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.

scholarly journals Lung clearance index: assessment and utility in children with asthma

2019 ◽  
Vol 28 (154) ◽  
pp. 190046 ◽  
Author(s):  
Amy G. L. Nuttall ◽  
Werner Velásquez ◽  
Caroline S. Beardsmore ◽  
Erol A. Gaillard
Keyword(s):  
Early Stage ◽  
Airway Disease ◽  
Small Airway ◽  
Small Airways ◽  
Lung Clearance ◽  
Additional Information ◽  
Small Airway Disease ◽  
Lung Clearance Index ◽  
Children With Asthma ◽  
Ventilation Heterogeneity

There is increasing evidence that ventilation heterogeneity and small airway disease are significant factors in asthma, with evidence suggesting that the small airways are involved from an early stage in childhood asthma. Spirometry is commonly used to monitor lung function in asthmatics; however, it is not sensitive to small airway disease. There has been renewed interest in multibreath washout (MBW) tests, with recognition of the lung clearance index (LCI) as a global index of abnormality in gas mixing of the lungs that therefore also reflects small airway disease. This review summarises the technical and practical aspects of the MBW/LCI in children, and the differences between commercially available equipment. Children with severe asthma are more likely to have an abnormal LCI, whereas most children with mild-to-moderate asthma have an LCI within the normal range, but slightly higher than age-matched healthy controls. Monitoring children with asthma with MBW alongside standard spirometry may provide useful additional information.

scholarly journals The validity of shortened multiple breath washout testing using sulphur hexafluoride in the assessment of patients with COPD

2021 ◽  
pp. 00379-2020
Author(s):  
Neil Greening ◽  
John Owers-Bradley ◽  
Sally Singh ◽  
Salman Siddiqui
Keyword(s):  
Chronic Obstructive ◽  
Small Airways ◽  
Clinical Use ◽  
Clinical Markers ◽  
Sulphur Hexafluoride ◽  
Obstructive Pulmonary Disease ◽  
Lung Clearance Index ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
End Tidal

IntroductionChronic Obstructive Pulmonary Disease (COPD) affects the small airways and is associated with ventilation heterogeneity. There is little data on the Multiple Breath Washout (MBW) in patients with COPD particularly the variability over eight weeks, using a shortened sulphur hexafluoride (SF6) washout. This work evaluated the repeatability of the LCI1/40 and LCI1/20 among subjects with COPD and compared to spirometry and clinical markers.MethodsThe MBW was performed on patients with COPD to determine ventilation heterogeneity globally (Lung Clearance Index (LCI)), at conductive (Scond) and acinar (Sacin) levels. The LCI was repeated in triplicate and measured at a traditional 1/40th washout and retrofitted to a shortened 1/20th end tidal SF6 concentration washout. Tests were repeated after 20 min and eight weeks to determine within and between visit repeatability and compared with spirometry.Results84 subjects were recruited to perform LCI and spirometry with 20 subjects performing the repeatability protocol. There were weak correlations between FEV1 percent predicted and LCI1/40th r=−0.311 (p=0.02), and LCI1/20th r=−0.40 (p<0.01). The LCI demonstrated excellent within and good between visit repeatability for both a 1/40th and 1/20th washout (ICC≥0.80). There was a statistically significant strong correlation between LCI1/40th and a shortened LCI1/20 0.86 (p<0.01).ConclusionsThe LCI is repeatable within and between visits. There are weak correlations with measures of spirometry. A shortened LCI1/20th starting concentration correlates highly with a 1/40th washout which may encourage clinical use.

scholarly journals The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis

Thorax ◽  
2017 ◽  
Vol 73 (1) ◽  
pp. 82-84 ◽  
Author(s):  
Sylvia Verbanck ◽  
Gregory G King ◽  
Wenxiao Zhou ◽  
Anne Miller ◽  
Cindy Thamrin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Disease Severity ◽  
Adult Patients ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Lung Disease Severity

In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.

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.

scholarly journals Ventilation heterogeneity in children with severe asthma

2021 ◽  
Author(s):  
Amy G. Nuttall ◽  
Caroline S. Beardsmore ◽  
Erol A. Gaillard
Keyword(s):  
Severe Asthma ◽  
Airway Disease ◽  
Asthma Severity ◽  
Small Airway ◽  
Cross Sectional ◽  
Lung Clearance ◽  
Moderate Asthma ◽  
Lung Clearance Index ◽  
Children With Asthma ◽  
Ventilation Heterogeneity

AbstractSmall airway disease, characterised by ventilation heterogeneity (VH), is present in a subgroup of patients with asthma. Ventilation heterogeneity can be measured using multiple breath washout testing. Few studies have been reported in children. We studied the relationship between VH, asthma severity, and spirometry in a cross-sectional observational cohort study involving children with stable mild-moderate and severe asthma by GINA classification and a group of healthy controls. Thirty-seven participants aged 5–16 years completed multiple breath nitrogen washout (MBNW) testing (seven controls, seven mild-moderate asthma, 23 severe asthma). The lung clearance index (LCI) was normal in control and mild-moderate asthmatics. LCI was abnormal in 5/23 (21%) of severe asthmatics. The LCI negatively correlated with FEV1z-score.Conclusion: VH is present in asthmatic children and appears to be more common in severe asthma. The LCI was significantly higher in the cohort of children with severe asthma, despite no difference in FEV1 between the groups. This supports previous evidence that LCI is a more sensitive marker of airway disease than FEV1. MBNW shows potential as a useful tool to assess children with severe asthma and may help inform clinical decisions. What is Known:• Increased ventilation heterogeneity is present in some children with asthma• Spirometry is not sensitive enough to detect small airway involvement in asthma What is New• Lung clearance index is abnormal in a significant subgroup of children with severe asthma but rarely in children with mild-moderate asthma• Our data suggests that LCI monitoring should be considered in children with severe asthma

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 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

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