Lung clearance index: a new measure of ventilation inhomogeneity in childhood respiratory diseases

2021 ◽  
Vol 17 ◽  
Author(s):  
Giuseppe Fabio Parisi ◽  
Emanuela Pignatone ◽  
Maria Papale ◽  
Enza Mulé ◽  
Sara Manti ◽  
...  
Keyword(s):  
Respiratory Diseases ◽  
Small Airways ◽  
Early Assessment ◽  
Lung Clearance ◽  
Ventilation Inhomogeneity ◽  
Lung Clearance Index ◽  
Multiple Breath Washout ◽  
Primary Test ◽  
Forced Breathing

: Conventional spirometry has long been considered the primary test for assessing respiratory function deficits in children and adults. However, the need to perform forced breathing maneuvers can make it challenging to perform these examinations in an uncooperative child. For these reasons, techniques such as gas dilutions and the multiple-breath-washout (MBW) method have been implemented because they allow for early assessment of damage to the small airways. These methods permit the determination of the possible presence of ventilatory inhomogeneity in the lungs by analyzing the clearance of an inert gas used as a tracer. The equipment consists of a mass spectrometer combined with a flow meter. The Lung Clearance Index (LCI) is most often used to evaluate ventilatory inhomogeneity. This narrative review aimed to review the literature on technical and practical aspects of the MBW test and evaluate the clinical implications of the LCI in pediatric respiratory disease.

Relationships between the lung clearance index and conductive and acinar ventilation heterogeneity

2012 ◽  
Vol 112 (5) ◽  
pp. 782-790 ◽  
Author(s):  
Sylvia Verbanck ◽  
Manuel Paiva ◽  
Daniel Schuermans ◽  
Shane Hanon ◽  
Walter Vincken ◽  
...  
Keyword(s):  
Compartment Model ◽  
Normal Subjects ◽  
Bronchial Tree ◽  
Small Airways ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Asthma Patients ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Washout Curves

The lung clearance index (LCI) derived from a multiple breath washout test has regained considerable popularity in recent years, alternatively being promoted as an early detection tool or a marker of small airways function. In this study, we systematically investigated the link between LCI and indexes of acinar and conductive airways ventilation heterogeneity (Sacin, Scond) to assess potential contributions from both lung zones. Relationships were examined in 55 normal subjects after provocation, where only Scond is known to be markedly increased, and in 55 asthma patients after bronchodilation, in whom both Scond and Sacin ranged between normal and abnormal. LCI was correlated to Scond in both groups ( R = 0.37–0.43; P < 0.01 for both); in the asthma group, LCI was also tightly correlated to Sacin ( R = 0.70; P < 0.001). Potential mechanisms operational at various levels of the bronchial tree were identified by considering washout curvilinearity in addition to LCI to distinguish specific ventilation and dead space effects (also illustrated by simple 2-compartment model simulations). Although the asthma data clearly demonstrate that LCI can reflect very peripheral ventilation heterogeneities, the normal provocation data also convincingly show that LCI increases may be the exclusive result of far more proximal ventilation heterogeneities. Because LCI potentially includes heterogeneities at all length scales, it is suggested that ventilation imaging in combination with LCI measurement at the mouth could identify the scale of relevant ventilation heterogeneities. In the meantime, interpretations of LCI results in the clinic based on washout curves collected at the mouth should be handled with caution.

scholarly journals Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout

2018 ◽  
Vol 52 (5) ◽  
pp. 1800821 ◽  
Author(s):  
Laurie J. Smith ◽  
Guilhem J. Collier ◽  
Helen Marshall ◽  
Paul J.C. Hughes ◽  
Alberto M. Biancardi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cystic Fibrosis ◽  
Total Lung Capacity ◽  
Resonance Imaging ◽  
Ventilation Distribution ◽  
Lung Clearance ◽  
Lung Capacity ◽  
Lung Clearance Index ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIVT). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection–diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIVT strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=−0.79 and r=−0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIVT, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities.

Reference values for lung clearance index (LCI) derived from sulphur hexafluoride multiple breath washout testing

2020 ◽  
Author(s):  
Frederik Trinkmann ◽  
Máté Maros ◽  
Katharina Roth ◽  
Arne Hermanns ◽  
Julia Schäfer ◽  
...  
Keyword(s):  
Reference Values ◽  
Sulphur Hexafluoride ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Multiple Breath Washout

scholarly journals Difference between SF6 and N2 multiple breath washout kinetics is due to N2 back diffusion and error in N2 offset

2018 ◽  
Vol 125 (4) ◽  
pp. 1257-1265 ◽  
Author(s):  
Lokesh Guglani ◽  
Ajay Kasi ◽  
Miah Starks ◽  
Knud E. Pedersen ◽  
Jørgen G. Nielsen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Care ◽  
Back Diffusion ◽  
Healthy Controls ◽  
Lung Clearance ◽  
Routine Clinical Care ◽  
Lung Clearance Index ◽  
Multiple Breath Washout ◽  
In Series ◽  
Offset Error

Measurement of lung clearance index (LCI) by multiple breath washout (MBW) is a sensitive method for monitoring lung disease in patients with cystic fibrosis (CF). To compare nitrogen MBW (N2-MBW) and sulfur hexafluoride MBW (SF6-MBW), we connected these two gas analysis systems in series to obtain truly simultaneous measurements, with no differences other than the gas used. Nonsmoking healthy controls (HC) and subjects with CF were recruited at two institutions. The Exhalyzer-D (for N2-MBW measurement) was connected in series with the Innocor (for SF6-MBW measurement). Subjects washed in SF6 from a Douglas bag with tidal breathing and washed out SF6 and nitrogen with 100% oxygen provided as bias flow. Washout of both gases was continued past the LCI point (1/40th of equilibration concentration) in triplicate. N2-MBW resulted in higher cumulative exhaled volume, functional residual capacity (FRC), and LCI when compared with SF6-derived parameters in HC subjects ( P < 0.0001 for all comparisons). All N2-MBW parameters were also significantly higher than SF6-MBW parameters in subjects with CF ( P < 0.01 for all comparisons). After recalculation with a common FRC, N2-MBW LCI was higher than SF6-MBW LCI in subjects with CF (19.73 vs. 11.39; P < 0.0001) and in HC (8.12 vs. 6.78; P < 0.0001). Adjusting for N2 back diffusion and an offset error in the nitrogen measurement resulted in near complete agreement between the two methodologies. We found significant differences in LCI and FRC measurements using two different gases for MBW. This may have significant implications for the future use and interpretation of LCI data in clinical trials and routine clinical care. NEW & NOTEWORTHY This study provides important insights into the differences between the two techniques used for measuring lung clearance index (LCI): N2 and SF6 multiple breath washout. Differences between measurements made by these two methods in subjects with cystic fibrosis and healthy controls could be explained by nitrogen back diffusion and N2 offset error. This is important for use and interpretation of LCI data as an outcome measure for clinical trials and in routine clinical care.

scholarly journals Elevated lung clearance index in infants with cystic fibrosis shortly after birth

2017 ◽  
Vol 50 (5) ◽  
pp. 1700580 ◽  
Author(s):  
Elisabeth Kieninger ◽  
Sophie Yammine ◽  
Insa Korten ◽  
Pinelopi Anagnostopoulou ◽  
Florian Singer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Specific Treatment ◽  
Lung Clearance ◽  
Time To Peak ◽  
Ventilation Inhomogeneity ◽  
Lung Clearance Index ◽  
Residual Capacity ◽  
Z Scores ◽  
Noninvasive Markers

It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening.We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF.We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02–0.60; p=0.034 and 14.5 mL, 95% CI 7.7–21.3 mL; p<0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC.Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.

scholarly journals WS15.3 Rapid and portable multiple breath washout (MBW) measurements for clinical application of lung clearance index (LCI)

2016 ◽  
Vol 15 ◽  
pp. S25
Author(s):  
A. Horsley ◽  
A. Maitra ◽  
F.J. Gilchrist ◽  
A. Shawcross ◽  
S. Cunningham ◽  
...  
Keyword(s):  
Clinical Application ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Multiple Breath Washout

scholarly journals An 8 week open-label interventional multicenter study to evaluate the lung clearance index as endpoint for clinical trials in cystic fibrosis patients ≥8 years of age, chronically infected with Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Sivagurunathan Sutharsan ◽  
Susanne Naehrig ◽  
Uwe Mellies ◽  
Christian Sieder ◽  
joerg Zeigler
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Lung Disease ◽  
Small Airways ◽  
Open Label ◽  
Lung Clearance ◽  
Efficacy Trials ◽  
Inhaled Antibiotics ◽  
Lung Clearance Index

Abstract Background Forced expiratory volume in 1 second (FEV 1 ) is the only parameter currently recognized as a surrogate endpoint in cystic fibrosis (CF) trials. However, FEV 1 is relatively insensitive to changes in the small airways of patients with milder lung disease. This pilot study aimed to evaluate the lung clearance index (LCI) as a marker for use in efficacy trials with inhaled antibiotics in CF. Methods This open-label, single-arm study enrolled CF patients with Pseudomonas aeruginosa infection, who were treated with tobramycin (28-day on/off regime). FEV 1 , LCI and bacterial load in sputum (CFU) were assessed at baseline, after 1, 4 and 8 weeks of treatment. Results All patients (n=17) showed elevated LCI of >11 despite 3 patients having normal FEV 1 (>90% predicted) at baseline. Overall, LCI improved in 8 (47%) patients and FEV 1 in 9 (53%) patients. At week 4, LCI improved by 0.88, FEV 1 increased by 0.52%, and P. aeruginosa reduced by 30481.3 CFU/mL. These changes were however statistically non-significant. Six adverse events occurred in 5/17 (29.4%) patients, most of which were mild-to-moderate in severity. Conclusions Due to the low evaluable sample size, no specific trend was observed related to the changes between LCI, FEV1 and CFU. Based on the individual data from this study and from recently published literature, LCI has been shown to be a more sensitive parameter than FEV1 for lung function. LCI can hypothesized to be an appropriate endpoint for efficacy trials in CF patients if the heterogeneity in lung function is limited by enrolling younger patients or patients with more milder lung disease and thus, limiting the ventilation inhomogeneities. Trial registration : The study is registered with ClinicalTrials.gov, identifier: NCT02248922

scholarly journals Association of lung clearance index with survival in individuals with cystic fibrosis

2021 ◽  
pp. 2100432
Author(s):  
Johanna Manuela Kurz ◽  
Kathryn Angela Ramsey ◽  
Romy Rodriguez ◽  
Ben Spycher ◽  
Reta Fischer Biner ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Sensitivity Analyses ◽  
Event Analysis ◽  
Z Score ◽  
Lung Clearance ◽  
Risk Of Death ◽  
Ventilation Inhomogeneity ◽  
Hazard Ratios ◽  
Lung Clearance Index ◽  
The Mean

BackgroundThe lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease.ObjectivesWe examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF.MethodsWe performed a retrospective analysis in a cohort of individuals with CF aged≥5 years with LCI and 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 hazard 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.ResultsIn 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 [95% CI] were 1.04 [1.01–1.06] per one z-score increase in LCI and 1.25 [1.11–1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01–1.07] for LCI, and 1.12 [0.95–1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations.ConclusionsIncreased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.

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