Methotrexate can halt the progression of bronchiolitis obliterans syndrome in lung transplant recipients

Abstract

Background: Methotrexate has been used successfully to treat refractory or recurrent rejection in heart transplant recipients. We therefore conducted an open pilot study to determine whether methotrexate is useful in the treatment of chronic rejection after lung transplantation.

Methods: Between December 1993 and January 1995 methotrexate was prescribed to 10 patients with persistent or progressive bronchiolitis obliterans despite multiple attempts to control the chronic rejection with conventional treatment (pulse steroids or antilymphocyte products, or both). Data from the nine patients with a minimum of 6 months of follow-up were collected.

Results: No patients have died. The spirometry data of the eight patients with declining values of forced expiratory volume in 1 second are presented. Before initiation of methotrexate therapy the median decline in forced expiratory volume in 1 second was 1.4 +/- 0.8 L, or 43% +/- 17%, from the highest preinterventional forced expiratory volume in 1 second value during the preceding 12 months. At 6 months the median decline in forced expiratory volume in 1 second from the time methotrexate therapy was started was 0.1 +/- 0.2 L, or 3% +/- 11%. At 9 months (n = 6) the value was 0.2 +/- 0.2 L, or 6% +/- 12%. At 12 months (n = 5) the median decline was 0.4 +/- 0.3 L, or 9% +/- 16%. In two patients there has been no further decline in forced expiratory volume in 1 second since methotrexate therapy was started (one patient has had a slight but sustained improvement). Five patients have had a reduction in forced expiratory volume in 1 second of 10% or less at most recent follow-up, and only one patient has derived no apparent benefit from methotrexate therapy. Toxicity has been minimal.

Conclusions: Methotrexate is a potentially promising therapeutic alternative in the therapy of bronchiolitis obliterans syndrome in lung transplant recipients.