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Title: | Long-term azithromycin therapy for bronchiolitis obliterans syndrome: Divide and conquer? | Authors: | Robin, Vos Vanaudenaerde, BM Ottevaere, A Verleden, SE De Vleeschauwer, SI WIDYASTUTI, Anna WAUTERS, Shana Van Raemdonck, DE NAWROT, Tim Dupont LJ Verleden GM |
Issue Date: | 2010 | Publisher: | Elsevier Science | Source: | JOURNAL OF HEART AND LUNG TRANSPLANTATION, 29(12). p. 1358-1368 | Abstract: | BACKGROUND: Azithromycin may reverse or halt the decline of pulmonary function (FEV(1)) in bronchiolitis obliterans syndrome (BOS). In this study we investigated the effects of long-term azithromycin treatment in lung transplant recipients with BOS. METHODS: A retrospective, observational, cohort study was performed on 107 patients with BOS (Stages 0p/1/2/3, n = 23/62/20/2), who were treated with azithromycin for 3.1 +/- 1.9 years. Patients were evaluated 6.3 +/- 3.8 years after transplantation and assessed for evolution of FEV(1), bronchoalveolar lavage neutrophilia and overall survival after initiation of azithromycin. Survival curves were analyzed using the log-rank test. Cox proportional hazard survival regression analysis was performed to estimate hazard ratios of clinical variables predicting outcome. RESULTS: FEV(1) increased >/=10% after 3 to 6 months of treatment in 40% of patients, of whom 33% later redeveloped BOS. FEV(1) further declined in 78% and stabilized in 22% of the remaining non-responders. Pre-treatment neutrophilia was higher in responders: 29.3% (9.3% to 69.7%) vs 11.5% (2.9% to 43.8%) (p = 0.025), in whom it significantly decreased to 4.2% (1.8% to 17.6%) (p = 0.041) after 3 to 6 months of azithromycin. Responders demonstrated better survival compared with non-responders (p = 0.050), with 6 and 21 patients, respectively, dying during follow-up (p = 0.027). Multivariate analysis identified initial azithromycin response and earlier post-transplant initiation of azithromycin to be protective for both BOS progression/relapse (hazard ratio [HR] = 0.12 [95% confidence interval 0.05 to 0.28], p < 0.0001; and HR = 0.98 [95% confidence interval 0.97 to 0.98], p < 0.0001, respectively) and retransplantation/death during follow-up (HR 0.10 [95% confidence interval 0.02 to 0.48], p = 0.004; and HR 0.96 [95% confidence interval 0.95 to 0.98], p < 0.0001, respectively). CONCLUSIONS: Long-term azithromycin benefits pulmonary function and survival in BOS, particularly in patients with increased lavage neutrophilia. | Notes: | Laboratory of Pneumology, Katholieke Universiteit Leuven and University Hospital Gasthuisberg, Leuven, Belgium. | Keywords: | azithromycin;bronchiolitis obliterans;syndrome;chronic allograft rejection;pulmonary function survival;survival | Document URI: | http://hdl.handle.net/1942/11102 | ISSN: | 1053-2498 | e-ISSN: | 1557-3117 | DOI: | 10.1016/j.healun.2010.05.023 | ISI #: | 000285220700006 | Rights: | 2010 International Society for Heart and Lung Transplantation All rights reserved | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2012 |
Appears in Collections: | Research publications |
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