Mechanism(s) of Airflow Limitation During Exacerbation of Asthma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: budesonide/formoterol or fluticasone/salmeterol	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Crossover Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Formoterol fumarate Budesonide Formoterol Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate Arformoterol Tartrate

U.S. FDA Resources

Further study details as provided by Gelb, Arthur F., M.D.:

Primary Outcome Measures:

Exhaled nitric oxide [ Time Frame: 20-60 days ] [ Designated as safety issue: No ]
evaluate the role of inhaled corticosteroid on exhaled nitric oxide production in large airways and peripheral small airways/alveoli

Secondary Outcome Measures:

site/mechanism(s)airflow limitation [ Time Frame: 20-60 days ] [ Designated as safety issue: No ]
evaluate the site of expiratory airflow limitation ie. small versus large airways and mechanism(s) of expiratory airflow limitation whether intrinsic airway obstruction versus loss of lung elastic recoil
dynamic hyperinflation [ Time Frame: 20-60 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	October 2007
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 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.	Drug: budesonide/formoterol or fluticasone/salmeterol budesonide 80ug/formoterol 4.5ug, 2 inhalations bid X 20-60 days or fluticasone 100ug/salmeterol 50ug, 1 inhalation bid X 20-60 days Other Names: symbicort 80/4.5 advair 100/50
Experimental: 2 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 and compared to the 1st Arm	Drug: budesonide/formoterol or fluticasone/salmeterol budesonide 160ug/formoterol 4.5ug, 2 inhalations bid or fluticasone 250ug/salmeterol 50ug, 1 inhalations bid Other Names: symbicort 160/4.5 advair 250/50

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.

Eligibility

Ages Eligible for Study:	10 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225913

Contacts

Contact: Arthur F Gelb, MD

562-633-2204

afgelb@msn.com

Locations

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

Sponsors and Collaborators

Gelb, Arthur F., M.D.

Investigators

Principal Investigator:

Arthur F Gelb, MD

Arthur F Gelb Medical Corporation

More Information

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.

Responsible Party:	Arthur F Gelb MD, Principal Investigator, Gelb, Arthur F., M.D.
ClinicalTrials.gov Identifier:	NCT01225913 History of Changes
Obsolete Identifiers:	NCT01225900
Other Study ID Numbers:	20070934A
Study First Received:	October 19, 2010
Last Updated:	April 8, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Gelb, Arthur F., M.D.:

asthma
lung function
inflammation

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Formoterol
Salmeterol
Albuterol
Fluticasone
Fluticasone, salmeterol drug combination

Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists

ClinicalTrials.gov processed this record on May 23, 2013