Robin Vos1, Ruben Vanden Eynde2, David Ruttens2, Stijn E Verleden3, Bart M Vanaudenaerde3, Lieven J Dupont4, Jonas Yserbyt4, Eric K Verbeken5, Arne P Neyrinck6, Dirk E Van Raemdonck7, Geert M Verleden4. 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.
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.
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.
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