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

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.