Asthma
Conditions
Keywords
asthma, lung function, inflammation
Brief summary
The purpose of this study is to evaluate the site and mechanisms responsible for expiratory airflow limitation in chronic, treated, non-smoking, stable asthmatics with moderate to severe persistent expiratory airflow obstruction. Treatment will include inhaled corticosteroids and long acting beta2agonists. The investigators are interested in determining whether the large and/or small airways are the predominant site of airflow limitation. The investigators are also interested in determining whether intrinsic small airways obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow limitation. The investigators are also interested to evaluate the role of varying doses of inhaled corticosteroids to suppress large and small airway inflammation using exhaled nitric oxide as surrogate markers of inflammation. For comparison purposes, spirometry and measurements of exhaled nitric oxide will also be obtained if possible during a naturally occurring exacerbation of asthma.
Detailed description
In addition we will also obtain above studies in asthmatics during naturally occuring exacerbation of asthma and following treatment. If available, results of lung function studies including measurements of lung elastic recoil will be compared to pathologic analyses of formalin fixed, air inflated lungs obtained at autopsy in asthmatics who die from asthma related or non-asthma related death. This kind of lung structure-function study will provide potential mechanism(s) to explain the loss of lung elastic recoil in acute and chronic asthmatics who are non-smokers. We will also obtain voxel quantification of high resolution thin section CT of lung obtained without IV contrast. Also, we will use fiberoptic bronchoscopy to obtain optical coherence tomography in stable asthmatics with mild to moderate to severe expiratory airflow limitation to assess integrity of the lung parenchyma.
Interventions
DRUGfluticasone/salmeterol in all asthmatics
budesonide 80ug/formoterol 4.5ug, 2 inhalations bid X 20-60 days or fluticasone 100ug/salmeterol 50ug, 1 inhalation bid X 20-60 days
DRUGbudesonide/formoterol or fluticasone/salmeterol in all asthmatics
budesonide 160ug/formoterol 4.5ug, 2 inhalations bid or fluticasone 250ug/salmeterol 50ug, 1 inhalations bid
Sponsors
Gelb, Arthur F., M.D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
To Better Understand the Mechanism(s) of Airflow Limitation During Exacerbation of Asthma
Eligibility
Sex/Gender
ALL
Age
10 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Current non-smoking (\<10 pack yr smoking history) * Stable, treated asthmatics * Age 10-80 yr * post 180ug albuterol by MDI: FEV 1/FVC \< 70% and FEV 1 \<80% predicted
Exclusion criteria
* Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled nitric oxide | 20-60 days | evaluate the role of inhaled corticosteroid on exhaled nitric oxide production in large airways and peripheral small airways/alveoli |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of unsuspected emphysema by autopsy or explanted lung | 1-5 years | Analysis of lungs obtained at autopsy or explanted lung for extent of emphysema |
| Mechanism(s) of expiratory airflow limitation | 1 to 5 years | loss of lung elastic recoil vs intrinsic airway obstruction |
Countries
United States
Contacts
Primary ContactArthur F Gelb, MD
Outcome results
None listed