Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome

Long-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade. 51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded. LCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p<0.001). 27 patients had HRCT within 12 months. LCI in those with HRCT evidence of OB was higher than those without OB (11.1 versus 8.2, p=0.006). 47% patients displayed abnormal LCI (>7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline). LCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS.