The Leaky Lung Test

Study Overview
=================
Brief Summary
-----------------
This is a clinical trial designed to test the hypothesis that measuring the absorption and excretion of inhaled mannitol will provide a clinically useful marker of airway epithelial permeability in asthma.

Detailed Description
-----------------
A cohort of subjects with asthma and healthy controls will be exposed to inhaled mannitol according to FDA approved protocols for bronchoprovocation. Mannitol will be measured in the bloodstream and urine and used to determine an airway permeability index. This is a proof of concept study and not a trial of new therapeutics.

Official Title
-----------------
A Novel Non-invasive Way to Measure Airway Epithelial Permeability in Human Subjects

Conditions
-----------------
Asthma, Allergy, Reactive Airway Disease, Lung Diseases, Obstructive

Intervention / Treatment
-----------------
* Drug: Mannitol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Asthma The diagnosis of asthma will be based on a consistent history, physical exam, and previous physician diagnosis of asthma. Consistent historical features of asthma include episodic wheezing, shortness of breath, chest tightness, or cough, often precipitated by known environmental triggers (e.g. respiratory viral infection, exposure to pollen, exercise, or stress). Consistent physical findings of asthma include audible expiratory wheezing and findings of associated diseases (e.g. eczema, allergic rhinitis), although the physical exam may be normal in between asthma attacks. Subjects will need to be free of asthma symptoms at time of challenge testing. Most asthmatic subjects should demonstrate bronchial reactivity during the mannitol challenge test. Inclusion criteria: Non-asthmatic controls Healthy control subjects will be recruited in order to define baseline values for serum and urine mannitol. Healthy control subjects will be defined by the lack of symptoms or physical findings of asthma or other allergic diseases (e.g. eczema, allergic rhinitis), and absence of any other chronic lung disease. Healthy subjects should also not demonstrate bronchial reactivity during a mannitol challenge test. Exclusion Criteria: >5 pack year history of tobacco use or active smoking. Other chronic or active lung diseases (e.g. COPD, pulmonary fibrosis, lung cancer) History of significant renal insufficiency of liver disease Asthma subjects with severe disease according to NAEPP guidelines (e.g. severe ongoing symptoms despite high-dose inhaled or oral glucocorticoids) Asthma subjects with a baseline FEV1<65% predicted Asthma subjects unwilling or unable to withhold medications prior to testing Pregnant women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asthma<br>Subjects with asthma will be exposed to inhaled mannitol according to FDA approved protocols. | Drug: Mannitol<br>* Subjects will be challenged with inhaled mannitol according to already approved protocols.<br>* Other names: Aridol for bronchoprovocation;|
| Experimental: Controls<br>Healthy control subjects will be exposed to inhaled mannitol according to FDA approved protocols. | Drug: Mannitol<br>* Subjects will be challenged with inhaled mannitol according to already approved protocols.<br>* Other names: Aridol for bronchoprovocation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway permeability index (Urinary clearance of mannitol overtime) | Urinary clearance of mannitol overtime | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absorption of mannitol (Absorption and clearance of mannitol from the bloodstream) | Absorption and clearance of mannitol from the bloodstream | 6 hours |