Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome.
BACKGROUND
Bronchiolitis obliterans syndrome (BOS) remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV(1). The exact mechanism of action is unclear.


OBJECTIVE
(1) Azithromycin reduces airway neutrophilia and interleukin (IL)-8 and (2) airway neutrophilia predicts the improvement in FEV(1).


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 FEV(1) 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 FEV(1) 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 FEV(1) after 3 mo (r = 0.79, p = 0.0019).


CONCLUSIONS
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 FEV(1) response to azithromycin.
Verleden
Geert M
GM
Department of Respiratory Diseases, University Hospital Gasthuisberg, Leuven, Belgium. geert.verleden@uz.kuleuven.ac.be
Vanaudenaerde
Bart M
BM
Dupont
Lieven J
LJ
Van Raemdonck
Dirk E
DE
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D012333:RNA, Messenger; D017963:Azithromycin