Ventilation heterogeneity imaged by multibreath wash‐ins of hyperpolarized 3 He and 129 Xe in healthy rabbits

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

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Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume

Respiration ◽

10.1159/000513954 ◽

2021 ◽

pp. 1-7

Author(s):

Roberta Pisi ◽

Marina Aiello ◽

Luigino Calzetta ◽

Annalisa Frizzelli ◽

Veronica Alfieri ◽

...

Keyword(s):

Total Lung Capacity ◽

Airflow Obstruction ◽

Diffusing Capacity ◽

Body Plethysmography ◽

Alveolar Volume ◽

Asthmatic Patients ◽

Lung Capacity ◽

Copd Patients ◽

Ventilation Heterogeneity ◽

Patient Groups

Background: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. Objectives: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. Method: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. Results: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. Conclusions: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

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

Thorax ◽

10.1136/thoraxjnl-2020-214717 ◽

2021 ◽

pp. thoraxjnl-2020-214717

Author(s):

Frederik Trinkmann ◽

Máté Maros ◽

Katharina Roth ◽

Arne Hermanns ◽

Julia Schäfer ◽

...

Keyword(s):

Reference Values ◽

Sulfur Hexafluoride ◽

Early Adulthood ◽

Anthropometric Parameters ◽

Cross Sectional ◽

Outcome Parameters ◽

Ventilation Heterogeneity ◽

Multiple Breath Washout ◽

Registration Number ◽

Never Smokers

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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The effect of conductive ventilation heterogeneity on diffusing capacity measurement

Journal of Applied Physiology ◽

10.1152/japplphysiol.00917.2007 ◽

2008 ◽

Vol 104 (4) ◽

pp. 1094-1100 ◽

Cited By ~ 9

Author(s):

Sylvia Verbanck ◽

Daniel Schuermans ◽

Sophie Van Malderen ◽

Walter Vincken ◽

Bruce Thompson

Keyword(s):

Carbon Monoxide ◽

Vital Capacity ◽

Experimental Situation ◽

Normal Subjects ◽

Diffusing Capacity ◽

Capacity Measurement ◽

Alveolar Volume ◽

Estimation Errors ◽

Single Breath ◽

Ventilation Heterogeneity

It has long been assumed that the ventilation heterogeneity associated with lung disease could, in itself, affect the measurement of carbon monoxide transfer factor. The aim of this study was to investigate the potential estimation errors of carbon monoxide diffusing capacity (DlCO) measurement that are specifically due to conductive ventilation heterogeneity, i.e., due to a combination of ventilation heterogeneity and flow asynchrony between lung units larger than acini. We induced conductive airway ventilation heterogeneity in 35 never-smoker normal subjects by histamine provocation and related the resulting changes in conductive ventilation heterogeneity (derived from the multiple-breath washout test) to corresponding changes in diffusing capacity, alveolar volume, and inspired vital capacity (derived from the single-breath DlCO method). Average conductive ventilation heterogeneity doubled ( P < 0.001), whereas DlCO decreased by 6% ( P < 0.001), with no correlation between individual data ( P > 0.1). Average inspired vital capacity and alveolar volume both decreased significantly by, respectively, 6 and 3%, and the individual changes in alveolar volume and in conductive ventilation heterogeneity were correlated ( r = −0.46; P = 0.006). These findings can be brought in agreement with recent modeling work, where specific ventilation heterogeneity resulting from different distributions of either inspired volume or end-expiratory lung volume have been shown to affect DlCO estimation errors in opposite ways. Even in the presence of flow asynchrony, these errors appear to largely cancel out in our experimental situation of histamine-induced conductive ventilation heterogeneity. Finally, we also predicted which alternative combination of specific ventilation heterogeneity and flow asynchrony could affect DlCO estimate in a more substantial fashion in diseased lungs, irrespective of any diffusion-dependent effects.

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

European Respiratory Journal ◽

10.1183/13993003.00821-2018 ◽

2018 ◽

Vol 52 (5) ◽

pp. 1800821 ◽

Cited By ~ 13

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.

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Assessment of the influence of lung inflation state on the quantitative parameters derived from hyperpolarized gas lung ventilation MRI in healthy volunteers

Journal of Applied Physiology ◽

10.1152/japplphysiol.00464.2018 ◽

2019 ◽

Vol 126 (1) ◽

pp. 183-192 ◽

Cited By ~ 7

Author(s):

Paul J. C. Hughes ◽

Laurie Smith ◽

Ho-Fung Chan ◽

Bilal A. Tahir ◽

Graham Norquay ◽

...

Keyword(s):

Healthy Volunteers ◽

Lung Volume ◽

Lung Ventilation ◽

Lung Volumes ◽

Lung Inflation ◽

Longitudinal Measurements ◽

Anatomical Images ◽

Lower Lung ◽

Ventilation Heterogeneity ◽

Residual Capacity

In this study, the effect of lung volume on quantitative measures of lung ventilation was investigated using MRI with hyperpolarized 3He and 129Xe. Six volunteers were imaged with hyperpolarized 3He at five different lung volumes [residual volume (RV), RV + 1 liter (1L), functional residual capacity (FRC), FRC + 1L, and total lung capacity (TLC)], and three were also imaged with hyperpolarized 129Xe. Imaging at each of the lung volumes was repeated twice on the same day with corresponding 1H lung anatomical images. Percent lung ventilated volume (%VV) and variation of signal intensity [heterogeneity score (Hscore)] were evaluated. Increased ventilation heterogeneity, quantified by reduced %VV and increased Hscore, was observed at lower lung volumes with the least ventilation heterogeneity observed at TLC. For 3He MRI data, the coefficient of variation of %VV was <1.5% and <5.5% for Hscore at all lung volumes, while for 129Xe data the values were 4 and 10%, respectively. Generally, %VV generated from 129Xe images was lower than that seen from 3He images. The good repeatability of 3He %VV found here supports prior publications showing that percent lung-ventilated volume is a robust method for assessing global lung ventilation. The greater ventilation heterogeneity observed at lower lung volumes indicates that there may be partial airway closure in healthy lungs and that lung volume should be carefully considered for reliable longitudinal measurements of %VV and Hscore. The results suggest that imaging patients at different lung volumes may help to elucidate obstructive disease pathophysiology and progression. NEW & NOTEWORTHY We present repeatability data of quantitative metrics of lung function derived from hyperpolarized helium-3, xenon-129, and proton anatomical images acquired at five lung volumes in volunteers. Increased regional ventilation heterogeneity at lower lung inflation levels was observed in the lungs of healthy volunteers.

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