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

Gelb, Arthur F., M.D.

Status: Enrolling

Conditions: Asthma

Treatments: Drug: fluticasone/salmeterol; Drug: budesonide/formoterol; Drug: mometasone/formoterol; Drug: Prednisone

Study type: Observational

Identifiers

NCT00576069

20070934

Details and patient eligibility

About

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.

Full description

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

Enrollment: 60 estimated patients

Sex: All

Ages: 10 to 95 years old

Volunteers: No Healthy Volunteers

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

Trial design

60 participants in 1 patient group

asthma, quality of life, lung function

Description:

All Asthmatics will be treated with 1 of 3 long acting beta 2 agonist + corticosteroid using low or medium dose of inhaled (Advair) fluticasone or equivalent corticosteroid 200-500mcg/day plus salmeterol 100 mcg/day or (Symbicort) budesonide 320-640 mcg +formoterol 18 mcg/day or (Dulera) mometasone 400-800mcg + formoterol 20 mcg/day. In addition tiotropium 18ucg/day will be used. Additionally, albuterol 0.083%/ipratropium 0.02% solution or MDI HFA for acute exacerbation.Will measure lung function and asthma quality of life questionaire

Treatment:

Drug: Prednisone

Drug: mometasone/formoterol

Drug: budesonide/formoterol

Drug: fluticasone/salmeterol