Mechanism(s) of Airflow Limitation During Exacerbation of Asthma

Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers

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.

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.

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