Are we near to an effective drug treatment for bronchiolitis obliterans?

Verleden, Geert M.; Vos, Robin; Dupont, Lieven; Raemdonck, Dirk Van; Vanaudenaerde, Bart M.; Verleden, Stijn E.

doi:10.1517/14656566.2014.954549

Cited by 11 publications

(11 citation statements)

References 20 publications

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“…Chronic lung allograft dysfunction is an umbrella term for all forms of chronic allograft dysfunction including bronchiolitis obliterans syndrome (BOS) with an obstructive ventilatory deficit, restrictive allograft syndrome (RAS) and others, like pleural processes or airway malacia, which result in permanent loss of lung function . Despite substantial progress over recent years and almost a decade after our group's first publication on extracorporeal photopheresis (ECP) for CLAD patients, therapy options addressing CLAD remain limited …”

Section: Introductionmentioning

confidence: 99%

Lung transplant recipients on long‐term extracorporeal photopheresis

Isenring

Robinson

Buergi

et al. 2017

Clinical Transplantation

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Extracorporeal photophoresis (ECP) is an increasingly used therapy to address chronic lung allograft dysfunction (CLAD) following lung transplantation. In 2008, we reported the first single-center experience showing that ECP not only reduces lung function decline in patients with bronchiolitis obliterans syndrome (BOS) but results in stabilization of patients with recurrent acute cellular rejection (ACR). In this study, the original cohort was followed up further 5 years. In addition, patients with CLAD were retrospectively classified according to recently published phenotypes. The current cohort included 21 of the original 24 patients, of which nine were initially treated for CLAD, 12 were initially treated for recurrent ACR. Our results show that survival of patients treated with ECP for CLAD was inferior to patients treated for recurrent ACR (66% vs. 82% survival rate). Long-term survivors in the CLAD subgroup were mostly classified as BOS 1 at time of ECP initiation. These long-term data show that patients started on ECP at early BOS stages have better long-term outcome. The subgroup of ECP patients with recurrent ACR has an overall superior survival. To assist prediction of therapy response, we agree with other authors that patients with CLAD should be aimed to be phenotyped and evaluated for an early treatment with ECP.

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Section: Introductionmentioning

confidence: 99%

Lung transplant recipients on long‐term extracorporeal photopheresis

Isenring

Robinson

Buergi

et al. 2017

Clinical Transplantation

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“…This clearly deserves attention in a large multicenter RCT. In the natural history of BOS, FEV1 very often stabilizes without any intervention, as also seen in the placebo arm of the current study [ 29 ]. As a consequence, the results of the post-hoc analysis should be interpreted with caution.…”

Section: Discussionmentioning

confidence: 67%

Montelukast for bronchiolitis obliterans syndrome after lung transplantation: A randomized controlled trial

et al. 2018

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Bronchiolitis obliterans syndrome (BOS) remains the major problem which precludes long-term survival after lung transplantation. Previously, an open label pilot study from our group demonstrated a possible beneficial effect of montelukast in progressive BOS patients with low airway neutrophilia (<15%), and already on azithromycin treatment, in whom the further decline in pulmonary function was attenuated. This was, however, a non-randomized and non-placebo controlled trial. The study design is a single center, prospective, interventional, randomized, double blind, placebo-controlled trial, with a two arm parallel group design and an allocation ratio of 1:1. Randomization to additional montelukast (10 mg/day, n = 15) or placebo (n = 15) was performed from 2010 to 2014 at the University Hospitals Leuven (Leuven, Belgium) in all consecutive patients with late-onset (>2years posttransplant) BOS ≥1. Primary end-point was freedom from graft loss 1 year after randomization; secondary end-points were acute rejection, lymphocytic bronchiolitis, respiratory infection rate; and change in FEV1, airway and systemic inflammation during the study period. Graft loss at 1 y and 2y was similar in both groups (respectively p = 0. 981 and p = 0.230). Montelukast had no effect on lung function decline in the overall cohort. However, in a post-hoc subanalysis of BOS stage 1 patients, montelukast attenuated further decline of FEV1 during the study period, both in absolute (L) (p = 0.008) and % predicted value (p = 0.0180). A linear mixed model confirmed this association. Acute rejection, lymphocytic bronchiolitis, respiratory infections, systemic and airway inflammation were comparable between groups over the study period. This randomized controlled trial showed no additional survival benefit with montelukast compared to placebo, although the study was underpowered. The administration of montelukast was associated with an attenuation of the rate of FEV1 decline, however, only in recipients with late-onset BOS stage 1.

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“…One study has reported that the 5-year survival rate is only 29 % among patients with both chronic GVHD and BOS [8]. Moreover, stabilization of lung function in BOS patients with HCT may be achieved by high-dose pulse corticosteroids [2], leukotriene receptor antagonists [9], and combinations of inhaled bronchodilators and glucocorticoids [10], whereas the efficacy of these drugs, except for leukotriene receptor antagonists, in BOS after lung transplant is unclear [20,21]. In addition, the diagnostic criteria for BOS after HCT and lung transplantation are slightly different [3,13,22].…”

Section: Discussionmentioning

confidence: 99%

The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Yoon

Song

et al. 2015

Int J Hematol

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The aim of this study was to determine whether prophylactic azithromycin treatment prevents bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HCT). A series of 1187 patients who underwent HCT between December 1993 and November 2013 at our tertiary referral center in South Korea were enrolled. The median age of these patients was 39.0 years, and 668 (56.3 %) were men. Acute leukemia was the most common indication for HCT. During a median follow-up of 30.7 months after HCT, BOS was diagnosed in 82 patients (6.9 %) at a median of 12.3 months after HCT. One hundred patients received prophylactic azithromycin, of whom 12 developed BOS. BOS was significantly more frequent in patients who were treated with than without prophylactic azithromycin (12.0 versus 6.4 %, P = 0.036). Multivariate analysis revealed that a busulfan-based conditioning regimen (HR 2.73, 95 % CI 1.66-6.45) was the only independent predictor of BOS. The prophylactic use of azithromycin was not associated with the development of BOS by multivariate analysis. Although the present study had some limitations such as its non-randomized retrospective design, differences in baseline patient characteristics between the two groups, and the preference for azithromycin use at our hospital, our findings suggest that prophylactic azithromycin seems to not prevent the development of BOS in HCT recipients.

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Are we near to an effective drug treatment for bronchiolitis obliterans?

Cited by 11 publications

References 20 publications

Lung transplant recipients on long‐term extracorporeal photopheresis

Lung transplant recipients on long‐term extracorporeal photopheresis

Montelukast for bronchiolitis obliterans syndrome after lung transplantation: A randomized controlled trial

The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

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