Lung Clearance Index in Adults and Children With Cystic Fibrosis

O’Neill, Katherine; Tunney, Michael; Johnston, E.; Rowan, Stephen; Downey, D.G.; Rendall, J.; Reid, Alastair; Bradbury, Ian; Elborn, J.S.; Bradley, J.M.

doi:10.1016/j.chest.2016.06.029

Cited by 41 publications

(35 citation statements)

References 44 publications

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“…LCI=7), a 15% change in LCI reflects a change of approximately 1 unit, which coincides with the Bland-Altman limits of agreement and coefficient of repeatability defined in this study. The inter-visit %CV and absolute change in LCI are consistent with previous literature; however the range of observed LCI values in previous studies was narrower, thus the relationship between the variability and magnitude may not have been apparent [6,12,15]. For instance, SINGER et al [12] reported a coefficient of repeatability of 0.96 units for measurements in cystic fibrosis made 24 h apart, which was similar to what we observed in healthy participants.…”

Section: Discussionsupporting

confidence: 81%

“…Previous studies define inter-test reproducibility as the %CV [5,7,8] or the ICC [6]. Both of these are useful parameters to summarise consistency and agreement, but do not provide a meaningful limit of reproducibility [33].…”

Section: Discussionmentioning

confidence: 99%

“…The LCI identifies early obstructive lung disease [1] and is feasible to perform in young children [2,3]. In addition, the LCI has good intra-test repeatability [4][5][6]; however, there are limited longitudinal data describing inter-test reproducibility.…”

Section: Introductionmentioning

confidence: 99%

“…Most notably, time intervals between repeated tests range from hours to years, and none report reproducibility for time intervals typically used to clinically track patients with cystic fibrosis (e.g. quarterly) [6,11,15]. Comparison between studies is further limited by the various methodologies that define reproducibility; coefficient of variation (%CV) [5,7,8], the intra-class correlation coefficient (ICC) [6], the limits of agreement from Bland-Altman plots [5,[9][10][11] or the coefficient of reproducibility [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Investigators report differing findings for the inter-test reproducibility of the LCI due to variability in protocol designs, study population and MBW methodology [5][6][7][8][9][10][11][12][13][14]. Most notably, time intervals between repeated tests range from hours to years, and none report reproducibility for time intervals typically used to clinically track patients with cystic fibrosis (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Inter-test reproducibility of the lung clearance index measured by multiple breath washout

et al. 2017

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The lung clearance index (LCI) has strong intra-test repeatability; however, the inter-test reproducibility of the LCI is poorly defined.The aim of the present study was to define a physiologically meaningful change in LCI in preschool children, which discriminates changes associated with disease progression from biological variability.Repeated LCI measurements from a longitudinal cohort study of children with cystic fibrosis and age-matched controls were collected to define the inter-visit reproducibility of the LCI. Absolute change, the coefficient of variation, Bland-Altman limits of agreement, the coefficient of repeatability, intra-class correlation coefficient, and percentage changes were calculated.LCI measurements (n=505) from 71 healthy and 77 cystic fibrosis participants (aged 2.6-6 years) were analysed. LCI variability was proportional to its magnitude, such that reproducibility defined by absolute changes is biased. A physiologically relevant change for quarterly LCI measurements in health was defined as exceeding ±15%. In clinically stable cystic fibrosis participants, the threshold was higher (±25%); however, for measurements made 24 h apart, the threshold was similar to that observed in health (±17%).A percentage change in LCI greater than ±15% in preschool children can be considered physiologically relevant and greater than the biological variability of the test.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inter-test reproducibility of the lung clearance index measured by multiple breath washout

et al. 2017

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The remaining barriers to normalcy in CF: Advances in assessment of CF lung disease

Muston

Perrem

Davis

et al. 2021

Pediatric Pulmonology

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Despite early diagnosis of cystic fibrosis (CF) through newborn screening, a substantial proportion of infants and young children with CF still demonstrate physiologic and structural evidence of lung disease progression, such as obstructive airway disease and bronchiectasis. The growing availability of highly effective CF transmembrane conductance regulatory modulator therapy to the vast majority of people with CF has led to the potential to alter the natural history of CF lung disease, but to assess the full impact of these therapies on CF lung disease and to help guide treatment, sensitive measures of early and mild disease are needed. Chest imaging using computed tomography or magnetic resonance imaging is one approach, but technologic barriers and/or concern about exposure to ionizing radiation may limit its use. However, advances in physiologic measurement techniques and exhaled breath analysis offer another option for assessment of CF lung disease

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Repeatability of lung clearance index in infants with cystic fibrosis and recurrent wheeze

Koucký

Komárek

Pohunek

2022

Pediatric Pulmonology

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Objectives: To describe the short-and medium-term repeatability of lung clearance index at 2.5% (LCI 2.5 ) in infants and calculate the number of patients needed to enroll in a study (N) using LCI 2.5 as a primary outcome.Methods: An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)] and medium-term repeatability (Bland-Altman method) of LCI 2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N 2 -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated.Results: Forty infants with CF and 21 with RW were enrolled. Initial N 2 -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI 2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI 2.5 value. In clinically stable patients, LCI 2.5 did not significantly change during the 8-month follow-up. Mean LCI 2.5 change was −0.08 (1% of baseline) in CF and −0.05 (0.6%) in RW, with 95% limits of agreement being 1.40) in RW patients. N = 23 infants if both intragroup differences of LCI 2.5 and minimal difference to be detected would be 2.0. Conclusion:N 2 -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies.

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Lung Clearance Index in Adults and Children With Cystic Fibrosis

Abstract: These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as in children.

Cited by 41 publications

References 44 publications

Inter-test reproducibility of the lung clearance index measured by multiple breath washout

Inter-test reproducibility of the lung clearance index measured by multiple breath washout

The remaining barriers to normalcy in CF: Advances in assessment of CF lung disease

Repeatability of lung clearance index in infants with cystic fibrosis and recurrent wheeze

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