Rationale The lung clearance index (LCI) is a promising endpoint for use in cystic fibrosis (CF) clinical trials, but correlations with validated clinical endpoints have not yet been established.

Objective This study aimed to demonstrate that, in young patients with CF, baseline LCI predicts subsequent pulmonary exacerbation (PE) and correlates with the respiratory domain of the CF Questionnaire-Revised (CFQ-R_resp).

Methods Baseline LCI, forced expiratory volume in 1 s (FEV₁), CFQ-R_resp and PEs over the subsequent year were prospectively recorded in 63 patients aged 5–19 years. The ability of baseline LCI to predict PE was assessed using negative binomial regression models and Kaplan–Meier plots.

Results Twenty-six patients (41%) experienced 48 PEs. Baseline LCI and FEV₁ were predictors of PE. Compared with the quartile with the lowest LCI, the annual PE rate in increasing LCI quartiles was 2.9 (95% CI 0.5 to 16.5, p=0.238), 5.4 (95% CI 1.0 to 29.0, p=0.045) and 13.6 (95% CI 2.8 to 67.1, p=0.001). Similarly, time to first PE decreased with worsening LCI quartiles (log-rank test for trend, p<0.001). Furthermore, LCI correlated with CFQ-R_resp (r=−0.43, p<0.001). In the subgroup of 53 patients with normal FEV₁, LCI was a predictor of PE. In this subgroup, LCI also correlated with CFQ-R_resp (r=−0.282, p=0.043).

Conclusions Baseline LCI predicts PE in young patients with CF and correlates with CFQ-R_resp, a validated patient-reported outcome, even in the subgroup with normal FEV₁. These data further support the use of LCI as a surrogate outcome measure in CF clinical trials.