Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

Stenlo, Martin; Hyllén, Snejana; Silva, Iran Augusto N; Bölükbas, Deniz A.; Pierre, Leif; Hällgren, Oskar; Wagner, Darcy E.; Lindstedt, Sandra

doi:10.1152/ajplung.00524.2019

Cited by 24 publications

(47 citation statements)

References 13 publications

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“…Significance was defined as p < 0.001 (***), p < 0.01 (**), p < 0.05 (*), and p > 0.05 (not significant) During the experiment, we sampled plasma and BALF. In the plasma, we found significant increases in TNF-α, IL-6, and IL-12 between 60 and 180 min in all animals who received LPS, which is similar to the cytokine profiles in other porcine models of ARDS shown by us and others (Stenlo et al, 2020;Wyns et al, 2015). The rapid and massive increases of TNF-α, IL-6, and IL-10 that were observed in our model have been shown to be linked with mortality in ARDS patients and COVID-19 patients (Han et al, 2020;Huang et al, 2020;Liu et al, 2017).…”

Section: F I G U R Esupporting

confidence: 89%

Monitoring lung injury with particle flow rate in LPS‐ and COVID‐19‐induced ARDS

Stenlo

Silva

Hyllén

et al. 2021

Physiological Reports

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In severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) is a life‐prolonging treatment, especially among COVID‐19 patients. Evaluation of lung injury progression is challenging with current techniques. Diagnostic imaging or invasive diagnostics are risky given the difficulties of intra‐hospital transportation, contraindication of biopsies, and the potential for the spread of infections, such as in COVID‐19 patients. We have recently shown that particle flow rate (PFR) from exhaled breath could be a noninvasive, early detection method for ARDS during mechanical ventilation. We hypothesized that PFR could also measure the progress of lung injury during ECMO treatment. Lipopolysaccharide (LPS) was thus used to induce ARDS in pigs under mechanical ventilation. Eight were connected to ECMO, whereas seven animals were not. In addition, six animals received sham treatment with saline. Four human patients with ECMO and ARDS were also monitored. In the pigs, as lung injury ensued, the PFR dramatically increased and a particular spike followed the establishment of ECMO in the LPS‐treated animals. PFR remained elevated in all animals with no signs of lung recovery. In the human patients, in the two that recovered, PFR decreased. In the two whose lung function deteriorated while on ECMO, there was increased PFR with no sign of recovery in lung function. The present results indicate that real‐time monitoring of PFR may be a new, complementary approach in the clinic for measurement of the extent of lung injury and recovery over time in ECMO patients with ARDS.

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Section: F I G U R Esupporting

confidence: 89%

Monitoring lung injury with particle flow rate in LPS‐ and COVID‐19‐induced ARDS

Stenlo

Silva

Hyllén

et al. 2021

Physiological Reports

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“…Lung tissue taken before LPS administration for histological analysis appeared normal, with no anomalies (Figure 2d). Following the administration of LPS, and as previously observed using a similar model of ARDS-induction (40), there was significant infiltration of the alveolar spaces by immune cells and notable atelectasis which affected the majority of alveolar spaces.…”

Section: Establishment Of Ards Using Lps In the Donorsupporting

confidence: 77%

“…Donors were treated intravenously with lipopolysaccharide (LPS) with dosage calculated according to weight and then monitored for development of ARDS. This follows an established model of ARDS, as previously published (40). All LPS-treated donors developed mild to moderate ARDS within 120 ± 30 min, as defined by two separate arterial blood gases within a 15-minute interval.…”

Section: Establishment Of Ards Using Lps In the Donormentioning

confidence: 96%

“…Lipopolysaccharide (LPS) from Gram-negative bacteria Escherichia coli (O111:B4, Sigma-Aldrich, Merck KGaA, Darmstadt, Germany) was used to induce an ARDS according to the Berlin criteria (42), as previously described (40). LPS was diluted in saline solution and administered intravenously as an infusion (2 µg/kg/min) for one hour, after which point it was reduced by 50% for another hour.…”

Section: Induction Of Ards Using Lps In Donor Animalsmentioning

confidence: 99%

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Reduction of primary graft dysfunction using cytokine filtration following acute respiratory distress syndrome in lung transplantation

Ghaidan¹,

Stenlo²,

Gvazava³

et al. 2021

Preprint

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Despite improvements, lung transplantation (LTx) 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 filtration as a means of restoring ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 12 donor pigs. Lungs were then treated with or without cytokine filtration during ex vivo lung perfusion (EVLP) and 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 filtration 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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“…The identity of particles collected using the PExA technique has been shown to be consistent with the particles collected from bronchoalveolar lavage fluid, indicating that EBPs originate from the RTLF [ 15 ]. In a recent publication, increased PFR was strongly connected to lung injury [ 16 ]. The PFR significantly increased indicating lung injury prior to other clinical indicators of injury, including respiratory parameters and the cytokine response in the blood.…”

Section: Introductionmentioning

confidence: 99%

Particle flow rate from the airways as fingerprint diagnostics in mechanical ventilation in the intensive care unit: a randomised controlled study

et al. 2021

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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.

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Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

Cited by 24 publications

References 13 publications

Monitoring lung injury with particle flow rate in LPS‐ and COVID‐19‐induced ARDS

Monitoring lung injury with particle flow rate in LPS‐ and COVID‐19‐induced ARDS

Reduction of primary graft dysfunction using cytokine filtration following acute respiratory distress syndrome in lung transplantation

Particle flow rate from the airways as fingerprint diagnostics in mechanical ventilation in the intensive care unit: a randomised controlled study

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