in their inspiratory duty cycle when inhaling room air versus a saline vapor (i.e. does an aerosol influence people's breathing pattern) | 1 hour | 
| Within-subject variability in provocative dose of methacholine causing a 20% fall in forced expiratory volume (PD20) between repeat methacholine challenges | Repeat PD20 measures collected for each participant will be compared to determine if there is any significant within-subject variability in PD20 | 24 hours | 
| Variability in inspiratory duty cycle with progressive airway constriction induced through methacholine challenge testing | The inspiratory duty cycle in each subject will be measured throughout a methacholine challenge during each inhalation period, which will allow for determination of whether the inspiratory duty cycle changes with the progressive airway constriction (or lack thereof) induced through methacholine challenge testing | 24 hours | 
| Variability in in inspiratory duty cycle between airway hyper-responsiveness group and group without airway-hyperresponsiveness | Analysis of variance to determine whether subjects differ in their inspiratory duty cycles based on their status as having or as not having airway-hyperresponsiveness | 1 hour | 
| Within-subject variability in inspiratory duty cycle measured using ultrasonic spirometer and tidal breathing during saline inhalation | Repeat measurements of inspiratory duty cycle during tidal breathing of nebulized saline collected at least 24 hours apart | 24 hours | 
| Between-subject variability within subject group (no airway hyper-responsiveness group) | Investigation of whether subjects differ in their inspiratory duty cycles (within their respective study group) | 1 hour |