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 and long acting muscarinic antagonists. We are interested in determining whether the large and/or small airways are the predominant site of airflow limitation. We are also interested in determining whether intrinsic small airways obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow limitation and to what extent may be attributed to loss of lung elastic recoil vs decreased airway conductance in peripheral airways. We 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. High resolution thin section CT of the lung will also be obtained. Analysis will evaluate integrity of the lung parenchyma as to absence and or presence of emphysema and extent of emphysema using voxel quantification. We will also investigate optical coherence tomography to detect clinically unsuspected emphysema. We will also obtain autopsy material when available in asthmatics who expire. Will also measure serum periostin as a marker of inflammation by collaborating with Genetech in San Francisco.

Population

Chronic Asthmatics

Brief Title

Mechanism(s)of Airflow Limitation in Moderate-severe Persistent Asthma

Official Title

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

Brief Summary

The purpose of this study is to evaluate the site and mechanisms responsible for expiratory <br /> airflow limitation in chronic, treated, non-smoking, stable asthmatics with moderate to <br /> severe persistent expiratory airflow obstruction. Treatment will include inhaled <br /> corticosteroids and long acting beta2agonists and long acting muscarinic antagonists. We are <br /> interested in determining whether the large and/or small airways are the predominant site of <br /> airflow limitation. We are also interested in determining whether intrinsic small airways <br /> obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow <br /> limitation and to what extent may be attributed to loss of lung elastic recoil vs decreased <br /> airway conductance in peripheral airways. We are also interested to evaluate the role of <br /> varying doses of inhaled corticosteroids to suppress large and small airway inflammation <br /> using exhaled nitric oxide as surrogate markers of inflammation. For comparison purposes, <br /> spirometry and measurements of exhaled nitric oxide will also be obtained if possible during <br /> a naturally occurring exacerbation of asthma. High resolution thin section CT of the lung <br /> will also be obtained. Analysis will evaluate integrity of the lung parenchyma as to absence <br /> and or presence of emphysema and extent of emphysema using voxel quantification. We will also <br /> investigate optical coherence tomography to detect clinically unsuspected emphysema. We will <br /> also obtain autopsy material when available in asthmatics who expire. Will also measure serum <br /> periostin as a marker of inflammation by collaborating with Genetech in San Francisco.

Detailed Description

Results will be evaluated during exacerbation and when stable following treatment.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.