Related Experiment Videos
Anti-inflammatory effect of roxithromycin in patients with aspirin-intolerant asthma
T Shoji1, S Yoshida, H Sakamoto
1Department of Internal Medicine, General Takatsu Chuo Hospital, Kawasaki, Japan.
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.
Conclusion:
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.
Insights
Roxithromycin reduced airway inflammation and symptoms in aspirin-intolerant asthma patients. However, it did not improve airway responsiveness or reduce urinary leukotriene E4 (u-LTE4) levels, suggesting anti-inflammatory rather than anti-leukotriene effects.
Area of Science:
- Pharmacology
- Respiratory Medicine
- Clinical Immunology
Background:
- Macrolides, like roxithromycin, possess anti-asthmatic properties beyond their antibiotic effects.
- Aspirin-intolerant asthma involves cysteinyl leukotriene overproduction, indicated by urinary leukotriene E4 (u-LTE4).
- Eosinophilic inflammation plays a role in the pathogenesis of aspirin-intolerant asthma.
Purpose of the Study:
- To evaluate roxithromycin's protective effect on airway responsiveness in aspirin-intolerant asthma.
- To determine if roxithromycin reduces aspirin-induced u-LTE4 excretion.
- To investigate roxithromycin's impact on eosinophilic inflammation in this patient group.
Main Methods:
- A double-blind, randomized, crossover study involving 14 adult patients with mild/moderate aspirin-intolerant asthma.
- Patients received roxithromycin or placebo for 8 weeks, followed by a sulpyrine provocation test.
- Measurements included airway responsiveness (PC20-sulpyrine), u-LTE4, blood and sputum eosinophils, and eosinophilic cationic protein (ECP).
Main Results:
- Roxithromycin significantly decreased patients' symptoms, blood and sputum eosinophils, and ECP levels.
- No significant improvement in PC20-sulpyrine values was observed after roxithromycin treatment.
- Sulpyrine challenge increased u-LTE4, but roxithromycin did not affect u-LTE4 excretion.
Conclusions:
- Roxithromycin exhibits anti-bronchial inflammatory effects, reducing eosinophilic infiltration in aspirin-intolerant asthma.
- The drug does not demonstrate anti-leukotriene effects in this context.
- Further research is warranted to explore new therapeutic strategies for aspirin-intolerant asthma.