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Characteristics of macrolide responders in persistent post-surgical rhinosinusitis
G M Oakley1, J M Christensen2, R Sacks3
1Department of Surgery, Division of Otolaryngology Head and Neck Surgery, University of Utah, Salt Lake City, UT, USA.
Introduction:
The anti-inflammatory effects of long term low dose macrolide therapy have shown benefit in the management of diffuse panbronchiolitis. Dramatic responses to macrolide in the upper airway are seen but our understanding of the patient phenotype predisposing to macrolide response in chronic rhinosinusitis (CRS) is poor.
Methods:
A case control study was performed in a tertiary level rhinology practice of consecutive chronic rhinosinusitis patients placed on a 3-month low dose macrolide therapy after failing at least 3 months of corticosteroid irrigation therapy post-endoscopic sinus surgery. Patients were defined as a macrolide responder when having near normal endoscopy after a 3-month period of clarithromycin treatment. Patient characteristics of smoking, asthma, atopy status, revision surgery, symptom severity (SNOT-22) along with biomarkers from serum and tissue histopathology results were compared between groups.
Results:
Of twenty-eight consecutive macrolide treated patients, 19 responders were compared to 9 non-responders. The groups were similar in age, female gender, non-smoking, asthma, and atopy. Macrolide response was associated with a lack of tissue eosinophilia (more than 10/HPF) and lower serum eosinophilia. Neutrophil expression was similar in tissue and serum. Squamous metaplasia was overexpressed in non-responders.
Conclusion:
Low tissue and serum eosinophilia, and absence of tissue squamous metaplasia may predict a CRS phenotype suitable to a trial of long-term macrolide therapy when surgery and topical therapy has failed.
Insights
Low eosinophilia and absence of squamous metaplasia may predict chronic rhinosinusitis (CRS) patients who will benefit from long-term macrolide therapy after surgery and topical treatments fail.
Area of Science:
- Otolaryngology
- Rhinology
- Pharmacology
Background:
- Long-term, low-dose macrolide therapy demonstrates anti-inflammatory benefits, particularly in diffuse panbronchiolitis.
- While macrolides yield dramatic upper airway responses, the specific patient phenotypes predicting macrolide responsiveness in chronic rhinosinusitis (CRS) remain poorly understood.
Purpose of the Study:
- To identify patient phenotypes that predict a positive response to low-dose macrolide therapy in chronic rhinosinusitis (CRS) patients.
- To investigate the association between clinical characteristics, biomarkers, and treatment outcomes in CRS patients undergoing macrolide therapy.
Main Methods:
- A case-control study involving 28 CRS patients treated with 3-month clarithromycin post-surgery and corticosteroid irrigation failure.
- Patients were classified as responders (near-normal endoscopy) or non-responders.
- Comparison of smoking status, asthma, atopy, revision surgery, symptom severity (SNOT-22), serum biomarkers, and tissue histopathology between groups.
Main Results:
- 19 responders were compared to 9 non-responders, with no significant differences in age, gender, smoking, asthma, or atopy.
- Macrolide response correlated with lower tissue eosinophilia (≤10/HPF) and serum eosinophilia.
- Non-responders showed overexpression of tissue squamous metaplasia; neutrophil expression was similar in both groups.
Conclusions:
- Low tissue and serum eosinophilia may indicate a CRS phenotype suitable for macrolide therapy.
- Absence of tissue squamous metaplasia is another potential predictor of successful macrolide treatment in refractory CRS.
- These findings suggest a targeted approach for long-term macrolide therapy in specific CRS patient subgroups.
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