BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated. METHODS: An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in 1 second [FEV1] 55+/-19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week. RESULTS: Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51+/-29 vs. 21+/-24%). A cutoff value of <20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491+/-165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1<90% baseline). CONCLUSIONS: Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.
BACKGROUND:Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated. METHODS: An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in 1 second [FEV1] 55+/-19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week. RESULTS: Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51+/-29 vs. 21+/-24%). A cutoff value of <20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491+/-165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1<90% baseline). CONCLUSIONS:Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.
Authors: Sharon A McGrath-Morrow; W Adam Gower; Cynthia Rothblum-Oviatt; Alan S Brody; Claire Langston; Leland L Fan; Maureen A Lefton-Greif; Thomas O Crawford; Michelle Troche; John T Sandlund; Paul G Auwaerter; Blaine Easley; Gerald M Loughlin; John L Carroll; Howard M Lederman Journal: Pediatr Pulmonol Date: 2010-09
Authors: R Knobler; G Berlin; P Calzavara-Pinton; H Greinix; P Jaksch; L Laroche; J Ludvigsson; P Quaglino; W Reinisch; J Scarisbrick; T Schwarz; P Wolf; P Arenberger; C Assaf; M Bagot; M Barr; A Bohbot; L Bruckner-Tuderman; B Dreno; A Enk; L French; R Gniadecki; H Gollnick; M Hertl; C Jantschitsch; A Jung; U Just; C-D Klemke; U Lippert; T Luger; E Papadavid; H Pehamberger; A Ranki; R Stadler; W Sterry; I H Wolf; M Worm; J Zic; C C Zouboulis; U Hillen Journal: J Eur Acad Dermatol Venereol Date: 2014-01 Impact factor: 6.166
Authors: Kirsten M Williams; Guang-Shing Cheng; Iskra Pusic; Madan Jagasia; Linda Burns; Vincent T Ho; Joseph Pidala; Jeanne Palmer; Laura Johnston; Sebastian Mayer; Jason W Chien; David A Jacobsohn; Steven Z Pavletic; Paul J Martin; Barry E Storer; Yoshihiro Inamoto; Xiaoyu Chai; Mary E D Flowers; Stephanie J Lee Journal: Biol Blood Marrow Transplant Date: 2015-10-22 Impact factor: 5.742
Authors: Hsuanwen C Huang; S Samuel Weigt; Ariss Derhovanessian; Vyacheslav Palchevskiy; Abbas Ardehali; Rajan Saggar; Rajeev Saggar; Bernard Kubak; Aric Gregson; David J Ross; Joseph P Lynch; Robert Elashoff; John A Belperio Journal: J Heart Lung Transplant Date: 2011-04-08 Impact factor: 10.247