Anti-inflammatory effect of roxithromycin in patients with aspirin-intolerant asthma.
BACKGROUND
Fourteen-membered macrolides, such as roxithromycin, have been reported to exhibit other pharmacological activity including anti-asthmatic effects, besides antibiotic activity.


OBJECTIVE
This study was designed to investigate the protective effect of roxithromycin on airway responsiveness to the sulpyrine provocation test and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary leucotriene E4 (u-LTE4), a marker of cysteinyl leucotriene overproduction that participates in the pathogenesis of aspirin-intolerant asthma. Also, the present study was designed to examine whether or not its anti-asthmatic activity was associated with a reduction in eosinophilic inflammation.


METHODS
For 8 weeks before analysis, subjects received 150 mg of roxithromycin or matching placebo twice daily. We assessed the effects of pretreatment with roxithromycin on bronchoconstriction precipitated by inhalation of sulpyrine in 14 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hyperresponsive to sulpyrine provocation test were allocated to this study. A double-blind, randomized, crossover design was used. Urinary LTE4 was measured by a combined reverse-phase high-performance liquid chromatography (rp-HPLC) enzyme immunoassay on sulpyrine provocation testing day. Blood and sputum samples were taken in the morning on the sulpyrine provocation testing day. Eosinophil counting and measurement of eosinophilic cationic protein (ECP) were performed.


RESULTS
After the 8 weeks of treatment with roxithromycin, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. On the other hand, values of PC20-sulpyrine did not improve after roxithromycin at all. Furthermore, although challenge with sulpyrine caused a significant increase in u-LTE4, pretreatment with roxithromycin or placebo did not affect excretion of u-LTE4.


CONCLUSIONS
Although roxithromycin does not have antileucotriene effects, it has an antibronchial inflammatory effect associated with eosinophilic infiltration. This study raises further interesting therapeutic possibilities and warrants further trials of new approaches to the treatment of aspirin-intolerant asthma.
Shoji
T
T
Department of Internal Medicine, General Takatsu Chuo Hospital, Kawasaki, Japan.
Yoshida
S
S
Sakamoto
H
H
Hasegawa
H
H
Nakagawa
H
H
Amayasu
H
H
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D001798:Blood Proteins / Q000032:analysis; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004177:Dipyrone; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases; D015575:Roxithromycin / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D015575:Roxithromycin; D004177:Dipyrone; D017999:Leukotriene E4; D012260:Ribonucleases; D001241:Aspirin