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Obstructive pulmonary diseases are associated with considerable morbidity. For an early diagnosis of these diseases, inert gas washouts can potentially be used. However, the complex interaction between lung anatomy and gas transport mechanisms complicates data analysis. In order to investigate this interaction, a numerical model, based on the finite difference method, consisting of two lung units connected in parallel, was developed to simulate the tracer gas transport within the human acinus. Firstly, the geometries of the units were varied and the diffusion coefficients (D) were kept constant. Secondly, D was changed and the geometry was kept constant. Furthermore, simple monoexponential growth functions were applied to evaluate the simulated data. In 109 of the 112 analyzed curves, monoexponential function matched simulated data with an accuracy of over 90%, potentially representing a suitable numerical tool to predict transport processes in further model extensions. For total flows greater than 5 × 10 -4  ml/s, the exponential growth constants increased linearly with linear increasing flow to an accuracy of over 95%. The slopes of these linear trend lines of 1.23 µl -1 (D = 0.6 cm 2 /s), 1.69 µl -1 (D = 0.3 cm 2 /s), and 2.25 µl -1 (D = 0.1 cm 2 /s) indicated that gases with low D are more sensitive to changes in flows than gases with high D., (© 2022. The Author(s).)

Background: Extracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited., Objective: To characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction., Methods: We measured e-DNA concentrations in induced sputum from 134 asthma patients and 28 healthy controls. We studied the correlation of e-DNA concentrations with sputum neutrophils, eosinophils and macrophages and the fractional exhaled nitric oxide (FeNO). Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. We stratified patients with asthma into low-DNA and high-DNA to compare lung function impairments and asthma outcomes., Results: Patients with severe asthma had higher e-DNA concentration (54.2 ± 42.4 ng/µl) than patients with mild-moderate asthma (41.0 ± 44.1 ng/µl) or healthy controls (26.1 ± 16.5 ng/µl), (all p values < 0.05). E-DNA concentrations correlated directly with sputum neutrophils (R = 0.49, p < 0.0001) and negatively with sputum macrophages (R = - 0.36, p < 0.0001), but neither with sputum eosinophils (R = 0.10, p = 0.26), nor with FeNO (R = - 0.10, p = 0.22). We found that 29% of asthma patients (n = 39) had high e-DNA concentrations above the upper 95th percentile value in healthy controls (55.6 ng /μl). High-DNA was associated with broad lung function impairments including: airflow obstruction of the large (FEV 1 ) and small airways (FEF50%, FEF25-75), increased air trapping (RV, RV/TLC), increased small airway resistance (R5-20, sReff), decreased lung elasticity (X5Hz) and increased ventilation heterogeneity (LCI), (all P values < 0.05). We also found that high e-DNA was associated with nearly three-fold greater risk of severe exacerbations (OR 2·93 [95% CI 1.2-7.5]; p = 0·012), worse asthma control test (p = 0.03), worse asthma control questionnaire scores (p = 0.01) and higher doses of inhaled corticosteroids (p = 0.026)., Conclusion: Increased production of extracellular DNA in the airway characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control and increased risk of severe exacerbations.

Purpose: Quantified computed tomography (qCT) is known for correlations with airflow obstruction and fibrotic changes of the lung. However, as qCT studies often focus on diseased and elderly subjects, current literature lacks physiological qCT values during body development. We evaluated chest CT examinations of a healthy cohort, reaching from infancy to adulthood, to determine physiological qCT values and changes during body development., Method: Dose-optimized chest CT examinations performed over the last 3 years using a dual-source CT were retrospectively analysed. Exclusion criteria were age >30 years and any known or newly diagnosed lung pathology. Lung volume, mean lung density, full-width-at-half-maximum and low attenuated volume (LAV) were semi-automated quantified in 151 patients. qCT values between different age groups as well as unenhanced (Group 1) and contrast-enhanced (Group 2) protocols were compared. Models for projection of age-dependant changes in qCT values were fitted., Results: Significant differences in qCT parameters were found between the age groups from 0 to 15 years (p < 0.05). All parameters except LAV merge into a plateau level above this age as shown by polynomial models (r2 between 0.85 and 0.67). In group 2, this plateau phase is shifted back around five years. Except for the volume, significant differences in all qCT values were found between group 1 and 2 (p < 0.01)., Conclusion: qCT parameters underly a specific age-dependant dynamic. Except for LAV, qCT parameters reach a plateau around adolescence. Contrast-enhanced protocols seem to shift this plateau backwards., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The importance of spirometry for management of COPD was reduced in the 2017 revision of the GOLD report. CT derived airway measurements show strong correlations with lung function tests and symptoms. However, these correlations are specific to the airway localization, and currently there is no evidence for the ideal spot. Therefore, the aim of this prospective study was to systematically correlate CT derived airway measurements with extensive lung function testing., Methods and Materials: 65 patients with diagnosed COPD underwent body plethysmography, impulse oscillometry and dose optimized qCT examination (Somatom Force, Healthineers, Germany) in inspiration and expiration. Eight airway parameters (e.g. outer diameter, maximal wall thickness) were acquired for both scans in every lobe for the third to fifth generation bronchus and correlated with the lung function tests., Results: The most significant correlations between airway parameters were found for the third generation bronchus of the upper left lobe during expiration (25 out of 48 correlation pairs, mean r = -0.39) and for the third generation bronchus of the upper right lobe during inspiration (9 out of 48 correlation pairs, mean r = -0.25). No significant correlations were for example found for the upper right lobe in expiration., Conclusion: Correlations between airway parameters and lung function tests vary widely between lobes, bronchus generations and breathing states. Our work suggests that the third generation bronchus of the upper left lobe in expiration could be the preferred localization for airway quantification in future studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Diagnostic guidelines for chronic obstructive pulmonary disease (COPD) are based on spirometry and clinical criteria. However, this does not address the pathophysiological complexity of the disease sufficiently. Until now, inspiratory chest computed tomography (CT) has been considered as the preferred imaging method in these patients. We hypothesized that expiratory CT may be superior to demonstrate pathophysiological changes. The aim of this prospective study was to systematically compare lung function tests with quantified CT parameters in inspiration and expiration., Materials and Methods: Forty-six patients with diagnosed COPD underwent spirometry, body plethysmography, and dose-optimized CT in maximal inspiration and expiration. Four quantified CT parameters were acquired in inspiration, expiration, and their calculated delta values. These parameters were correlated with seven established lung function parameters., Results: For inspiratory scans, a weak-to-moderate correlation with the lung function parameters was found. These correlations significantly improved when adding the expiratory scan ( p < 0.05). Moreover, some parameters showed a significant correlation only in expiratory datasets. Calculated delta values showed even stronger correlation with lung function testing., Conclusions: Expiratory quantified CT and calculated delta values significantly improve the correlation with lung function parameters. Thus, an additional expiratory CT may improve image-based phenotyping of patients with COPD.

Background: Multiple breath washout (MBW) became a valuable research tool assessing ventilation heterogeneity. However, routine clinical application still faces several challenges. Deriving MBW parameters from three technically acceptable measurements according to current recommendations prolongs test times. We therefore aimed to evaluate reporting only duplicate measurements in healthy adults and pulmonary disease., Methods: One hundred and fifty-three subjects prospectively underwent conventional lung function testing and closed-circuit SF 6 -MBW. Three technically acceptable MBW-measurements were obtained in 103 subjects., Results: Lung clearance index (LCI) differed significantly among 19 controls (7.4 ± 0.8), 19 patients with sarcoidosis (8.1 ± 1.2), 32 with bronchial asthma (9.2 ± 1.9) and 33 with COPD (10.8 ± 2.2, p < 0.001). Within-test repeatability was high (coefficient of variation between 2.5% in controls and 3.6% in COPD) and remained unchanged when only including the first two measurements. Likewise, LCI remained stable with mean absolute changes ranging from 0.9 ± 0.8% in controls to 1.5 ± 0.9% in COPD (p = 0.1). Mean test time reduction differed significantly between groups reaching 200 s in COPD (p = 0.01)., Conclusions: Duplicate SF 6 -MBW-measurements are sufficient in adult patients with pulmonary disease and healthy controls. LCI values and intra-test repeatability are not affected reducing total test time statistically significant. Our findings have the potential to further facilitate application of MBW in research and clinical routine., Trial Registration: NCT03176745 , June 2, 2017 retrospectively registered.

Purpose: Non-invasive inert gas rebreathing (IGR) has shown promising results in the determination of pulmonary blood flow. The volume of the rebreathing bag (V bag) is proposed by the system. However, elderly patients or those with severe pulmonary disease may be unable to rebreathe this volume entirely. We evaluated the effect of adapting V bag on the reproducibility of IGR., Methods: A total of 270 valid measurements were obtained from 45 patients with obstruction (group A), restriction (group B), and in healthy controls (group C). Two measurements for each of three different V bag of 1,200, 1,700, and 2,200 ml were conducted in the supine position., Results: We found no statistically significant difference of the repeated measurements neither between the different V bag in groups A to C nor between the three groups for identical V bag. There was a weak yet significantly worse coefficient of variation between a V bag of 2,200 ml in group A compared with group C with 2,200 and 1,200 ml, respectively. Intraclass correlation coefficient and repeatability coefficient yielded significantly worse values in group A for a V bag of 2,200 ml compared with healthy controls and lower bag volumes. No difference could be found intraclass nor interclass in groups B and C., Conclusions: V bag can be altered between 1,200 and 2,200 ml in most situations without affecting the reproducibility. Attention has to be paid to extreme volumes in obstructive patients. Nevertheless, V bag should be chosen as large as possible and therefore has to be carefully adapted, particularly in patients with obstruction or restriction.