Effect of a 4-week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naive asthmatics.
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.


METHODS
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.


CONCLUSIONS
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.
Louis
R
R
Respiratory Medicine, CHU Sart-Tilman, 4000 Liège, Belgium.
Bettiol
J
J
Cataldo
D
D
Sele
J
J
Henquet
M
M
Radermecker
M
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001798:Blood Proteins / Q000032:analysis / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000503:physiopathology; D012260:Ribonucleases; D013183:Sputum / Q000166:cytology* / Q000187:drug effects*; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D010919:Placebos; D013806:Theophylline; D012260:Ribonucleases