ARDS Lung Research Articles

Full-lung simulations of mechanically ventilated lungs incorporating recruitment/derecruitment dynamics.

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency. This model successfully reproduces realistic pressure-volume (PV) behavior, dynamic surface tension, and time-dependent descriptions of RD events as a function of the ventilation scenario. Simulations of Time-Controlled Adaptive Ventilation (TCAV) modes, with short and long durations of exhalation (T Low - and T Low +, respectively), reveal a higher incidence of RD for T Low + despite reduced surface tensions due to interfacial compression. This finding aligns with experimental evidence emphasizing the critical role of timing in protective ventilation strategies. Quantitative analysis of energy dissipation indicates that while alveolar recruitment contributes only a small fraction of total energy dissipation, its spatial concentration and brief duration may significantly contribute to VILI progression due to its focal nature and higher intensity. Leveraging the computational framework, the model may be extended to facilitate the development of personalized protective ventilation strategies to enhance patient outcomes. As such, this computational modeling approach offers valuable insights into the complex dynamics of VILI that may guide the optimization of ventilation strategies in ARDS management.

Bletilla striata polysaccharides protect against ARDS by modulating the NLRP3/caspase1/GSDMD and HMGB1/TLR4 signaling pathways to improve pulmonary alveolar macrophage pyroptosis

Ethnopharmacological relevanceBletilla striata polysaccharides (BSP) extracted from the B. striata tuber, have been demonstrated to possess anti-inflammatory properties. However, their potential protective effect against ARDS and their role in regulating cell pyroptosis remained unexplored. Aim of the studyThe aim of this study was to investigate the therapeutic effect of BSP in the alleviation of lipopolysaccharide (LPS)-induced ARDS, and to explore its mechanism of action. MethodsThe effect of BSP was assessed by LPS injection into the intraperitoneal cavity in vivo; pathological changes of ARDS mice were gauged by immunohistochemical, hematoxylin and eosin staining, and immunofluorescence assays. MH-S cells were used to model the pyroptosis in vitro. Finally, the pyroptosis of alveolar macrophage was detected by western blots, qPCR, and flow cytometry for NLRP3/caspase1/GSDMD and HMGB1/TLR4 pathway-associated proteins and mRNA. ResultsBSP could significantly increase the weight and survival rate of mice with ARDS, alleviate the cytokine storm in the lungs, and reduce lung damage in vivo. BSP inhibited the inflammation caused by LPS/Nigericin significantly in vitro. Compared with the control group, there was a remarkable surge in the incidence of pyroptosis observed in ARDS lung tissue and alveolar macrophages, whereas BSP significantly diminished the pyroptosis ratio. Besides, BSP reduced NLRP3/caspase1/GSDMD and HMGB1/TLR4 levels in ARDS lung tissue and MH-S cells. ConclusionsThese findings proved that BSP could improve LPS-induced ARDS via inhibiting pyroptosis, and this effect was mediated by NLRP3/caspase1/GSDMD and HMGB1/TLR4, suggesting a therapeutic potential of BSP as an anti-inflammatory agent for ARDS treatment.

Mechanical ventilation variables associated with high pulmonary artery pressures in ARDS patients: a post hoc analysis

BackgroundThe relationship between indices of mechanical ventilation and pulmonary artery pressures remains ill-defined in ARDS. As our understanding of mechanical ventilation has progressed, there is now a greater appreciation of the impact of high driving pressures and mechanical power in perpetuating lung injury. However, the relationship between the newer derived indices of mechanical ventilation and pulmonary artery pressure is unclear. We performed a post hoc analysis of the Fluid and Catheters Treatment Trial (FACTT) trial to investigate the associations between mechanical ventilation indices in ARDS patients and the prevalence of pulmonary hypertension. This may help elucidate future clinical targets for more, right ventricular protective, mechanical ventilation strategies.MethodsWe performed a post hoc analysis of the FACTT database to identify ARDS patients who had a pulmonary artery catheter (PAC) inserted and pulmonary artery pressure readings recorded. We excluded any patient with a PAC inserted who was spontaneously breathing, as driving pressure and mechanical power are not validated in this cohort. Three independent analyses were performed: a univariate analysis, to assess for associations between mPAP and mechanical ventilation parameters using Pearson correlation coefficients, a multivariate analysis, to assess for independent associations with mPAP using a multiple regression model according to Akaike’s information criteria and finally an analysis for nonlinearity, using the best-fitting model according to the Bayesian information criterion (BIC) from linear, quadratic, fractional polynomial and restricted cubic spline models.ResultsAll the ventilation parameters demonstrated a significant correlation with mPAP, except tidal volume (once adjusted for respiratory rate) in the univariate analysis. The multivariate analysis demonstrated that the blood pH level, P/F ratio, PaCO2 level, mean airway pressure and the mechanical power indexed to compliance were independently associated with mPAP. In the final nonlinear analysis, associations did not differ from linearity except for 4 variables for which the fractional polynomial was the best-fitting model. These were mechanical power (p = 0.01 compared to the linear model), respiratory rate (p = 0.04), peak pressure (p = 0.03) and mean airway pressure (p = 0.01). Two nonlinear variables associated with mPAP were assessed in more detail, respiratory rate and mechanical power. Inflexion points at a respiratory rate of 16.8 cycles per minute and a mechanical power of 8.8 J/min were demonstrated.ConclusionsThe associations identified between mPAP and mechanical ventilation variables in this analysis would suggest that classical ARDS lung protective strategies, including low tidal volume ventilation and permissive hypercapnia, may negatively impact the management of the subset of ARDS patients with associated right ventricular dysfunction or ACP. Additionally, respiratory rates above 17 cycles per minute show an incremental increase in mPAP. Therefore, increases in tidal volume (within the limitation of driving pressure < 18 cmH20) may represent a more right ventricular protective way to control CO2 and pH.

Efficacy of recruitment manoeuvre with or without antiderecruitment strategy in ARDS patients: A prospective study

Introduction: Lung recruitment manoeuvre (RM) opens up collapsed segments of the ARDS lung but the collapse may reappear once the RM is complete and pre-RM positive end-expiratory pressure (PEEP) is applied. Aim: Evaluation of the outcome of setting PEEP using decrement PEEP titration (antiderecruitment manoeuvre - ADRM) after an alveolar recruitment manoeuvre (RM) in ARDS patients. Methods: Twenty four mechanically ventilated adult patients with ARDS were enrolled. This was a randomised, prospective study. After recording baseline parameters, on pressure control ventilation and stabilisation, RM was performed. The responders were randomly assigned to one of two groups: ‘Antiderecruitment RM’ (ADRM) group and ‘Only RM’ (RM) group. ADRM group received RM using volume control ventilation and optimal PEEP was set after RM using decremental PEEP titration method. The RM group patients were returned to baseline ventilator settings after manoeuvre. Results: Of the 24 patients, 13 were males and 11 female. The mean (± SD) age was 43 (± 13.43) years. Twelve patients responded to the initial recruitment manoeuvre of which six were assigned to RM group and six to ADRM group. There was no difference in survival rate between the groups. The ICU and hospital stay were shorter in patients in ADRM group as compared to only RM group. Conclusion: Only half of the patients with ARDS respond to recruitment manoeuvres with an improvement in oxygenation. In most responders, the improvement is sustained irrespective of whether RM only or ADRM was used. Mortality is high if the baseline P/F ratio is below 90.

Exposure modality influences viral kinetics but not respiratory outcome of COVID-19 in multiple nonhuman primate species.

The novel coronavirus SARS-CoV-2 emerged in late 2019, rapidly reached pandemic status, and has maintained global ubiquity through the emergence of variants of concern. Efforts to develop animal models have mostly fallen short of recapitulating severe disease, diminishing their utility for research focusing on severe disease pathogenesis and life-saving medical countermeasures. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species of nonhuman primates (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM). Species-specific cohorts were experimentally infected with SARS-CoV-2 by either direct mucosal (intratracheal + intranasal) instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated analogous viral loads in all compartments by either exposure route although the magnitude and duration of viral loading was marginally greater in AGMs than RMs. Clinical onset was nearly immediate (+1dpi) in the mucosal exposure cohort whereas clinical signs and cytokine responses in aerosol exposure animals began +7dpi. Pathologies conserved in both species and both exposure modalities include pulmonary myeloid cell influx, development of pleuritis, and extended lack of regenerative capacity in the pulmonary compartment. Demonstration of conserved pulmonary pathology regardless of species and exposure route expands our understanding of how SARS-CoV-2 infection may lead to ARDS and/or functional lung damage and demonstrates the near clinical response of the nonhuman primate model for anti-fibrotic therapeutic evaluation studies.

Thoracic Computed Tomography to Assess ARDS and COVID-19 Lungs.

This review was designed to discuss the role of thoracic-computed tomography (CT) in the evaluation and treatment of patients with ARDS and COVID-19 lung disease. Non-aerated lungs characterize the ARDS lungs, compared to normal lungs in the lowermost lung regions, compressive atelectasis. Heterogenous ARDS lungs have a tomographic vertical gradient characterized by progressively more aerated lung tissues from the gravity-dependent to gravity-independent lungs levels. The application of positive pressure ventilation to these heterogeneous ARDS lungs provides some areas of high shear stress, others of tidal hyperdistension or tidal recruitment that increases the chances of appearance and perpetuation of ventilator-induced lung injury. Other than helping to the correct diagnosis of ARDS, thoracic-computed tomography can help to the adjustments of PEEP, ideal tidal volume, and a better choice of patient position during invasive mechanical ventilation. Thoracic tomography can also help detect possible intra-thoracic complications and in the follow-up of the ARDS patients’ evolution during their hospital stay. In COVID-19 patients, thoracic-computed tomography was the most sensitive imaging technique for diagnosing pulmonary involvement. The most common finding is diffuse pulmonary infiltrates, ranging from ground-glass opacities to parenchymal consolidations, especially in the lower portions of the lungs’ periphery. Tomographic lung volume loss was associated with an increased risk for oxygenation support and patient intubation and the use of invasive mechanical ventilation. Pulmonary dual-energy angio-tomography in COVID-19 patients showed a significant number of pulmonary ischemic areas even in the absence of visible pulmonary arterial thrombosis, which may reflect micro-thrombosis associated with COVID-19 pneumonia. A greater thoracic tomography severity score in ARDS was independently related to poor outcomes.

The Effects of Endotracheal Tube Size During Bronchoscopy in Simulated Models of Intubated Patients.

The aim is to use a simulation lung model to assess the possibility of performing bronchoscopy through endotracheal tubes (ETT) less than 8.0-mm while appropriately ventilating patients with normal and ARDS lungs in the setting of SARS-CoV-2. Five SHERIDAN® ETTs were used to ventilate SimMan® 3G under respiratory compliance levels representing normal and severe ARDS lungs. Baseline measurements of peak pressure, plateau pressure, and auto-positive end expiratory pressure (auto-PEEP) were recorded at four different inspiratory times (Ti). Three different-sized disposable bronchoscopes were inserted, and all measurements were repeated. Normal lung model: Slim bronchoscopes in 6.0-mm ETTs resulted in plateau pressures <30 cm H2 O, and increasing Ti to minimize peak pressure resulted in low auto-PEEP. Regular bronchoscopes in 7.0-mm ETTs had similar results. Large bronchoscopes in 7.5-mm ETTs generated plateau pressures ranging from 28 to 35 cm H2 O with modest auto-PEEP. Severe ARDS lung model: Slim bronchoscopes in 6.0-mm ETTs resulted in plateau pressures of 46 and an auto-PEEP of 5cm H2 O. Regular bronchoscopes in 7.0-mm ETTs generated similar results. Large bronchoscopes in 8.0-mm ETTs displayed plateau pressures of 44 and an auto-PEEP of 2cm H2 O. To mitigate risk of laryngeal injury, larger ETTs during bronchoscopy should be avoided. Our data show bronchoscopy with any ETT causes auto-PEEP and high plateau pressures, especially in lungs with poor compliance; however, ETT less than 7.5 mm can be used when considering several factors. Our data also suggest similar studies in patients with varying degrees of ARDS would be informative. NA Laryngoscope, 133:147-153, 2023.

ENAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling

Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.

MiR-29a-3p Improves Acute Lung Injury by Reducing Alveolar Epithelial Cell PANoptosis.

Alveolar epithelial cell damage is an important determinant of the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the molecular mechanisms of alveolar epithelial death during the development of ALI/ARDS remain unclear. In this study, we explore the role of miR-29a-3p in ALI/ARDS and its molecular mechanism. Plasma samples were collected from healthy controls and ARDS patients. Mice were intratracheally instilled with lipopolysaccharide (LPS) to establish acute lung injury. N6-adenosine (m6A) quantification, RNA-binding protein immunoprecipitation, cell viability assay, quantitative real-time polymerase chain reaction, and western blotting were performed. We found that miR-29a-3p was down-regulated in plasma of ARDS patients and lung tissue of ALI model mice, and miR-29a-3p agomir injection down-regulated the levels of the inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the lungs, reducing alveolar epithelial cell PANoptosis as evaluated by the downregulation of Z-DNA binding protein 1 (ZBP1), gasdermin D (GSDMD), caspase-3, caspase-8, and mixed lineage kinase domain-like protein (MLKL), ultimately improving lung injury in the ALI model mice. Mechanism studies demonstrated that the knockout of methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed the m6A modification of miR-29a-3p and reduced miR-29a-3p expression. Our findings suggest that miR-29a-3p is a potential target that can be manipulated for ALI/ARDS.

Pulmonary function, computerized tomography features and six-minute walk test at three months in severe COVID-19 patients treated with intravenous pulsed methylprednisolone: a preliminary report.

COVID-19 acute respiratory distress syndrome (ARDS) has a high mortality and few therapeutic options. We present a preliminaryreport on our experience using high-dose pulsed methylprednisolone in COVID-19 ARDS and three-month outcomes.We performed a retrospective analysis of all patients treated with high-dose methylprednisolone for COVID-19ARDS and three-month lung function, 6-minutes walking test (6MWT), and computerized tomography (CT) findings. Fifteenpatients were treated of which 10 survived to discharge. Reduced diffusion capacity for carbon monoxide (DLCO) was the commonestabnormality in lung function tests and had the lowest mean value. Parenchymal bands were the commonest CT findingand 50% of patients had fibrosis at three months. Mean 6-minutes walk distance (6MWD) was 65.4% predicted and wasabnormal in 62.5% of patients. In this cohort of patients with COVID-19 ARDS treated with high-dose methylprednisolonepulses, CT, lung function, and 6MWT abnormalities were unsurprisingly common at three months, although all 10 patients treatedearly in their disease course survived, a possible therapeutic effect. Further randomised controlled trials are needed to assessthe benefits of this treatment.

COVID-19 Associated ARDS Lung's Histopathological Findings:&amp;nbsp;A Systematic Review and Meta-Analysis

Background: COVID-19 is a relatively new disease that can progress to ARDS, respiratory failure and death. Identifying specific morphological lung injury in COVID-19 patients, can give a better understanding of subjacent physiopathology.Our aim is to provide a rigorous summary of the evidence available of lung histological findings in COVID-19 patients.Methods:Eligibility criteria: Any quantitative design, reporting raw data of lung histological findings in COVID-19 patients. Reviews, guidelines, other organs’ histological features were excluded.Information sources: The centralized repository L·OVE (Living OVerview of Evidence), PubMed/Medline, Cochrane Central Register of Controlled Trials (CENTRAL), LitCovid, WHO Covid-19 Database, and medRxiv. The search covered the period from January 1, 2020 until April 3, 2021.Risk of bias: was assessed using Joanna Briggs Institute tools, by four observers and consensus.Synthesis of Results: Each and every lung histopathological finding was extracted. Frequencies for each finding were calculated, and then data from the two most frequent findings were pooled by meta-analysis using a Der Simmonian-Liard model with random-effects model. Heterogeneity was measured.Results:Included studies: From 252 references, 69 articles fulfilled inclusion criteria, summarizing 594 subjects.Synthesis of results: Demographic: 381 men, 179 female and 34 not specified. Mean age in case series was 87.57 years (SD+ 1.57), and in case reports 61.85 years (SD + 1.51). Fourteen case series (45.16%), and 21 case reports (55.26%) presented low risk of bias. Meta-analysis of proportions showed DAD in 0.62 (CI 95% 0.51-0.72), I2 59% (pDiscussion: The limitations of the evidence included in the review was a relative selection bias for included subjects. Interpretation: Early DAD was the most frequent histopathological finding in lung samples from severe COVID-19 patients. Registration Details: Study’s registration number PROSPERO CRD4202018936.Funding Information: There was no source of funding.Declaration of Interests: We all declare no conflict of interest.

Lung mechanics in type L CoVID-19 pneumonia: a pseudo-normal ARDS

BackgroundThis study was conceived to provide systematic data about lung mechanics during early phases of CoVID-19 pneumonia, as long as to explore its variations during prone positioning.MethodsWe enrolled four patients hospitalized in the Intensive Care Unit of “M. Bufalini” hospital, Cesena (Italy); after the positioning of an esophageal balloon, we measured mechanical power, respiratory system and transpulmonary parameters and arterial blood gases every 6 hours, just before decubitus change and 1 hour after prono-supination.ResultsBoth respiratory system and transpulmonary compliance and driving pressure confirmed the pseudo-normal respiratory mechanics of early CoVID-19 pneumonia (respectively, CRS 40.8 ml/cmH2O and DPRS 9.7 cmH2O; CL 53.1 ml/cmH2O and DPL 7.9 cmH2O). Interestingly, prone positioning involved a worsening in respiratory mechanical properties throughout time (CRS,SUP 56.3 ml/cmH2O and CRS,PR 41.5 ml/cmH2O – P 0.37; CL,SUP 80.8 ml/cmH2O and CL,PR 53.2 ml/cmH2O – P 0.23).ConclusionsDespite the severe ARDS pattern, respiratory system and lung mechanical properties during CoVID-19 pneumonia are pseudo-normal and tend to worsen during pronation.Trial registrationRestrospectively registered.

Therapeutic Potential of Heme Oxygenase-1 and Carbon Monoxide in Acute Organ Injury, Critical Illness, and Inflammatory Disorders.

Heme oxygenase-1 (HO-1) is an inducible stress protein that catalyzes the oxidative conversion of heme to carbon monoxide (CO), iron, and biliverdin (BV), the latter of which is converted to bilirubin (BR) by biliverdin reductase. HO-1 has been implicated as a cytoprotectant in various models of acute organ injury and disease (i.e., lung, kidney, heart, liver). Thus, HO-1 may serve as a general therapeutic target in inflammatory diseases. HO-1 may function as a pleiotropic modulator of inflammatory signaling, via the removal of heme, and generation of its enzymatic degradation-products. Iron release from HO activity may exert pro-inflammatory effects unless sequestered, whereas BV/BR have well-established antioxidant properties. CO, derived from HO activity, has been identified as an endogenous mediator that can influence mitochondrial function and/or cellular signal transduction programs which culminate in the regulation of apoptosis, cellular proliferation, and inflammation. Much research has focused on the application of low concentration CO, whether administered in gaseous form by inhalation, or via the use of CO-releasing molecules (CORMs), for therapeutic benefit in disease. The development of novel CORMs for their translational potential remains an active area of investigation. Evidence has accumulated for therapeutic effects of both CO and CORMs in diseases associated with critical care, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS), mechanical ventilation-induced lung injury, pneumonias, and sepsis. The therapeutic benefits of CO may extend to other diseases involving aberrant inflammatory processes such as transplant-associated ischemia/reperfusion injury and chronic graft rejection, and metabolic diseases. Current and planned clinical trials explore the therapeutic benefit of CO in ARDS and other lung diseases.

Higher Tissue Factor (TF) Expression in the Lungs of COVID-19 Pneumonia Patients Than Patients with Acute Respiratory Distress Syndrome: Association with Thrombi Formation

A substantial proportion of patients with severe COVID-19 pneumonia develop thrombosis (both venous and arterial) via an undefined mechanism. Systemic elevation of high levels of D-dimer, a marker of coagulation activation and thrombolysis, is evident in almost all advanced COVID-19 patients and is associated with disease severity and mortality. However, the extrinsic factors that initiate blood coagulation in COVID-19 is not clear. Because tissue factor (TF) is the prime initiator of the extrinsic coagulation cascade, and because it is expressed and exposed under inflammatory conditions leading to vascular damage, we tested the hypothesis that higher TF expression is responsible for thrombi formation in the lungs of patients with severe COVID-19.To this end, we examined autopsy lung tissues from five COVID-19 pneumonia patients with acute respiratory syndrome (ARDS) who required ICU hospitalization, with 4 of the 5 patients requiring mechanical ventilation before they died, and five controls with acute ARDS caused by bacterial pneumonia, one with a prior influenza infection, and all on mechanical ventilation. Histological findings revealed all the COVID-19 lungs had characteristics of ARDS, including DAD with hyaline deposition and inflammatory cell invasion. Immunofluorescence staining showed TF expression throughout all lung tissues and in many blood vessels that were filled with thrombi with either fibrin, activated platelets, or both. TF expression was significantly higher in COVID-19 than control ARDS lung tissues (1.2 ± 0.3% in COVID-19 vs. 0.52 ± 0.2% in ARDS controls (p=0.004). Fibrin-enriched thrombi areas were higher in COVID-19 cases than in controls (1.6 ± 0.36% vs. 0.94 ± 0.4%; p=0.008) and correlated with TF expression (R2=0.4, p=0.02). Platelet factor 4 (PF4)-enriched thrombi areas were also higher in COVID-19 lung, but this trend was not statistically significant (0.94 ± 0.4% in COVID-19 and 0.54 ± 0.3% in controls; p=0.09), although it did, however, correlate with TF expression (R2=0.4, p=0.02). Many thrombi were in close proximity to TF-expressing areas in both COVID-19 and ARDS pneumonia controls.Dual RNA in situ hybridization with SARS-CoV-2 and TF fluorescence probes showed variable viral and TF mRNA expression. Increased TF mRNA expression was seen in COVID-19 vs. control lung (0.77 ± 0.4 % vs. 0.31 ± 0.15 %, p=0.05). TF mRNA expression correlated with viral mRNA in COVID-19 patients (R2=0.78, p=0.01). High-resolution images identified both sporadic and clustered SARS-CoV-2, and some areas co-localized with TF mRNA expression.We conclude that higher TF expression might be responsible for fibrin formation and platelet activation in the lungs of both COVID-19 and ARDS controls. Our observation of higher TF expression in COVID-19 patients was documented by two very sensitive methods, RNA in situ hybridization and immunostaining with very specific antibodies against TF and mRNA probes. Its correlation with SARS-CoV-2 mRNA suggests that SARS-CoV-2 infection induces both de novo gene transcription and protein synthesis in the lungs of COVID-19 patients. Thus, TF-initiated extrinsic coagulation might be responsible for the critical thrombi formation observed in many COVID-19 cases, rendering TF a potential therapeutic target.DisclosuresLaurence:Alexion Pharmaceuticals: Honoraria, Research Funding.

Dapsone as treatment adjunct in ARDS

Multiple pharmacological interventions tested over the last decades have failed to reduce ARDS mortality. This short note recounts past data indicating that (i) neutrophils home along an IL-8 gradient, (ii) in ARDS, massive neutrophil accumulation and degranulation in and along bronchoalveolar spaces contributes to damage and hypoxia, (iii) large increases in IL-8 are one of the chemotaxic signals drawing neutrophils to the ARDS lung, and (iv) old data from dermatology and glioblastoma research showed that the old drug against Hansen’s disease, dapsone, inhibits neutrophils’ chemotaxis to IL-8. Therefore dapsone might lower neutrophils’ contributions to ARDS lung pathology. Dapsone can create methemoglobinemia that although rarely problematic it would be particularly undesirable in ARDS. The common antacid drug cimetidine lowers risk of dapsone related methemoglobinemia and should be given concomitantly.

Incidence of Biofilm Formation in ET Tube and Correlation with Occurrence of VAP in a Tertiary Care ICU

Introduction: VAP is one of the most frequent hospital-acquired infections occurring in mechanically ventilated patients and is associated with increased mortality, morbidity, and health-related costs. Bacterial biofilm has been observed universally on the surface of endotracheal tubes in mechanically ventilated patients. Some data show a good concordance between bacterial colonization of the airway and microbial findings in the biofilm. Even the same microorganisms causing VAP could be found in the ETT biofilm leading to the potential implication of biofilm in the genesis of VAP. Aims and Objectives: The objective was to investigate the involvement of ETT biofilm in VAP pathogenesis. Materials and Methods: This observational descriptive study was conducted in Department of Pulmonary Medicine, D.Y Patil Hospital, Nerul, Navi Mumbai. Approval of Institutional Ethics Committee was taken before start of the study. A written signed informed consent was taken prior to enrolling the subjects in the study. Patients requiring mechanical ventilation for at least 24 hours were included in the study. The following data were recorded in a standardized form: age and sex of the patient, cause of mechanical ventilation, duration of ventilation, manoeuvres to prevent VAP, the occurrence or not of nosocomial pneumonia, together with data of pathogen isolated in respiratory samples and/or ETT biofilm, antibiotic therapy and sensitivity patterns. Statistical Method: Descriptive and analytical statistics was done. The data was analyzed using statistical software (IBM SPSS V20.1, IBM Corporation, Armonk, NY, USA). The results are expressed as mean ± standard deviation and proportions. Categorical variables were compared using chi-square tests. The statistical significance was determined at p<0.05.Results: A total of 55 subjects fulfilling the inclusion criteria were participated in the study. The mean age of the study population was 46.56 19.79 with a range of 18 to 87 years. There were 23 (41.8%) males and 32 (58.2%) female’s subjects in the study population. The patients were intubated for mainly three reasons – AHF, ARF and CVA. The diagnosis of the ventilated patients was as follows – pneumonia (25.4%), ARDS (18.2%), cerebral stroke (16.4%), septic shock (16.4%), hemorrhagic shock (9.1%), cardiac arrest (7.3%), cardiopulmonary failure (5.4%) and interstitial lung disease (1.8%). The mean duration of intubation was 10.23 1.55, ICU days was 13.45 1.34 and hospital days was 19.72 2.84. Out of the 55 ventilated patients, 9 (16.3%) patients developed VAP. Biofilm was found positive in 30 (54.5%) patients. In the present study the three most common organisms found in ET tube were Acinetobacter (23.6%), klebsiella (18.2%), E.Coli (7.3%). The other organisms found were Pseudomonas (7.3%), Candida Albicans (3.6%) and staphylococcus (1.8%). The incidence of VAP development in biofilm positive cases was 30%. Conclusion: Biofilms are highly organized microbial communities which in vivo play an important part in evading the defence mechanism and obstinate the antimicrobial therapy. The precise link between biofilm productions in mechanically ventilated patients is still obscure apart from some limited studies which have described role of a specific pathogen or virulence factor. The present study, thus, showed that majority of the pathogens isolated possessed capability to produce biofilm.

Mechanical Ventilation in the Prehospital and Emergency Department Environment.

Patients who require mechanical ventilation in the prehospital and emergency department environments experience high mortality and are at high risk of ventilator-associated ventilator-induced lung injury and ARDS. In addition, little attention has been given in the literature, trainee education, or clinical emphasis to ventilator management in these patients. ARDS and ventilator-induced lung injury are time-sensitive disease processes that develop early in mechanical ventilation and could potentially be prevented with early lung-protective ventilation. Prehospital and emergency department ventilation, in general, is characterized by potentially injurious tidal volume, high FIO2 , and low PEEP. Recent literature highlights improved subjects outcomes in the setting of early lung-protective ventilation in both subjects with and those without ARDS. This review of the literature led us to recommend that lung-protective ventilation with avoidance of hyperoxia be the default goal ventilator strategy for all patients with prehospital and emergency department mechanical ventilation. This can be achieved by delivering low tidal volumes with stepwise, concurrent titration of FIO2 and PEEP to facilitate adequate oxygenation.

Prone Positioning in Moderate-Severe ARDS: Preliminary Data From a Community-Based Teaching Hospital

SESSION TITLE: ARDS and Acute Lung Injury SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: In 2013, after publication of a randomized controlled trial that demonstrated a mortality benefit to ventilation in the prone versus supine position in ARDS, critical care physicians at our institution began to implement this approach. Prior to this, we rarely used prone positioning in our medical ICU and we did not know if the mortality and low complication rate observed in the trial, at centers with >5 years of experience with proning, could be replicated at our institution or what impact this intervention would have on functional outcomes. METHODS: We conducted a retrospective cohort study of all proned patients from June 2013 to November 2014 at Christiana Care Health System. Patients were identified by respiratory care data. We collected demographic data, pre- and post- proning data, respiratory mechanics, diagnoses, complications, and outcomes including mortality, length of stay, and distance walked prior to discharge. Descriptive statistics are used to describe our cohort. RESULTS: Thirty seven patients underwent ventilation in the prone position. Of these, 23 (62%) survived to hospital discharge. The mean age was 56.3 years and 60% were male. The mean sequential organ failure score was 8.6. Immediately prior to proning, the mean positive end expiratory pressure was 14, mean driving pressure was 14 centimeters of water, mean partial pressure of arterial oxygen to fraction of inspired oxygen was 100 and mean tidal volume was 5.5 ml/kg of predicted body weight. Patients were proned for a mean of 41 hours. One patient received extracorporal membrane oxygenation, 31 (84%) received neuromuscular blocking agents, 6 (16.2%) received inhaled nitric oxide, and 21(57%) received steroids. None developed ventilator associated pneumonia or had cardiac arrests while proned. In terms of complications, 6 patients had dependent edema, 7 had dislodged devices, and 2 had skin breakdown. The mean hospital and ICU length of stays were 23 and 14, respectively. A total of 23 patients were able to ambulate a mean of 138 feet prior to hospital discharge. CONCLUSIONS: Hospital mortality was higher in this cohort than the 28-day mortality reported in the trial. However, serious complications from prone positioning were uncommon. The higher mortality rate could be due to differences in clinical care including use of adjuvent therapies or differences in patient selection. Additionally, during our study period in December 2013, we implemented a protocol for ventilation in the prone position. We plan additional data collection and analysis to determine is outcomes differ before and after protocol implementation.All of the survivors were ambulatory prior to hospital discharge. CLINICAL IMPLICATIONS: It is feasible to implement a proning protocol at a community hospital with limited prior experience; however, close monitoring of outcomes is needed to determine whether expected benefits are achieved. DISCLOSURE: The following authors have nothing to disclose: Fahmida Khan, Christa Fistler, Jefferson Mixell, Patricia McGraw, Michael Vest No Product/Research Disclosure Information

Lung inhomogeneities, inflation and [18F]FDG uptake rate in ards

In ARDS lung parenchyma presents great variability in inflation, lung inhomogeneities and [18F]FDG uptake. In fact, inflation progressively decreases along the sternum-vertebral axis[1] leading to further inhomogeneities that may act as “stress raiser”.[2] That can activate a local inflammatory response leading to edema.

Regional distribution of excess tissue mass in ARDS lung

ARDS is characterized by edema diffuse to all lung fields. Distribution of excess tissue mass had been studied with CT scan in a few patients on a single slice, comparing with data obtained in healthy controls.