Inert Gas Washout in Bronchiolitis Obliterans Following Hematopoietic Cell Transplantation

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a leading cause of chronic graft-vs-host disease (cGvHD) and is associated with mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). The nitrogen multiple breath washout test (N-2-MBW) measures ventilation inhomogeneity, a biomarker of central and peripheral airway obstruction. The aim of this study was to examine ventilation inhomogeneity according to cGvHD score and histologically defined bronchiolitis obliterans (BO). METHODS: This single-center prospective cross-sectional study included 225 adults (mean age, 52.8 years; median, 5.4 years [interquartile range, 2.0-11 years]) after alloHSCT. Outcomes were global (lung clearance index [LCI]) and acinar ventilation inhomogeneity index (SACIN) from N-2-MBW. Patients were categorized into five groups: (1) no cGvHD and no obstruction (cGvHD overall score 0 and FEV1/FVC >= 70) (2) cGvHD and no obstruction (cGvHD overall score 1-3 and FEV1/FVC >= 70), (3) BOS with or without cGvHD (if available, no BO on histologic examination, and FEV1/FVC < 70), (4) histologically proven BO, and (5) diffuse parenchymal lung disease other than BO. RESULTS: The LCI and SACIN differed significantly between groups (P < .001) and increased progressively according to cGvHD score. In BO, the LCI and SACIN were elevated in 95.5% and 81.8% of patients, respectively, whereas FEV1/FVC was abnormal in only 56.5% of patients, respectively. CONCLUSIONS: N-2-MBW is highly sensitive for detecting abnormal lung function in patients following alloHSCT. LCI and SACIN seem to be promising biomarkers of lung involvement in cGvHD.