scholarly journals The Hemagglutinin Stem-Binding Monoclonal Antibody VIS410 Controls Influenza Virus-Induced Acute Respiratory Distress Syndrome

2016 ◽  
Vol 60 (4) ◽  
pp. 2118-2131 ◽  
Author(s):  
Tatiana Baranovich ◽  
Jeremy C. Jones ◽  
Marion Russier ◽  
Peter Vogel ◽  
Kristy J. Szretter ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza Virus ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Pulmonary Complications ◽  
Lung Injury Score ◽  
Dependent Manner ◽  
Dose Dependent

ABSTRACTMost cases of severe influenza are associated with pulmonary complications, such as acute respiratory distress syndrome (ARDS), and no antiviral drugs of proven value for treating such complications are currently available. The use of monoclonal antibodies targeting the stem of the influenza virus surface hemagglutinin (HA) is a rapidly developing strategy for the control of viruses of multiple HA subtypes. However, the mechanisms of action of these antibodies are not fully understood, and their ability to mitigate severe complications of influenza has been poorly studied. We evaluated the effect of treatment with VIS410, a human monoclonal antibody targeting the HA stem region, on the development of ARDS in BALB/c mice after infection with influenza A(H7N9) viruses. Prophylactic administration of VIS410 resulted in the complete protection of mice against lethal A(H7N9) virus challenge. A single therapeutic dose of VIS410 given 24 h after virus inoculation resulted in dose-dependent protection of up to 100% of mice inoculated with neuraminidase inhibitor-susceptible or -resistant A(H7N9) viruses. Compared to the outcomes in mock-treated controls, a single administration of VIS410 improved viral clearance from the lungs, reduced virus spread in lungs in a dose-dependent manner, resulting in a lower lung injury score, reduced the extent of the alteration in lung vascular permeability and protein accumulation in bronchoalveolar lavage fluid, and improved lung physiologic function. Thus, antibodies targeting the HA stem can reduce the severity of ARDS and show promise as agents for controlling pulmonary complications in influenza.

scholarly journals Mesenchymal Stromal Cells Attenuate Infection-Induced Acute Respiratory Distress Syndrome in Animal Experiments: A Meta-Analysis

2020 ◽  
Vol 29 ◽  
pp. 096368972096918
Author(s):  
Wang Fengyun ◽  
Zhou LiXin ◽  
Qiang Xinhua ◽  
Fang Bin
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Meta Analysis ◽  
Weight Ratio ◽  
Lung Injury Score ◽  
Control Group ◽  
Inflammatory Factor

Mesenchymal stromal cell (MSC) therapy is a potential therapy for treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which was widely studied in the last decade. The purpose of our meta-analysis was to investigate the efficacy of MSCs for simulated infection-induced ALI/ARDS in animal trials. PubMed and EMBASE were searched to screen relevant preclinical trials with a prespecified search strategy. 57 studies met the inclusion criteria and were included in our study. Our meta-analysis showed that MSCs can reduce the lung injury score of ALI caused by lipopolysaccharide or bacteria (standardized mean difference (SMD) = −2.97, 95% CI [−3.64 to −2.30], P < 0.00001) and improve the animals’ survival (odds ratio = 3.64, 95% CI [2.55 to 5.19], P < 0.00001). Our study discovered that MSCs can reduce the wet weight to dry weight ratio of the lung (SMD = −2.58, 95% CI [−3.24 to −1.91], P < 0.00001). The proportion of the alveolar sac in the MSC group was higher than that in the control group (SMD = 1.68, 95% CI [1.22 to 2.13], P < 0.00001). Moreover, our study detected that MSCs can downregulate the levels of proinflammatory factors such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung and it can upregulate the level of anti-inflammatory factor IL-10. MSCs were also found to reduce the level of neutrophils and total protein in bronchoalveolar lavage fluid, decrease myeloperoxidase (MPO) activity in the lung, and improve lung compliance. MSC therapy may be a promising treatment for ALI/ARDS since it may mitigate the severity of lung injury, modulate the immune balance, and ameliorate the permeability of lung vessels in ALI/ARDS, thus facilitating lung regeneration and repair.

scholarly journals Rapid-Onset Acute Respiratory Distress Syndrome (ARDS) in a Patient Undergoing Metastatic Liver Resection: A Case Report and Review of the Literature

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Thorsten Brenner ◽  
Johann Motsch ◽  
Jens Werner ◽  
Lars Grenacher ◽  
Eike Martin ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Liver Resection ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Surgical Procedure ◽  
Distress Syndrome ◽  
Rapid Onset ◽  
Pulmonary Complications ◽  
Life Threatening ◽  
Metastatic Liver

Metastatic liver resection following cytoreductive chemotherapy is an accepted treatment for oligometastatic tumor diseases. Although pulmonary complications are frequently reported in patients undergoing liver surgery including liver transplantation, life-threatening acute respiratory failures in the absence of aspiration, embolism, transfusion-related acute lung injury (TRALI), pulmonary infection, or an obvious source of systemic sepsis are rare. We performed an extensive clinical review of a patient undergoing metastatic liver resection who had a clinical course compatible to an acute respiratory distress syndrome (ARDS) without an obvious cause except for the surgical procedure and multiple preoperative chemotherapies. We hypothesize that either the surgical procedure mediated by cytokines and tumor necrosis factor or possible toxic effects of oxygen applied during general anesthesia were associated with life-threatening respiratory failure in the patient. Discrete and subclinical inflammated alveoli (probably due to multiple preoperative chemotherapies with substances at potential risk for interstitial pneumonitis as well as chest radiation) might therefore be considered as risk factors.

scholarly journals Protective reactive thymus hyperplasia in COVID-19 acute respiratory distress syndrome

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Pelagia Cuvelier ◽  
Hélène Roux ◽  
Anne Couëdel-Courteille ◽  
Jacques Dutrieux ◽  
Cécile Naudin ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Cell Receptor ◽  
Pulmonary Involvement ◽  
Ct Scans ◽  
Initial Assessment ◽  
Lung Injury Score ◽  
Control Group

Abstract Background Patients with COVID-19 (COVID) may develop acute respiratory distress syndrome with or without sepsis, coagulopathy and visceral damage. While chest CT scans are routinely performed in the initial assessment of patients with severe pulmonary forms, thymus involvement and reactivation have not been investigated so far. Methods In this observational study, we systematically scored the enlargement of the thymus and the lung involvement, using CT scans, in all adult patients admitted to the ICU for COVID or any other cause (control group) at one centre between March and April 2020. Initial biological investigations included nasal detection of SARS-CoV-2 ribonucleic acid by polymerase chain reaction (PCR). In a subgroup of 24 patients with different degrees of pulmonary involvement and thymus hypertrophy, plasma cytokine concentrations were measured and the export of mature T cells from the thymus was estimated simultaneously by PCR quantification of T cell receptor excision circles (TRECs). Results Eighty-seven patients were studied: 50 COVID patients and 37 controls. Non-atrophic or enlarged thymus was more commonly observed in COVID patients than in controls (66% vs. 24%, p < 0.0001). Thymus enlargement in COVID patients was associated with more extensive lung injury score on CT scans (4 [3–5] vs. 2 [1.5–4], p = 0.01), but a lower mortality rate (8.6% vs. 41.2%, p < 0.001). Other factors associated with mortality were age, lymphopaenia, high CRP and co-morbidities. COVID patients had higher concentrations of IL-7 (6.00 [3.72–9.25] vs. 2.17 [1.76–4.4] pg/mL; p = 0.04) and higher thymic production of new lymphocytes (sj/βTREC ratio = 2.88 [1.98–4.51] vs. 0.23 [0.15–0.60]; p = 0.004). Thymic production was also correlated with the CT scan thymic score (r = 0.38, p = 0.03) and inversely correlated with the number of lymphocytes (r = 0.56, p = 0.007). Conclusion In COVID patients, thymus enlargement was frequent and associated with increased T lymphocyte production, which appears to be a beneficial adaptation to virus-induced lymphopaenia. The lack of thymic activity/reactivation in older SARS-CoV-2 infected patients could contribute to a worse prognosis.

scholarly journals NEMO-Binding Domain Peptide Ameliorates Alveolar Hypercoagulation and Fibrinolytic Inhibition in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via NF-κB Signaling Pathway in Mice

2020 ◽  
Author(s):  
Yahui WANG ◽  
Yanqi WU ◽  
Bo LIU ◽  
Huilin YANG ◽  
Hong QIAN ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Signaling Pathway ◽  
Distress Syndrome ◽  
Dependent Manner ◽  
Domain Peptide ◽  
Nemo Binding Domain ◽  
Dose Dependent ◽  
Pai 1 ◽  
Coagulation And Fibrinolysis

Abstract Background It was confirmed that alveolar hypercoagulation and fibrinolytic inhibition were associated with refractory hypoxemia in acute respiratory distress syndrome (ARDS), and NF-κB pathway was involved in this process. The purpose of the present study is to explore the effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBDP) to alleviate alveolar hypercoagulation and fibrinolytic inhibition aroused by lipopolysaccharide in ARDS mice. Materials and Methods Adult male BALB/c mice inhaled lipopolysaccharide (LPS, mg/L) to induce ARDS. 30 minutes before LPS administration, we treated the mice with increasing concentrations of intratracheally inhaled NBDP or saline aerosol. Six hours after LPS treatment, bronchoalveolar lavage fluids (BALF) were collected and then all mice were executed. We checked coagulation and fibrinolysis associated factors in lung tissues and in BALF as well. We simultaneously observed the activation of NF-κB signaling pathway as well. Results NBDP pretreatment dose-dependently inhibited either the expressions of tissue factor (TF) and plasminogen activator inhibitor (PAI) 1 in lung tissues or the secretions of TF, PAI-1, thrombin-antithrombin complex (TAT) and promoted activated protein C (APC) secretion in BALF induced by LPS. LPS-induced high expression of pulmonary procollagen peptide type Ⅲ (PⅢP) was also declined by NBDP pretreatment in dose-dependent manner. Western blotting showed that NBDP pretreatment obviously attenuated LPS-induced IKKα/β, Iκα and NF-κB p65 activation. LPS-induced p65 DNA binding activity was inhibited by NBDP pretreatment either. We also noticed NBDP protected mice against LPS-induced lung injury in a dose-dependent manner.Conclusions Our experimental findings demonstrate that NBDP dose-dependently ameliorated LPS-induced alveolar hypercoagulation and fibrinolytic inhibition through inhibiting NF-κB signaling pathway. NBDP is expected to be a new therapeutic target to correct the abnormalities of alveolar coagulation and fibrinolysis in ARDS.

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