scholarly journals CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Mathieu Blot ◽  
◽  
Marine Jacquier ◽  
Ludwig-Serge Aho Glele ◽  
Guillaume Beltramo ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Mitochondrial Dna ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Cd40 Ligand ◽  
Response Patterns ◽  
Alveolar Cell ◽  
Epithelial Lining Fluid ◽  
Gm Csf ◽  
Cell Counts

Abstract Background COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). Methods Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. Results COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations. Conclusion CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. Trial registration ClinicalTrials.gov, NCT03955887

Low-tidal-volume Mechanical Ventilation Induces a Toll-like Receptor 4–dependent Inflammatory Response in Healthy Mice

2008 ◽  
Vol 109 (3) ◽  
pp. 465-472 ◽  
Author(s):  
Michiel Vaneker ◽  
Leo A. Joosten ◽  
Leo M. A. Heunks ◽  
Dirk G. Snijdelaar ◽  
Feico J. Halbertsma ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Ventilator Induced Lung Injury ◽  
Factor Alpha ◽  
Necrosis Factor

Background Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. Methods Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. Results MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of keratinocyte-derived chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. Conclusions The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.

Conventional Mechanical Ventilation Is Associated with Bronchoalveolar Lavage-induced Activation of Polymorphonuclear Leukocytes

2002 ◽  
Vol 97 (6) ◽  
pp. 1426-1433 ◽  
Author(s):  
Haibo Zhang ◽  
Gregory P. Downey ◽  
Peter M. Suter ◽  
Arthur S. Slutsky ◽  
V. Marco Ranieri
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Polymorphonuclear Leukocytes ◽  
Bronchoalveolar Lavage Fluid ◽  
Distress Syndrome ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Multiple Organ ◽  
Protective Strategy ◽  
Oxidant Production

Background Protective ventilatory strategies have resulted in a decreased mortality rate in acute respiratory distress syndrome, but the underlying mechanisms remain unclear. The authors hypothesized that (1) mechanical ventilation modulates activation of polymorphonuclear leukocytes (PMNs), (2) the consequent release of proteinases is correlated with a systemic inflammatory response and with multiple organ dysfunction, and (3) these deleterious effects can be minimized by a protective ventilatory strategy. Methods Human PMNs were incubated with bronchoalveolar lavage fluid obtained from patients at entry or 36 h after randomization to ventilation with either a conventional (control) or a lung-protective strategy. PMN oxidant production and surface expression of adhesion molecules and granule markers, including CD18, CD63, and L-selectin, were measured by flow cytometry. Extracellular elastase activity was quantified using a fluorescent substrate. Results Bronchoalveolar lavage obtained from both groups of patients at entry showed similar effects on PMN oxidant production and expression of surface markers. At 36 h, exposure of PMNs to bronchoalveolar lavage fluid from the control group resulted in increased PMN activation as manifested by a significant increase in oxidant production, CD18, and CD63 surface expression, and shedding of L-selectin. By contrast, these variables were unchanged at 36 h in the lung-protective group. There was a significant correlation between the changes of the variables and changes in interleukin-6 level and the number of failing organs. Conclusions Polymorphonuclear leukocytes can be activated by mechanical ventilation, and the consequent release of elastase was correlated with the degree of systemic inflammatory response and multiple organ failure. This result may possibly explain the decreased mortality in acute respiratory distress syndrome patients treated with a lung-protective strategy.

scholarly journals Mild hypothermia attenuates changes in respiratory system mechanics and modifies cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation

2010 ◽  
pp. 937-944
Author(s):  
P Dostál ◽  
M Šenkeřík ◽  
R Pařízková ◽  
D Bareš ◽  
P Živný ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Respiratory System ◽  
Bronchoalveolar Lavage Fluid ◽  
Mild Hypothermia ◽  
Lavage Fluid ◽  
Cytokine Concentration ◽  
Volume Ventilation ◽  
Hypothermia Group

Hypothermia was shown to attenuate ventilator-induced lung injury due to large tidal volumes. It is unclear if the protective effect of hypothermia is maintained under less injurious mechanical ventilation in animals without previous lung injury. Tracheostomized rats were randomly allocated to non-ventilated group (group C) or ventilated groups of normothermia (group N) and mild hypothermia (group H). After two hours of mechanical ventilation with inspiratory fraction of oxygen 1.0, respiratory rate 60 min-1, tidal volume 10 ml·kg-1, positive end-expiratory pressure (PEEP) 2 cm H2O or immediately after tracheostomy in non-ventilated animals inspiratory pressures were recorded, rats were sacrificed, pressure-volume (PV) curve of respiratory system constructed, bronchoalveolar lavage (BAL) fluid and aortic blood samples obtained. Group N animals exhibited a higher rise in peak inspiratory pressures in comparison to group H animals. Shift of the PV curve to right, higher total protein and interleukin6 levels in BAL fluid were observed in normothermia animals in comparison with hypothermia animals and non-ventilated controls. Tumor necrosis factor-α was lower in the hypothermia group in comparison with normothermia and non-ventilated groups. Mild hypothermia attenuated changes in respiratory system mechanics and modified cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation in animals without previous lung injury.

scholarly journals The Extent of Ventilator-Induced Lung Injury in Mice Partly Depends on Duration of Mechanical Ventilation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Maria A. Hegeman ◽  
Sabrine N. T. Hemmes ◽  
Maria T. Kuipers ◽  
Lieuwe D. J. Bos ◽  
Geartsje Jongsma ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Capillary Permeability ◽  
Statistical Significance ◽  
Lung Compliance ◽  
Alveolar Cell ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cell Counts ◽  
Alveolar Capillary

Background. Mechanical ventilation (MV) has the potential to initiate ventilator-induced lung injury (VILI). The pathogenesis of VILI has been primarily studied in animal models using more or less injurious ventilator settings. However, we speculate that duration of MV also influences severity and character of VILI.Methods. Sixty-four healthy C57Bl/6 mice were mechanically ventilated for 5 or 12 hours, using lower tidal volumes with positive end-expiratory pressure (PEEP) or higher tidal volumes without PEEP. Fifteen nonventilated mice served as controls.Results. All animals remained hemodynamically stable and survived MV protocols. In both MV groups, PaO2to FiO2ratios were lower and alveolar cell counts were higher after 12 hours of MV compared to 5 hours. Alveolar-capillary permeability was increased after 12 hours compared to 5 hours, although differences did not reach statistical significance. Lung levels of inflammatory mediators did not further increase over time. Only in mice ventilated with increased strain, lung compliance declined and wet to dry ratio increased after 12 hours of MV compared to 5 hours.Conclusions. Deleterious effects of MV are partly dependent on its duration. Even lower tidal volumes with PEEP may initiate aspects of VILI after 12 hours of MV.

scholarly journals Dissecting the inflammatory twitch in allergically inflamed mice

2016 ◽  
Vol 310 (10) ◽  
pp. L1003-L1009 ◽  
Author(s):  
Joshua J. Pothen ◽  
Matthew E. Poynter ◽  
Lennart K. A. Lundblad ◽  
Jason H. T. Bates
Keyword(s):  
Inflammatory Response ◽  
Refractory Period ◽  
Time Course ◽  
Lavage Fluid ◽  
Gm Csf ◽  
Refractory Periods ◽  
Sequence Of Events ◽  
Cell Counts ◽  
Airways Resistance ◽  
Predetermined Time

We have previously advanced the hypothesis that the allergic inflammatory response in the lungs occurs as a self-limited sequence of events that begins with the onset of inflammation and then resolves back to baseline over a predetermined time course (Pothen JJ, Poynter ME, Bates JH. J Immunol 190: 3510–3516, 2013). In the present study we tested a key prediction of this hypothesis, which is that the instigation of the allergic inflammatory response should be accompanied by a later refractory period during which the response cannot be reinitiated. We challenged groups of ovalbumin-sensitized BALB/c mice for 3, 14, 21 and 31 consecutive days with aerosolized ovalbumin. We measured airways responsiveness as well as cell counts and cytokines in bronchoalveolar lavage fluid after the final challenge in subgroups from each group. In other subgroups we performed the same measurements following rest periods and after a final single recall challenge with antigen. We determined that the refractory periods for GM-CSF, KC, and IL-5 are no longer than 10 days, while those for IFNγ and IL-10 are no longer than 28 days. The refractory periods for total leukocytes and neutrophils were no greater than 28 days, while that for eosinophils was more than 28 days. The refractory period for airways resistance was less than 17, while for lung elastance it was longer than 28 days. Our results thus demonstrate that the components of the allergic inflammatory response in the lung have finite refractory periods, with the refractory period of the entire response being in the order of a month.

scholarly journals Sigh maneuver protects healthy lungs during mechanical ventilation in adult Wistar rats

2020 ◽  
Vol 245 (15) ◽  
pp. 1404-1413
Author(s):  
Andréa Cristiane Lopes da Silva ◽  
Natália Alves de Matos ◽  
Ana Beatriz Farias de Souza ◽  
Thalles de Freitas Castro ◽  
Leandro da Silva Cândido ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Partial Pressure ◽  
Wistar Rats ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Protective Role ◽  
Arterial Blood

Mechanical ventilation (MV) is a tool used for the treatment of patients with acute or chronic respiratory failure. However, MV is a non-physiological resource, and it can cause metabolic disorders such as release of pro-inflammatory cytokines and production of reactive oxygen species. In clinical setting, maneuvers such as sigh, are used to protect the lungs. Thus, this study aimed to evaluate the effects of sigh on oxidative stress and lung inflammation in healthy adult Wistar rats submitted to MV. Male Wistar rats were divided into four groups: control (CG), mechanical ventilation (MVG), MV set at 20 sighs/h (MVG20), and MV set at 40 sighs/h (MVG40). The MVG, MVG20, and MVG40 were submitted to MV for 1 h. After the protocol, all animals were euthanized and the blood, bronchoalveolar lavage fluid, and lungs were collected for subsequent analysis. In the arterial blood, MVG40 presented higher partial pressure of oxygen and lower partial pressure of carbon dioxide compared to control. The levels of bicarbonate in MVG20 were lower compared to CG. The neutrophil influx in bronchoalveolar lavage fluid was higher in the MVG compared to CG and MVG40. In the lung parenchyma, the lipid peroxidation was higher in MVG compared to CG, MVG20, and MVG40. Superoxide dismutase and catalase activity were higher in MVG compared to CG, MVG20, and MVG40. The levels of IL-1, IL-6, and TNF in the lung homogenate were higher in MVG compared to CG, MVG20, and MVG40. The use of sigh plays a protective role as it reduced redox imbalance and pulmonary inflammation caused by MV.

scholarly journals Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy.

Thorax ◽  
1980 ◽  
Vol 35 (5) ◽  
pp. 328-339 ◽  
Author(s):  
P L Haslam ◽  
C W Turton ◽  
A Lukoszek ◽  
A J Salsbury ◽  
A Dewar ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Fibrosing Alveolitis ◽  
Cell Counts ◽  
Cryptogenic Fibrosing Alveolitis ◽  
Fluid Cell

Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits

2005 ◽  
Vol 99 (2) ◽  
pp. 433-444 ◽  
Author(s):  
Edgardo D'Angelo ◽  
Matteo Pecchiari ◽  
Patrizia Della Valle ◽  
Antonia Koutsoukou ◽  
Joseph Milic-Emili
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Albumin Concentration ◽  
Open Chest ◽  
Interstitial Pulmonary Edema ◽  
Tnf Α ◽  
Low Volume

Lung mechanics, exhaled NO (NOe), and TNF-α in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3–4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (−42 and −25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (−25 and −20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-α was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-α levels.

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