Lung clearance index in healthy volunteers, measured using a novel portable system with a closed circuit wash-in

Horsley, Alex; Alrumuh, Amnah; Bianco, B.; Bayfield, Katie J; Tomlinson, Joanne; Jones, Andrew M.; Maitra, Anirban; Cunningham, Steve; Smith, Jaclyn A.; Fullwood, Catherine; Pandyan, Anand; Gilchrist, Francis J

doi:10.1371/journal.pone.0229300

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…The MBW test is repeatable, reproducible, and user-friendly [42]. The narrow (essentially fixed) range of LCI values across different populations and ages [33,34,39,56,57] makes it a useful marker for tracking disease progression [14]. Abnormal LCI values can be detected in patients with CF shortly after birth [53], which corroborates the separate observations of early lung inflammation in the absence of infection [54].…”

Section: Multiple-breath Washout Test (Lung Clearance Index)supporting

confidence: 58%

A multimodal approach to detect and monitor early lung disease in cystic fibrosis

Mondéjar-López

Horsley

Ratjen

et al. 2021

Expert Review of Respiratory Medicine

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Introduction: In the early stages, lung involvement in cystic fibrosis (CF) can be silent, with disease progression occurring in the absence of clinical symptoms. Irreversible airway damage is present in the early stages of disease; however, reliable biomarkers of early damage due to inflammation and infection that are universally applicable in day-to-day patient management have yet to be identified. Areas covered: At present, the main methods of detecting and monitoring early lung disease in CF are the lung clearance index (LCI), computed tomography (CT), and magnetic resonance imaging (MRI). LCI can be used to detect patients who may require more intense monitoring, identify exacerbations, and monitor responses to new interventions. High-resolution CT detects structural alterations in the lungs of CF patients with the best resolution of current imaging techniques. MRI is a radiation-free imaging alternative that provides both morphological and functional information. The role of MRI for short-term follow-up and pulmonary exacerbations is currently being investigated. Expert opinion: The roles of LCI and MRI are expected to expand considerably over the next few years. Meanwhile, closer collaboration between pulmonology and radiology specialties is an important goal toward improving care and optimizing outcomes in young patients with CF.

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Section: Multiple-breath Washout Test (Lung Clearance Index)supporting

confidence: 58%

A multimodal approach to detect and monitor early lung disease in cystic fibrosis

Mondéjar-López

Horsley

Ratjen

et al. 2021

Expert Review of Respiratory Medicine

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“…No correlation between age and LCI was found when including younger collectives. 27 28 With the normal range appearing to remain stable for the first four decades of life, a fixed ULN of 6.8 and 7.0 was proposed by Horsley et al 28 and Fuchs et al 29 In patients older than 40 years a larger dispersion was seen. Despite all of these approaches being based on SF 6 , small differences may be partly explained by system set-ups and tracer gas concentrations.…”

Section: Discussionmentioning

confidence: 98%

Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters

Maros

Roth

Hermanns

et al. 2021

Thorax

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BackgroundMultiple breath washout (MBW) using sulfur hexafluoride (SF6) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF6-MBW reference values in pulmonary healthy adults.MethodsWe evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20–88 years). Lung clearance index (LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from triplicate SF6-MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI2.5) and 5% (LCI5) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile.ResultsAge was the only meaningful parameter influencing SF6-MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in Sacin and 10% (CI 2% to 22%) in Scond. Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in Sacin and 3% (CI 0% to 13%) in Scond.ConclusionSF6-MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF6-MBW outcome parameters over the whole age range.Trial registration numberNCT04099225.

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“…Agreeing on an upper limit of normal for LCI was challenging. Based on a study conducted in different hospitals in the United Kingdom, LCI was found to have a wider range of normal results for adults than for children [7]. In addition, multiple MBW devices exist at present, and the values of LCI are not interchangeable.…”

Section: Discussionmentioning

confidence: 99%

“…Spirometry is, in fact, limited in its ability because it is dependent on the airway resistance, which is very low in the airways starting at the eighth to tenth generation. MBW has been proven to be useful in patients with CF, but its place in the follow-up of patients with PCD-BE and nCFnPCD-BE remains unclear [7]. Studies conducted on MBW in PCD-BE patients are conflicting and often not comparable because of differences in MBW devices, tracer gases, and the equipment being used [8].…”

Section: Introductionmentioning

confidence: 99%

A Pilot Study of Lung Clearance Index as a Useful Outcome Marker in the Follow-Up of Pediatric Patients with Non-Cystic Fibrosis Bronchiectasis?

et al. 2023

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The forced expiratory volume in one second (FEV1) is regularly used for the follow-up of patients with non-cystic fibrosis bronchiectasis (nCF-BE). The lung clearance index (LCI), measured by the multiple breath washout test, has been recently proposed as a lung function measure and a potential tool more sensitive than the FEV1 measured by spirometry in assessing airway changes seen on imaging. While several data have been endorsed as a useful endpoint in clinical trials of patients with early or mild CF lung disease and as the main outcome measure in clinical trials with CFTR modulators in children and adolescents with CF, few data are available in the context of non-CF bronchiectasis. The aim of this pilot study was to compare the LCI with the FEV1 as well as the forced vital capacity (FVC), the forced expiratory flow at 25–75% of the FVC (FEF 25–75%), and chest imaging based on the modified Reiff score in patients with primary ciliary dyskinesia (PCD) and non-CF, non-PCD bronchiectasis (PCD-BE and nCFnPCD-BE). Additionally, we compared each test’s duration and the preferred technique. Twenty children were included; nine had PCD-BE and eleven had nCFnPCD-BE. The median age was twelve years (ages ranging between five and eighteen years). The median LCI was seven while the median z-scores of the FEV1, FVC, and FEF 25–75% were −0.6, 0, and −0.9, respectively. No significant associations or correlations were observed between LCI, spirometric parameters, or the modified Reiff score. However, nearly half of the population (n = 9) had an abnormal LCI, while only 10% had an abnormal FEV1. A total of 75% of children preferred MBW, despite it lasting five times longer than spirometry. In this paper, the authors suggest that LCI might be useful in a cohort of pediatric patients with PCD-BE and nCFnPCD-BE for detecting early lung function changes during their follow-up. Additionally, MBW seems to be preferred by patients. These data may encourage further studies on this topic.

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Lung clearance index in healthy volunteers, measured using a novel portable system with a closed circuit wash-in

Cited by 6 publications

References 34 publications

A multimodal approach to detect and monitor early lung disease in cystic fibrosis

A multimodal approach to detect and monitor early lung disease in cystic fibrosis

Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters

A Pilot Study of Lung Clearance Index as a Useful Outcome Marker in the Follow-Up of Pediatric Patients with Non-Cystic Fibrosis Bronchiectasis?

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