Montelukast in chronic lung allograft dysfunction after lung transplantation

Robin Vos; Ruben Vanden Eynde; David Ruttens; Stijn E Verleden; Bart M Vanaudenaerde; Lieven J Dupont; Jonas Yserbyt; Eric K Verbeken; Arne P Neyrinck; Dirk E Van Raemdonck; Geert M Verleden; Leuven Lung Transplant Group

doi:10.1016/j.healun.2018.11.014

Montelukast in chronic lung allograft dysfunction after lung transplantation

J Heart Lung Transplant. 2019 May;38(5):516-527. doi: 10.1016/j.healun.2018.11.014. Epub 2018 Dec 6.

Affiliations

¹ Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases, Metabolism & Ageing, Division of Respiratory Diseases, KU Leuven, Leuven, Belgium. Electronic address: robin.vos@uzleuven.be.
² Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
³ Department of Chronic Diseases, Metabolism & Ageing, Division of Respiratory Diseases, KU Leuven, Leuven, Belgium.
⁴ Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases, Metabolism & Ageing, Division of Respiratory Diseases, KU Leuven, Leuven, Belgium.
⁵ Department of Histopathology, KU Leuven, Leuven, Belgium.
⁶ Department of Anesthesiology, University Hospitals Leuven, Leuven, Belgium.
⁷ Department of Experimental Thoracic Surgery, KU Leuven, Leuven, Belgium.

PMID: 30638839
DOI: 10.1016/j.healun.2018.11.014

Abstract

Background: Chronic lung allograft dysfunction (CLAD) is a major cause of post‒lung transplant mortality, with limited medical treatment options. In this study we assessed the association of montelukast treatment with pulmonary function and outcome in lung transplant recipients with progressive CLAD.

Methods: We performed a retrospective study of all lung transplant recipients transplanted between July 1991 and December 2016 at our center and who were treated for at least 3 months with montelukast for progressive CLAD, despite at least 3 months of prior azithromycin therapy. Main outcome parameters included evolution of pulmonary function and progression-free and overall survival.

Results: A total of 153 patients with CLAD (115 with bronchiolitis obliterans syndrome and 38 with restrictive allograft syndrome) were included, of whom 46% had a forced expiratory volume in 1 second (FEV₁) measure of between 66% and 80%, 31% an FEV₁ between 51% and 65%, and 23% an FEV₁ ≤50% of best post-operative FEV₁ at start of montelukast. Montelukast was associated with attenuation in rate of FEV₁ decline after 3 and 6 months, respectively (both p < 0.0001). Patients in whom FEV₁ improved or stabilized after 3 months of montelukast (81%) had significantly better progression-free (p < 0.0001) and overall (p = 0.0002) survival after CLAD onset, as compared to those with further decline of FEV₁ (hazard ratio [HR] 2.816, 95% confidence interval [CI] 1.450 to 5.467, p = 0.0022 for overall survival after CLAD onset in risk-adjusted multivariate analysis).

Conclusions: Montelukast was associated with a significant attenuation in rate of FEV₁ decline in a substantial proportion of patients with established CLAD, which correlated with better outcome. Further study is required regarding use of montelkast.

Keywords: chronic lung allograft dysfunction; leukotriene receptor antagonist; lung transplantation; montelukast; outcome; treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetates / therapeutic use*
Adult
Allografts
Chronic Disease
Cyclopropanes
Cytochrome P-450 CYP1A2 Inducers / therapeutic use
Female
Follow-Up Studies
Forced Expiratory Volume
Graft Rejection / drug therapy*
Graft Rejection / physiopathology
Humans
Lung Transplantation / adverse effects*
Male
Middle Aged
Postoperative Period
Quinolines / therapeutic use*
Retrospective Studies
Sulfides
Transplant Recipients*

Substances

Acetates
Cyclopropanes
Cytochrome P-450 CYP1A2 Inducers
Quinolines
Sulfides
montelukast