Mechanism(s) of Airflow Limitation During Exacerbation of Asthma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Asthma observational study arm 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. |
Drug: fluticasone/salmeterol in all asthmatics
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:
Drug: budesonide/formoterol or fluticasone/salmeterol in all asthmatics
budesonide 160ug/formoterol 4.5ug, 2 inhalations bid or fluticasone 250ug/salmeterol 50ug, 1 inhalations bid
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arthur F Gelb Medical Corporation | Lakewood | California | United States | 90712 |
Sponsors and Collaborators
- Gelb, Arthur F., M.D.
Investigators
- Principal Investigator: Arthur F Gelb, MD, Arthur F Gelb Medical Corporation
Study Documents (Full-Text)
None provided.More Information
Publications
- 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, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60.
- 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, 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, Yamamoto A, Verbeken EK, Schein MJ, Moridzadeh R, Tran D, Fraser C, Barbers R, Elatre W, Koss MN, Glassy EF, Nadel JA. Further Studies of Unsuspected Emphysema in Nonsmoking Patients With Asthma With Persistent Expiratory Airflow Obstruction. Chest. 2018 Mar;153(3):618-629. doi: 10.1016/j.chest.2017.11.016. Epub 2017 Nov 29.
- 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.
- Gelb AF, Zamel N. Unsuspected pseudophysiologic emphysema in chronic persistent asthma. Am J Respir Crit Care Med. 2000 Nov;162(5):1778-82.
- 20070934A
- NCT01225900