Abstract
Background Forced expiratory volume in 1 second (FEV 1 ) is the only parameter currently recognized as a surrogate endpoint in cystic fibrosis (CF) trials. However, FEV 1 is relatively insensitive to changes in the small airways of patients with milder lung disease. This pilot study aimed to evaluate the lung clearance index (LCI) as a marker for use in efficacy trials with inhaled antibiotics in CF. Methods This open-label, single-arm study enrolled CF patients with Pseudomonas aeruginosa infection, who were treated with tobramycin (28-day on/off regime). FEV 1 , LCI and bacterial load in sputum (CFU) were assessed at baseline, after 1, 4 and 8 weeks of treatment. Results All patients (n=17) showed elevated LCI of >11 despite 3 patients having normal FEV 1 (>90% predicted) at baseline. Overall, LCI improved in 8 (47%) patients and FEV 1 in 9 (53%) patients. At week 4, LCI improved by 0.88, FEV 1 increased by 0.52%, and P. aeruginosa reduced by 30481.3 CFU/mL. These changes were however statistically non-significant. Six adverse events occurred in 5/17 (29.4%) patients, most of which were mild-to-moderate in severity. Conclusions Due to the low evaluable sample size, no specific trend was observed related to the changes between LCI, FEV1 and CFU. Based on the individual data from this study and from recently published literature, LCI has been shown to be a more sensitive parameter than FEV1 for lung function. LCI can hypothesized to be an appropriate endpoint for efficacy trials in CF patients if the heterogeneity in lung function is limited by enrolling younger patients or patients with more milder lung disease and thus, limiting the ventilation inhomogeneities. Trial registration : The study is registered with ClinicalTrials.gov, identifier: NCT02248922
Lung clearance index during hospital admission in school-age children with cystic fibrosis
