The efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans after hematopoietic stem cell transplantations

Abstract

Introduction: Bronchiolitis obliterans syndrome (BOS) is the manifestation of chronic graft-versus-host disease in the lung.

Aims and objectives: This study aimed to evaluate the efficacy of tiotropium add-on in patients with post-HSCT BOS.

Methods: Patients treated with budesonide/formoterol and tiotropium combination therapy after budesonide/formoterol monotherapy during the period between January 2011 and June 2019 were enrolled.

Results: Among 86 patients, 45 (52.3%) were male.  Mean time duration between HSCT and diagnosis of BOS was 20.0±16.5 months. After the tiotropium add-on, both in percentage predicted and absolute value. FEV1 (absolute) increased significantly from 1.47±0.49L to 1.53±0.57L (p = 0.023), and FEV1 (% predicted) also increased significantly from 45.0±12.8% to 46.8±14.5 (p = 0.031). FEV1/FVC also increased from 56.4±18.7% to 57.2±17.8% (p = 0.041). DLCO (%predicted) showed significant increase after tiotropium add-on (61.6±16.7 to 64.3±16.3, p = 0.028). After tiotropium add on, the total CAT score did not show significant change (p = 0.833). However, when separate score criteria were compared, question 4 (breathlessness going up) and 8 (energy) showed significant difference. CAT 4 decreased from 4 (3-4) to 3 (2.25-4) (p = 0.038). CAT 8 showed interval increase of 2 (1-3) to 3 (2-3) (p = 0.006). When the FEV1 and CAT score were combined, the overall response rate to tiotropium add-on was (41/73) 56.2 %.

Measurements and Main Results: Add-on of inhaled tiotropium to a combination treatment including budesonide/formoterol significantly improved lung function, but not respiratory symptoms in patients with post-HSCT BOS.