Mechanism(s) of Airflow Limitation During Exacerbation of Asthma

Phase 4

Recruiting

• Conditions: Asthma
• Interventions: Drug: fluticasone/salmeterol in all asthmatics; Drug: budesonide/formoterol or fluticasone/salmeterol in all asthmatics

• Registration Number: NCT01225913
• Lead Sponsor: Gelb, Arthur F., M.D.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2010-10-19
• Study First Submitted QC: 2010-10-20
• Study First Posted: 2010-10-21
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-25
• Last Update Posted: 2023-10-26
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Asthma observational study arm	fluticasone/salmeterol in all asthmatics	Asthmatics in this arm may be on varying dose of inhaled fluticasone 100-500mcg/salmeterol 50mcg bid via Advair MDI or equivalent dose via Diskus bid or Symbicort (budesonide 80-160mcg/formoterol 4.5mcg bid)or Dulera 100-200mcg mometasone/5 mcg formoterol bid, tiotropium 18mcg capsule daily. This is an observational study and additional pharmacologic intervention may include antibiotic and tapering doses of corticosteroids.
Asthma observational study arm	budesonide/formoterol or fluticasone/salmeterol in all asthmatics	Asthmatics in this arm may be on varying dose of inhaled fluticasone 100-500mcg/salmeterol 50mcg bid via Advair MDI or equivalent dose via Diskus bid or Symbicort (budesonide 80-160mcg/formoterol 4.5mcg bid)or Dulera 100-200mcg mometasone/5 mcg formoterol bid, tiotropium 18mcg capsule daily. This is an observational study and additional pharmacologic intervention may include antibiotic and tapering doses of corticosteroids.

Primary Outcome Measures

Name	Time	Method
Exhaled nitric oxide	20-60 days	evaluate the role of inhaled corticosteroid on exhaled nitric oxide production in large airways and peripheral small airways/alveoli

Secondary Outcome Measures

Name	Time	Method
Mechanism(s) of expiratory airflow limitation	1 to 5 years	loss of lung elastic recoil vs intrinsic airway obstruction
Presence of unsuspected emphysema by autopsy or explanted lung	1-5 years	Analysis of lungs obtained at autopsy or explanted lung for extent of emphysema

Trial Locations

Locations (1)

Arthur F Gelb Medical Corporation; 🇺🇸 Lakewood, California, United States