Defining the Clinical Utility of the Lung Clearance Index. Are We There Yet?

Spano, Jacquelyn; Milla, Carlos

doi:10.1164/rccm.202010-3899ed

Cited by 6 publications

(7 citation statements)

References 22 publications

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“…The lung clearance index (LCI) is a sensitive physiological outcome measure and is a potentially useful diagnostic tool to guide treatment decisions in children with early cystic fibrosis lung disease (CF) 1 2. In a prospective observational study, we showed that LCI is more sensitive than FEV 1 in detecting worsening lung function and treatment effects in preschool and school-age children with acute respiratory symptoms 3–6.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of clinically relevant changes in the lung clearance index in children with cystic fibrosis and healthy controls

Perrem

Stanojevic

Solomon

et al. 2022

Thorax

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BackgroundThe limits of reproducibility of the lung clearance index (LCI) are higher in children with cystic fibrosis (CF) compared with healthy children, and it is currently unclear what defines a clinically meaningful change.MethodsIn a prospective multisite observational study of children with CF and healthy controls (HCs), we measured LCI, FEV1% predicted and symptom scores at quarterly visits over 2 years. Two reviewers performed a detailed review of visits to evaluate the frequency that between visit LCI changes outside ±10%, ±15%, ±20% represented a clinically relevant signal. In the setting of acute respiratory symptoms, we used a generalised estimating equation model, with a logit link function to determine the ability of LCI worsening at different thresholds to predict failure of lung function recovery at follow-up.ResultsClinically relevant LCI changes outside ±10%, ±15% and ±20% were observed at 25.7%, 15.0% and 8.3% of CF visits (n=744), respectively. The proportions of LCI changes categorised as noise, reflecting biological variability, were comparable between CF and HC at the 10% (CF 9.9% vs HC 13.0%), 15% (CF 4.3% vs HC 3.1%) and 20% (CF 2.4% vs HC 1.0%) thresholds. Compared with symptomatic CF visits without a worsening in LCI, events with ≥10% LCI increase were more likely to fail to recover baseline LCI at follow-up.ConclusionThe limits of reproducibility of the LCI in healthy children can be used to detect clinically relevant changes and thus inform clinical care in children with CF.

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Section: Introductionmentioning

confidence: 99%

Evaluation of clinically relevant changes in the lung clearance index in children with cystic fibrosis and healthy controls

Perrem

Stanojevic

Solomon

et al. 2022

Thorax

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“…Evidence collected so far has recognized LCI as an outcome measure in interventional trials [ 3 – 5 ]. Only recently, LCI was found sensitive to assess CF disease progression without overt clinical symptoms [ 6 ], however the utility of LCI as a clinical marker to guide the multidisciplinary practice of the CF team is still a matter of discussion [ 7 , 8 ]. Considering that personalized medicine not only aims to target therapies but also to identify individuals at elevated risk that could benefit most from therapies, we hypothesized that LCI can help to characterize clinical phenotypes of children with CF with regards to severity of lung disease.…”

Section: Introductionmentioning

confidence: 99%

Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis

et al. 2022

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Background Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE). Methods Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE. Results We collected 313 multiple breath washout tests on 125 children aged 5.5–16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6–4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34–0.62). Conclusions LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.

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“…Data on variability and clinically and physiologically relevant changes are essential for the use of LCI in the clinical surveillance of CF lung disease and to guide therapeutic decisions 19 . This study adds important data on the variability of LCI in routine clinical surveillance.…”

Section: Discussionmentioning

confidence: 95%

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

Frauchiger

Ramsey

Usemann

et al. 2022

Pediatric Pulmonology

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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.

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Defining the Clinical Utility of the Lung Clearance Index. Are We There Yet?

Cited by 6 publications

References 22 publications

Evaluation of clinically relevant changes in the lung clearance index in children with cystic fibrosis and healthy controls

Evaluation of clinically relevant changes in the lung clearance index in children with cystic fibrosis and healthy controls

Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis

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

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