Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a pilot study

Abstract

Summary Bronchiolitis obliterans syndrome (BOS) remains the major hurdle to improve long‐term survival after lung transplantation, as its treatment remains troublesome. In this pilot study, we investigated the effect of montelukast (a leukotriene receptor antagonist) on the FEV1 decline after diagnosis of BOS and compared this with a control group. In both groups, 11 patients were included with BOS stage <3 and bronchoalveolar lavage (BAL) neutrophilia <15%, already being treated or concurrently being started on azithromycin. Control patients were selected retrospectively. After adding montelukast (10 mg/day) to the immunosuppressive regimen, the FEV1 decline significantly decreased from 112 ± 26 ml/month before BOS diagnosis to 13 ± 13 ml/month after 6 months of montelukast therapy (P = 0.001). In the control group, there was no significant change in the rate of FEV1 decline: 103 ± 20 ml/month before BOS diagnosis to 114 ± 27 ml/month (P = 0.55). Adding montelukast may be a promising treatment option in patients with low neutrophilic (<15%) BOS after lung transplantation, already or concurrently being treated with azithromycin.

The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

“…One study has reported that the 5-year survival rate is only 29 % among patients with both chronic GVHD and BOS [8]. Moreover, stabilization of lung function in BOS patients with HCT may be achieved by high-dose pulse corticosteroids [2], leukotriene receptor antagonists [9], and combinations of inhaled bronchodilators and glucocorticoids [10], whereas the efficacy of these drugs, except for leukotriene receptor antagonists, in BOS after lung transplant is unclear [20,21]. In addition, the diagnostic criteria for BOS after HCT and lung transplantation are slightly different [3,13,22].…”

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

“…However, this beneficial effect seems to occur predominantly in patients with lymphocytic bronchiolitis, but not in those with bronchiolitis obliterans, and thus indicates that only in conditions with considerable inflammatory cell infiltrate can the progression of disease be delayed, whereas with only scant inflammation but pronounced fibrosis the potential benefit might be limited. Importantly, neutrophilia of .15% in the BAL fluid has been demonstrated to be predictive of FEV1 response to azithromycin in patients with BOS after lung transplantation [58], whereas patients without neutrophilia in the BAL benefited from the addition of the leukotriene receptor antagonist montelukast [59]. Transferring these findings to our study group, one would add azithromycin to the immunosuppressive regimen in those patients with histological lymphocytic bronchiolitis and relevant BAL neutrophilia, and additional montelukast for those patients with low neutrophilic lymphocytic bronchiolitis.…”

Are we near to an effective drug treatment for bronchiolitis obliterans?

“…In the control group (n = 11), there was no significant change in the rate of FEV 1 decline (from 103 ± 20 ml/month before BOS diagnosis to 114 ± 27 ml/ month). Although it was concluded from this study that adding montelukast may be a promising treatment option in patients with low neutrophilic (< 15%) BOS and already or concurrently being treated with azithromycin, this data certainly need confirmation in a prospective placebo-controlled trial [14].…”