P195 Prospective longitudinal evaluation of the lung clearance index (LCI) in the clinical setting

Abstract

Lung clearance index (LCI) is recognized of great value as an endpoint for CF clinical trials, particularly among young children. However, there are still gaps in the information required to understand its role in the clinical care setting. We conducted a longitudinal study to evaluate the potential of LCI as a clinical decision tool. We enrolled 55 children with CF (mean age 10.9 + 3.6 years) and followed for 2 years LCI, FEV1 and other clinical parameters during quarterly routine visits. Reported symptoms, findings of exacerbation and changes in therapies were recorded for each visit. LCI was significantly increased from the previous visit in the presence of new respiratory symptoms reported (p = 0.0006), as well as being associated with changes in respiratory regimen (p = 0.0008), but not with prescription for antibiotics (p > 0.2). In contrast, FEV1 did not change significantly under any of these conditions (p > 0.2). A significant increase in LCI was noted for children diagnosed at the visit with a pulmonary exacerbation (1.3 vs 0.005 units, p = 0.04), this was not the case with FEV1 (+0.7 vs –2.4%-pred., p = 0.26). Most exacerbations were mild and treated as an outpatient, only 2 led to hospitalization. In addition, a mild decline in lung function with age during the study period was noted, with an increase of LCI by 0.32 units per year (p = 0.002) and a drop in FEV1 of –1.12%-pred. per year (p = 0.02). The decline in FEV1 was associated with LCI, with a drop of –2.0%-pred./year for every unit of increase in LCI (p < 0.0001). Further, there was a strong correlation between the change in FEV1 between visits and the change in LCI (p < 0.0001). We are conducting additional sensitivity analyses to evaluate cut-offs for minimal clinically important difference (MCID) considerations. We conclude that LCI has high sensitivity to progression of CF airway disease in children with what could be considered as well preserved lung function based on FEV1 criteria alone.