Variability of clinically measured lung clearance index in children with cystic fibrosis

Abstract

RATIONALE: The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and physiologically relevant changes in LCI during routine clinical surveillance. Objectives: To evaluate the long-term variability of LCI and propose a threshold for a physiologically relevant change. Methods: In children aged 4-18 years with CF, LCI was measured every 3 months as part of routine clinical surveillance during 2011-2020 in two centers. The variability of LCI during periods of clinical stability was assessed using mixed-effects models and was used to identify thresholds for physiologically relevant changes.Results: Repeated LCI measurements of acceptable quality (N = 858) were available in 100 patients with CF; for 74 patients, 399 visits at clinical stability were available.The variability of repeated LCI measurements over time expressed as the coefficient of variation (CV%) was 7.4%. The upper limit of normal (ULN) for relative changes in LCI between visits was 19%. Conclusion:We report the variability of LCI in children and adolescents with CF during routine clinical surveillance. According to our data, a change in LCI beyond 19% may be considered physiologically relevant. These findings will help guide clinical decisions according to LCI changes.

Lung clearance index (LCI2.5) changes after initiation of Elexacaftor/Tezacaftor/Ivacaftor in children with cystic fibrosis aged between 6 and 11 years: The “real‐world” differs from trial data

“…8,9 The clinical significance of the observed (−0.7) mean difference in LCI 2.5 post-ETI is unclear, as minimum clinically important difference for LCI 2.5 remains to be determined. 16 It has, however, been reported that the coefficient of variation for LCI 2.5 averages 7.4% with variations of up to 19% between visits reported, 17 such that 75% of the within-subject changes seen in this two time-point study would lie within a 19% limit of "natural variability" (Figure 1). The importance of stability and maintenance of normal lung function including LCI 2.5 is perhaps an important difference in the "realworld" approach to young children with CF, rather than seeking the large improvements seen in trials.…”

“…The clinical significance of the observed (−0.7) mean difference in LCI 2.5 post‐ETI is unclear, as minimum clinically important difference for LCI 2.5 remains to be determined 16 . It has, however, been reported that the coefficient of variation for LCI 2.5 averages 7.4% with variations of up to 19% between visits reported, 17 such that 75% of the within‐subject changes seen in this two time‐point study would lie within a 19% limit of “natural variability” (Figure 1).…”

Impact of Reanalysis of Nitrogen Multiple-Breath Washout on its Relationship with Chest Magnetic Resonance Imaging Findings in Clinically Stable and Pulmonary Exacerbated Children with Cystic Fibrosis

“…Furthermore, the inter-individual variability of N 2 LCI cor , especially in CF patients during PEx, was smaller than of N 2 LCI pre (▶fig. 3), which was previously described by several groups reanalyzing MBW data [17,19,24,25]. As shown by other research groups, the reduced inter-individual variability of N 2 LCI cor provides a rather precise estimate on potentially reversible pulmonary complications in children with CF [17,25].…”

Pediatric pulmonology year in review 2023: Physiology

“…Frauchiger et al studied 100 children with CF ages 4−18 years longitudinally over an average of 4.8 years each, measuring LCI quarterly. 3 They found that the upper limit of normal for long-term variability was 19%, and thus concluded that a relative change in LCI of ≥19% between visits can be considered physiologically relevant. This adds important information on interpretation of MBW as part of routine clinical surveillance.…”

“…Two studies published in Pediatric Pulmonology in the past year provide increased insight into this question. Frauchiger et al studied 100 children with CF ages 4−18 years longitudinally over an average of 4.8 years each, measuring LCI quarterly 3 . They found that the upper limit of normal for long‐term variability was 19%, and thus concluded that a relative change in LCI of ≥19% between visits can be considered physiologically relevant.…”