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Background: Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days. Results: Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH2O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP. Conclusions: Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch. Clinical Trial Registration: ClinicalTrials.gov; Identifier: NCT03201263. [ABSTRACT FROM AUTHOR]

Due to its ability to induce heterogenous, patient-specific damage in pulmonary alveoli and capillaries, COVID-19 poses challenges in defining a uniform profile to elucidate infection across all patients. Computational models that integrate changes in ventilation and perfusion with heterogeneous damage profiles offer valuable insights into the impact of COVID-19 on pulmonary health. This study aims to develop an in silico hypothesis-testing platform specifically focused on studying microvascular pulmonary perfusion in COVID-19-infected lungs. Through this platform, we explore the effects of various acinar-level pulmonary perfusion abnormalities on global lung function. Our modelling approach simulates changes in pulmonary perfusion and the resulting mismatch of ventilation and perfusion in COVID-19-afflicted lungs. Using this coupled modelling platform, we conducted multiple simulations to assess different scenarios of perfusion abnormalities in COVID-19-infected lungs. The simulation results showed an overall decrease in ventilation-perfusion (V/Q) ratio with inclusion of various types of perfusion abnormalities such as hypoperfusion with and without microangiopathy. This model serves as a foundation for comprehending and comparing the spectrum of findings associated with COVID-19 in the lung, paving the way for patient-specific modelling of microscale lung damage in emerging pulmonary pathologies like COVID-19. [ABSTRACT FROM AUTHOR]

Swyer James Macleod Syndrome, also known as unilateral hyperlucent lung syndrome, is a rare lung condition characterized by the underdevelopment of one lung. This syndrome typically occurs in childhood and is often discovered incidentally during imaging studies for unrelated conditions. Individuals with Swyer James Macleod Syndrome may experience symptoms such as recurrent respiratory infections, shortness of breath, and decreased exercise tolerance. Diagnosis is typically made through imaging studies such as chest X-rays,computed tomography or ventilation-perfusion scans. [ABSTRACT FROM AUTHOR]

Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and remove carbon dioxide from blood in alveolar capillaries. In a lung model without ventilation and perfusion (V̇ A Q̇) mismatch, alveolar partial pressures of oxygen and carbon dioxide are primarily determined by inspiratory pressures and alveolar ventilation. Regions with shunt or low ratios worsen arterial oxygenation while alveolar dead space and high lung units lessen CO 2 elimination efficiency. Although less common, diffusion limitation might cause hypoxemia in some situations. This review covers the principles of lung gas exchange and therefore mechanisms of hypoxemia or hypercapnia. In addition, we discuss different metrics that quantify the deviation from ideal gas exchange. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance (MR) imaging to quantify regional ventilation-perfusion ( V˙A/Q˙ ) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2 , which alters the local MR signal intensity, in an FI O2 -dependent manner. Specific ventilation imaging data are acquired during five wash-in/wash-out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FI O2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FI O2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated-SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙ , and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p = .84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p = .04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p = .54); Deadspace was not significantly different (p = .54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p = .052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized.

Pulmonary gas exchanges are vital to human health, and disruptions to this process have been associated with many respiratory diseases. Previous gas exchange studies have predominately relied on whole-body testing and theoretical analysis with 1D or static models. However, pulmonary gas exchanges are inherently a dynamic process in 3D spaces with instantaneous interactions between air, blood, and tissue. This study aimed to develop a computational model for oxygen exchange that considered all factors mentioned above. Therefore, an integrated alveolus–membrane–capillary geometry was developed with prescribed rhythmic expansion/contraction. Airflow ventilation, blood perfusion, and oxygen diffusion were simulated using COMSOL. The temporal and spatial distribution of blood flow and oxygen within the capillaries were simulated under varying breathing depths and cardiac outputs. The results showed highly nonuniform blood flow distributions in the capillary network, while the rhythmic oscillation further increased this nonuniformity, leading to stagnant blood flow in the distal vessels. A static alveolus–capillary geometry underestimated perfusion by 11% for normal respirations, and the deviation grew with breathing depth. The rhythmic motion caused a phase lag in the blood flow. The blood PO2 reached equilibrium with the alveolar air after traveling 1/5–1/3 of the capillary network. The time to reach this equilibrium was significantly influenced by the air–blood barrier diffusivity, while it was only slightly affected by the perfusion rate. The computational platform in this study could be instrumental in obtaining refined knowledge of pulmonary O2 exchanges.

Purpose: To evaluate whether a subtraction CT angiography (sCTA) perfusion score may have prognostic value in patients with COVID-19 pneumonia. Method: This prospective cohort study included adult patients with RT-PCR-confirmed SARS-CoV-2 infection admitted to the ED and a sCTA performed within 24 h of admission between June and September 2020. Perfusion abnormalities (PA) in areas of apparently spared lung parenchyma on conventional CT images were assessed with sCTA perfusion score. Airspace disease extension was assessed with CT severity scores, which were then correlated with clinical outcomes (admission to ICU, requirement of IMV, and death). Inter-rater reliability (IRR) was assessed using Cohen's Kappa. Independent predictors of adverse outcomes were evaluated by multivariable logistic regression analyses using the Hosmer and Lemeshow's test. Results: 191 patients were included: 112 males (58%), median age of 60.8 years (SD ± 16.0). The IRR was very high (median Kappa statistic: 0.95). No association was found between perfusion CT scores and D-dimer levels (Kendall's Tau-B coefficient = 0.08, p = 0.16) or between PaO2/FiO2 ratios and D-dimer levels (Kendall's Tau-B coefficient = −0.10, p = 0.07). Multivariate analyses adjusting for parenchymal disease extension, vascular beaded appearance, pulmonary embolism, sex, and age showed that severe PA remained a significant predictor for ICU admission (AOR: 6.25, 95% CI 2.10–18.7, p = 0.001). The overall diagnostic capacity of this model was adequate (ROC AUC: 0.83; 95% CI 0.77–0.89). Conclusions: The assessment of pulmonary perfusion abnormalities in areas of apparently spared lung parenchyma on conventional CT images via sCTA perfusion scoring has prognostic value in COVID-19 pneumonia.

Abstract Background Veno-venous extracorporeal membrane oxygenation (ECMO) provides blood oxygenation and carbon dioxide removal in acute respiratory distress syndrome. However, during ECMO support, the native lungs still play an important role in gas exchange, functioning as a second oxygenator in series with ECMO. The hypoxic vasoconstriction mechanism diverts regional blood flow within the lungs away from regions with low oxygen levels, optimizing ventilation/perfusion matching. ECMO support has the potential to reduce this adaptive pulmonary response and worsen the ventilation/perfusion mismatch by raising venous oxygen partial pressure. Thus, the objective of this study was to evaluate the effect of ECMO on regional pulmonary perfusion and pulmonary hemodynamics during unilateral ventilation and posterior lung collapse. Methods Five Agroceres pigs were instrumented, monitored and submitted to ECMO. We used the Electrical Impedance Tomography (EIT) to evaluate lung ventilation and perfusion in all protocol steps. Effects of ECMO support on pulmonary hemodynamics and perfusion involving two different scenarios of ventilation/perfusion mismatch: (1) right-lung selective intubation inducing collapse of the normal left lung and (2) dorsal lung collapse after repeated lung lavage. Data including hemodynamics, respiratory, lung perfusion/ventilation, and laboratory data over time were analyzed with a mixed generalized model using the subjects as a random factor. Results The initiation of ECMO support provided a significant reduction in Mean Pulmonary Artery Pressure (PAPm) in both situations of ventilation/perfusion mismatch. However, distribution of lung perfusion did not change with the use of ECMO support. Conclusions We found that the use of ECMO support with consequent increase in venous oxygen pressure induced a significant drop in PAPm with no detectable effect on regional lung perfusion in different scenarios of ventilation/perfusion mismatch.

BACKGROUND: COVID-19--related ARDS is characterized by severe hypoxemia with initially preserved lung compliance and impaired ventilation/perfusion (V/Q) matching. PEEP can increase end-expiratory lung volume, but its effect on V/Q mismatch in COVID-19--related ARDS is not clear. METHODS: We enrolled intubated and mechanically ventilated subjects with COVID-19 ARDS and used the automatic lung parameter estimator (ALPE) to measure V/Q. Respiratory mechanics measurements, shunt, and V/Q mismatch (low V/Q and high V/Q) were collected at 3 PEEP levels (clinical PEEP = intermediate PEEP, low PEEP [clinical - 50%], and high PEEP [clinical + 50%]). A mixed-effect model was used to evaluate the impact of PEEP on V/Q. We also investigated if PEEP might have a different effect on V/Q mismatch in 2 different respiratory mechanics phenotypes, that is, high elastance/low compliance (phenotype H) and low elastance/high compliance (phenotype L). RESULTS: Seventeen subjects with COVID-related ARDS age 66 [60-71] y with a PaO2/FIO2 of 141 ± 74 mm Hg were studied at low PEEP = 5.6 ± 2.2 cm H2O, intermediate PEEP = 10.6 ± 3.8 cm H2O, and high PEEP = 15 ± 5 cm H2O. Shunt, low V/Q, high V/Q, and alveolar dead space were not significantly influenced, on average, by PEEP. Respiratory system compliance decreased significantly when increasing PEEP without significant variation of PaO2/FIO2 (P = .26). In the 2 phenotypes, PEEP had opposite effects on shunt, with a decrease in the phenotype L and an increase in phenotype H (P = .048). CONCLUSIONS: In subjects with COVID-related ARDS placed on invasive mechanical ventilation for > 48 h, PEEP had a heterogeneous effect on V/Q mismatch and, on average, higher levels were not able to reduce shunt. The subject's compliance could influence the effect of PEEP on V/Q mismatch since an increased shunt was observed in subjects with lower compliance, whereas the opposite occurred in those with higher compliance. [ABSTRACT FROM AUTHOR]

Objective. Prone positioning has been established as a therapeutic strategy for severe acute respiratory distress syndrome (ARDS). In COVID-19-associated ARDS (CARDS), the application of prone position has shown varying responses, influenced by factors such as lung recruitability and SARS-CoV-2-induced pulmonary endothelial dysfunction. This study aimed to compare the early impact of pronation on lung ventilation-perfusion matching (VQmatch) in CARDS and non-COVID-19 ARDS patients (non-CARDS). Approach. This was a two-center, prospective study comparing between CARDS and non-CARDS. Electrical impedance tomography (EIT) was used to compare the VQmatch between supine and early-stage prone positions (∼2 h). The study identified the areas of Deadspace, shunt, and VQmatch. Within the defined VQmatch region, the global inhomogeneity index (VQmatch-GI) was computed to evaluate the degree of heterogeneity. Paired Wilcoxon signed-rank test and Chi-square test were used in statistical analysis. Main results. 15 CARDS patients and 14 non-CARDS patients undergoing mechanical ventilation were included. In comparison to the non-CARDS group, the CARDS group exhibited a higher prevalence of diffuse lung disease (15 [100%] vs. 4 [28.6%], CARDS vs. Non-CARDS, p < 0.001), along with elevated SOFA score, PCO 2 , PEEP, and Ppeak. Among non-CARDS patients, 11/14 demonstrated improved oxygenation, whereas only 5/15 CARDS patients exhibited oxygenation improvement in prone ventilation. In 13/29 patients with oxygenation improvement (defined as above 20% increase in SpO 2 /FiO 2 ), there was a significant decreased deadspace (21.3 [11.5, 33.1] vs. 9.7 [7.3, 16.9], p = 0.039), and VQmatch showed an upward trend. When comparing prone ventilation to supine ventilation, non-CARDS patients showed a significant improvement in overall VQmatch (Supine 65.7 [49.7, 68.5] vs. Prone 67.4 [60.8, 72.6], p = 0.019). CARDS patients had a notable decrease in ventral VQmatch (VQmatch&#95;Ventral: Supine 35.0 [26.9, 42.0] vs. Prone 22.7 [12.4, 32.9], p = 0.003), and an improvement in dorsal VQmatch (VQmatch&#95;Dorsal: Supine 33.4 [20.4, 39.4] vs. Prone 46.4 [37.4, 48.4], p = 0.031), leading to no significant improvement in overall VQmatch. Ten CARDS patients with no improvement in VQmatch had increased shunting and VQmatch-GI. Significance. In non-CARDS patients, the improvement in oxygenation and VQmatch following prone positioning exhibits a consistent pattern. Conversely, in CARDS patients, the impact of prone positioning reveals considerable individual variability. This study indicates that the response to short-time prone ventilation can vary in ARDS patients with different etiologies. Trial registration: NCT05816928, 04/17/2023, retrospectively registered. Ventilation-Perfusion Matching in Early-stage Prone Position Ventilation, NCT05816928. Registered 17 April 2023 - Retrospectively registered,https://clinicaltrials.gov/study/NCT05816928., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objectives: Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch., Design: Prospective observational study., Setting: General ICU of a university-affiliated hospital., Patients: Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation., Interventions: Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers., Measurements and Main Results: Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure ( r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph ( r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue ( r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan., Conclusions: In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance., Competing Interests: Dr. Grasselli received personal fees from Getinge, Draeger Medical (payment for lectures), Aerogen, and Fisher & Paykel (payment for lectures and unrestricted research grant) outside the submitted work; he disclosed the Italian Ministry of Health. Dr. Mauri received personal fees for speaking at sponsored symposia by Draeger, Fisher and Paykel, and Aerogen, outside of the submitted work. Dr. Rosso’s institution received funding from Agenzia Italiana del Farmaco. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Prone positioning (PP) improves oxygenation in awake patients with acute hypoxemic respiratory failure (AHRF). However, the underlying mechanisms remain unclear in patients with diverse lung morphology. We aimed to determine the short-term effects of awake prone positioning (APP) in AHRF patients with focal and non-focal lung morphology., Methods: This is a prospective physiological study. Twenty-four non-intubated patients with PaO 2 /FiO 2  ≤ 300 mm Hg were included. Gas exchange, ventilation and perfusion distribution, and hemodynamics variables were recorded in the supine position (SP1), 2 h after PP, and 1 h after re-supine (SP2). Lung morphology was classified as focal and non-focal patterns using computed tomography., Results: Twelve of the included patients were classified to the focal group and 12 to the non-focal group. PaO 2 /FiO 2 improved after PP in all patients (161 [137, 227] mmHg vs. 236 [202, 275] mmHg, p < 0.001). Ventilation-perfusion (V/Q) matching increased after PP in all patients (61.9 [53.9, 66.5] vs. 77.5 [68.3, 80.0], p < 0.001). Shunt exhibited a significant decrease in patients of the non-focal group (28.6 [22.5, 30.3] vs. 11.3 [9.0, 14.5], p < 0.001), whereas no difference was found in the focal group after PP. Dead space decreased significantly in patients of the focal group (25.6 [21.5, 28.4] vs. 12.0 [10.8, 14.1], p < 0.001), whereas no difference was found in the non-focal group after PP., Conclusions: APP improves V/Q matching, and large-scale, bias-free studies are needed to find more definitive differences between patients with focal and non-focal lung morphyology., Trial Registration: The study is registered in ClinicalTrials.gov (trial No. NCT04754113, date of registration: 2021-02-15)., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the local ethics committee for clinical research of Zhongda Hospital, Southeast University (2020ZDSYLL057-P01). Written informed consent was obtained from patients before enrollment. For patients who were unable to write due to underlying medical conditions, written informed consent were obtained from the patients’ legal representatives with their authorization. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Abstract Background SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation–perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. Methods Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. Results Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41–68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7–12 days vs. 12 IQR 9–21 days, p = 0.04). Conclusions No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. Trial Registration: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .

We have developed a novel functional proton magnetic resonance imaging (MRI) technique to measure regional ventilation-perfusion (V̇A/Q̇) ratio in the lung. We conducted a comparison study of this technique in healthy subjects (n = 7, age = 42 ± 16 yr, Forced expiratory volume in 1 s = 94% predicted), by comparing data measured using MRI to that obtained from the multiple inert gas elimination technique (MIGET). Regional ventilation measured in a sagittal lung slice using Specific Ventilation Imaging was combined with proton density measured using a fast gradient-echo sequence to calculate regional alveolar ventilation, registered with perfusion images acquired using arterial spin labeling, and divided on a voxel-by-voxel basis to obtain regional V̇A/Q̇ ratio. LogSDV̇ and LogSDQ̇, measures of heterogeneity derived from the standard deviation (log scale) of the ventilation and perfusion vs. V̇A/Q̇ ratio histograms respectively, were calculated. On a separate day, subjects underwent study with MIGET and LogSDV̇ and LogSDQ̇ were calculated from MIGET data using the 50-compartment model. MIGET LogSDV̇ and LogSDQ̇ were normal in all subjects. LogSDQ̇ was highly correlated between MRI and MIGET (R = 0.89, P = 0.007); the intercept was not significantly different from zero (-0.062, P = 0.65) and the slope did not significantly differ from identity (1.29, P = 0.34). MIGET and MRI measures of LogSDV̇ were well correlated (R = 0.83, P = 0.02); the intercept differed from zero (0.20, P = 0.04) and the slope deviated from the line of identity (0.52, P = 0.01). We conclude that in normal subjects, there is a reasonable agreement between MIGET measures of heterogeneity and those from proton MRI measured in a single slice of lung.NEW & NOTEWORTHY We report a comparison of a new proton MRI technique to measure regional V̇A/Q̇ ratio against the multiple inert gas elimination technique (MIGET). The study reports good relationships between measures of heterogeneity derived from MIGET and those derived from MRI. Although currently limited to a single slice acquisition, these data suggest that single sagittal slice measures of V̇A/Q̇ ratio provide an adequate means to assess heterogeneity in the normal lung.

Purpose: Exercise-induced arterial hypoxemia (EIAH) has been reported in patients with juvenile thyroid cancer treated with radioiodine for lung metastases. This retrospective study tested the hypothesis that EIAH is due to ventilation-perfusion-mismatch in this rare pulmonary condition. Methods: 50 patients (age 13-23 years) treated for juvenile thyroid carcinoma and lung metastasis with 131I and 24 controls with thyroid cancer but without lung metastases and prior 131I-treatment were assessed in a state of acute hypothyroidism by computed tomography of the lungs, pulmonary function testing, cardiopulmonary exercise test with measurements of gas exchange, oxygen saturation, alveolar-arterial difference in pO2 (p(A-a)O2) and pCO2 (p(ET-a)CO2). Results: 10 of the 50 patients with lung metastases showed EIAH. They had more pronounced pulmonary fibrosis on computed tomography, a widened p(A-a)O2, and p(ET-a)CO2, a lower DVE/DVCO2-slope, a lower respiratory rate and no increased dead space ventilation. A more pronounced EIAH was associated with male gender, younger age, lower diffusion capacity, higher p(ET-a)CO2 during exercise and a higher peak exercise tidal volume over vital capacity ratio. Conclusion: EIAH in patients with thyroid carcinoma and pulmonary metastases is not related to ventilation-perfusion mismatch but to alveolar hypoventilation, possibly related to an increased work of breathing with pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Objective: To study ventilation-perfusion ratio (VPR) in patients with chronic obstructive pulmonary disease (COPD) using method of volumetric capnography. Methods: 35 patients with COPD II-IV stages and 17 volunteers without pathology of the respiratory system (control group) were examined. Using SpiroScout (Ganshorn, Germany) with built-in function of volumetric capnography, spirography and volumetric capnography were implemented. Symptoms in patients with COPD were evaluated using mMRC and CAT. Results: Statistically significant differences between the patients with COPD and the control group were identified in a number of parameters of volumetric capnography characterizing VPR. VDBohr, VDalv and their ratio to VT in patients with COPD were higher than in individuals of the control group (VDBohr – 361 [299-486] and 280 [215-463] ml, p=0.042; VDBohr/VT – 0.43 [0.40-0.51] and 0.35 [0.31-0.44], p=0.001; VDalv – 211 [142-290] and 81 [49.5-244.5] ml, p=0.012; VDalv/VT – 0.24 [0.20-0.34] and 0.13 [0.08-0.23], p=0.001). The slope of the 2nd phase of the capnogram in COPD was more smooth (dMM/dV2 – 2.0 [1.7-2.7] and 2.5 [2.2-3.2] g/mol×l, respectively; p=0.013), and the slope of the 3rd phase was steeper than in the individuals without pathology of the respiratory system (dMM/dV3 – 0.38 [0.29-0.51] and 0.22 [0.13-0.34] g/mol×l, respectively; p

Background: Veno-venous extracorporeal membrane oxygenation (ECMO) provides blood oxygenation and carbon dioxide removal in acute respiratory distress syndrome. However, during ECMO support, the native lungs still play an important role in gas exchange, functioning as a second oxygenator in series with ECMO. The hypoxic vasoconstriction mechanism diverts regional blood flow within the lungs away from regions with low oxygen levels, optimizing ventilation/perfusion matching. ECMO support has the potential to reduce this adaptive pulmonary response and worsen the ventilation/perfusion mismatch by raising venous oxygen partial pressure. Thus, the objective of this study was to evaluate the effect of ECMO on regional pulmonary perfusion and pulmonary hemodynamics during unilateral ventilation and posterior lung collapse. Methods: Five Agroceres pigs were instrumented, monitored and submitted to ECMO. We used the Electrical Impedance Tomography (EIT) to evaluate lung ventilation and perfusion in all protocol steps. Effects of ECMO support on pulmonary hemodynamics and perfusion involving two different scenarios of ventilation/perfusion mismatch: (1) right-lung selective intubation inducing collapse of the normal left lung and (2) dorsal lung collapse after repeated lung lavage. Data including hemodynamics, respiratory, lung perfusion/ventilation, and laboratory data over time were analyzed with a mixed generalized model using the subjects as a random factor. Results: The initiation of ECMO support provided a significant reduction in Mean Pulmonary Artery Pressure (PAPm) in both situations of ventilation/perfusion mismatch. However, distribution of lung perfusion did not change with the use of ECMO support. Conclusions: We found that the use of ECMO support with consequent increase in venous oxygen pressure induced a significant drop in PAPm with no detectable effect on regional lung perfusion in different scenarios of ventilation/perfusion mismatch. [ABSTRACT FROM AUTHOR]

Background: Postoperative pulmonary complications can increase hospital length of stay, postoperative morbidity, and mortality. Although many factors can increase the risk of postoperative pulmonary complications, it is not known whether intraoperative ventilation/perfusion (V/Q) mismatch can be associated with an increased risk of postoperative pulmonary complications after major noncardiac surgery., Methods: This study enrolled patients undergoing general anesthesia for noncardiac surgery and evaluated intraoperative V/Q distribution using the automatic lung parameter estimator technique. The assessment was done after anesthesia induction, after 1 h from surgery start, and at the end of surgery. Demographic and procedural information were collected, and intraoperative ventilatory and hemodynamic parameters were measured at each timepoint. Patients were followed up for 7 days after surgery and assessed daily for postoperative pulmonary complication occurrence., Results: The study enrolled 101 patients with a median age of 71 [62 to 77] years, a body mass index of 25 [22.4 to 27.9] kg/m2, and a preoperative Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score of 41 [34 to 47]. Of these patients, 29 (29%) developed postoperative pulmonary complications, mainly acute respiratory failure (23%) and pleural effusion (11%). Patients with and without postoperative pulmonary complications did not differ in levels of shunt at T1 (postoperative pulmonary complications: 22.4% [10.4 to 35.9%] vs. no postoperative pulmonary complications:19.3% [9.4 to 24.1%]; P = 0.18) or during the protocol, whereas significantly different levels of high V/Q ratio were found during surgery (postoperative pulmonary complications: 13 [11 to 15] mmHg vs. no postoperative pulmonary complications: 10 [8 to 13.5] mmHg; P = 0.007) and before extubation (postoperative pulmonary complications: 13 [11 to 14] mmHg vs. no postoperative pulmonary complications: 10 [8 to 12] mmHg; P = 0.006). After adjusting for age, ARISCAT, body mass index, smoking, fluid balance, anesthesia type, laparoscopic procedure and surgery duration, high V/Q ratio before extubation was independently associated with the development of postoperative pulmonary complications (odds ratio, 1.147; 95% CI, 1.021 to 1.289; P = 0.02). The sensitivity analysis showed an E-value of 1.35 (CI, 1.11)., Conclusions: In patients with intermediate or high risk of postoperative pulmonary complications undergoing major noncardiac surgery, intraoperative V/Q mismatch is associated with the development of postoperative pulmonary complications. Increased high V/Q ratio before extubation is independently associated with the occurrence of postoperative pulmonary complications in the first 7 days after surgery., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

This commentary refers to the article "Heterogeneity of Ventilation/Perfusion Mismatch at Different Levels of PEEP and in Mechanical Phenotypes of COVID-19 ARDS," by G. Scaramuzzo, D. S. Karbing, A. Foragnolo and colleagues, that was published within the issue. Topics discussed include acute respiratory distress syndrome (ARDS), positive end-expiratory pressure, and oxygenation-based definition and severity assignment of ARDS.

The article describes the case of a 56-year-old man with diabetes and hypertension presented to the emergency department with shortness of breath, dizziness and an unsteady gait for two days. Topics include the presence of a unilateral right main pulmonary artery embolus without an appreciable clot on the left, finding on perfusion on the lung base and at the apex, and lateral decubitus positioning in spontaneously breathing patients.

Background: SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation-perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA.Methods: Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis.Results: Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41-68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7-12 days vs. 12 IQR 9-21 days, p = 0.04).Conclusions: No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results.Trial Registration: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 . [ABSTRACT FROM AUTHOR]

Background: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (VA/Q) of normal lungs influences the kinetics of inhaled anesthetics.Methods: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different VA/Q conditions: normal, low, and high. For each VA/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of VA/Q on paired differences in arterial and mixed venous partial pressures.Results: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 ± 0.10, 0.93 ± 0.08, and 0.82 ± 0.07 for the low, normal, and high VA/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 ± 0.06, 0.77 ± 0.04, and 0.75 ± 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 ± 0.04, 0.88 ± 0.02, and 0.92 ± 0.01 for the low, normal, and high VA/Q conditions. Equivalent measurements for sevoflurane were 0.79 ± 0.05, 0.85 ± 0.03, and 0.90 ± 0.03.Conclusions: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global VA/Q ratio for normal lungs.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Abstract Background Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V T) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V T (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH2O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V T) was used, with a three-way mixed analysis of variance (ANOVA). Results Two-way interactions between PEEP and group, and V T and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and VT in the injured group than in the control group. A two-way interaction between PEEP and V T was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions Large PEEP and V T levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.

The article focuses on breathing in the prone position in health and disease. Topics include the prone position eliminates compression of the lungs by the heart, the gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung, and the prone position in acute respiratory distress syndrome.

V/P SPECT from 4 consecutive patients with COVID-19 suggests that ventilation and perfusion images may be applied to diagnose or exclude pulmonary embolism, verify nonsegmental diversion of perfusion from the ventilated areas (dead space ventilation) that may represent inflammation of the pulmonary vasculature, detect the reversed mismatch of poor ventilation and better preserved perfusion (shunt perfusion) in bilateral pulmonary inflammation and indicate redistribution of lung perfusion (antigravitational hyperperfusion) due to cardiac congestion. V/P mismatch and reversed mismatch may be extensive enough to diminish dramatically preserved matching ventilation/perfusion and to induce severe hypoxemia in COVID-19. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to retrospectively assess the benefits of combining low-dose computed tomography (LDCT) with ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE)., Methods: A retrospective analysis was performed on 92 patients with suspected PE who underwent V/Q SPECT with ldCT (V/Q SPECT CT) between January 2020 and December 2022 at King Khalid Hospital Najran. Data were collected using the hospital's picture archiving and communication system. Scans were categorized on the basis of perfusion defects, matched or mismatched ventilation, and CT findings. The specificity of V/Q SPECT CT was compared with that of Q SPECT CT., Results: This study included 92 patients (54 females and 38 males; median age, 53 years). The results demonstrated that V/Q SPECT CT had higher specificity (93%) than V/Q SPECT alone (88%). If CT had been used as a ventilation substitute, 21% of patients would have been reported to be positive for PE (8% false-positive), yielding a specificity of 60% for Q SPECT CT. These findings align with the existing literature, although discrepancies in specificity values were noted due to the different study designs and sample sizes., Conclusion: This study highlights the enhanced specificity of V/Q SPECT CT compared to V/Q SPECT and Q SPECT CT alone. Including low-dose CT improves diagnostic accuracy by reducing false positives and providing detailed anatomical information. V/Q SPECT CT offers superior specificity in diagnosing PE compared with V/Q SPECT alone, supporting its use in clinical practice.

Aim: The aim of this study is to investigate whether computer-aided, semi-automated 3D lung lobe quantification can support decision-making on PE diagnosis based on the ventilation-perfusion ratio in clinical practice., Methods: A study cohort of 100 patients (39 male, 61 female, age 64.8±15.8 years) underwent ventilation/perfusion single photon emission computed tomography (V/Q-SPECT/CT) to exclude acute PE on SPECT/CT OPTIMA NM/CT 640 (GE Healthcare). Two 3D lung lobe quantification software tools (Q. Lung: Xeleris 4.0, GE Healthcare and LLQ: Hermes Hybrid 3D Lung Lobar Quantification, Hermes Medical Solutions) were used to evaluate the numerical lobar ventilation/perfusion ratio (VQR) and lobar volume/perfusion ratio (VPR). A test of linearity and equivalence of the two 3D software tools was performed using Pearson, Spearman, quadratic weighted kappa and the mean squared deviation for VPR/VQR. An algorithm was developed that identified PE candidates using ROC analysis. The agreement between the PE findings of an experienced nuclear medicine expert and the calculated PE candidates was represented by the magnitude of the YOUDEN index (J) and the size of the area under the receiver operating curve (AUC)., Results: Both 3D software tools showed good comparability. The YOUDEN index for QLUNG(VPR/VQR)/LLQ(VPR/VQR) was in the range from 0.2 to 0.5. The mean AUC averaged over all lung lobes for QLUNG(VPR) was 0.66, CI95%: ±14.0%, for QLUNG(VQR) 0.66, CI95%: ±13.3%, for LLQ(VPR) 0.64, CI95%: ±14.7% and for LLQ(VQR) 0.65, CI95%: ±13.1%., Conclusion: This study reveals that 3D software tools are feasible for numerical PE detection. The clinical decision can be supported by using a numerical algorithm based on ROC analysis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Abstract Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion ( V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p = .84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p = .04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p = .54); Deadspace was not significantly different (p = .54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p = .052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized.

Difficulties have risen while managing Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19, although it meets the Berlin definition. Severe hypoxemia with near-normal compliance was noted along with coagulopathy. Understanding the precise pathophysiology of this atypical ARDS will assist researchers and physicians in improving their therapeutic approach. Previous work is limited to postmortem studies, while our report addresses patients under protective lung mechanical ventilation. An open-lung minithoracotomy was performed in 3 patients who developed ARDS related to COVID-19 and were admitted to the intensive care unit to carry out a pathological and microbiological analysis on lung tissue biopsy. Diffused alveolar damage with hyaline membranes was found, as well as plurifocal fibrin microthrombi and vascular congestion in all patients' specimens. Microbiological cultures were negative, whereas qualitative Reversed Transcriptase Polymerase Chain Reaction (RT-PCR) detected SARS-CoV-2 in the pulmonary parenchyma and pleural fluid in two patients. COVID-19 causes progressive ARDS with onset of severe hypoxemia, underlying a dual mechanism: shunt effect through diffused alveolar damage and dead space effect through thrombotic injuries in microvascular beds. It seems reasonable to manage this ventilation-perfusion ratio mismatch using a high dose of anticoagulant combined with glucocorticoids. [ABSTRACT FROM AUTHOR]

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar PO2 and the calculated arterial PO2. The end-tidal PO2 is measured using a rapid gas analyzer, and the arterial PO2 is derived from pulse oximetry after allowing for the effect of the PCO2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal PO2 and PCO2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial PO2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley’s criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same PCO2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal PO2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar PO2, but that it is easier to obtain. [ABSTRACT FROM AUTHOR]

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar PO2 and the calculated arterial PO2. The end-tidal PO2 is measured using a rapid gas analyzer, and the arterial PO2 is derived from pulse oximetry after allowing for the effect of the PCO2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal PO2 and PCO2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial PO2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley’s criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same PCO2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal PO2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar PO2, but that it is easier to obtain. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion (V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p =.84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p =.04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p =.54); Deadspace was not significantly different (p =.54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p =.052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized. [ABSTRACT FROM AUTHOR]

Background: Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS.Methods: In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample.Results: Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = - 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch.Conclusions: The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration.Trial Registration: ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019. [ABSTRACT FROM AUTHOR]

Objectives: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia.Design: Preclinical study.Setting: Research laboratory.Subjects: Seven anesthetized pigs 28.7 kg (SD, 2.1 kg).Interventions: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis.Measurements and Main Results: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729-908 µL/g]) than the dependent region (149 µL/g [120-178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12-46 µL/g]) and increased in the dependent region (39 µL/g [30-48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with PaO2/FIO2 ratio (ρ = -0.77 and -0.93, respectively).Conclusions: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening PaO2/FIO2. [ABSTRACT FROM AUTHOR]

Chronic obstructive and interstitial lung diseases impair pulmonary gas exchange leading to wasted ventilation (alveolar dead space) and wasted perfusion (venous admixture). These two fundamental types of abnormality represent opposite ends of the spectrum of ventilation-perfusion mismatch with V/Q ratios of infinity and zero. Treatment approaches that improve airway function, reduce air trapping and hyperinflation have received much attention and might be successful at ameliorating the problems associated with high V/Q. However, in patients with low V/Q abnormality in whom venous admixture leads to hypoxemia, there are few therapeutic options. Indeed, some patients are refractory to treatment with supplemental oxygen particularly during exercise. Theoretically these patients could benefit from an intervention that increased mixed venous oxygen content thereby ameliorating the deleterious effects of venous admixture. In this perspective article we discuss the mechanisms whereby venous admixture contributes to hypoxemia and reduced oxygen delivery to tissues. We explore methods which could potentially increase mixed venous oxygen content thus ameliorating the deleterious effects of venous admixture. One such intervention that warrants further investigation is the therapeutic creation of an arterio-venous fistula. Such an approach would be novel, simple and minimally invasive. There is reason to believe that complications would be minor leading to a favorable risk-benefit analysis. This approach to treatment could have significant impact for patients with COPD but should also benefit any patient with chronic hypoxemia that impairs exercise performance.

The purpose of this investigation was to determine whether either the differentiated ratings of perceived exertion (RPE) for the legs (RPE-L) or chest (RPE-C) were higher than the overall body RPE (RPE-O) in children performing treadmill walking. A differentiated RPE that was higher than the RPE-O was considered the dominant perceptual signal. Thirty-one 10-year-old participants (16 boys, 15 girls) performed six separate 5-min bouts of level treadmill walking at different speeds. During each bout of exercise, RPEs were recorded using the modified Children's OMNI Scale. Oxygen consumption (VO2), heart rate (HR), and ventilation (VE) were measured during Minutes 4 and 5 at each walking speed. VO2, HR, and VE increased as walking speed increased, as did perceived exertion. No differences were observed among RPE-O, RPE-L, and RPE-C at any speed. In addition, boys and girls exhibited similar responses for each perceptual and physiological variable. In conclusion, a dominant differentiated perceptual rating was not found at slow-to-moderate treadmill walking speeds for either boys or girls. Neither the respiratory-metabolic nor peripheral ratings of perceived exertion appeared to dominate the whole-body sensory-integration process in this sample. [ABSTRACT FROM AUTHOR]

Abstract Objectives : To check if ventilatory inefficiency is related to low cardiorespiratory fitness in the elderly and to identify the variable(s) of the cardiopulmonary exercise test (CPET) best suited to determining this relationship. Methods : A retrospective analysis of 1357 CPETs was performed. Sixty-one subjects over 60 years old with a ventilatory efficiency slope (VE/VCO2) index >35 were selected and divided into two groups: low cardiorespiratory fitness (VO280% predicted) (n=39) and were compared with a control group of healthy elderly persons with normal cardiorespiratory fitness and VE/VCO2 slope index 0.05); the COP showed an area under the curve of 0.84 (p

Introduction: Pulmonary embolism (PE) is a challenge to diagnose and when missed, exposes patients to potentially fatal recurrent events. Beyond CT pulmonary angiography (CTPA) and planar ventilation/perfusion (V/Q) scan, single photon emission CT (SPECT) V/Q emerged a new diagnostic modality of scintigraphic acquisition that has been reported to improve diagnostic performances. To date, no management outcome study or randomised trial evaluated an algorithm based on SPECT V/Q for PE diagnosis. We present the design of a randomised multicentre, international management study comparing SPECT V/Q with validated strategies., Material and Methods: We will include a total of 3672 patients with suspected PE requiring chest imaging, randomised into three different groups, each using a different diagnostic strategy based on SPECT V/Q, CTPA and planar V/Q scan. Randomisation will be unbalanced (2:1:1), with twice as many patients in SPECT V/Q arm (n=1836) as in CTPA and planar V/Q arms (n=918 in each). Our primary objective will be to determine whether a diagnostic strategy based on SPECT V/Q is non-inferior to previously validated strategies in terms of diagnostic exclusion safety as assessed by the 3-month risk of thromboembolism in patients with a negative diagnostic workup. Secondary outcomes will be the proportion of patients diagnosed with PE in each arm, patients requiring additional tests, the incidence of major and clinically relevant non-major bleeding and the incidence and cause of death in each arm., Ethics and Dissemination: This trial is funded by a grant from Brest University Hospital and by INVENT. The study protocol was approved by Biomedical Research Ethics Committee. The investigator or delegate will obtain signed informed consent from all patients prior to inclusion in the trial. Our results will inform future clinical practice guidelines and solve the current discrepancy between nuclear medicine guidelines and clinical scientific society guidelines., Trial Registration Number: NCT02983760., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Ventilation Perfusion SPECT is important in the diagnostics of e.g. pulmonary embolism and chronic obstructive pulmonary disease. Classical and reverse mismatched defects can be identified by utilizing the ventilation-perfusion ratio. Unfortunately, this ratio is only linear in the ventilation, the scale is not symmetrical regarding classical and reversed mismatches and small perfusion values give rise to artifacts. The ventilation-perfusion (VQ) difference is developed as an alternative., Methods: For both VQ-ratio and VQ-difference a scaling factor for the perfusion is computed, so that voxels with matched ventilation and perfusion (on average) yield zero signal. The relative VQ-difference is calculated by scaling with the summed VQ-signal in each voxel. The scaled VQ-difference is calculated by scaling with the global maximum of this sum., Results: The relative and scaled differences have a scale from -1 (perfusion only) to + 1 (ventilation only). Image quality of relative VQ-difference and VQ-ratio images is hampered by artifacts from areas with both low perfusion and low ventilation. Ratio and differences have been investigated in ten patients and are shown for three patients (one without defects). Clinical thresholds for the difference images are derived resulting in color maps of relevant (reversed) mismatches with a (reciprocal) ratio larger than two., Conclusions: The relative ventilation-perfusion difference is a methodological improvement on the ventilation-perfusion ratio, because it has a symmetrical scale and is bound on a closed domain. A better diagnostic value is expected by utilizing the scaled difference, which represents functional difference instead of relative difference., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Ventilation-perfusion (V/Q) scan coupled with single photon emission computed tomography (SPECT) is commonly used for the diagnosis of pulmonary embolism (PE). An abnormal chest x-ray (CXR) is deemed to hinder the interpretation of V/Q scan and therefore a normal CXR is recommended prior to V/Q scan., Aims: To determine if an abnormal CXR impacted on V/Q scan interpretation and subsequent management., Methods: A retrospective cohort analysis of all patients who underwent a V/Q scan for diagnosis of suspected acute PE between March 2016 and 2022 was performed. CXR reports were reviewed and classified as normal or abnormal. Low-dose computerised tomography was routinely performed in patients above the age of 70. Data regarding V/Q scan results and subsequent management including initiation of anticoagulation for PE or further diagnostic investigations were collected., Results: A total of 340 cases were evaluated. Of the positive V/Q scans (92/340), 98.3% of the normal CXR were anticoagulated compared to 100% of the abnormal CXR group. Of the negative V/Q scans (239/340), no cases were started on anticoagulation and no further investigations were performed across both normal and abnormal CXR groups. Indeterminate results occurred in only 9 cases with no significant difference in management between normal and abnormal CXR groups., Conclusion: An abnormal CXR does not affect the reliability of V/Q scan interpretation in the diagnosis of PE when coupled with SPECT. Unless clinically indicated, the mandate by clinical society guidelines for a normal CXR prior to V/Q should be revisited., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (VT) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three VT (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH2O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and VT) was used, with a three-way mixed analysis of variance (ANOVA). Results: Two-way interactions between PEEP and group, and VT and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and VT in the injured group than in the control group. A two-way interaction between PEEP and VT was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions: Large PEEP and VT levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups. [ABSTRACT FROM AUTHOR]

Adult respiratory distress syndrome (ARDS) is a clinical entity characterized by hypoxemic respiratory failure in the setting of noncardiogenic pulmonary edema. It is associated with significant morbidity and mortality. Prone positioning is a beneficial strategy in patients with severe ARDS because it improves alveolar recruitment, ventilation/perfusion (V/Q) ratio, and decreases lung strain. The outcome is improved oxygenation, decreased severity of lung injury, and, subsequently, mortality benefit. In this article, we discuss the physiology of prone positioning on chest mechanics and V/Q ratio, the placement and maintenance of patients in the prone position with use of a prone bed and the current literature regarding benefits of prone positioning in patients with ARDS. [ABSTRACT FROM AUTHOR]

Background: Endoscopic lung volume reduction (ELVR) therapy using one-way valves is used to treat chronic obstructive pulmonary disease patients with severe heterogeneous emphysema. A successful treatment results in atelectasis of the treated pulmonary lobe with subsequent reduction of ventilation (V) and perfusion (Q). Objective: We evaluated the effects of ELVR on the targeted lobe using a new 3-dimensional ventilation and perfusion (V/Q) single-photon emission computed tomography (SPECT)/computed tomography (CT) analysis, which allows for simultaneous semi-automatic lobar pulmonary quantification of volume, ventilation and perfusion, on the first consecutive patients treated with ELVR at Rigshospitalet, Denmark. V/Q planar scintigraphy and V/Q SPECT/CT and lung function measurements were performed before and 6 months after intervention. Results: We included 24 subjects (60 years, range 46–74 years; 37.5% men) with a baseline FEV1 of 25% predicted and RV of 257% predicted. V/Q SPECT/CT-assessed volume of the targeted lobe decreased by a mean of –395 mL and a relative mean of –26.8%, whilst ventilation and perfusion decreased by a relative mean of –37.1 and –25.7%. There was a significant increase in the same parameters of the non-targeted lobe(s) on the ipsilateral side. None of these changes were found in the analysis of planar V/Q imaging. The total lung volume decreased on average by –420 mL. Six months after ELVR, FEV1 had increased by 22%. Significant correlations were found between changes in FEV1 and changes in the volume of the treated lobe (SPECT/CT). Conclusion: Semi-automatic SPECT/CT analysis can quantify volume, ventilation and perfusion changes in pulmonary lobes and may be used in the assessment of patient eligibility for ELVR, identifying target lobes, and evaluation of the regional effects of treatment. [ABSTRACT FROM AUTHOR]

Objective: To review and discuss the existing research on the pathophysiology, impact and management of inhalational injury on the larynx and lower respiratory tract.Data Sources: A literature search was conducted on the PubMed, MedLine, Embase, Web of Science and Google Scholar databases based on the keywords "airway burn", "inhalational injury" and "larynx".Review Methods: Inclusion criteria included English language studies containing original and review data on airway injury. Data was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Conclusions: Abnormal laryngeal and lower airway findings are common in burns patients and the incidence tends to increase with severity of the burns. Most patients with abnormal findings remain dysphonic decades after the initial injury. Larynx, the inlet to the airway, is exposed to the most intense thermal damage and highest concentration of chemical in inhalational injury. Airway injury is common and may result in long term morbidity. Healing of this tissue architecture is prolonged and different from cutaneous burn. Many patients receive prolonged intubation for medical complications that arise due to the burn injury. The degree of subglottic damage, however, is more extensive and occurs sooner compared with those without inhalational injuries.Implications For Practice: With advances in acute medical and surgical management of burn and inhalational injury, airway injury is an important secondary outcome with lasting impact. Awareness of these potential complications and early involvement of medical and allied health team are important steps in improving patient care. A multi-disciplinary approach to management will optimise the short and long-term morbidity management and ultimately our patients' quality of life. [ABSTRACT FROM AUTHOR]

The optimization of ventilation during cardiopulmonary resuscitation (CPR) is a broad field of research. Recent physiological observations in this field challenge the current understanding of respiratory and circulatory interactions. Thanks to different models available (bench, animal, human), the understanding of physiological phenomena occurring during CPR has progressed. In this review, we describe the clinical observations that have led to the emerging concept of lung volume reduction and associated thoracic airway closure. We summarize the clinical and animal observations supporting these concepts. We then discuss the different contributions of bench, animal, and human models to the understanding of airway closure and their impact on intrathoracic pressure, airway closure, and hemodynamics generated by chest compression. The limitation of airway pressure and ventilation, resulting from airway closure reproducible in models, may play a major role in ventilation and gas exchange impairment observed during prolonged resuscitation. [ABSTRACT FROM AUTHOR]

The MetaSwim (MS) metabolic cart can assess pulmonary gas exchange and ventilation in aquatic environments. The aims of this study were: (a) to determine the agreement between minute ventilation (VE), pulmonary oxygen uptake (VO2), and carbon dioxide output (VCO2) using the MS and Douglas bag (DB) methods during flume swimming; and (b) to assess the repeatability of these and other MS-derived parameters. Sixteen trained swimmers completed a combined incremental and supramaximal verification cardiopulmonary swimming test to determine maximal VO2, 2 progressive intensity swimming tests during which MS and DB measurements were made (agreement protocol), and 3-4 constant-velocity submaximal swimming tests during which only the MS was used (repeatability protocol). Agreement was determined using limits of agreement (LoA), bias, random error, and 95% confidence intervals with systematic bias assessed using paired samples t-tests. Within-trial and between-trial repeatability were determined using the coefficient of variation (CV) and the repeatability coefficient (CR). Where data were heteroscedastic, LoA and CR were log-transformed, antilogged, and displayed as ratios. MetaSwim underestimated peak VO2 and VCO2 (≤0.39 L·min) and VE (9.08 L·min), whereas submaximal values varied between 2 and 5% for CV and ±1.09-1.22 for ratio CR. The test-retest CV during constant-velocity swimming for VE, tidal volume, breathing frequency, VO2, VCO2, and end-tidal pressures of O2 and CO2 was <9% (ratio CR of ±1.09-1.34). Thus, the MS and DB cannot be used interchangeably. Whether the MS is suitable for evaluating ventilatory and pulmonary responses in swimming will depend on the size of effect required. [ABSTRACT FROM AUTHOR]