title: A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation.
abstract: Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s (FEV₁) in chronic rejection or bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Azithromycin prophylaxis might prevent BOS. A double-blind randomised controlled trial of azithromycin (n = 40) or placebo (n = 43), initiated at discharge and administered three times a week for 2 yrs, was performed in 2005-2009 at the Leuven University Hospital (Leuven, Belgium). Primary end-points were BOS-free and overall survival 2 yrs after LTx; secondary end-points were acute rejection, lymphocytic bronchiolitis and pneumonitis rate, prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux, and change in FEV₁, airway and systemic inflammation over time. Patients developing BOS were assessed for change in FEV₁ with open-label azithromycin. BOS occurred less in patients receiving azithromycin: 12.5 versus 44.2% (p = 0.0017). BOS-free survival was better with azithromycin (hazard ratio 0.27, 95% CI 0.092-0.816; p = 0.020). Overall survival, acute rejection, lymphocytic bronchiolitis, pneumonitis, colonisation and reflux were comparable between groups. Patients receiving azithromycin demonstrated better FEV₁ (p = 0.028), and lower airway neutrophilia (p = 0.015) and systemic C-reactive protein levels (p = 0.050) over time. Open-label azithromycin for BOS improved FEV₁ in 52.2% patients. No serious adverse events were noted. Azithromycin prophylaxis attenuates local and systemic inflammation, improves FEV₁ and reduces BOS 2 yrs after LTx.
authors.affiliation: Laboratory of Pneumology, Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Vos
authors.forename: B M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: S E
authors.initials: SE
authors.lastname: Verleden
authors.forename: S I
authors.initials: SI
authors.lastname: De Vleeschauwer
authors.forename: A
authors.initials: A
authors.lastname: Willems-Widyastuti
authors.forename: D E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.forename: A
authors.initials: A
authors.lastname: Schoonis
authors.forename: T S
authors.initials: TS
authors.lastname: Nawrot
authors.forename: L J
authors.initials: LJ
authors.lastname: Dupont
authors.forename: G M
authors.initials: GM
authors.lastname: Verleden
mesh_terms: D000328:Adult; D017963:Azithromycin / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000517:prevention & control; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010919:Placebos; D017963:Azithromycin