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 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.

Short- and mid-term reproducibility of lung clearance index in children with cystic fibrosis and healthy controls

2018 ◽  
Author(s):  
Bettina Sarah Frauchiger ◽  
Sylvia Nyilas ◽  
Kathryn Ramsey ◽  
Philipp Latzin ◽  
Sophie Yammine
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Controls ◽  
Lung Clearance ◽  
Lung Clearance Index

Correction of sensor crosstalk error in Exhalyzer D multiple-breath washout device significantly impacts outcomes in children with cystic fibrosis

2021 ◽  
Author(s):  
Florian Wyler ◽  
Marc-Alexander H. Oestreich ◽  
Bettina Sarah Frauchiger ◽  
Kathryn A. Ramsey ◽  
Philipp T. Latzin
Keyword(s):  
Carbon Dioxide ◽  
Cystic Fibrosis ◽  
Functional Residual Capacity ◽  
Nitrogen Concentration ◽  
Lung Clearance ◽  
Cross Sensitivity ◽  
Carbon Dioxide Gas ◽  
Lung Clearance Index ◽  
Multiple Breath Washout ◽  
Residual Capacity

Rationale: Nitrogen multiple-breath washout is an established technique to assess functional residual capacity and ventilation inhomogeneity in the lung. Accurate measurement of gas concentrations is essential for the appropriate calculation of clinical outcomes. Objectives: We investigated the accuracy of oxygen and carbon dioxide gas sensor measurements used for the indirect calculation of nitrogen concentration in a commercial multiple-breath washout device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and its impact on functional residual capacity and lung clearance index. Methods: High precision calibration gas mixtures and mass spectrometry were used to evaluate sensor output. We assessed the impact of corrected signal processing on multiple-breath washout outcomes in a dataset of healthy children and children with cystic fibrosis using custom analysis software. Results: We found inadequate correction for the cross sensitivity of the oxygen and carbon dioxide sensors in the Exhalyzer D device. This results in an overestimation of expired nitrogen concentration, and consequently multiple-breath washout outcomes. Breath-by-breath correction of this error reduced the mean (SD) cumulative expired volume by 19.6 (5.0)%, functional residual capacity by 8.9 (2.2)%, and lung clearance index by 11.9 (4.0)%. It also substantially reduced the level of the tissue nitrogen signal at the end of measurements. Conclusions: Inadequate correction for cross sensitivity in the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of functional residual capacity and lung clearance index. Correction of this error is possible and could be applied by re-analyzing the measurements in an updated software version.

Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis

2021 ◽  
pp. 2003380
Author(s):  
Sanja Stanojevic ◽  
Stephanie D. Davis ◽  
Lucy Perrem ◽  
Michelle Shaw ◽  
George Retsch-Bogart ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Disease Progression ◽  
Forced Expiratory Volume ◽  
School Age ◽  
Lung Clearance ◽  
Time Period ◽  
Early School ◽  
Lung Clearance Index ◽  
Multiple Breath Washout

BackgroundThe lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis (CF). While LCI worsens during the preschool years in CF, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.MethodsA cohort of children (healthy (HC) and CF) previously studied for 12 months as preschoolers were followed during school age (5–10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer® D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.ResultsA total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 CF subjects were available. The majority of children with CF had elevated LCI at the first preschool and first school age visits (57.8% (37/64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (−0.02 units·year−1 (95% CI −0.14; 0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age.ConclusionPreschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.

scholarly journals The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

2018 ◽  
Vol 4 (1) ◽  
pp. 00094-2017 ◽  
Author(s):  
Rachel E. Foong ◽  
Alana J. Harper ◽  
Billy Skoric ◽  
Louise King ◽  
Lidija Turkovic ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Fluid Collection ◽  
Lavage Fluid ◽  
Sufficient Information ◽  
Healthy Children ◽  
Success Rates ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Multiple Breath Washout

The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed.Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan.MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials.This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible.

scholarly journals Longitudinal Course of Clinical Lung Clearance Index in Children with Cystic Fibrosis

2020 ◽  
pp. 2002686
Author(s):  
Bettina S. Frauchiger ◽  
Severin Binggeli ◽  
Sophie Yammine ◽  
Ben Spycher ◽  
Linn Krüger ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Care ◽  
Airway Disease ◽  
Underlying Disease ◽  
Mixed Effect ◽  
Lung Clearance ◽  
Longitudinal Course ◽  
Lung Clearance Index ◽  
Clinical Surveillance ◽  
Over Time

RationaleWhile lung clearance index (LCI) is a sensitive marker of small airway disease in individuals with cystic fibrosis (CF), less is known about longitudinal changes in LCI during routine clinical surveillance.ObjectivesTo describe the longitudinal course of LCI in children with CF during routine clinical surveillance and assess influencing factors.MethodsChildren with CF aged 3–18 years performed LCI measurements every 3 months as part of routine clinical care between 2011 and 2018. We recorded clinical data at every visit. We used a multilevel mixed-effect model to determine changes in LCI over time and identify clinical factors that influence LCI course.Measurements and Main ResultsWe collected LCI from 1204 visits (3603 trials) in 78 participants, of which 907 visits had acceptable LCI data. The average unadjusted increase in LCI for the entire population was 0.29 LCI units·year−1 (95% CI 0.20–0.38). The increase in LCI was more pronounced in adolescence, with 0.41 units·year−1 (95% CI 0.27–0.54). Colonisation with either Pseudomonas aeruginosa or Aspergillus fumigatus, pulmonary exacerbations, CF-related diabetes, and bronchopulmonary aspergillosis were associated with a higher increase in LCI over time. Adjusting for clinical risk factors reduced the increase in LCI over time to 0.24 LCI units·year−1 (95% CI 0.16–0.33).ConclusionLCI measured during routine clinical surveillance is associated with underlying disease progression in children with CF. An increased change in LCI over time should prompt further diagnostic intervention.

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

2017 ◽  
Vol 50 (4) ◽  
pp. 1700433 ◽  
Author(s):  
Esther Oude Engberink ◽  
Felix Ratjen ◽  
Stephanie D. Davis ◽  
George Retsch-Bogart ◽  
Reshma Amin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Preschool Children ◽  
Biological Variability ◽  
Meaningful Change ◽  
Limits Of Agreement ◽  
Intra Class Correlation ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Multiple Breath Washout ◽  
Intra Class Correlation Coefficient

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.

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.

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