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.

scholarly journals Leaks during multiple-breath washout: characterisation and influence on outcomes

2018 ◽  
Vol 4 (1) ◽  
pp. 00012-2017 ◽  
Author(s):  
Nina Lenherr ◽  
Kathryn A. Ramsey ◽  
Kerstin Jost ◽  
Linn Hornwall ◽  
Florian Singer ◽  
...  
Keyword(s):  
Functional Residual Capacity ◽  
Cycle Duration ◽  
European Respiratory Society ◽  
Physiological Noise ◽  
Lung Clearance ◽  
Air Leaks ◽  
Heterogeneous Effects ◽  
Lung Clearance Index ◽  
Multiple Breath Washout ◽  
Residual Capacity

Nitrogen multiple-breath washout (N2MBW) is increasingly used in patients with cystic fibrosis. The current European Respiratory Society/American Thoracic Society consensus statement for MBW recommends the rejection of measurements with leaks. However, it is unclear whether this is necessary for all types of leaks. Here, our aim was to 1) model and 2) apply air leaks, and 3) to assess their influence on the primary MBW outcomes of lung clearance index and functional residual capacity.We investigated the influence of air leaks at various locations (pre-, intra- and post-capillary), sizes, durations and stages of the washout. Modelled leaks were applied to existing N2MBW data from 10 children by modifying breath tables. In addition, leaks were applied to the equipment during N2MBW measurements performed by one healthy adolescent.All modelled and applied leaks resulted in statistically significant but heterogeneous effects on lung clearance index and functional residual capacity. In all types of continuous inspiratory leaks exceeding a certain size, the end of the washout was not reached. For practical application, we illustrated six different “red flags”, i.e. signs that enable easy identification of leaks during measurements.Air leaks during measurement significantly influence N2MBW outcomes. The influence of leaks on MBW outcomes is dependent on the location, relation to breath cycle, duration, stage of washout and size of the leak. We identified a range of signs to help distinguish leaks from physiological noise.

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 The effect of inert gas choice on multiple breath washout in healthy infants: differences in lung function outcomes and breathing pattern

2017 ◽  
Vol 123 (6) ◽  
pp. 1545-1554 ◽  
Author(s):  
Per M. Gustafsson ◽  
Lovisa Bengtsson ◽  
Anders Lindblad ◽  
Paul D. Robinson
Keyword(s):  
Functional Residual Capacity ◽  
Sulfur Hexafluoride ◽  
Breathing Pattern ◽  
Inert Gas ◽  
Respiratory Drive ◽  
Quiet Sleep ◽  
Lung Clearance ◽  
Healthy Infants ◽  
Lung Clearance Index ◽  
Residual Capacity

The detrimental effects on breathing pattern during multiple breath inert gas washout (MBW) have been described with different inhaled gases [100% oxygen (O2) and sulfur hexafluoride (SF6)] but detailed comparisons are lacking. N2- and SF6-based tests were performed during spontaneous quiet sleep in 10 healthy infants aged 0.7–1.3 yr using identical hardware. Differences in breathing pattern pre and post 100% O2 and 4% SF6 exposure were investigated, and the results obtained were compared [functional residual capacity (FRC) and lung clearance index (LCI)]. During 100% O2 exposure. mean inspiratory flow (“respiratory drive”) decreased transiently by mean (SD) 28 (9)% ( P < 0.001), and end-tidal CO2 (carbon dioxide) increased by mean (SD) 0.3 (0.4)% units ( P < 0.05) vs. air breathing prephase. During subsequent N2 washin (i.e., recovery phase), the pattern of change reversed. No significant effect on breathing pattern was observed during SF6 testing. In vitro testing confirmed that technical artifacts did not explain these changes. Mean (SD) FRC and LCI in vivo were significantly higher with N2 vs. SF6 washout: 216 (33) vs. 186 (22) ml ( P < 0.001) and 8.25 (0.85) vs. 7.55 (0.57) turnovers ( P = 0.021). Based on these results, SF6 based MBW is the preferred methodology for tests in this age range. NEW & NOTEWORTHY Inert gas choice for multiple breath inert gas washout (MBW) in infants has important consequences on both breathing pattern during test performance and the functional residual capacity and lung clearance index values obtained. Data suggest the detrimental effect of breathing pattern of 100% O2 and movement of O2 across the alveolar capillary membrane, with direct effects on MBW outcomes. SF6 MBW during infancy avoids this and can be further optimized by addressing the sources of technical artifact identified in this work.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document