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Randomized Controlled Trial
. 2018 Apr 6;13(4):e0193564.
doi: 10.1371/journal.pone.0193564. eCollection 2018.

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

David Ruttens  1 , Stijn E Verleden  1 , Heleen Demeyer  2 , Dirk E Van Raemdonck  1 , Jonas Yserbyt  1 , Lieven J Dupont  1 , Bart M Vanaudenaerde  1 , Robin Vos  1 , Geert M Verleden  1
Affiliations
Randomized Controlled Trial

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

David Ruttens et al. PLoS One. .

Abstract

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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of the randomized controlled trial of montelukast versus placebo in LTx patients with BOS.
IIT = intention to treat analysis.
Fig 2
Fig 2. Kaplan-Meier survival curve of the placebo and the montelukast arm at 2 years.
Fig 3
Fig 3. FEV1 evolution (% predicted, absolute value) comparing montelukast to placebo.
MLK = montelukast. Dotted line is the time-point of inclusion.
Fig 4
Fig 4. FEV1 evolution (% predicted, absolute value) comparing montelukast to placebo in BOS stage 1 patients (upper part) and BOS stage 2 and 3 (lower part).
MLK = montelukast. Dotted line is the time-point of inclusion.
See this image and copyright information in PMC

References

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