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-Rresp). METHODS: Baseline LCI, forced expiratory volume in 1 s (FEV1), CFQ-Rresp 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-Rresp (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-Rresp (r=-0.282, p=0.043). CONCLUSIONS: Baseline LCI predicts PE in young patients with CF and correlates with CFQ-Rresp, 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.
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-Rresp). METHODS: Baseline LCI, forced expiratory volume in 1 s (FEV1), CFQ-Rresp 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-Rresp (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-Rresp (r=-0.282, p=0.043). CONCLUSIONS: Baseline LCI predicts PE in young patients with CF and correlates with CFQ-Rresp, 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.
Authors: Philip A Reid; David A McAllister; A Christopher Boyd; J Alastair Innes; David Porteous; Andrew P Greening; Robert D Gray Journal: Am J Respir Crit Care Med Date: 2015-01-15 Impact factor: 21.405
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