| 1. |
- Broberg, Ellen, et al.
(författare)
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A new way of monitoring mechanical ventilation by measurement of particle flow from the airways using Pexa method in vivo and during ex vivo lung perfusion in DCD lung transplantation
- 2018
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters. Methods: Particle flow was monitored in vivo, post mortem, and in ex vivo lung perfusion (EVLP) in six porcines with the Pexa (particles in exhaled air) instrument. Volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) were used to compare small versus large tidal volumes. The surfactant lipids dipalmitoylphosphatidylcholine (DPPC) and phosphatidylcholine (PC) were quantified by mass spectrometry. Results: In vivo the particle mass in VCV1 was significantly lower than in VCV2 (p= 0.0186), and the particle mass was significantly higher in PCV1 than in VCV1 (p= 0.0322). In EVLP, the particle mass in VCV1 was significantly higher than in PCV1 (p= 0.0371), and the particle mass was significantly higher in PCV2 than in PCV1 (p= 0.0127). DPPC was significantly higher in EVLP than in vivo. Conclusions: Here, we introduce a new method for measuring particle flow during mechanical ventilation and confirm that these particles can be collected and analyzed. VCV resulted in a lower particle flow in vivo but not in EVLP. In all settings, large tidal volumes resulted in increased particle flow. We found that DPPC was significantly increased comparing in vivo with EVLP. This technology may be useful for developing strategies to preserve the lung and has a high potential to detect biomarkers.
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| 2. |
- Broberg, Ellen, et al.
(författare)
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Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients
- 2020
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Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this cohort study, we evaluated whether the particles in exhaled air (PExA) device can be used in conjunction with mechanical ventilation during surgery. The PExA device consists of an optical particle counter and an impactor that collects particles in exhaled air. Our aim was to establish the feasibility of the PExA device in combination with mechanical ventilation (MV) during surgery and if collected particles could be analysed. Patients with and without nonsmall cell lung cancer (NSCLC) undergoing lung surgery were compared to normal breathing (NB) patients with NSCLC. Methods: A total of 32 patients were included, 17 patients with NSCLC (MV-NSCLC), nine patients without NSCLC (MV-C) and six patients with NSCLC and not intubated (NB). The PEx samples were analysed for the most common phospholipids in surfactant using liquid-chromatography-mass-spectrometry (LCMS). Results: MV-NSCLC and MV-C had significantly lower numbers of particles exhaled per minute ( particle flow rate; PFR) compared to NB. MV-NSCLC and MV-C also had a siginificantly lower amount of phospholipids in PEx when compared to NB. MV-NSCLC had a significantly lower amount of surfactant A compared to NB. Conclusion: We have established the feasibility of the PExA device. Particles could be collected and analysed. We observed lower PFR from MV compared to NB. High PFR during MV may be due to more frequent opening and closing of the airways, known to be harmful to the lung. Online use of the PExA device might be used to monitor and personalise settings for mechanical ventilation to lower the risk of lung damage.
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| 3. |
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| 4. |
- Broberg, Ellen, et al.
(författare)
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Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction
- 2019
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Ingår i: Experimental and clinical transplantation. - : Baskent University. - 1304-0855 .- 2146-8427. ; 17:6, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Primary graft dysfunction is a severe form of acute lung injury and a major cause of early morbidity and mortality encountered after lung transplant.We used a customized PExA 2.0 instrument (PExA, Gothenburg, Sweden) to measure particle flow in exhaled air during mechanical ventilation in the intensive care unit. Our objective was to discover whether patients who developed primary graft dysfunction had different particle flow patterns from the airways. We used volume-controlled ventilation and pressure-controlled ventilation to see whether changes in particle patterns could be observed in both mechanical ventilation settings.MATERIALS AND METHODS: First, we investigated whether it was safe to use a customized PExA 2.0 in conjunction with mechanical ventilation. Next, 12 lung transplant patients were randomized to either daily volumecontrolled ventilation or pressure-controlled ventilation as the first mode of treatment until extubation.RESULTS: In our study group, 6 patients did not develop primary graft dysfunction and 6 developed primary graft dysfunction. Patients with primary graft dysfunction underwent mechanical ventilation significantly longer; they also showed a stepwise increase in particle count from day 0 until extubation. We observed no adverse events related to the PExA 2.0 device.CONCLUSIONS: This study suggests that the PExA 2.0 device is safe to use in conjunction with mechanical ventilation in the intensive care unit. Lung transplant patients who developed primary graft dysfunction showed a different particle profile from the airways before clinical signs of primary graft dysfunction developed. Online assessment of ventilation impact before presentation of tissue changes may allow realtime detection of primary graft dysfunction, thus preventing or reducing its effects.
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| 5. |
- Broberg, Ellen, et al.
(författare)
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Releasing high positive end-expiratory pressure to a low level generates a pronounced increase in particle flow from the airways
- 2023
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Detecting particle flow from the airways by a non-invasive analyzing technique might serve as an additional tool to monitor mechanical ventilation. In the present study, we used a customized particles in exhaled air (PExA) technique, which is an optical particle counter for the monitoring of particle flow in exhaled air. We studied particle flow while increasing and releasing positive end-expiratory pressure (PEEP). The aim of this study was to investigate the impact of different levels of PEEP on particle flow in exhaled air in an experimental setting. We hypothesized that gradually increasing PEEP will reduce the particle flow from the airways and releasing PEEP from a high level to a low level will result in increased particle flow. Methods: Five fully anesthetized domestic pigs received a gradual increase of PEEP from 5 cmH2O to a maximum of 25 cmH2O during volume-controlled ventilation. The particle count along with vital parameters and ventilator settings were collected continuously and measurements were taken after every increase in PEEP. The particle sizes measured were between 0.41 µm and 4.55 µm. Results: A significant increase in particle count was seen going from all levels of PEEP to release of PEEP. At a PEEP level of 15 cmH2O, there was a median particle count of 282 (154–710) compared to release of PEEP to a level of 5 cmH2O which led to a median particle count of 3754 (2437–10,606) (p < 0.009). A decrease in blood pressure was seen from baseline to all levels of PEEP and significantly so at a PEEP level of 20 cmH2O. Conclusions: In the present study, a significant increase in particle count was seen on releasing PEEP back to baseline compared to all levels of PEEP, while no changes were seen when gradually increasing PEEP. These findings further explore the significance of changes in particle flow and their part in pathophysiological processes within the lung.
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| 6. |
- Edström, Dag, et al.
(författare)
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Amniotic fluid derived mesenchymal stem cells reduce inflammation and improve lung function following transplantation in a porcine model
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Ingår i: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - 1557-3117.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes.METHODS: In a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion before transplantation. Treatment consisted of three doses of 2x10 6 cells/kg: one during ex vivo lung perfusion and two after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD). RESULTS: Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO 2/FiO 2 ratios and reduced incidence of PGD. CONCLUSIONS: Repeated injection of lung-specific cell treatment during EVLP and post-transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of post-operative outcomes.
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| 7. |
- Edström, Dag, et al.
(författare)
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Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome
- 2023
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Ingår i: Respiratory Research. - 1465-9921. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 10 6 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.
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| 8. |
- Fakhro, Mohammed, et al.
(författare)
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Double lung, unlike single lung transplantation might provide a protective effect on mortality and bronchiolitis obliterans syndrome
- 2017
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Survival after lung transplantation (LTx) is often limited by bronchiolitis obliterans syndrome (BOS).METHOD: Survey of 278 recipients who underwent LTx. The endpoint used was BOS (BOS grade ≥ 2), death or Re-lung transplantation (Re-LTx) assessed by competing risk regression analyses.RESULTS: The incidence of BOS grade ≥ 2 among double LTx (DLTx) recipients was 16 ± 3% at 5 years, 30 ± 4% at 10 years, and 37 ± 5% at 20 years, compared to single LTx (SLTx) recipients whose corresponding incidence of BOS grade ≥ 2 was 11 ± 3%, 20 ± 4%, and 24 ± 5% at 5, 10, and 20 years, respectively (p > 0. 05). The incidence of BOS grade ≥ 2 by major indications ranked in descending order: other, PF, CF, COPD, PH and AAT1 (p < 0. 05). The mortality rate by major indication ranked in descending order: COPD, PH, AAT1, PF, Other and CF (p < 0. 05).CONCLUSION: No differences were seen in the incidence of BOS grade ≥ 2 regarding type of transplant, however, DLTx recipients showed a better chance of survival despite developing BOS compared to SLTx recipients. The highest incidence of BOS was seen among CF, PF, COPD, PH, and AAT1 recipients in descending order, however, CF and PF recipients showed a better chance of survival despite developing BOS compared to COPD, PH, and AAT1 recipients.
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| 9. |
- Ghaidan, Haider, et al.
(författare)
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Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.
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| 10. |
- Hallgren, Filip, et al.
(författare)
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Particle flow rate from the airways as fingerprint diagnostics in mechanical ventilation in the intensive care unit : A randomised controlled study
- 2021
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Mechanical ventilation can be monitored by analysing particles in exhaled air as measured by particle flow rate (PFR). This could be a potential method of detecting ventilator-induced lung injury (VILI) before changes in conventional parameters can be detected. The aim of this study was to investigate PFR during different ventilation modes in patients without lung pathology. Method A prospective study was conducted on patients on mechanical ventilation in the cardiothoracic intensive care unit (ICU). A PExA 2.0 device was connected to the expiratory limb on the ventilator for continuous measurement of PFR in 30 patients randomised to either volume-controlled ventilation (VCV) or pressure-controlled ventilation (PCV) for 30 min including a recruitment manoeuvre. PFR measurements were continued as the patients were transitioned to pressure-regulated volume control (PRVC) and then pressure support ventilation (PSV) until extubation. Results PRVC resulted in significantly lower PFR, while those on PSV had the highest PFR. The distribution of particles differed significantly between the different ventilation modes. Conclusions Measuring PFR is safe after cardiac surgery in the ICU and may constitute a novel method of continuously monitoring the small airways in real time. A low PFR during mechanical ventilation may correlate to a gentle ventilation strategy. PFR increases as the patient transitions from controlled mechanical ventilation to autonomous breathing, which most likely occurs as recruitment by the diaphragm opens up more distal airways. Different ventilation modes resulted in unique particle patterns and could be used as a fingerprint for the different ventilation modes.
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