Ventilation Heterogeneity Research Articles

Peripheral ventilation heterogeneity determines the extent of bronchoconstriction in asthma.

In asthma, bronchoconstriction causes topographically heterogeneous airway narrowing, as measured by three-dimensional ventilation imaging. Computation modeling suggests that peripheral airway dysfunction is a potential determinant of acute airway narrowing measured by imaging. We hypothesized that the development of low-ventilation regions measured topographically by three-dimensional imaging after bronchoconstriction is predicted by peripheral airway function. Fourteen asthmatic subjects underwent ventilation single-photon-emission computed tomography/computed tomography scan imaging before and after methacholine challenge. One-liter breaths of Technegas were inhaled from functional residual capacity in upright posture before supine scanning. The lung regions with the lowest ventilation (Ventlow) were calculated using a thresholding method and expressed as a percentage of total ventilation (Venttotal). Multiple-breath nitrogen washout was used to measure diffusion-dependent and convection-dependent ventilation heterogeneity (Sacin and Scond, respectively) and lung clearance index (LCI), before and after challenge. Forced expiratory volume in 1 s (FEV1) was 87.6 ± 15.8% predicted, and seven subjects had airway hyperresponsiveness. Ventlow at baseline was unrelated to spirometry or multiple-breath nitrogen washout indices. Methacholine challenge decreased FEV1 by 23 ± 5% of baseline while Ventlow increased from 21.5 ± 2.3%Venttotal to 26.3 ± 6.7%Venttotal (P = 0.03). The change in Ventlow was predicted by baseline Sacin (rs = 0.60, P = 0.03) and by LCI (rs = 0.70, P = 0.006) but not by Scond (rs = 0.30, P = 0.30). The development of low-ventilation lung units in three-dimensional ventilation imaging is predicted by ventilation heterogeneity in diffusion-dependent airways. This relationship suggests that acinar ventilation heterogeneity in asthma may be of mechanistic importance in terms of bronchoconstriction and airway narrowing.NEW & NOTEWORTHY Using ventilation SPECT/CT imaging in asthmatics, we show induced bronchoconstriction leads to the development of areas of low ventilation. Furthermore, the relative volume of the low-ventilation regions was predicted by ventilation heterogeneity in diffusion-dependent acinar airways. This suggests that the pattern of regional airway narrowing in asthma is determined by acinar airway function.

Air trapping in early cystic fibrosis lung disease-Does CT tell the full story?

Mosaic attenuation on expiratory chest computed tomography (CT) is common in early life cystic fibrosis (CF) and often referred to as "air trapping". It is presumed to be localized hyperinflation due to small airway obstruction. In order to test this assumption, we compared air trapping extent to lung volumes measured on CT in young children with CF. Children aged below 7 years undergoing inspiratory/expiratory CT were recruited from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis cohort. Automated lung segmentation was used to determine functional residual capacity (FRC), total lung capacity (TLC), and their ratio (FRC/TLC). Structural lung disease (%Disease) and air trapping (%TrappedAir) extent were assessed using PRAGMA-CF. Lung clearance index (LCI), an index of ventilation heterogeneity, was measured. Linear mixed model analysis was used to determine associations. Seventy-three scans from 55 patients were obtained. %TrappedAir was associated with %Disease (0.19 [0.07, 0.31]; P = 0.003) and LCI (0.22 [0.04, 0.39]; P = 0.016), but not FRC/TLC (0.00 [-0.02, 0.02]; P = 0.931). CT mosaic attenuation is associated with CF lung disease, however it is not always accompanied by physiologic hyperinflation. Other pathologies may contribute to mosaic attenuation. A better understanding of these factors could guide future therapies.

Ventilation and cardiac/perfusion related impedance changes of the lung determined by Electrical Impedance Tomography in cystic fibrosis

Electrical impedance tomography (EIT) has the potential to measure ventilation and perfusion related impedance changes in the lung. Ventilation heterogeneity has already been confirmed by EIT in patients with obstructive lung diseases, such as chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). In the present study, ventilation and cardiac/perfusion associated impedance changes (∆IV and ∆IC) were investigated in 12 CF patients. Differences in ∆IV and ∆IC ratios over the course of inspiration and expiration during normal tidal breathing were analyzed. Significant differences in ∆IV/∆IC within the expiration were determined (p < 0.01), whereas there were no significant differences in ∆I V/∆IC during inspiration. Differences in ΔIV/ΔIC during the expiration seemed to be mainly caused by variations in the cardiac/perfusion related impedance signal, which might possibly be induced by an impaired lung function in CF.

Gas Exchange in the Prone Posture.

The prone posture is known to have numerous effects on gas exchange, both under normal conditions and in patients with ARDS. Clinical studies have consistently demonstrated improvements in oxygenation, and a multi-center randomized trial found that, when implemented within 48 h of moderate-to-severe ARDS, placing subjects in the prone posture decreased mortality. Improvements in gas exchange occur via several mechanisms: alterations in the distribution of alveolar ventilation, redistribution of blood flow, improved matching of local ventilation and perfusion, and reduction in regions of low ventilation/perfusion ratios. Ventilation heterogeneity is reduced in the prone posture due to more uniform alveolar size secondary to a more uniform vertical pleural pressure gradient. The prone posture results in more uniform pulmonary blood flow when compared with the supine posture, due to an anatomical bias for greater blood flow to dorsal lung regions. Because both ventilation and perfusion heterogeneity decrease in the prone posture, gas exchange improves. Other benefits include a more uniform distribution of alveolar stress, relief of left-lower-lobe lung compression by the heart, enhanced secretion clearance, and favorable right-ventricular and systemic hemodynamics.

Free-breathing Functional Pulmonary MRI: Response to Bronchodilator and Bronchoprovocation in Severe Asthma

Ventilation heterogeneity is a hallmark feature of asthma. Our objective was to evaluate ventilation heterogeneity in patients with severe asthma, both pre- and post-salbutamol, as well as post-methacholine (MCh) challenge using the lung clearance index, free-breathing pulmonary 1H magnetic resonance imaging (FDMRI), and inhaled-gas MRI ventilation defect percent (VDP). Sixteen severe asthmatics (49 ± 10 years) provided written informed consent to an ethics board-approved protocol. Spirometry, plethysmography, and multiple breath nitrogen washout to measure the lung clearance index were performed during a single visit within 15 minutes of MRI. Inhaled-gas MRI and FDMRI were performed pre- and post-bronchodilator to generate VDP. For asthmatics with forced expiratory volume in 1 second (FEV1) >70%predicted, MRI was also performed before and after MCh challenge. Wilcoxon signed-rank tests, Spearman correlations, and a repeated-measures analysis of variance were performed. Hyperpolarized 3He (P = .02) and FDMRI (P = .02) VDP significantly improved post-salbutamol and for four asthmatics who could perform MCh (n = 4). 3He and FDMRI VDP significantly increased at the provocative concentration of MCh, resulting in a 20% decrease in FEV1 (PC20) and decreased post-bronchodilator (P = .02), with a significant difference between methods (P = .01). FDMRI VDP was moderately correlated with 3He VDP (ρ = .61, P = .01), but underestimated VDP relative to 3He VDP (-6 ± 9%). Whereas 3He MRI VDP was significantly correlated with the lung clearance index, FDMRI was not (ρ = .49, P = .06). FDMRI VDP generated in free-breathing asthmatic patients was correlated with static inspiratory breath-hold 3He MRI VDP but underestimated VDP relative to 3He MRI VDP. Although less sensitive to salbutamol and MCh, FDMRI VDP may be considered for asthma patient evaluations at centers without inhaled-gas MRI.

Small airway function before and after cold dry air challenge in pediatric asthma patients during remission.

We wanted to compare cold dry air challenge (CACh) induced changes in spirometric parameters with changes in nitrogen multiple breath washout (N2 MBW) parameters in pediatric asthma patients during clinical remission over the past year (ie, with "inactive asthma"). As N2 MBW assesses ventilation heterogeneity we expected to gain detailed information about peripheral airways contribution. In subjects with normal spirometry N2 MBW, spirometry and body plethysmography were performed at baseline, after CACh, and after salbutamol inhalation. An initial measurement of the fraction of exhaled nitric oxide (FeNO) was conducted. Forty-three (20 female) subjects, mean age 13.7 years (range 6.5-18.6) performed reproducible N2 MBW measurements. Ten were tested hyperresponsive (23.3%) and 33 normoresponsive (76.7%). Baseline spirometry and body plethysmography as well as FRC (N2 MBW) were similar in both groups. Scond (0.031 vs 0.022), Sacin (0.057 vs 0.067), and FeNO (92.0 vs 28.5 ppb) were not statistically different between hyperresponsive and nomoresponsive subjects at baseline. Subjects with airway hyperresponsiveness (AHR) showed significant increases in lung clearance index (LCI, P = 0.011) and Scond (P = 0.008) after CACh, and significant decreases after salbutamol (LCI: P = 0.005; Scond: P = 0.005). In contrast, normoresponsive subjects showed no relevant changes after CACh, and only a decrease of Scond after salbutamol (P = 0.007). There were significant correlations between the CACh induced changes in FEV1 and changes in LCI (r = -0.45, P = 0.003), Scond (r = -0.30, P = 0.047), and Sacin (r = -0.47, P = 0.008), respectively. Our study provides evidence of small airway involvement in children and adolescents with inactive asthma and airway hyperresponsiveness.

A four-dimensional computed tomography comparison of healthy and asthmatic human lungs

The purpose of this study was to explore new insights in non-linearity, hysteresis and ventilation heterogeneity of asthmatic human lungs using four-dimensional computed tomography (4D-CT) image data acquired during tidal breathing. Volumetric image data were acquired for 5 non-severe and one severe asthmatic volunteers. Besides 4D-CT image data, function residual capacity and total lung capacity image data during breath-hold were acquired for comparison with dynamic scans. Quantitative results were compared with the previously reported analysis of five healthy human lungs. Using an image registration technique, local variables such as regional ventilation and anisotropic deformation index (ADI) were estimated. Regional ventilation characteristics of non-severe asthmatic subjects were similar to those of healthy subjects, but different from the severe asthmatic subject. Lobar airflow fractions were also well correlated between static and dynamic scans (R2>0.84). However, local ventilation heterogeneity significantly increased during tidal breathing in both healthy and asthmatic subjects relative to that of breath-hold perhaps because of airway resistance present only in dynamic breathing. ADI was used to quantify non-linearity and hysteresis of lung motion during tidal breathing. Non-linearity was greater on inhalation than exhalation among all subjects. However, exhalation non-linearity among asthmatic subjects was greater than healthy subjects and the difference diminished during inhalation. An increase of non-linearity during exhalation in asthmatic subjects accounted for lower hysteresis relative to that of healthy ones. Thus, assessment of non-linearity differences between healthy and asthmatic lungs during exhalation may provide quantitative metrics for subject identification and outcome assessment of new interventions.

A computational comparison of the multiple-breath washout and forced oscillation technique as markers of bronchoconstriction

Many types of lung disease lead to constriction of airways within the conducting zone, causing increases in airway resistance and ventilation heterogeneity (VH). The multiple-breath washout (MBW) and forced oscillation technique (FOT) are two clinical measures of small airway bronchoconstriction. Within this study computational modelling of the MBW and FOT was applied to the analysis of thousands of bronchoconstriction scenarios in the conducting zone of the lungs. The simulations show that MBW indices primarily respond to the severity of constriction, while FOT indices may be able to distinguish between constrictions at differing airway depths. Following this, we show the potential utility in the joint interpretation of indices from the two tests, providing motivations for future clinical investigations.

Ventilation heterogeneity measured by multiple breath inert gas testing is not affected by inspired oxygen concentration in healthy humans.

Multiple breath washout (MBW) and oxygen-enhanced MRI techniques use acute exposure to 100% oxygen to measure ventilation heterogeneity. Implicit is the assumption that breathing 100% oxygen does not induce changes in ventilation heterogeneity; however, this is untested. We hypothesized that ventilation heterogeneity decreases with increasing inspired oxygen concentration in healthy subjects. We performed MBW in 8 healthy subjects (4 women, 4 men; age = 43 ± 15 yr) with normal pulmonary function (FEV1 = 98 ± 6% predicted) using 10% argon as a tracer gas and oxygen concentrations of 12.5%, 21%, or 90%. MBW was performed in accordance with ERS-ATS guidelines. Subjects initially inspired air followed by a wash-in of test gas. Tests were performed in balanced order in triplicate. Gas concentrations were measured at the mouth, and argon signals rescaled to mimic a N2 washout, and analyzed to determine the distribution of specific ventilation (SV). Heterogeneity was characterized by the width of a log-Gaussian fit of the SV distribution and from Sacin and Scond indexes derived from the phase III slope. There were no significant differences in the ventilation heterogeneity due to altered inspired oxygen: histogram width (hypoxia 0.57 ± 0.11, normoxia 0.60 ± 0.08, hyperoxia 0.59 ± 0.09, P = 0.51), Scond (hypoxia 0.014 ± 0.011, normoxia 0.012 ± 0.015, hyperoxia 0.010 ± 0.011, P = 0.34), or Sacin (hypoxia 0.11 ± 0.04, normoxia 0.10 ± 0.03, hyperoxia 0.12 ± 0.03, P = 0.23). Functional residual capacity was increased in hypoxia (P = 0.04) and dead space increased in hyperoxia (P = 0.0001) compared with the other conditions. The acute use of 100% oxygen in MBW or MRI is unlikely to affect ventilation heterogeneity.NEW & NOTEWORTHY Hyperoxia is used to measure the distribution of ventilation in imaging and MBW but may alter the underlying ventilation distribution. We used MBW to evaluate the effect of inspired oxygen concentration on the ventilation distribution using 10% argon as a tracer. Short-duration exposure to hypoxia (12.5% oxygen) and hyperoxia (90% oxygen) during MBW had no significant effect on ventilation heterogeneity, suggesting that hyperoxia can be used to assess the ventilation distribution.

Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation.

High-altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high-altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows that HAPE-susceptible (with a history of HAPE), but not HAPE-resistant (with a history of repeated ascents without illness) individuals develop greater heterogeneity of regional pulmonary perfusion breathing hypoxic gas (O2 = 12.5%), consistent with uneven hypoxic pulmonary vasoconstriction (HPV). Why HPV is uneven in HAPE-susceptible individuals is unknown but may arise from regionally heterogeneous ventilation resulting in an uneven stimulus to HPV. We tested the hypothesis that ventilation is more heterogeneous in HAPE-susceptible subjects (n = 6) compared with HAPE-resistant controls (n = 7). MRI specific ventilation imaging (SVI) was used to measure regional specific ventilation and the relative dispersion (SD/mean) of SVI used to quantify baseline heterogeneity. Ventilation heterogeneity from conductive and respiratory airways was measured in normoxia and hypoxia (O2 = 12.5%) using multiple-breath washout and heterogeneity quantified from the indexes Scond and Sacin, respectively. Contrary to our hypothesis, HAPE-susceptible subjects had significantly lower relative dispersion of specific ventilation than the HAPE-resistant controls [susceptible = 1.33 ± 0.67 (SD), resistant = 2.36 ± 0.98, P = 0.05], and Sacin tended to be more uniform (susceptible = 0.085 ± 0.009, resistant = 0.113 ± 0.030, P = 0.07). Scond was not significantly different between groups (susceptible = 0.019 ± 0.007, resistant = 0.020 ± 0.004, P = 0.67). Sacin and Scond did not change significantly in hypoxia (P = 0.56 and 0.19, respectively). In conclusion, ventilation heterogeneity does not change with short-term hypoxia irrespective of HAPE susceptibility, and lesser rather than greater ventilation heterogeneity is observed in HAPE-susceptible subjects. This suggests that the basis for uneven HPV in HAPE involves vascular phenomena.NEW & NOTEWORTHY Uneven hypoxic pulmonary vasoconstriction (HPV) is thought to incite high-altitude pulmonary edema (HAPE). We evaluated whether greater heterogeneity of ventilation is also a feature of HAPE-susceptible subjects compared with HAPE-resistant subjects. Contrary to our hypothesis, ventilation heterogeneity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.

Relationship between ventilation heterogeneity and exercise intolerance in adults with sickle cell anemia.

Sickle cell anemia (SCA) causes dysfunction of multiple organs, with pulmonary involvement as a major cause of mortality. Recently, there has been growing interest in the nitrogen single-breath washout (N2SBW) test, which is able to detect ventilation heterogeneity and small airway disease when the results of other pulmonary function tests (PFTs) are still normal. Thus, the objectives of the present study were to assess the heterogeneity in the ventilation distribution in adults with SCA and to determine the association between the ventilation distribution and the clinical, cardiovascular, and radiological findings. This cross-sectional study included 38 adults with SCA who underwent PFTs, echocardiography, computed tomography (CT), and 6-min walk test. To evaluate the ventilation heterogeneity, the patients were categorized according to the phase III slope of the N2SBW (SIIIN2). Compared with adults with lower SIIIN2 values, adults with higher SIIIN2 values showed lower hemoglobin levels (P=0.048), a history of acute chest syndrome (P=0.001), an elevated tricuspid regurgitation velocity (P=0.039), predominance of a reticular pattern in the CT (P=0.002), a shorter 6-min walking distance (6MWD) (P=0.002), and lower peripheral oxygen saturation (SpO2) after exercise (P=0.03). SIIIN2 values correlated significantly with hemoglobin (rs=-0.344; P=0.034), forced vital capacity (rs=-0.671; P<0.0001), diffusing capacity for carbon monoxide (rs=-0.376; P=0.019), 6MWD (rs=-0.554; P=0.0003), and SpO2 after exercise (P=0.040). Heterogeneity in the ventilation distribution is one of the most common pulmonary dysfunctions in adults with SCA. Moreover, relationships exist between ventilation heterogeneity, worsening of pulmonary structural damage, and reduced tolerance for exercise.

Tidal airway closure in asthma and COPD

Functional closure of small airways can occur during tidal breathing above functional residual capacity (FRC) both in asthma and COPD patients, especially during exacerbations. Such event has several noxious consequences on gas exchange, airway hyperresponsiveness and mechanical stress and strain within lung tissue and airway wall, mostly due to increase in ventilation heterogeneity. The availability of simple functional tests based on sequential measurements of lung volumes (i.e.: FRC), by plethysmography and dilutional techniques may reveal and monitor easily tidal airway closure that can be and should be treated with the aim of abolishing or at least reducing this dangerous condition.

Ultrashort echo time MRI biomarkers of asthma.

To develop and assess ultrashort echo-time (UTE) magnetic resonance imaging (MRI) biomarkers of lung function in asthma patients. Thirty participants including 13 healthy volunteers and 17 asthmatics provided written informed consent to UTE and pulmonary function tests in addition to hyperpolarized-noble-gas 3T MRI and computed tomography (CT) for asthmatics only. The difference in MRI signal-intensity (SI) across four lung volumes (full-expiration, functional-residual-capacity [FRC], FRC+1L, and full-inspiration) was determined on a voxel-by-voxel basis to generate dynamic proton-density (DPD) maps. MRI ventilation-defect-percent (VDP), UTE SI, and DPD values as well as CT radiodensity were determined for whole lung and individual lobes. Mean SI at full-expiration (P < 0.01), FRC (P < 0.05), and DPD (P < 0.01) were greater in healthy volunteers compared to asthmatics. In asthmatics, UTE SI at full-expiration and DPD were correlated with FEV1 /FVC (SI r = 0.73/P = 0.002; DPD r = 0.75/P = 0.003), RV/TLC (SI r = -0.57/P = 0.02), or RV (DPD r = -0.62/P = 0.02), CT radiodensity (SI r = 0.83/P = 0.006; DPD r = 0.71/P = 0.01), and lobar VDP (SI rs = -0.33/P = 0.02; DPD rs = -0.47/P = 0.01). In patients with asthma, UTE SI and dynamic proton-density were related to pulmonary function measurements, whole lung and lobar VDP, as well as CT radiodensity. Thus, UTE MRI biomarkers may reflect ventilation heterogeneity and/or gas-trapping in asthmatics using conventional equipment, making this approach potentially amenable for clinical use. 2 J. Magn. Reson. Imaging 2017;45:1204-1215.

Modelling responses of the inert-gas washout and MRI to bronchoconstriction

Many lung diseases lead to an increase in ventilation heterogeneity (VH). Two clinical practices for the measurement of patient VH are in vivo imaging, and the inert gas multiple breath washout (MBW). In this study computational modelling was used to compare the responses of MBW indices LCI and scond and MRI measured global and local ventilation indices, σr and σlocal, to constriction of airways in the conducting zone of the lungs. The simulations show that scond, LCI and σr behave quite similarly to each other, all being sensitive to increases in the severity of constriction, while exhibiting little sensitivity to the depth at which constriction occurs. In contrast, the local MRI index σlocal shows strong sensitivity to depth of constriction, but lowered sensitivity to constriction severity. We finish with an analysis of the sensitivity of MRI indices to grid sizes, showing that results should be interpreted with reference to the image resolution. Overall we conclude that the application of both local and global VH measures may help to classify different types of bronchoconstriction.

Strain heterogeneity in the injured lung: cause or consequence?

ventilation heterogeneity is an established marker of pulmonary dysfunction in asthma and other conditions such as acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). The nonuniform delivery of inspired gas leads to regional over- and under-ventilation causing a

Using Hyperpolarized 129Xe MRI to Quantify the Pulmonary Ventilation Distribution

Ventilation heterogeneity is impossible to detect with spirometry. Alternatively, pulmonary ventilation can be imaged three-dimensionally using inhaled 129Xe magnetic resonance imaging (MRI). To date, such images have been quantified primarily based on ventilation defects. Here, we introduce a robust means to transform 129Xe MRI scans such that the underlying ventilation distribution and its heterogeneity can be quantified. Quantitative 129Xe ventilation MRI was conducted in 12 younger (24.7 ± 5.2 years) and 10 older (62.2 ± 7.2 years) healthy individuals, as well as in 9 younger (25.9 ± 6.4 yrs) and 10 older (63.2 ± 6.1 years) asthmatics. The younger healthy population was used to establish a reference ventilation distribution and thresholds for six intensity bins. These bins were used to display and quantify the ventilation defect region (VDR), the low ventilation region (LVR), and the high ventilation region (HVR). The ventilation distribution in young subjects was roughly Gaussian with a mean and standard deviation of 0.52 ± 0.18, resulting in VDR = 2.1 ± 1.3%, LVR = 15.6 ± 5.4%, and HVR = 17.4 ± 3.1%. Older healthy volunteers exhibited a significantly right-skewed distribution (0.46 ± 0.20, P = 0.034), resulting in significantly increased VDR (7.0 ± 4.8%, P = 0.008) and LVR (24.5 ± 11.5%, P = 0.025). In the asthmatics, VDR and LVR increased in the older population, and HVR was significantly reduced (13.5 ± 4.6% vs 18.9 ± 4.5%, P = 0.009). Quantitative 129Xe MRI also revealed altered ventilation heterogeneity in response to albuterol in two asthmatics with normal spirometry. Quantitative 129Xe MRI provides a robust and objective means to display and quantify the pulmonary ventilation distribution, even in subjects who have airway function impairment not appreciated by spirometry.

Commentaries on Viewpoint: Could lobar flow sequencing account for convection-dependent ventilation heterogeneity in normal humans?

to the editor: Based on 4DCT imaging ([3][1]), this Viewpoint ([5][2]) investigates how lobar flow sequencing can contribute to generate a positive phase III slope. Results suggest that interlobar differences in expansion and deflation during the respiratory cycle contribute to Scond. We agree that

Capnogram slope and ventilation dead space parameters: comparison of mainstream and sidestream techniques

BackgroundCapnography may provide useful non-invasive bedside information concerning heterogeneity in lung ventilation, ventilation–perfusion mismatching and metabolic status. Although the capnogram may be recorded by mainstream and sidestream techniques, the capnogram indices furnished by these approaches have not previously been compared systematically. MethodsSimultaneous mainstream and sidestream time and volumetric capnography was performed in anaesthetized, mechanically ventilated patients undergoing elective heart surgery. Time capnography was used to assess the phase II (SII,T) and III slopes (SIII,T). The volumetric method was applied to estimate phase II (SII,V) and III slopes (SIII,V), together with the dead space values according to the Fowler (VDF), Bohr (VDB), and Enghoff (VDE) methods and the volume of CO2 eliminated per breath ( VCO2). The partial pressure of end-tidal CO2 ( PETCO2) was registered. ResultsExcellent correlation and good agreement were observed in SIII,T measured by the mainstream and sidestream techniques [ratio=1.05 (sem 0.16), R2=0.92, P<0.0001]. Although the sidestream technique significantly underestimated VCO2 and overestimated SIII,V [1.32 (0.28), R2=0.93, P<0.0001], VDF, VDB, and VDE, the agreement between the mainstream and sidestream techniques in the difference between VDE and VDB, reflecting the intrapulmonary shunt, was excellent [0.97 (0.004), R2=0.92, P<0.0001]. The PETCO2 exhibited good correlation and mild differences between the mainstream and sidestream approaches [0.025 (0.005) kPa]. ConclusionsSidestream capnography provides adequate quantitative bedside information about uneven alveolar emptying and ventilation–perfusion mismatching, because it allows reliable assessments of the phase III slope, PETCO2 and intrapulmonary shunt. Reliable measurement of volumetric parameters (phase II slope, dead spaces, and eliminated CO2 volumes) requires the application of a mainstream device.

Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis.

Little is known about the comparative diagnostic value of lung clearance index (LCI) and maximal mid-expiratory flow (MMEF) in bronchiectasis. We compared the diagnostic performance, correlation and concordance with clinical variables, and changes of LCI and MMEF% predicted during bronchiectasis exacerbations (BEs). Patients with stable bronchiectasis underwent history inquiry, chest high-resolution computed tomography (HRCT), multiple-breath nitrogen wash-out test, spirometry and sputum culture. Patients who experienced BEs underwent these measurements during onset of BEs and 1 week following antibiotics therapy. Sensitivity analyses were performed in mild, moderate and severe bronchiectasis. We recruited 110 bronchiectasis patients between March 2014 and September 2015. LCI demonstrated similar diagnostic value with MMEF% predicted in discriminating moderate-to-severe from mild bronchiectasis. LCI negatively correlated with MMEF% predicted. Both parameters had similar concordance in reflecting clinical characteristics of bronchiectasis and correlated significantly with forced expiratory flow in one second, age, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, ventilation heterogeneity and bilateral bronchiectasis. In exacerbation cohort (n = 22), changes in LCI and MMEF% predicted were equally minimal during BEs and following antibiotics therapy. In sensitivity analyses, both parameters had similar diagnostic value and correlation with clinical variables. MMEF% predicted is a surrogate of LCI for assessing bronchiectasis severity.

Physiological phenotyping of pediatric chronic obstructive airway diseases.

Inert tracer gas washout (IGW) measurements detect increased ventilation inhomogeneity (VI) in chronic lung diseases. Their suitability for different diseases, such as cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), has already been shown. However, it is still unclear if physiological phenotypes based on different IGW variables can be defined independently of underlying disease. Eighty school-age children, 20 with CF, 20 with PCD, 20 former preterm children, and 20 healthy children, performed nitrogen multiple-breath washout, double-tracer gas (DTG) single-breath washout, and spirometry. Our primary outcome was the definition of physiological phenotypes based on IGW variables. We applied principal component analysis, hierarchical Ward's clustering, and enrichment analysis to compare clinical characteristics between the clusters. IGW variables used for clustering were lung clearance index (LCI) and convection-dependent [conductive ventilation heterogeneity index (Scond)] and diffusion-convection-dependent variables [acinar ventilation heterogeneity index (Sacin) and carbon dioxide and DTG phase III slopes]. Three main phenotypes were identified. Phenotype I (n = 38) showed normal values in all IGW outcome variables. Phenotype II (n = 21) was characterized by pronounced global and convection-dependent VI while diffusion-dependent VI was normal. Phenotype III (n = 21) was characterized by increased global and diffusion- and convection-dependent VI. Enrichment analysis revealed an overrepresentation of healthy children and former preterm children in phenotype I and of CF and PCD in phenotypes II and III. Patients in phenotype III showed the highest proportion and frequency of exacerbations and hospitalization in the year prior to the measurement. IGW techniques allow identification of clinically meaningful, disease-independent physiological clusters. Their predictive value of future disease outcomes remains to be determined.