Imaging the acute respiratory distress syndrome: past, present and future.

In patients with the acute respiratory distress syndrome (ARDS), lung imaging is a fundamental tool in the study of the morphological and mechanistic features of the lungs. Chest computed tomography studies led to major advances in the understanding of ARDS physiology. They allowed the in vivo study of the syndrome's lung features in relation with its impact on respiratory physiology and physiology, but also explored the lungs' response to mechanical ventilation, be it alveolar recruitment or ventilator-induced lung injuries. Coupled with positron emission tomography, morphological findings were put in relation with ventilation, perfusion or acute lung inflammation. Lung imaging has always been central in the care of patients with ARDS, with modern point-of-care tools such as electrical impedance tomography or lung ultrasounds guiding clinical reasoning beyond macro-respiratory mechanics. Finally, artificial intelligence and machine learning now assist imaging post-processing software, which allows real-time analysis of quantitative parameters that describe the syndrome's complexity. This narrative review aims to draw a didactic and comprehensive picture of how modern imaging techniques improved our understanding of the syndrome, and have the potential to help the clinician guide ventilatory treatment and refine patient prognostication.

Lung Ultrasound and Electrical Impedance Tomography During Ventilator-Induced Lung Injury.

OBJECTIVES: Lung damage during mechanical ventilation involves lung volume and alveolar water content, and lung ultrasound (LUS) and electrical impedance tomography changes are related to these variables. We investigated whether these techniques may detect any signal modification during the development of ventilator-induced lung injury (VILI). DESIGN: Experimental animal study. SETTING: Experimental Department of a University Hospital. SUBJECTS: Forty-two female pigs (24.2 ± 2.0 kg). INTERVENTIONS: The animals were randomized into three groups (n = 14): high tidal volume (TV) (mean TV, 803.0 ± 121.7 mL), high respiratory rate (RR) (mean RR, 40.3 ± 1.1 beats/min), and high positive-end-expiratory pressure (PEEP) (mean PEEP, 24.0 ± 1.1 cm H2O). The study lasted 48 hours. At baseline and at 30 minutes, and subsequently every 6 hours, we recorded extravascular lung water, end-expiratory lung volume, lung strain, respiratory mechanics, hemodynamics, and gas exchange. At the same time-point, end-expiratory impedance was recorded relatively to the baseline. LUS was assessed every 12 hours in 12 fields, each scoring from 0 (presence of A-lines) to 3 (consolidation). MEASUREMENTS AND MAIN RESULTS: In a multiple regression model, the ratio between extravascular lung water and end-expiratory lung volume was significantly associated with the LUS total score (p < 0.002; adjusted R2, 0.21). The variables independently associated with the end-expiratory difference in lung impedance were lung strain (p < 0.001; adjusted R2, 0.18) and extravascular lung water (p < 0.001; adjusted R2, 0.11). CONCLUSIONS: Data suggest as follows. First, what determines the LUS score is the ratio between water and gas and not water alone. Therefore, caution is needed when an improvement of LUS score follows a variation of the lung gas content, as after a PEEP increase. Second, what determines the end-expiratory difference in lung impedance is the strain level that may disrupt the intercellular junction, therefore altering lung impedance. In addition, the increase in extravascular lung water during VILI development contributed to the observed decrease in impedance.

Effects of the Prone Position on Regional Neutrophilic Lung Inflammation According to 18F-FDG Pet in an Experimental Ventilator-Induced Lung Injury Model.

ABSTRACT: Ventilator-induced lung injury (VILI) can be life-threatening and it is important to prevent the development of VILI. It remains unclear whether the prone position affects neutrophilic inflammation in the lung regions in vivo, which plays a crucial role in the pathogenesis of VILI. This study aimed to assess the relationship between the use of the prone position and the development of VILI-associated regional neutrophilic lung inflammation. Regional neutrophilic lung inflammation and lung aeration during low tidal volume mechanical ventilation were assessed using in vivo 2-deoxy-2-[(18)F] fluoro-D-glucose (18F-FDG) positron emission tomography and computed tomography in acutely experimentally injured rabbit lungs (lung injury induced by lung lavage and excessive ventilation). Direct comparisons were made among three groups: control, supine, and prone positions. After approximately 7 h, tissue-normalized 18F-FDG uptake differed significantly between the supine and prone positions (SUP: 0.038 ±â€Š0.014 vs. PP: 0.029 ±â€Š0.008, P = 0.038), especially in the ventral region (SUP: 0.052 ±â€Š0.013 vs. PP: 0.026 ±â€Š0.007, P = 0.003). The use of the prone position reduced lung inhomogeneities, which was demonstrated by the correction of the disproportionate rate of voxel gas over the given lung region. The progression of neutrophilic inflammation was affected by the interaction between the total strain (for aeration) and the inhomogeneity. The prone position is effective in slowing down the progression of VILI-associated neutrophilic inflammation. Under low-tidal-volume ventilation, the main drivers of its effect may be homogenization of lung tissue and that of mechanical forces.

Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects.

BACKGROUND: We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. METHODS: Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. RESULTS: At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. CONCLUSIONS: In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Imaging atelectrauma in Ventilator-Induced Lung Injury using 4D X-ray microscopy.

Mechanical ventilation can damage the lungs, a condition called Ventilator-Induced Lung Injury (VILI). However, the mechanisms leading to VILI at the microscopic scale remain poorly understood. Here we investigated the within-tidal dynamics of cyclic recruitment/derecruitment (R/D) using synchrotron radiation phase-contrast imaging (PCI), and the relation between R/D and cell infiltration, in a model of Acute Respiratory Distress Syndrome in 6 anaesthetized and mechanically ventilated New-Zealand White rabbits. Dynamic PCI was performed at 22.6 µm voxel size, under protective mechanical ventilation [tidal volume: 6 ml/kg; positive end-expiratory pressure (PEEP): 5 cmH2O]. Videos and quantitative maps of within-tidal R/D showed that injury propagated outwards from non-aerated regions towards adjacent regions where cyclic R/D was present. R/D of peripheral airspaces was both pressure and time-dependent, occurring throughout the respiratory cycle with significant scatter of opening/closing pressures. There was a significant association between R/D and regional lung cellular infiltration (p = 0.04) suggesting that tidal R/D of the lung parenchyma may contribute to regional lung inflammation or capillary-alveolar barrier dysfunction and to the progression of lung injury. PEEP may not fully mitigate this phenomenon even at high levels. Ventilation strategies utilizing the time-dependence of R/D may be helpful in reducing R/D and associated injury.

Monitoring lung impedance changes during long-term ventilator-induced lung injury ventilation using electrical impedance tomography.

OBJECTIVE: The target of this methodological evaluation was the feasibility of long-term monitoring of changes in lung conditions by time-difference electrical impedance tomography (tdEIT). In contrast to ventilation monitoring by tdEIT, the monitoring of end-expiratory (EELIC) or end-inspiratory (EILIC) lung impedance change always requires a reference measurement. APPROACH: To determine the stability of the used Pulmovista 500® EIT system, as a prerequisite it was initially secured on a resistive phantom for 50 h. By comparing the slopes of EELIC for the whole lung area up to 48 h from 36 pigs ventilated at six positive end-expiratory pressure (PEEP) levels from 0 to 18 cmH2O we found a good agreement (range of r 2 = 0.93-1.0) between absolute EIT (aEIT) and tdEIT values. This justified the usage of tdEIT with its superior local resolution compared to aEIT for long-term determination of EELIC. MAIN RESULTS: The EELIC was between -0.07 Ωm day-1 at PEEP 4 and -1.04 Ωm day-1 at PEEP 18 cmH2O. The complex local time pattern for EELIC was roughly quantified by the new parameter, centre of end-expiratory change (CoEEC), in equivalence to the established centre of ventilation (CoV). The ventrally located mean of the CoV was fairly constant in the range of 42%-46% of thorax diameter; however, on the contrary, the CoEEC shifted from about 40% to about 75% in the dorsal direction for PEEP levels of 14 and 18 cmH2O. SIGNIFICANCE: The observed shifts started earlier for higher PEEP levels. Changes of EELI could be precisely monitored over a period of 48 h by tdEIT on pigs.

A Window on the Lung: Molecular Imaging as a Tool to Dissect Pathophysiologic Mechanisms of Acute Lung Disease.

In recent years, imaging has given a fundamental contribution to our understanding of the pathophysiology of acute lung diseases. Several methods have been developed based on computed tomography (CT), positron emission tomography (PET), and magnetic resonance (MR) imaging that allow regional, in vivo measurement of variables such as lung strain, alveolar size, metabolic activity of inflammatory cells, ventilation, and perfusion. Because several of these methods are noninvasive, they can be successfully translated from animal models to patients. The aim of this paper is to review the advances in knowledge that have been accrued with these imaging modalities on the pathophysiology of acute respiratory distress syndrome (ARDS), ventilator-induced lung injury (VILI), asthma and chronic obstructive pulmonary disease (COPD).

Lung protective ventilation during pulmonary resection in children: a prospective, single-centre, randomised controlled trial.

BACKGROUND: Perioperative ventilatory strategies for lung protection in children are underexplored. This study evaluated the effects of lung protective ventilation (LPV) on postoperative clinical outcomes in children requiring one-lung ventilation (OLV) for pulmonary resection. METHODS: Children age ≤5 yr scheduled for video-assisted thoracoscopic lung lobectomy or segmentectomy were randomly assigned to LPV or control ventilation. For LPV, tidal volume (VT) was 6 ml kg-1 during two-lung ventilation (TLV(VT)), 4 ml kg-1 during OLV, with 6 cm H2O PEEP maintained throughout. In the control group, TLV(VT) was 10 ml kg-1, 8 ml kg-1 during OLV, but without PEEP. The primary outcome was the incidence of pulmonary complications within 72 h after operation. Secondary outcomes included intraoperative desaturation, arterial oxygen partial pressure/inspiratory fraction of oxygen (P/F) ratio >40 kPa, and development of consolidation and B-lines (assessed by lung ultrasound at the end of surgery, by an investigator masked to group allocation). Odds ratio (OR) with 95% confidence intervals are reported. RESULTS: Overall, 19/110 (17.3%) children sustained pulmonary complications after surgery. LPV reduced pulmonary complications (5/55; 9.1%), compared with 14/55 (25.5%) children sustaining complications in the control group (OR=0.29 [0.10-0.88]; P=0.02). Masked ultrasound assessment showed less consolidation, and fewer B-lines, after LPV (P<0.001). Intraoperative desaturation was more common in control mode (eight/55; 14.5%), compared with 1/55 (1.8%) after LPV (OR=9.2 [1.1-76]; P=0.015). LPV maintained (P/F) ratio >40 more frequently (53/55; 96.4%) than control-mode (45/55; 81.8%) ventilation (OR=5.9 [1.2-28.3%]; P<0.01). CONCLUSIONS: Lung protective ventilation decreased postoperative pulmonary complications compared with conventional ventilation in children requiring one-lung ventilation for pulmonary resection. CLINICAL TRIAL REGISTRATION: NCT02680925.

The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation.

The aim of this study was to assess the association between regional tidal volume (Vt), regional functional residual capacity (FRC), and the expression of genes linked with ventilator-induced lung injury. Two groups of BALB/c mice (n = 8 per group) were ventilated for 2 hours using a protective or injurious ventilation strategy, with free-breathing mice used as control animals. Regional Vt and FRC of the ventilated mice was determined by analysis of high-resolution four-dimensional computed tomographic images taken at baseline and after 2 hours of ventilation and corrected for the volume of the region (i.e., specific [s]Vt and specific [s]FRC). RNA concentrations of 21 genes in 10 different lung regions were quantified using a quantitative PCR array. sFRC at baseline varied regionally, independent of ventilation strategy, whereas sVt varied regionally depending on ventilation strategy. The expression of IL-6 (P = 0.04), Ccl2 (P < 0.01), and Ang-2 (P < 0.05) was associated with sVt but not sFRC. The expression of seven other genes varied regionally (IL-1ß and RAGE [receptor for advanced glycation end products]) or depended on ventilation strategy (Nfe2l2 [nuclear factor erythroid-derived 2 factor 2], c-fos, and Wnt1) or both (TNF-α and Cxcl2), but it was not associated with regional sFRC or sVt. These observations suggest that regional inflammatory responses to mechanical ventilation are driven primarily by tidal stretch.

T1 , T1 contrast, and Ernst-angle images of four rat-lung pathologies.

PURPOSE: To initiate the archive of relaxation-weighted images that may help discriminate between pulmonary pathologies relevant to acute respiratory distress syndrome. MRI has the ability to distinguish pathologies by providing a variety of different contrast mechanisms. Lungs have historically been difficult to image with MRI but image quality is sufficient to begin cataloging the appearance of pathologies in T1 - and T2 -weighted images. This study documents T1 and the use of T1 contrast with four experimental rat lung pathologies. METHODS: Inversion-recovery and spoiled steady state images were made at 1.89 T to measure T1 and document contrast in rats with atelectasis, lipopolysaccharide-induced inflammation, ventilator-induced lung injury (VILI), and injury from saline lavage. Higher-resolution Ernst-angle images were made to see patterns of lung infiltrations. RESULTS: T1 -weighted images showed minimal contrast between pathologies, similar to T1 -weighted images of other soft tissues. Images taken shortly after magnetization inversion and displayed with inverted contrast highlight lung pathologies. Ernst-angle images distinguish the effects of T1 relaxation and spin density and display distinctive patterns. T1 for pathologies were: atelectasis, 1.25 ± 0.046 s; inflammation from instillation of lipopolysaccharide, 1.24 ± 0.015 s; VILI, 1.55 ± 0.064 s (p = 0.0022 vs. normal lung); and injury from saline lavage, 1.90±0.080 s (p = 0.0022 vs. normal lung; p = 0.0079 vs. VILI). T1 of normal lung and erector spinae muscle were 1.25 ± 0.028 s and 1.02 ± 0.027 s, respectively (p = 0.0022). CONCLUSIONS: Traditional T1 -weighting is subtle. However, images made with inverted magnetization and inverted contrast highlight the pathologies and Ernst-angle images aid in distinguishing pathologies.

Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

OBJECTIVE: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. DESIGN: Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. SETTING: University animal research laboratory. SUBJECTS: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. MEASUREMENTS AND MAIN RESULTS: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals. CONCLUSION: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

Mechanical ventilation in acute respiratory distress syndrome: The open lung revisited.

Acute respiratory distress syndrome (ARDS) is still related to high mortality and morbidity rates. Most patients with ARDS will require ventilatory support. This treatment has a direct impact upon patient outcome and is associated to major side effects. In this regard, ventilator-associated lung injury (VALI) is the main concern when this technique is used. The ultimate mechanisms of VALI and its management are under constant evolution. The present review describes the classical mechanisms of VALI and how they have evolved with recent findings from physiopathological and clinical studies, with the aim of analyzing the clinical implications derived from them. Lastly, a series of knowledge-based recommendations are proposed that can be helpful for the ventilator assisted management of ARDS at the patient bedside.

Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury.

Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 ± 1.6 h) than it was detected by altered lung mechanics (9.5 ± 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration (P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI.

Effect of Electrode Belt and Body Positions on Regional Pulmonary Ventilation- and Perfusion-Related Impedance Changes Measured by Electric Impedance Tomography.

Ventilator-induced or ventilator-associated lung injury (VILI/VALI) is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT) can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation-related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion.

Detection of optimal PEEP for equal distribution of tidal volume by volumetric capnography and electrical impedance tomography during decreasing levels of PEEP in post cardiac-surgery patients.

BACKGROUND: Homogeneous ventilation is important for prevention of ventilator-induced lung injury. Electrical impedance tomography (EIT) has been used to identify optimal PEEP by detection of homogenous ventilation in non-dependent and dependent lung regions. We aimed to compare the ability of volumetric capnography and EIT in detecting homogenous ventilation between these lung regions. METHODS: Fifteen mechanically-ventilated patients after cardiac surgery were studied. Ventilator settings were adjusted to volume-controlled mode with a fixed tidal volume (Vt) of 6-8 ml kg(-1) predicted body weight. Different PEEP levels were applied (14 to 0 cm H2O, in steps of 2 cm H2O) and blood gases, Vcap and EIT were measured. RESULTS: Tidal impedance variation of the non-dependent region was highest at 6 cm H2O PEEP, and decreased significantly at 14 cm H2O PEEP indicating decrease in the fraction of Vt in this region. At 12 cm H2O PEEP, homogenous ventilation was seen between both lung regions. Bohr and Enghoff dead space calculations decreased from a PEEP of 10 cm H2O. Alveolar dead space divided by alveolar Vt decreased at PEEP levels ≤6 cm H2O. The normalized slope of phase III significantly changed at PEEP levels ≤4 cm H2O. Airway dead space was higher at higher PEEP levels and decreased at the lower PEEP levels. CONCLUSIONS: In postoperative cardiac patients, calculated dead space agreed well with EIT to detect the optimal PEEP for an equal distribution of inspired volume, amongst non-dependent and dependent lung regions. Airway dead space reduces at decreasing PEEP levels.

Visualizing the Propagation of Acute Lung Injury.

BACKGROUND: Mechanical ventilation worsens acute respiratory distress syndrome, but this secondary "ventilator-associated" injury is variable and difficult to predict. The authors aimed to visualize the propagation of such ventilator-induced injury, in the presence (and absence) of a primary underlying lung injury, and to determine the predictors of propagation. METHODS: Anesthetized rats (n = 20) received acid aspiration (hydrochloric acid) followed by ventilation with moderate tidal volume (V(T)). In animals surviving ventilation for at least 2 h, propagation of injury was quantified by using serial computed tomography. Baseline lung status was assessed by oxygenation, lung weight, and lung strain (V(T)/expiratory lung volume). Separate groups of rats without hydrochloric acid aspiration were ventilated with large (n = 10) or moderate (n = 6) V(T). RESULTS: In 15 rats surviving longer than 2 h, computed tomography opacities spread outward from the initial site of injury. Propagation was associated with higher baseline strain (propagation vs. no propagation [mean ± SD]: 1.52 ± 0.13 vs. 1.16 ± 0.20, P < 0.01) but similar oxygenation and lung weight. Propagation did not occur where baseline strain was less than 1.29. In healthy animals, large V(T) caused injury that was propagated inward from the lung periphery; in the absence of preexisting injury, propagation did not occur where strain was less than 2.0. CONCLUSIONS: Compared with healthy lungs, underlying injury causes propagation to occur at a lower strain threshold and it originates at the site of injury; this suggests that tissue around the primary lesion is more sensitive. Understanding how injury is propagated may ultimately facilitate a more individualized monitoring or management.

Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth.

Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.