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

Condition(s) targeted: Asthma

Intervention: budesonide/formoterol or fluticasone/salmeterol (Drug); budesonide/formoterol or fluticasone/salmeterol (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Gelb, Arthur F., M.D.

Official(s) and/or principal investigator(s):
Arthur F Gelb, MD, Principal Investigator, Affiliation: Arthur F Gelb Medical Corporation

Overall contact:
Arthur F Gelb, MD, Phone: 562-633-2204, Email: afgelb@msn.com

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. 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. 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.

Official title: Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-Smokers

Study design: Treatment, Randomized, Single Blind (Outcomes Assessor), Dose Comparison, Crossover Assignment, Bio-availability Study

Primary outcome:

use exhaled nitric oxide as a surrogate marker of large airway vs small airway/lung inflammation following various doses of inhaled corticosteroids

determine site of airflow limitation, whether predominantly large and /or small airways using expiratory flow volume curves obtained before and after asthmatics breathe a 80% helium-20% oxygen gas mixture

Secondary outcome:

investigate the mechanisms that limit expiratory airflow: intrinsic airway obstruction vs loss of lung elastic recoil

dynamic hyperinflation

Minimum age: 12 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

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

- Stable, treated asthmatics

- Age 12-80 yr

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

Exclusion Criteria:

- Pregnancy

Arthur F Gelb, MD, Phone: 562-633-2204, Email: afgelb@msn.com

Arthur F Gelb Medical Corporation, Lakewood, California 90712, United States; Recruiting
Arthur F Gelb, MD, Principal Investigator

Related publications:

Gelb AF, Zamel N. Unsuspected pseudophysiologic emphysema in chronic persistent asthma. Am J Respir Crit Care Med. 2000 Nov;162(5):1778-82.

Gelb AF, Licuanan J, Shinar CM, Zamel N. Unsuspected loss of lung elastic recoil in chronic persistent asthma. Chest. 2002 Mar;121(3):715-21.

Gelb AF, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60.

Gelb AF, Flynn Taylor C, Shinar CM, Gutierrez C, Zamel N. Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics. Chest. 2006 Jun;129(6):1492-9.

Gelb AF, Taylor CF, Nussbaum E, Gutierrez C, Schein A, Shinar CM, Schein MJ, Epstein JD, Zamel N. Alveolar and airway sites of nitric oxide inflammation in treated asthma. Am J Respir Crit Care Med. 2004 Oct 1;170(7):737-41. Epub 2004 Jun 30.

Gelb AF, Zamel N, Krishnan A. Physiologic similarities and differences between asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2008 Jan;14(1):24-30. Review.

Starting date: October 2007
Ending date: December 2009
Last updated: August 13, 2008