Association of lung clearance index with survival in individuals with cystic fibrosis

Abstract

BackgroundThe lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease.ObjectivesWe examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF.MethodsWe performed a retrospective analysis in a cohort of individuals with CF aged≥5 years with LCI and FEV1 measurements performed between 1980 and 2006. The outcome was time until death or LTX. We used the earliest available LCI and FEV1 values in a Cox proportional hazard regression adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1.ResultsIn total, 237 individuals with CF with a mean (range) age of 13.9 (5.6–41.0) years were included. The time-to-event analysis accrued 3813 person-years and 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01–1.06] per one z-score increase in LCI and 1.25 [1.11–1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01–1.07] for LCI, and 1.12 [0.95–1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations.ConclusionsIncreased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.

Cystic fibrosis year in review 2022

“…for every increase in LCI z-score and 18% for every decrease in FEV1 z-score, thereby leading the authors to conclude the potential utility of LCI as a novel surrogate marker of survival. 57 Moreover, a 3-year multicenter observational study of repeated LCI measurements demonstrated feasibility and reproducibility over time. 58 PwCF with predominantly mild disease had stable LCI over time, while PwCF with worsening LCI had a higher baseline LCI, increased age, lower baseline FEV1pp, PA infection, and increased number of IV antibiotics courses.…”

“…LCI is an alternate measure of pulmonary function, often used in younger ages. In a single‐center retrospective examination from 1980 to 2006 of 237 patients over age 5, the risk of death increased by 4% for every increase in LCI z‐score and 18% for every decrease in FEV1 z‐score, thereby leading the authors to conclude the potential utility of LCI as a novel surrogate marker of survival 57 . Moreover, a 3‐year multicenter observational study of repeated LCI measurements demonstrated feasibility and reproducibility over time 58 .…”

TRACK-CF prospective cohort study: Understanding early cystic fibrosis lung disease

“…Its principal read-out parameter, the lung clearance index 2.5% (LCI 2.5 ), detects progression of CF lung disease (13,28). It furthermore correlates with infection with Pseudomonas aeruginosa and airway inflammation and serves as predictor for later spirometry results and survival of patients with CF (13,(29)(30)(31).…”

Association of Oxygen Therapy with the Natural Disease Progression of Cystic Fibrosis: A Multi-State Model of the European Cystic Fibrosis Society Patient Registry

“…[35][36][37] The decision to include LCI as a variable in the ECFSPR from 2018 onwards is therefore rather appropriate since it can help to diagnose earlier stage lung disease than if only a decrease in FEV 1 is considered; this has promising implications for future prognostication in CF, as recently presented elsewhere. 38 We hope it is, or will become, available and reimbursed in as many countries as possible.…”