Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation

Abstract:

Background: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease, and a noninfectious pulmonary sequela of hematopoietic stem cell transplantation (HSCT). Despite the combination regimen including budesonide/formoterol that was previously shown as effective, a significant proportion of patients are unresponsive. We assessed whether inhaled tiotropium add-on to the combination regimen improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS.

Methods: Post-HSCT patients with significant respiratory symptoms or poor pulmonary function referred to the pulmonology department of the HSCT Center of Seoul St. Mary’s Hospital, were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled.

Results: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase (both absolute (p < 0.001) and % predicted (p < 0.001)), and a significant decrease in the RV/TLC ratio compared to the no-response group (p = 0.006).

Conclusions: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.