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.

BackgroundDifferent 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.MethodsParticle 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.ResultsIn 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.ConclusionsHere, 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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ObjectivesNoninvasive online monitoring of different particle flows from the airways may serve as an additional tool to assess mechanical ventilation. In the present study, we used a customised PExA, an optical particle counter for monitoring particle flow and size distribution in exhaled air, to analyse airway particle flow for three subsequent days. We compared volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) and performed recruitment manoeuvres (RM).MethodsSix animals were randomised into two groups: half received VCV before PCV and the other half received PCV before VCV. Measurements were taken daily for 1 h in each mode during three subsequent days in six fully anaesthetised domestic pigs. A RM was performed twice daily for 60 s at positive end-expiratory pressure (PEEP) of 10, 4 breaths/min and inspiratory-expiratory ratio (I:E) of 2:1. Measurements were taken for 3 min before the RM, 1 min during the RM and for 3 min after the RM. The particle sizes measured were between 0.48 and 3.37 μm.ResultsA significant stepwise decrease was observed in total particle count from day 1 to day 3, and at the same time, an increase in fluid levels was seen. Comparing VCV to PCV, a significant increase in total particle count was observed on day 2, with the highest particle count occurring during VCV. A significant increase was observed comparing before and after RM on day 1 and 2 but not on day 3. One animal developed ARDS and showed a different particle pattern compared to the other animals.ConclusionsThis study shows the safety and useability of the PExA technique used in conjunction with mechanical ventilation. We detected differences between the ventilation modes VCV and PCV in total particle count without any significant changes in ventilator pressure levels, FiO2 levels or the animals’ vital parameters. The findings during RM indicate an opening of the small airways, but the effect is short lived. We have also showed that VCV and PCV may affect the lung physiology differently during recruitment manoeuvres. These findings might indicate that this technique may provide more refined information on the impact of mechanical ventilation.

IntroductionIn 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.MethodsA 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).ResultsMV-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.ConclusionWe 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.

IntroductionMechanical ventilation (MV) 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.MethodA prospective study was conducted on patients on MV 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 (RM). PFR measurements were continued as the patients were transitioned to pressure regulated volume control (PRVC) and then pressure support ventilation (PSV) until extubation.ResultsPRVC resulted in significantly lower PFR while those on PSV had the highest PFR. The distribution of particles differed significantly between the different ventilation modes.ConclusionsMeasuring 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 MV 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.

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 Relung 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.

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 × 106 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.