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

Departments of Respiratory Disease and Thoracic Surgery, and Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium

Correspondence and requests for reprints should be addressed to Professor G. M. Verleden, Ph.D., University Hospital Gasthuisberg, Department of Respiratory Diseases and Lung Transplantation Unit, 49 Herestraat, B-3000 Leuven, Belgium. E-mail: geert.verleden{at}uz.kuleuven.ac.be

Rationale: Bronchiolitis obliterans syndrome (BOS) 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.

Hypotheses: (1) Azithromycin reduces airway neutrophilia and interleukin (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 mo after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage (BAL) was performed for cell differentiation and to measure IL-8 and IL-17 mRNA ratios.

Results: The FEV₁ increased from 2.36 (± 0.82 L) to 2.67 L (± 0.85 L; p = 0.007), whereas the percentage of BAL neutrophilia decreased from 35.1 (± 35.7%) to 5.7% (± 6.5%; p = 0.0024). There were six responders to azithromycin (with an FEV₁ increase of > 10%) and eight nonresponders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and nonresponders 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 percentage of BAL neutrophilia and the changes in FEV₁ after 3 mo (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 with nonresponders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV₁ response to azithromycin.

Key Words: azithromycin • bronchoalveolar lavage neutrophilia • bronchiolitis obliterans syndrome • lung transplantation

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