scholarly journals A damaged-informed lung model for ventilator waveforms

2020 ◽  
Author(s):  
Deepak. K. Agrawal ◽  
Bradford J. Smith ◽  
Peter D. Sottile ◽  
David J. Albers
Keyword(s):  
Lung Injury ◽  
Diffuse Alveolar Damage ◽  
Lung Model ◽  
Lung Damage ◽  
General Strategy ◽  
Waveform Data ◽  
Pulmonary Physiology ◽  
Lung Physiology ◽  
Complex Models ◽  
Ventilator Settings

AbstractThe acute respiratory distress syndrome (ARDS) is characterized by the acute development of diffuse alveolar damage (DAD) resulting in increased vascular permeability and decreased alveolar gas exchange. Mechanical ventilation is a potentially lifesaving intervention to improve oxygen exchange but has the potential to cause ventilator-induced lung injury (VILI). A general strategy to reduce VILI is to use low tidal volume and low-pressure ventilation, but optimal ventilator settings for an individual patient are difficult for the bedside physician to determine and mortality from ARDS remains unacceptably high. Motivated by the need to minimize VILI, scientists have developed models of varying complexity to understand diseased pulmonary physiology. However, simple models often fail to capture real-world injury while complex models tend to not be estimable with clinical data, limiting the clinical utility of existing models. To address this gap, we present a physiologically anchored data-driven model to better model lung injury. Our approach relies on using clinically relevant features in the ventilator waveform data that contain information about pulmonary physiology, patients-ventilator interaction and ventilator settings. Our lung model can reproduce essential physiology and pathophysiology dynamics of differently damaged lungs for both controlled mouse model data and uncontrolled human ICU data. The estimated parameters values that are correlated with a known measure of lung physiology agree with the observed lung damage. In future endeavors, this model could be used to phenotype ventilator waveforms and serve as a basis for predicting the course of ARDS and improving patient care.

scholarly journals A Damaged-Informed Lung Ventilator Model for Ventilator Waveforms

2021 ◽  
Vol 12 ◽  
Author(s):  
Deepak K. Agrawal ◽  
Bradford J. Smith ◽  
Peter D. Sottile ◽  
David J. Albers
Keyword(s):  
Laboratory Mouse ◽  
Lung Compliance ◽  
Lung Model ◽  
Model Parameters ◽  
Waveform Data ◽  
Pulmonary Physiology ◽  
Lung Physiology ◽  
Baseline Evaluation ◽  
Complex Models ◽  
Lung Ventilator

Motivated by a desire to understand pulmonary physiology, scientists have developed physiological lung models of varying complexity. However, pathophysiology and interactions between human lungs and ventilators, e.g., ventilator-induced lung injury (VILI), present challenges for modeling efforts. This is because the real-world pressure and volume signals may be too complex for simple models to capture, and while complex models tend not to be estimable with clinical data, limiting clinical utility. To address this gap, in this manuscript we developed a new damaged-informed lung ventilator (DILV) model. This approach relies on mathematizing ventilator pressure and volume waveforms, including lung physiology, mechanical ventilation, and their interaction. The model begins with nominal waveforms and adds limited, clinically relevant, hypothesis-driven features to the waveform corresponding to pulmonary pathophysiology, patient-ventilator interaction, and ventilator settings. The DILV model parameters uniquely and reliably recapitulate these features while having enough flexibility to reproduce commonly observed variability in clinical (human) and laboratory (mouse) waveform data. We evaluate the proof-in-principle capabilities of our modeling approach by estimating 399 breaths collected for differently damaged lungs for tightly controlled measurements in mice and uncontrolled human intensive care unit data in the absence and presence of ventilator dyssynchrony. The cumulative value of mean squares error for the DILV model is, on average, ≈12 times less than the single compartment lung model for all the waveforms considered. Moreover, changes in the estimated parameters correctly correlate with known measures of lung physiology, including lung compliance as a baseline evaluation. Our long-term goal is to use the DILV model for clinical monitoring and research studies by providing high fidelity estimates of lung state and sources of VILI with an end goal of improving management of VILI and acute respiratory distress syndrome.

scholarly journals IL-4/IL-13 Remodeling Pathway of Covid-19 Lung Injury

2020 ◽  
Author(s):  
Caroline Busatta Vaz de Paula ◽  
Marina Luise Viola Azevedo ◽  
Seigo Nagashima ◽  
Ana Paula Camargo Martins ◽  
Mineia Alessandra Scaranello Malaquias ◽  
...  
Keyword(s):  
Lung Injury ◽  
Transforming Growth Factor Beta ◽  
Influenza A ◽  
Transforming Growth Factor ◽  
Diffuse Alveolar Damage ◽  
Tissue Expression ◽  
Lung Damage ◽  
Control Group ◽  
M2 Macrophages ◽  
Th17 Response

Abstract Background: The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification.Objective: To analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury.Methods: Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC).Results and conclusion: Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages was observed in the COVID-19 group when compared to both the H1N1 and the CONTROL groups. Different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-COV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. The understanding and management of the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping)

2019 ◽  
Author(s):  
Sanjay Mukhopadhyay ◽  
Mitra Mehrad ◽  
Pedro Dammert ◽  
Andrea V Arrossi ◽  
Rakesh Sarda ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Biopsy ◽  
Diffuse Alveolar Damage ◽  
Lung Damage ◽  
Cigarette Use ◽  
Lipoid Pneumonia ◽  
Lung Biopsies ◽  
Severe Lung

Abstract Objectives The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. Methods Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. Results The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. Conclusions The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.

scholarly journals Increased effort during partial ventilatory support is not associated with lung damage in experimental acute lung injury

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Dietrich Henzler ◽  
Alf Schmidt ◽  
Zhaolin Xu ◽  
Nada Ismaiel ◽  
Haibo Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pressure Support ◽  
Diffuse Alveolar Damage ◽  
Ventilatory Support ◽  
Lung Damage ◽  
Respiratory Effort ◽  
Sprague Dawley ◽  
Mechanical Pressure ◽  
Acid Aspiration

Abstract Background An on-going debate exists as to whether partial ventilatory support is lung protective in an acute phase of ARDS. So far, the effects of different respiratory efforts on the development of ventilator-associated lung injury (VALI) have been poorly understood. To test the hypothesis whether respiratory effort itself promotes VALI, acute lung injury (ALI) was induced in 48 Sprague Dawley rats by hydrochloric acid aspiration model. Hemodynamics, gas-exchange, and respiratory mechanics were measured after 4 h of ventilation in pressure control (PC), assist-control (AC), or pressure support with 100% (PS100), 60% (PS60), or 20% (PS20) of the driving pressure during PC. VALI was assessed by histological analysis and biological markers. Results ALI was characterized by a decrease in PaO2/FiO2 from 447 ± 75 to 235 ± 90 mmHg (p < 0.001) and dynamic respiratory compliance from 0.53 ± 0.2 to 0.28 ± 0.1 ml/cmH2O (p < 0.001). There were no differences in hemodynamics or respiratory function among groups at baseline or after 4 h of ventilation. The reduction of mechanical pressure support was associated with a compensatory increase in an inspiratory effort such that peak inspiratory transpulmonary pressures were equal in all groups. The diffuse alveolar damage score showed significant lung injury but was similar among groups. Pro- and anti-inflammatory proteins in the bronchial fluid were comparable among groups. Conclusions In experimental ALI in rodents, the respiratory effort was increased by reducing the pressure support during partial ventilatory support. In the presence of a constant peak inspiratory transpulmonary pressure, an increased respiratory effort was not associated with worsening ventilator-associated lung injury measured by histologic score and biologic markers.

Oxygen-dependent reperfusion injury in the isolated rat lung

1992 ◽  
Vol 72 (4) ◽  
pp. 1454-1460 ◽  
Author(s):  
R. G. Eckenhoff ◽  
C. Dodia ◽  
Z. Tan ◽  
A. B. Fisher
Keyword(s):  
Electron Microscopy ◽  
Lipid Peroxidation ◽  
Lactate Dehydrogenase ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Lung Model ◽  
Lung Damage ◽  
Rat Lung ◽  
Wet Weight

To further define the relationship between oxygen dependence of lung injury during ischemia and ischemia-reperfusion, we used the isolated, perfused, and ventilated rat lung model, so that oxygenation and perfusion could be separated. During ischemia, lungs were ventilated with various oxygen concentrations and then ventilated with 95% oxygen during the 60-min reperfusion period. Other lungs were ventilated with 0% oxygen (nitrogen) during ischemia, and the reperfusion phase oxygen concentration was varied. Tissue and perfusate lipid peroxidation products (thiobarbituric acid-reactive substances and conjugated dienes), dry-to-wet weight ratio, and lactate dehydrogenase were measured as indexes of lung damage. In addition, electron microscopy of some lungs was performed. Results demonstrate an oxygen dependence of lipid peroxidation in both the ischemic and reperfusion phases, but lipid peroxidation is severalfold greater in the reperfusion than in the ischemic phase. Products of lipid peroxidation closely correlate with indexes of lung injury (dry-to-wet weight ratio, lactate dehydrogenase, and electron microscopy).

scholarly journals A new experimental model of acid- and endotoxin-induced acute lung injury in rats

2016 ◽  
Vol 311 (2) ◽  
pp. L229-L237 ◽  
Author(s):  
F. Puig ◽  
R. Herrero ◽  
R. Guillamat-Prats ◽  
M. N. Gómez ◽  
J. Tijero ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Aspiration Pneumonia ◽  
Inflammatory Responses ◽  
Diffuse Alveolar Damage ◽  
Intratracheal Instillation ◽  
Lung Damage ◽  
Long Term Effects ◽  
Protein Permeability

The majority of the animal models of acute lung injury (ALI) are focused on the acute phase. This limits the studies of the mechanisms involved in later phases and the effects of long-term treatments. Thus the goal of this study was to develop an experimental ALI model of aspiration pneumonia, in which diffuse alveolar damage continues for 72 h. Rats were intratracheally instilled with one dose of HCl (0.1 mol/l) followed by another instillation of one dose of LPS (0, 10, 20, 30, or 40 μg/g body weight) 2 h later, which models aspiration of gastric contents that progresses to secondary lung injury from bacteria or bacterial products. The rats were euthanized at 24, 48, and 72 h after the last instillation. The results showed that HCl and LPS at all doses caused activation of inflammatory responses, increased protein permeability and apoptosis, and induced mild hypoxemia in rat lungs at 24 h postinstillation. However, this lung damage was present at 72 h only in rats receiving HCl and LPS at the doses of 30 and 40 μg/g body wt. Mortality (∼50%) occurred in the first 48 h and only in the rats treated with HCl and LPS at the highest dose (40 μg/g body wt). In conclusion, intratracheal instillation of HCl followed by LPS at the dose of 30 μg/g body wt results in severe diffuse alveolar damage that continues at least 72 h. This rat model of aspiration pneumonia-induced ALI will be useful for testing long-term effects of new therapeutic strategies in ALI.

scholarly journals IL-4/IL-13 Remodeling Pathway of Covid-19 Lung Injury

2020 ◽  
Author(s):  
Caroline Busatta Vaz de Paula ◽  
Marina Luise Viola Azevedo ◽  
Seigo Nagashima ◽  
Ana Paula Camargo Martins ◽  
Mineia Alessandra Scaranello Malaquias ◽  
...  
Keyword(s):  
Lung Injury ◽  
Transforming Growth Factor Beta ◽  
Influenza A ◽  
Transforming Growth Factor ◽  
Diffuse Alveolar Damage ◽  
Tissue Expression ◽  
Lung Damage ◽  
Control Group ◽  
M2 Macrophages ◽  
Th17 Response

Abstract Background: The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification.Objective: To analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury.Methods: Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC).Results and conclusion: Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages was observed in the COVID-19 group when compared to both the H1N1 and the CONTROL groups. Different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-COV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. The understanding and management of the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

Lung Damage and Thrombocytopenia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4638-4638
Author(s):  
Mo Yang ◽  
En Yu Liang ◽  
Li Xia Zhou ◽  
Beng H Chong ◽  
Chunfu Li
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Lung Injury ◽  
Platelet Activation ◽  
Cell Damage ◽  
Diffuse Alveolar Damage ◽  
Lung Damage ◽  
Right Atrial ◽  
Peripheral Arteries ◽  
Central Venous

Abstract Hematological changes in patients with lung damage were common and included thrombocytopenia (55%) (Yang et al, Int J Mol Med. 2004; Hon et al, Lancet. 2003). A number of potential mechanisms have been investigated. The lungs of patients who died of lung infection show diffuse alveolar damage with pulmonary congestion, edema, formation of hyaline membrane, and fibrosis. Viral infection, oxygen toxicity and/or barotrauma contribute to the lung damage. The lung tissue and pulmonary endothelial cell damage result in platelet activation, aggregation, and thrombi formation at the site of the injury. All these mechanisms may induce the consumption of platelets and megakaryocytes (MK). The association between lung injury and thrombocytopenia was investigated by comparing the MK and platelet counts, and platelet activation using P-selectin as a marker, between the prepulmonary (right atrial) and postpulmonary (left atrial) blood in rats with and without hyperoxic lung injury. In the healthy controls, the postpulmonary blood had lower megakaryocyte count, higher platelet count, but similar P-selectin expression. In contrast, the lung-damaged animals did not show any such differences in either MK or platelet count, but P-selectin expression was greater in the postpulmonary blood. Peripheral platelet and intra-pulmonary MK counts in the lung-damaged rats were significantly lower than those in their respective controls. Intra-pulmonary thrombi or platelet aggregation were detected in the lung-damaged rats but not in the controls. These findings showed that lung damage reduced circulating platelets through (i) failure of the lungs to retain and fragment MK to release platelets, (ii) and platelet activation leading to platelet aggregation, thrombi formation and platelet consumption. The number and morphology of circulating MK were also investigated before, during and after cardiopulmonary bypass (CPB) in 22 patients undergoing routine cardiac surgery. Results showed that: (i) The total number of MK in central venous was higher than those of peripheral arteries during normal circulation (P<0.01). There was significant decrease of Type-4 MK (mature and large MK) number in peripheral arteries compared with that in central venous (P<0.001); and (ii) During CPB, the total MK and Type-4 MK of central venous and peripheral arteries were significant increased when compared with that in normal circulation (P<0.01). Our observation supports that the lungs may remove large MK during normal circulation. This physiological effect would be lost on CPB. On the other hand, the lungs may be the sites of platelet release from mature MK. The inflammation, the long term ventilation and/or oxygen therapy may result in pulmonary fibrosis and other pathological changes. The reduced or morphologically altered pulmonary capillary bed would affect the MK fragmentation in the lung. The increased consumption of platelet and/or the decreased production of platelet may lead to thrombocytopenia. Disclosures Yang: National Natural Science Foundation of China(81270580): Research Funding.

scholarly journals IL-4/IL-13 Remodeling Pathway of Covid-19 Lung Injury

2020 ◽  
Author(s):  
Caroline Busatta Vaz de Paula ◽  
Marina Luise Viola Azevedo ◽  
Seigo Nagashima ◽  
Ana Paula Camargo Martins ◽  
Mineia Alessandra Scaranello Malaquias ◽  
...  
Keyword(s):  
Lung Injury ◽  
Transforming Growth Factor Beta ◽  
Influenza A ◽  
Transforming Growth Factor ◽  
Diffuse Alveolar Damage ◽  
Tissue Expression ◽  
Lung Damage ◽  
Control Group ◽  
M2 Macrophages ◽  
Th17 Response

Abstract Background: The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification.Objective: To analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury.Methods: Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC).Results and conclusion: Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages was observed in the COVID-19 group when compared to both the H1N1 and the CONTROL groups. Different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-COV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. The understanding and management of the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury*

2005 ◽  
Vol 33 (5) ◽  
pp. 1077-1083 ◽  
Author(s):  
Josefina López-Aguilar ◽  
Ana Villagrá ◽  
Francesca Bernabé ◽  
Gastón Murias ◽  
Enrique Piacentini ◽  
...  
Keyword(s):  
Brain Injury ◽  
Lung Injury ◽  
Lung Model ◽  
Lung Damage ◽  
Ventilator Induced Lung Injury ◽  
Isolated Lung
Sign in / Sign up

Export Citation Format

Share Document