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

Abstract

BackgroundLong-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.Methods51 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.ResultsLCI 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).ConclusionsLCI 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.

Pulmonary Dysfunction after Treatment for Childhood Cancer. Comparing Multiple-Breath Washout with Spirometry

“…In the current study, 60% of high risk patients had abnormal LCI and 33% abnormal FEV 1 . A publication on lung transplant recipients reported that LCI increased with severity of bronchiolitis obliterans syndrome (27). A significant proportion of patients had abnormal LCI but not FEV 1 values, which also suggests LCI to be more sensitive than spirometry in the early detection of pulmonary disease (27).…”

“…A publication on lung transplant recipients reported that LCI increased with severity of bronchiolitis obliterans syndrome (27). A significant proportion of patients had abnormal LCI but not FEV 1 values, which also suggests LCI to be more sensitive than spirometry in the early detection of pulmonary disease (27). In the only study that assessed N 2 MBW in pediatric HSCT recipients who were still under active cancer treatment (14), 28 children underwent pulmonary function assessment before and after HSCT.…”

Multiple breath washout: measuring early manifestations of lung pathology

“…While the vast majority of MBW research to date has been in the CF population, increasingly MBW is also being used in other obstructive lung diseases. For example, MBW outcomes have been used in adults to detect the early damage from cigarette smoking [39], bronchiectasis [16], COPD [40] and early post-transplant bronchiolitis obliterans syndrome (BOS) [41,42]. Ventilation inhomogeneity is present in asthma (both mild and uncontrolled) [43][44][45].…”

Multiple breath washout: A noninvasive tool for identifying lung disease in symptomatic military deployers

“…The expert panel concluded that gaps in practice guidelines for LCI interpretation, the need for more J o u r n a l P r e -p r o o f standardized operating procedures, and limited normative data were problematic, but that recommendations for MBW use in clinical settings were likely in the near future. In 2019, Driskel et al (47) found that MBW was both feasible and reproducible in detecting early BOS in adults following lung transplant. Our study underscores the feasibility of LCI as a sensitive, noninvasive tool in an adult outpatient setting that requires less than 60 minutes to perform.…”