Effective Lung Volume Research Articles

Insights from 3D modeling and fluid dynamics in COVID-19 pneumonia.

We address the lack of research regarding aerodynamic events behind respiratory distress at COVID-19. The use of chest CT enables quantification of pneumonia extent; however, there is a paucity of data regarding the impact of airflow changes. We reviewed 31 COVID-19 patients who were admitted in March 2020 with varying severity of pulmonary disease. Lung volumes were segmented and measured on CT images and patient-specific models of the lungs were created. Incompressible, laminar, and three-dimensional Navier-Stokes equations were used for the fluid dynamics (CFD) analyses of ten patients (five mild, five pneumonia). Of 31 patients, 17 were female, 18 had pneumonia, and 2 were deceased. Effective lung volume decreased in the general group, but the involvement of the right lung was prominent in dyspnea patients. CFD analyses revealed that the mass flow distribution was significantly distorted in pneumonia cases with diminished flow rate towards the right lung. In addition, the distribution of flow parameters showed mild group had less airway resistance with higher velocity (1.228 m/s vs 1.572 m/s) and higher static pressure values at airway branches (1.5112 Pa vs 1.3024 Pa). Therefore, we conclude that airway resistance and mass flow rate distribution are as important as the radiological involvement degree in defining the disease severity.

Depicting and predicting changes of lung after lobectomy for cancer by using CT images.

Lobectomy is an effective and well-established therapy for localized lung cancer. This study aimed to assess the lung and lobe change after lobectomy and predict the postoperative lung volume. The study included 135 lung cancer patients from two hospitals who underwent lobectomy (32, right upper lobectomy (RUL); 31, right middle lobectomy (RML); 24, right lower lobectomy (RLL); 26, left upper lobectomy (LUL); 22, left lower lobectomy (LLL)). We initially employ a convolutional neural network model (nnU-Net) for automatically segmenting pulmonary lobes. Subsequently, we assess the volume, effective lung volume (ELV), and attenuation distribution for each lobe as well as the entire lung, before and after lobectomy. Ultimately, we formulate a machine learning model, incorporating linear regression (LR) and multi-layer perceptron (MLP) methods, to predict the postoperative lung volume. Due to the physiological compensation, the decreased TLV is about 10.73%, 8.12%, 13.46%, 11.47%, and 12.03% for the RUL, RML, RLL, LUL, and LLL, respectively. The attenuation distribution in each lobe changed little for all types of lobectomy. LR and MLP models achieved a mean absolute percentage error of 9.8% and 14.2%, respectively. Radiological findings and a predictive model of postoperative lung volume might help plan the lobectomy and improve the prognosis.

Quantitative evaluation of disease severity in connective tissue disease-associated interstitial lung disease by dual-energy computed tomography

BackgroundHigh-resolution computed tomography (HRCT) is recommended diagnosing and monitoring connective tissue disease-associated interstitial lung disease (CTD-ILD). Quantitative computed tomography has the potential to precisely assess the radiological severity of CTD-ILD, but has still been under study.ObjectiveTo investigate whether dual-energy computed tomography (DECT), a novel quantitative technique, can be used for quantitative severity assessment in CTD-ILD.MethodsThis cross sectional study recruited adult CTD-ILD patients who underwent DECT scans from the ICE study between October 2019 and November 2021. DECT parameters, including effective atomic number (Zeff), lung (lobe) volume, and monochromatic CT number (MCTN) of each lung lobe, were evaluated. CTD-ILD was classified into extensive CTD-ILD and limited CTD-ILD by staging algorithm using combined forced vital capacity (FVC)%predicted and total extent of ILD (TEI) on CT. Dyspnea, cough, and life quality were scored by Borg dyspnea score, Leicester cough questionnaire (LCQ), and short-form 36 health survey questionnaire (SF-36), respectively.ResultsThere was a total of 147 patients with DECT scans enrolled. Higher Zeff value (3.104 vs 2.256, p < 0.001), higher MCTN (− 722.87 HU vs − 802.20 HU, p < 0.001), and lower lung volume (2309.51cm3 vs 3475.21cm3, p < 0.001) were found in extensive CTD-ILD compared with limited CTD-ILD. DECT parameters had significant moderate correlations with FVC%predicted (|r|= 0.542–0.667, p < 0.01), DLCO%predicted (|r|= 0.371–0.427, p < 0.01), and TEI (|r|= 0.485–0.742, p < 0.01). Receiver operating characteristic (ROC) analysis indicated MCTN averaged over the whole lung had the best performance for extensive CTD-ILD discrimination (AUC = 0.901, cut-off: − 762.30 HU, p < 0.001), with a sensitivity of 82.1% and a specificity of 85.4%. The Zeff value was the independent risk factor for dyspnea (OR = 3.644, 95% CI: 1.846–7.192, p < 0.001) and cough (OR = 3.101, 95% CI: 1.528–6.294, p = 0.002), and lung volume significantly contributed to the mental component summary (MCS) in SF-36 (standardized β = 0.198, p < 0.05).ConclusionsDECT can be applied to evaluate the severity of CTD-ILD.

Assessment of Ventilatory Heterogeneity in Chronic Obstructive Pulmonary Disease Using the Inspired Sinewave Test.

BackgroundThere is marked variability in the symptoms and outcomes of patients with chronic obstructive pulmonary disease (COPD) which are poorly predicted by spirometry/FEV1%pred. Furthermore, as spirometry requires the performance of potentially distressing respiratory manoeuvres which are to some extent user-effort dependent, there is need for non-invasive and simple-to-perform techniques to identify subtypes of COPD which are more closely related to clinically relevant outcomes.Materials and MethodsThe inspired sinewave test (IST) sinusoidally modulates the inspired concentration of a tracer gas (N2O) over successive tidal breaths. A single-compartment tidal-ventilation lung model processes the amplitude/phase of the expired N2O sinewave and estimates cardiopulmonary variables including: effective lung volume and indices of ventilatory heterogeneity (VH; ELV180/FRCpleth and ELV180/ELVpred). 83 COPD patients and 53 healthy controls performed the IST test, standard pulmonary function tests (Spirometry, body plethysmography and the single breath test of carbon monoxide uptake), and symptom severity questionnaires (COPD assessment test, CAT; mMRC dyspnoea-scale, mMRC-DS; Cough+Mucus score; C+M score).ResultsELV180/FRCpleth and ELV180/ELVpred were significantly lower in patients with COPD vs healthy participants (0.34±0.11 vs 0.68±0.14 and 0.7±0.27 vs 0.98±0.15, respectively; P<0.05). Multivariable regression analysis demonstrated that ELV180/FRCpleth was a stronger and independent predictor of CAT, mMRC-DS and C+M score vs FEV1%pred. ELV180/ELVpred was a stronger and independent and better predictor of C+M score vs FEV1%pred. Phenotyping patients, based upon ELV180/ELVpred and FRC%pred, uncovered significant symptomatic differences between groups.ConclusionThe IST indices of VH were superior and independent predictors of symptom severity vs FEV1%pred and has potential as a non-invasive and simple-to-perform method to stratify patients into subgroups related to clinically relevant features of COPD.

Lung heterogeneity and deadspace volume in animals with acute respiratory distress syndrome using the inspired sinewave test

Acute respiratory distress syndrome (ARDS) is associated with a high rate of morbidity and mortality, as patients undergoing mechanical ventilation are at risk of ventilator-induced lung injuries. Objective: To measure the lung heterogeneity and deadspace volume to find safer ventilator strategies. The ventilator settings could then offer homogeneous ventilation and theoretically equalize and reduce tidal strain/stress in the lung parenchyma. Approach: The inspired sinewave test (IST) is a non-invasive lung measurement tool which does not require cooperation from the patient. The IST can measure the effective lung volume, pulmonary blood flow and deadspace volume. We developed a computational simulation of the cardiopulmonary system to allow lung heterogeneity to be quantified using data solely derived from the IST. Then, the method to quantify lung heterogeneity using two IST tracer gas frequencies (180 and 60 s) was introduced and used in lung simulations and animal models. Thirteen anaesthetized pigs were studied with the IST both before and after experimental lung injury (saline-lavage ARDS model). The deadspace volume was compared between the IST and the SF6 washout method. Main results: The IST could measure lung heterogeneity using two tracer gas frequencies. Furthermore, the value of IST ventilation heterogeneity in ARDS lungs was higher than in control lungs at a positive end-expiratory pressure of 10 cmH2O (area under the curve = 0.85, ). Values for the deadspace volume measured by the IST have a strong relationship with the measured values of SF6 (9 ml bias and limits of agreement from −79 to 57 ml in control animals). Significance: The IST technique has the potential for use in the identification of ventilation and perfusion heterogeneity during ventilator support.

Consolidating Lung Volume Reduction Surgery After Endoscopic Lung Volume Reduction Failure

Bronchoscopic valve placement constitutes an effective endoscopic lung volume reduction (ELVR) therapy in patients with severe emphysema and low collateral ventilation. After the most destroyed lobe is occluded with valves, significant target lobe volume reduction leads to improvements in lung function, exercise capacity, and quality of life. The effects are not consistent in some patients, leading to long-term therapy failure. We hypothesized that surgical lung volume reduction (LVRS) would reestablish ELVR short-term clinical improvements after ELVR long-term failure. This retrospective single-center analysis included all patients who underwent consolidating LVRS by lobectomy after long-term failure of valve therapy between 2010 and 2015. Changes in forced expiratory volume in 1 second, residual volume, 6-minute walking distance, and Modified Medical Research Council dyspnea score 90 days after ELVR and LVRS were analyzed, and the outcomes of both procedures were compared. LVRS was performed in 20 patients after ELVR failure. A lower lobectomy was performed in 90%. The 30-day mortality of the cohort was 0% and 90-day mortality was 5% (1 of 20). The remaining 19 patients showed a significant increase in forced expiratory volume in 1 second (+27.5% ± 19.4%) and a reduction in residual volume (-21.0% ± 17.4%) and total lung capacity (-11.1% ± 11.1%). This resulted in significant improvements in exercise tolerance (6-minute walking distance:+56 ± 60 m) and relief of dyspnea (ΔModified Medical Research Council:-1.8 ± 1.4 points.). Consolidating LVRS by lobectomy after failure of a previously successful ELVR is feasible and results in significant symptom relief and improvement of lung function.

Morphological and functional reserves of the right middle lobe: Radiological analysis of changes after right lower lobectomy in healthy individuals

ObjectivesRemaining lung tissue after pulmonary resection can expand without decline in structural complexity and compensate for functional loss, showing morphological and functional reserves. However, the distribution of these reserves is unknown. This study examined the heterogeneity of morphological and functional reserves of the remaining lung tissue. MethodsWe retrospectively analyzed 53 donors who underwent right lower lobectomy for living-donor lobar lung transplantation. We examined morphometric changes in computed tomography images from 3 to 12 months after lobectomy. We assessed lung volume and structural complexity expressed as the fractal dimension. We also assessed effective lung volume (the volume of the lung with intermediate density) and volumetric fluctuation during respiration. Changes were compared between the right upper lobe, middle lobe, and left lung. ResultsThe expansion of lung tissue was greater in the middle lobe (130.9% ± 19.7%) than in the upper lobe (109.7% ± 9.2%; P < .001). The fractal dimension declined in the upper lobe (P < .001) but was maintained in the middle lobe (P = .39). The increase in effective lung volume was larger in the middle lobe (97.2 ± 73.5 mL) than in the upper lobe (62.7 ± 87.1 mL; P < .001), but not significantly different from that of the left lung (55.8 ± 186.3 mL; P = .052). A similar pattern was seen in respiratory fluctuation. ConclusionsMorphological and functional changes in lung tissue remaining after pulmonary resection were heterogeneous. The right middle lobe demonstrated morphological and functional reserves after right lower lobectomy.

Clinical and experimental validation of a capnodynamic method for end-expiratory lung volume assessment.

Lung protective ventilation can decrease post-operative pulmonary complications. The aim of this study was to evaluate a capnodynamic method estimating effective lung volume (ELV) as a proxy for end-expiratory lung volume in response to PEEP changes in patients, healthy subjects and a porcine model. Agreement and trending ability for ELV in anaesthetized patients and agreement in awake subjects were evaluated using nitrogen multiple breath wash-out/in and plethysmography as a reference respectively. Agreement and trending ability were evaluated in pigs during PEEP elevations with inert gas wash-out as reference. In anaesthetized patients bias (95% limits of agreement [LoA]) and percentage error (PE) at PEEP 0cm H2 O were 133mL (-1049 to 1315) and 71%, at PEEP 5cm H2 O 161mL (-1291 to 1613mL) and 66%. In healthy subjects: 21mL (-755 to 796mL) and 26%. In porcines, at PEEP 5-20cm H2 O bias decreased from 223mL to 136mL LoA (34-412) to (-30 to 902) and PE 29%-49%. Trending abilities in anaesthetized patients and porcines were 100% concordant. The ELV-method showed low bias but high PE in anaesthetized patients. Agreement was good in awake subjects. In porcines, agreement was good at lower PEEP levels. Concordance related to PEEP changes reached 100% in all settings. This method may become a useful trending tool for monitoring lung function during mechanical ventilation, if findings are confirmed in other clinical contexts.

Validating the inspired sinewave technique to measure the volume of the ‘baby lung’ in a porcine lung-injury model

BackgroundBedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model. MethodsAnaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELVIST) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELVSF6] and computed tomography (CT) [ELVCT]). Measured volumes were used to calculate changes in ELV (ΔELV) between PEEP levels for each method (ΔELVIST, ΔELVSF6, and ΔELVCT). ResultsThe coefficient of variation was <5% for repeated ELVIST measurements (n=13 pigs). There was a strong linear relationship between ELVIST and ELVSF6 in uninjured lungs (r2=0.97), and with both ELVSF6 and ELVCT in the ARDS model (r2=0.87 and 0.92, respectively). ELVIST had a mean bias of –12 to 13% (95% limits=±17 – 25%) compared with ELVSF6 and ELVCT. ΔELVIST was concordant with ΔELVSF6 and ΔELVCT in 98–100% of measurements, and had a mean bias of –73 to –77 ml (95% limits=±128 – 186 ml) compared with ΔELVSF6 and –1 ml (95% limits ±333 ml) compared with ΔELVCT. ConclusionsIST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.

Cardiorespiratory Alterations Following Acute Normovolemic Hemodilution in a Pediatric and an Adult Porcine Model: A Prospective Interventional Study.

Acute normovolemic hemodilution (ANH) is considered as a blood-sparing intervention during the perioperative management. We aimed at comparing the cardiopulmonary consequences of ANH between adult pigs and weaned piglets to establish the effects of lowering hematocrit in these age groups, and thereby testing the hypothesis that difference in the age-related physiological behavior will be reflected in the cardiorespiratory changes following ANH. ANH was achieved in anesthetized, mechanically ventilated adult minipigs and 5-week-old weaned piglets by stepwise blood withdrawal (10 mL/kg) with crystalloids replacement. Cardiorespiratory assessments consisted of measuring airway resistance, respiratory tissue elastance, effective lung volume, extravascular lung water, mean arterial pressure, pulmonary blood flow, and cardiac output. Respiratory and hemodynamic measurements were made at control conditions and following each ANH condition obtained with 5 to 7 steps. ANH induced immediate and progressive increases in airway resistance and tissue elastance in both groups, with more pronounced worsening in adults despite the similar decreases in hematocrit. The increases in extravascular lung water were significantly greater in the adult population with the differences in mean (DM) of 25.1% (95% confidence interval [CI], 5.3%-44.9%). Progressive ANH led to significant decreases in the DM of pulmonary blood flow (45.3%; 95% CI, 19.8%-70.8%) and mean arterial pressure (36.3%; 95% CI, 18.7%-53.9%) only in adults, whereas cardiac output increased significantly only in the piglets (DM, 51.6; 95% CI, 14.2%-89.0%). While ANH led to mild detrimental cardiorespiratory changes in weaned piglets, gradual developments of bronchoconstriction, lung tissue extravasation and stiffening, and deteriorations in systemic and pulmonary hemodynamics were observed in adults. ANH may exert age-dependent cardiorespiratory effect.

Evaluation of the influence of decellularization on the changes in biomechanical properties of primate lungs.

The effect of decellularization on the biomechanical properties of macaque lungs was studied. The quality of the biological scaffold was additionally assessed by morphological methods, and the contents of extracellular matrix (ECM) fibers were determined both qualitatively and quantitatively. Histological analysis revealed no damage of structural integrity of ECM components, but the scaffold elasticity significantly decreased, which was confirmed by the changes in the hysteresis loop without a concomitant decrease in peak loads, with the mechanical strength of the samples being retained. These changes require taking additional measures to prevent a decrease in the effective lung volume.

Capnodynamic assessment of effective lung volume during cardiac output manipulations in a porcine model.

A capnodynamic calculation of effective pulmonary blood flow includes a lung volume factor (ELV) that has to be estimated to solve the mathematical equation. In previous studies ELV correlated to reference methods for functional residual capacity (FRC). The aim was to evaluate the stability of ELV during significant manipulations of cardiac output (CO) and assess the agreement for absolute values and trending capacity during PEEP changes at different lung conditions. Ten pigs were included. Alterations of alveolar carbon dioxide were induced by cyclic reoccurring inspiratory holds. The Sulphur hexafluoride technique for FRC measurements was used as reference. Cardiac output was altered by preload reduction and inotropic stimulation at PEEP 5 and 12cmH2O both in normal lung conditions and after repeated lung lavages. ELV at baseline PEEP 5 was [mean (SD)], 810 (163)mL and decreased to 400 (42)mL after lavage. ELV was not significantly affected by CO alterations within the same PEEP level. In relation to FRC the overall bias (limits of agreement) was -35 (-271 to 201)mL, and percentage error 36%. A small difference between ELV and FRC was seen at PEEP 5cmH2O before lavage and at PEEP 12cmH2O after lavage. ELV trending capability between PEEP steps, showed a concordance rate of 100%. ELV was closely related to FRC and remained stable during significant changes in CO. The trending capability was excellent both before and after surfactant depletion.

Cardiorespiratory effects of recruitment maneuvers and positive end expiratory pressure in an experimental context of acute lung injury and pulmonary hypertension.

BackgroundRecruitment maneuvers (RM) and positive end expiratory pressure (PEEP) are the cornerstone of the open lung strategy during ventilation, particularly during acute lung injury (ALI). However, these interventions may impact the pulmonary circulation and induce hemodynamic and respiratory effects, which in turn may be critical in case of pulmonary hypertension (PHT). We aimed to establish how ALI and PHT influence the cardiorespiratory effects of RM and PEEP.MethodsRabbits control or with monocrotaline-induced PHT were used. Forced oscillatory airway and tissue mechanics, effective lung volume (ELV), systemic and right ventricular hemodynamics and blood gas were assessed before and after RM, during baseline and following surfactant depletion by whole lung lavage.ResultsRM was more efficient in improving respiratory elastance and ELV in the surfactant-depleted lungs when PHT was concomitantly present. Moreover, the adverse changes in respiratory mechanics and ELV following ALI were lessened in the animals suffering from PHT.ConclusionsDuring ventilation with open lung strategy, the role of PHT in conferring protection from the adverse respiratory consequences of ALI was evidenced. This finding advocates the safety of RM and PEEP in improving elastance and advancing lung reopening in the simultaneous presence of PHT and ALI.

Lung volume assessments in normal and surfactant depleted lungs: agreement between bedside techniques and CT imaging.

BackgroundBedside assessment of lung volume in clinical practice is crucial to adapt ventilation strategy. We compared bedside measures of lung volume by helium multiple-breath washout technique (EELVMBW,He) and effective lung volume based on capnodynamics (ELV) to those assessed from spiral chest CT scans (EELVCT) under different PEEP levels in control and surfactant-depleted lungs.MethodsLung volume was assessed in anaesthetized mechanically ventilated rabbits successively by measuring i) ELV by analyzing CO2 elimination traces during the application of periods of 5 consecutive alterations in inspiratory/expiratory ratio (1:2 to 1.5:1), ii) measuring EELVMBW,He by using helium as a tracer gas, and iii) EELVCT from CT scan images by computing the normalized lung density. All measurements were performed at PEEP of 0, 3 and 9 cmH2O in random order under control condition and following surfactant depletion by whole lung lavage.ResultsVariables obtained with all techniques followed sensitively the lung volume changes with PEEP. Excellent correlation and close agreement was observed between EELVMBW,He and EELVCT (r = 0.93, p < 0.0001). ELV overestimated EELVMBW,He and EELVCT in normal lungs, whereas this difference was not evidenced following surfactant depletion. These findings resulted in somewhat diminished but still significant correlations between ELV and EELVCT (r = 0.58, p < 0.001) or EELVMBW,He (0.76, p < 0.001) and moderate agreements.ConclusionsLung volume assessed with bedside techniques allow the monitoring of the changes in the lung aeration with PEEP both in normal lungs and in a model of acute lung injury. Under stable pulmonary haemodynamic condition, ELV allows continuous lung volume monitoring, whereas EELVMBW,He offers a more accurate estimation, but intermittently.

A novel carbon-dioxide based method for continuous measurement of effective lung volume in mechanical ventilation

A novel carbon-dioxide based method for continuous measurement of effective lung volume in mechanical ventilation

Capnodynamic Estimation of Lung Volumes: Teething Issues of a Potential Early Warning System

I would like to commend Albu et al.1 for their well-designed study evaluating the correlation between effective lung volume (ELV) and end-expiratory lung volume (EELV) in healthy and surfactant-depleted rabbit lungs with various levels of positive end-expiratory pressure.The results have indicated that the correlation between ELV and EELV improves with higher positive end-expiratory pressure, and is best in surfactant-depleted lungs, with the ELV being an overestimate of ELV in healthy lungs by as much as 150 ± 13% at 0 cm H2O. The authors have hypothesized that this is due to carbon dioxide being an intrinsic gas and the ELV/EELV difference is affected by changes in pulmonary capillary volume and ventilation–perfusion mismatch. There are other methodological factors that may affect this correlation, but no method is able to satisfactorily correct for those, and any attempt may potentially require a more complicated set-up than the elegant one Albu et al. propose.2However, for neonatal patients (whom a rabbit model is supposed to simulate), lung injury is on a continuum from healthy to surfactant-depleted. Generally a surfactant-depleted state is avoided by the following two interventions—antenatal glucocorticoid therapy and the instillation of exogenous surfactant into the neonatal lung. Therefore, most neonates requiring ventilator support for perioperative or critical care will be somewhere in the middle—having neither healthy nor surfactant-depleted lungs. The lack of demonstrable reliability of ELV in this gray zone undermines the utility of its absolute value as an estimation of the EELV in this setting.The authors imply that trending the change in ELV would be more useful than the absolute value. I would be concerned however that the percentage change in ELV and EELV postlavage differs significantly between different positive end-expiratory pressure values. The difference is greatest at 0 and 9 cm H2O, but this mitigates the issue somewhat because an optimal and protective lung ventilation strategy in neonates is unlikely to be at these extremes. Nevertheless, it may be difficult to estimate the degree of change in actual lung volumes after a decrease in ELV, and may lead a provider to utilize an overly aggressive recruitment strategy that could potentially result in barotrauma.It should be noted that the sensitivity of ELV to changes to effectiveness in ventilation and as a rough measure of physiological dead space could be useful when paired with other indices that together may indicate lung dysfunction.3 For example, a decreasing ELV with increasing airway resistance and pressures can serve as a preliminary warning before an appreciable increase in ETco2 or a suboptimal arterial blood gas result. At present, such dysfunction is only detected after an arterial blood gas result, and there is no simple, continuous and noninvasive method to detect lung atelectasis and institute recruitment measures early.I believe the greatest value of this study is that the method they describe can be easily implemented as part of an early warning protocol for recruitment manoeuvres, and then a gauge of the effectiveness of the intervention.3 Further studies and modification of the algorithm should be done to improve the accuracy of ELV as an estimate of EELV in various lung states and ventilator settings. This may then allow its potential to be realized as a simple yet powerful tool currently absent from the arsenal available to modern anesthesiologists and intensivists.The author declares no competing interests.

Comparison of Static End-expiratory and Effective Lung Volumes for Gas Exchange in Healthy and Surfactant-depleted Lungs

Effective lung volume (ELV) for gas exchange is a new measure that could be used as a real-time guide during controlled mechanical ventilation. The authors established the relationships of ELV to static end-expiratory lung volume (EELV) with varying levels of positive end-expiratory pressure (PEEP) in healthy and surfactant-depleted rabbit lungs. Nine rabbits were anesthetized and ventilated with a modified volume-controlled mode where periods of five consecutive alterations in inspiratory/expiratory ratio (1:2-1.5:1) were imposed to measure ELV from the corresponding carbon dioxide elimination traces. EELV and the lung clearance index were concomitantly determined by helium wash-out technique. Airway and tissue mechanics were assessed by using low-frequency forced oscillations. Measurements were collected at PEEP 0, 3, 6, and 9 cm H2O levels under control condition and after surfactant depletion by whole-lung lavage. ELV was greater than EELV at all PEEP levels before lavage, whereas there was no evidence for a difference in the lung volume indices after surfactant depletion at PEEP 6 or 9 cm H2O. Increasing PEEP level caused significant parallel increases in both ELV and EELV levels, decreases in ventilation heterogeneity, and improvement in airway and tissue mechanics under control condition and after surfactant depletion. ELV and EELV exhibited strong and statistically significant correlations before (r=0.84) and after lavage (r=0.87). The parallel changes in ELV and EELV with PEEP in healthy and surfactant-depleted lungs support the clinical value of ELV measurement as a bedside tool to estimate dynamic changes in EELV in children and infants.

Respiratory and haemodynamic changes during decremental open lung positive end-expiratory pressure titration in patients with acute respiratory distress syndrome

IntroductionTo investigate haemodynamic and respiratory changes during lung recruitment and decremental positive end-expiratory pressure (PEEP) titration for open lung ventilation in patients with acute respiratory distress syndrome (ARDS) a prospective, clinical trial was performed involving 12 adult patients with ARDS treated in the surgical intensive care unit in a university hospital.MethodsA software programme (Open Lung Tool™) incorporated into a standard ventilator controlled the recruitment (pressure-controlled ventilation with fixed PEEP at 20 cmH2O and increased driving pressures at 20, 25 and 30 cmH2O for two minutes each) and PEEP titration (PEEP lowered by 2 cmH2O every two minutes, with tidal volume set at 6 ml/kg). The open lung PEEP (OL-PEEP) was defined as the PEEP level yielding maximum dynamic respiratory compliance plus 2 cmH2O. Gas exchange, respiratory mechanics and central haemodynamics using the Pulse Contour Cardiac Output Monitor (PiCCO™), as well as transoesophageal echocardiography were measured at the following steps: at baseline (T0); during the final recruitment step with PEEP at 20 cmH2O and driving pressure at 30 cmH2O, (T20/30); at OL-PEEP, following another recruitment manoeuvre (TOLP).ResultsThe ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) increased from T0 to TOLP (120 ± 59 versus 146 ± 64 mmHg, P < 0.005), as did dynamic respiratory compliance (23 ± 5 versus 27 ± 6 ml/cmH2O, P < 0.005). At constant PEEP (14 ± 3 cmH2O) and tidal volumes, peak inspiratory pressure decreased (32 ± 3 versus 29 ± 3 cmH2O, P < 0.005), although partial pressure of arterial carbon dioxide (PaCO2) was unchanged (58 ± 22 versus 53 ± 18 mmHg). No significant decrease in mean arterial pressure, stroke volume or cardiac output occurred during the recruitment (T20/30). However, left ventricular end-diastolic area decreased at T20/30 due to a decrease in the left ventricular end-diastolic septal-lateral diameter, while right ventricular end-diastolic area increased. Right ventricular function, estimated by the right ventricular Tei-index, deteriorated during the recruitment manoeuvre, but improved at TOLP.ConclusionsA standardised open lung strategy increased oxygenation and improved respiratory system compliance. No major haemodynamic compromise was observed, although the increase in right ventricular Tei-index and right ventricular end-diastolic area and the decrease in left ventricular end-diastolic septal-lateral diameter during the recruitment suggested an increased right ventricular stress and strain. Right ventricular function was significantly improved at TOLP compared with T0, although left ventricular function was unchanged, indicating effective lung volume optimisation.

Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates

To define clinical and dosimetric parameters correlated with the risk of clinically relevant radiation pneumonitis (RP) after thoracic radiotherapy. Records of consecutive patients treated with definitive thoracic radiotherapy were retrospectively reviewed for the incidence of RP of Grade 2 or greater by the Common Toxicity Criteria. Dose-volume histograms using total lung volume (TL) and TL minus gross tumor volume (TL-G) were created with and without heterogeneity corrections. Mean lung dose (MLD), effective lung volume (V(eff)), and percentage of TL or TL-G receiving greater than or equal to 10, 13, 15, 20, and 30 Gy (V10-V30, respectively) were analyzed by logistic regression. Receiver operating characteristic (ROC) curves were generated to estimate RP predictive values. Twelve cases of RP were identified in 92 eligible patients. Mean lung dose, V10, V13, V15, V20, and V(eff) were significantly correlated to RP. Combinations of MLD, V(eff), V20, and V30 lost significance using TL-G and heterogeneity corrections. Receiver operating characteristic analysis determined V10 and V13 as the best predictors of RP risk, with a decrease in predictive value above those volumes. Intrathoracic radiotherapy should be planned with caution when using radiotherapy techniques delivering doses of 10 to 15 Gy to large lung volumes.

Fibroblast Growth Factor-1 Therapy for Advanced Emphysema???A New Tissue Engineering Approach for Achieving Lung Volume Reduction

Background Remodeling of damaged, hyperinflated lung tissue using injectable hydrogels has produced lung volume reduction in experimental emphysema, and initial results in patients have confirmed safety, and demonstrated physiologic and clinical benefit. By characterizing the underlying biology of this response in experimental models, a novel, efficient growth factor-based method for achieving lung volume reduction has been developed for testing. Methods Experimental heterogeneous emphysema was generated in healthy sheep using injected intrabronchial elastase. After model maturation, animals were treated at target sites with fibrin hydrogels containing fibroblast growth factor-1 (FGF-1) complexed with chondriotin sulfate. Clinical responses, qualitative computed tomography assessment, lung volume measurements, tissue histopathology, and tissue immunohistochemistry were assessed 4 weeks posttreatment and compared with control animals that received hydrogel without FGF-1. Results Intrabronchial instillation of hydrogels supplemented with FGF-1 was well tolerated. Transient fever was observed in 2 of 4 treatment animals. Treatment at 8 sites was associated with a mean reduction in total lung capacity of 12% without evidence of short-term local or systemic toxicity. The treatment produced contracted, organized scar tissue limited to target sites after only 4 weeks. Immunohistochemistry revealed α-smooth muscle actin, vimentin-positive cells at these sites, consistent with myofibroblasts, without accompanying epithelial cell hyperplasia. Conclusions FGF-1-chondroitin sulfate complexes delivered to target sites in the lung using a biodegradable hydrogel produce rapid, effective, and safe lung volume reduction in experimental emphysema.