251. Effect of a 4-week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naive asthmatics.
- Author
-
Louis R, Bettiol J, Cataldo D, Sele J, Henquet M, and Radermecker M
- Subjects
- Administration, Oral, Adolescent, Adult, Anti-Inflammatory Agents immunology, Anti-Inflammatory Agents pharmacology, Blood Proteins analysis, Blood Proteins drug effects, Cell Count drug effects, Chemotaxis, Leukocyte drug effects, Chemotaxis, Leukocyte immunology, Double-Blind Method, Eosinophil Granule Proteins, Eosinophils physiology, Female, Humans, Lung physiopathology, Male, Middle Aged, Placebos, Pulmonary Eosinophilia physiopathology, Theophylline administration & dosage, Asthma immunology, Asthma pathology, Eosinophils drug effects, Pulmonary Eosinophilia drug therapy, Ribonucleases, Sputum cytology, Sputum drug effects, Theophylline pharmacology, Theophylline therapeutic use
- Abstract
Background: The precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti-inflammatory effect., Objective: The purpose of this study was to assess the effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naive asthmatics., Method: We performed a 4-week randomized double-blind, placebo-controlled, parallel group study in 21 mild to moderate steroid-naive asthmatics whose sputum eosinophilia was found twice > 5% during the run in period. Eleven subjects received 600 mg/24 h theophylline for the first 2 weeks and 900 mg/24 h for the last 2 weeks while 10 subjects took a placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1 week after stopping the treatment. The sputum samples were compared for their cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic activity using micro-Boyden chambers., Results: Serum theophylline concentrations reached 7 and 11 microg/mL at V3 and V4, respectively. Intragroup comparisons showed that theophylline, but not placebo, caused a significant reduction in sputum eosinophil counts at V3 (62 +/- 10% from baseline, P < 0.01) and a strong trend at V4 (67 +/- 16% from baseline, P = 0.07) when compared to baseline. The intergroup difference obtained after comparing the area under the curve over the 4 week treatment period only approached the statistical significance (P = 0.08). At baseline the fluid phase of the sputum contained a significant eosinophil chemotactic activity which was inhibited after a 4-week treatment by theophylline (P < 0. 01) but not by placebo. The mean sputum theophylline levels after 4 weeks of treament (1.7 microg/mL) was lower than that required to cause significant inhibition of eosinophil chemotaxis in vitro., Conclusion: Theophylline decreases the natural sputum eosinophil chemotactic activity present in asthmatics. However, when using a small sample size, the 35% reduction in sputum eosinophilia achieved by theophylline failed to reach statistical significance when compared to that seen after placebo.
- Published
- 2000
- Full Text
- View/download PDF