Mechanism(s)of Airflow Limitation in Moderate-severe Persistent Asthma
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.
Results will be evaluated during exacerbation and when stable following treatment.
Inclusion Criteria:

 -  Current non-smoking (<10 pack yr smoking history)

 -  Stable, treated asthmatics

 -  Age 12-95 yr

 -  post 180ug albuterol by MDI: FEV 1/FVC < 70% and FEV 1 <80% predicted

 Exclusion Criteria:

 -  Pregnancy