Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Respir Res. 2016 May 26;17(1):63. doi: 10.1186/s12931-016-0380-1.

Abstract

Background: Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which are suggested as treatment options for BOS after HSCT.

Methods: After diagnosis of BOS, 61 patients were treated with budesonide/formoterol, montelukast and n-acetylcysteine for 3 months. Pulmonary function test and COPD assessment test (CAT) were performed before and after the combination therapy. Therapeutic response was evaluated by changes in forced expiratory volume in 1 s (FEV1) or CAT score.

Results: After 3 months of combination treatment, mean FEV1 increased by 220 mL (p < 0.001) and residual volume decreased by 200 mL (p =0 .005). Median CAT score also significantly decreased from 15.5 to 11.0 (p = 0.001). The overall response rate to combination therapy was 82 %. Comparing the no-response group and the response group, the forced vital capacity (% predicted) decline between pre-HSCT and BOS diagnosis was significantly greater in the response group (p = 0.036).

Conclusion: Combination treatment with budesonide/formoterol, montelukast and n-acetylcysteine significantly improved lung function and respiratory symptoms in patients with BOS after allogeneic HSCT without serious side effects.

Keywords: Bronchiolitis obliterans syndrome; Inhaled corticosteroid; Long-acting β2-adrenergic agonist; Montelukast; n-acetylcysteine.

MeSH terms

  • Acetates / adverse effects
  • Acetates / therapeutic use*
  • Acetylcysteine / adverse effects
  • Acetylcysteine / therapeutic use*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Adult
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use*
  • Bronchiolitis Obliterans / diagnosis
  • Bronchiolitis Obliterans / drug therapy*
  • Bronchiolitis Obliterans / etiology
  • Bronchiolitis Obliterans / physiopathology
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Budesonide, Formoterol Fumarate Drug Combination / adverse effects
  • Budesonide, Formoterol Fumarate Drug Combination / therapeutic use*
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Leukotriene Antagonists / adverse effects
  • Leukotriene Antagonists / therapeutic use*
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Quinolines / adverse effects
  • Quinolines / therapeutic use*
  • Recovery of Function
  • Retrospective Studies
  • Sulfides
  • Time Factors
  • Treatment Outcome
  • Vital Capacity

Substances

  • Acetates
  • Adrenergic beta-2 Receptor Agonists
  • Anti-Inflammatory Agents
  • Antioxidants
  • Bronchodilator Agents
  • Budesonide, Formoterol Fumarate Drug Combination
  • Cyclopropanes
  • Glucocorticoids
  • Leukotriene Antagonists
  • Quinolines
  • Sulfides
  • montelukast
  • Acetylcysteine