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Published ahead of print on June 1, 2006, doi:10.1164/rccm.200601-071OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 5, September 2006, 566-570

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Submitted on January 17, 2006
Accepted on June 1, 2006

Azithromycin Reduces Airway Neutrophilia and IL-8 in Patients with Bronchiolitis Obliterans Syndrome

Geert M Verleden1, Bart M Vanaudenaerde2*, Lieven J Dupont1, and Dirk E Van Raemdonck3

1 Department of Respiratory Disease, University Hospital Gasthuisberg, Leuven, Belgium; Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium, 2 Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium, 3 Department of Thoracic Surgery, University Hospital Gasthuisberg, Leuven, Belgium; Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium

* To whom correspondence should be addressed. E-mail: Bart.Vanaudenaerde{at}med.kuleuven.be.

Rationale: Bronchiolitis obliterans syndrome remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV1. The exact mechanism of action is unclear. Hypothesis: 1. azithromycin reduces airway neutrophilia and IL-8, and 2. airway neutrophilia predicts the improvement in FEV1. Methods: Fourteen lung transplant patients with BOS (between BOS 0-p and BOS 3) were treated with azithromycin, in addition to their current immunosuppressive treatment. Before and 3 months after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage was performed for cell differentiation and to measure interleukin-8 and -17 mRNA ratios. Results: The FEV1 increased from 2.36 (± 0.82) L to 2.67 (± 0.85) L (p=0.007), whereas the % BAL neutrophilia decreased from 35.1 (± 35.7) % to 5.7 (± 6.5) % (p=0.0024). There were 6 responders to azithromycin (with an FEV1 increase of > 10%) and 8 non-responders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and non-responders were the initial BAL neutrophilia (p<0.0001), IL-8 mRNA ratio (p=0.0009) and the postoperative day at which azithromycin was started (p=0.036). There was a significant correlation between the initial % BAL neutrophilia and the changes in FEV1 after 3 months (r=0.79, p=0.0019). Conclusion: Azithromycin significantly reduces airway neutrophilia and IL-8 mRNA in patients with BOS. Responders have a significantly higher BAL neutrophilia and IL-8 compared to non-responders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV1 response to azithromycin.
Key words: Azithromycin, BAL neutrophilia, BOS, lung transplantation




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