Abstract
Background The lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease. We examined the association of LCI with the risk of death or lung transplantation (LTx) in individuals with CF.
Methods We performed a retrospective analysis in a cohort of individuals with CF aged ≥5 years with LCI and forced expired volume in 1 s (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 hazards 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.
Results In 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 were 1.04 (95% CI 1.01–1.06) per 1.0 z-score increase in LCI and 1.25 (95% CI 1.11–1.41) per 1.0 z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, body mass index and number of hospitalisations, hazard ratios were 1.04 (95% CI 1.01–1.07) for LCI and 1.12 (95% CI 0.95–1.33) for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations.
Conclusions Increased ventilation inhomogeneity is associated with greater risk of death or LTx. Our data support LCI as novel surrogate of survival in individuals with CF.
Abstract
The lung clearance index (LCI) is a measure of global ventilation inhomogeneity that increases early during the course of cystic fibrosis (CF) lung disease. This study shows that LCI is associated with death or lung transplantation in individuals with CF. https://bit.ly/2T3ia9C
Footnotes
This study is registered at ClinicalTrials.gov with identifier number NCT04016194.
Author contributions: J.M. Kurz: data curation, methodology, formal analysis, investigation, visualisation, writing (original draft, review and editing). K.A. Ramsey: methodology, writing (review and editing). R. Rodriguez: data curation, investigation, writing (review and editing). B. Spycher: methodology, formal analysis, writing (review and editing). R. Fischer Biner: data curation, investigation, writing (review and editing). P. Latzin: funding acquisition, methodology, resources, writing (review and editing). F. Singer: funding acquisition, conceptualisation, methodology, resources, writing (review and editing), supervision, project administration.
Conflict of interest: J.M. Kurz has nothing to disclose.
Conflict of interest: K.A. Ramsey reports grants from Vertex, outside the submitted work.
Conflict of interest: R. Rodriguez has nothing to disclose.
Conflict of interest: B. Spycher has nothing to disclose.
Conflict of interest: R. Fischer Biner reports personal fees from Vertex, OM Pharma and Boehringer Ingelheim, outside the submitted work.
Conflict of interest: P. Latzin reports grants from Vertex, during the conduct of the study; personal fees from Vertex, Novartis, Roche, Polyphor, OM Pharma, Gilead, Schwabe, Zambon and Santhera, outside the submitted work.
Conflict of interest: F. Singer reports grants from the Swiss Society for Cystic Fibrosis, during the conduct of the study; personal fees from Vertex and Novartis, and a grant from Lungenliga Bern, outside the submitted work.
Support statement: This project was funded by unrestricted educational grants from Vertex Pharmaceuticals Inc. (grant IS-20-045), the Swiss National Science Foundation (SNSF; grant 182719) and the Swiss Society of Cystic Fibrosis (CFCH). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received February 11, 2021.
- Accepted June 28, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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