A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms

Ther Adv Respir Dis. 2024 Jan-Dec:18:17534666241232284. doi: 10.1177/17534666241232284.

Abstract

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

Keywords: GVHD; HSCT; bronchiolitis obliterans syndrome; cysteinyl leukotrienes; lung transplant; montelukast.

Plain language summary

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

Publication types

  • Review

MeSH terms

  • Acetates*
  • Bronchiolitis Obliterans Syndrome*
  • Bronchiolitis Obliterans* / diagnosis
  • Bronchiolitis Obliterans* / drug therapy
  • Bronchiolitis Obliterans* / etiology
  • Cyclopropanes*
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Leukotriene Antagonists / adverse effects
  • Leukotrienes / pharmacology
  • Leukotrienes / therapeutic use
  • Lung
  • Lung Transplantation* / adverse effects
  • Quinolines*
  • Sulfides*

Substances

  • Leukotriene Antagonists
  • montelukast
  • Leukotrienes
  • Acetates
  • Cyclopropanes
  • Quinolines
  • Sulfides