INTRODUCTION: A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible. OBJECTIVE: To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained. METHODS: We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor. RESULTS: There was a significant increase in FEV(1) of median 110 ml (range, -70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up). CONCLUSIONS: This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.
INTRODUCTION: A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible. OBJECTIVE: To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained. METHODS: We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor. RESULTS: There was a significant increase in FEV(1) of median 110 ml (range, -70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up). CONCLUSIONS: This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.
Authors: E A Lendermon; J M Dodd-O; T A Coon; X Wang; C R Ensor; N Cardenes; C L Koodray; H L Heusey; M F Bennewitz; P Sundd; G C Bullock; I Popescu; L Guo; C P O'Donnell; M Rojas; J F McDyer Journal: Transplant Proc Date: 2018-03-09 Impact factor: 1.066
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
Authors: J M Kwakkel-van Erp; A W M Paantjens; D A van Kessel; J C Grutters; J M M van den Bosch; E A van de Graaf; H G Otten Journal: Clin Exp Immunol Date: 2011-06-27 Impact factor: 4.330