Neonatal Cardio-Pulmonary Outcome Measure
Congenital Heart DefectRespiratory Distress Syndrome in Premature InfantNeonatal Cardio-Pulmonary outcome measure (N-COM) will be used to assess the overall status of pulmonary and cardiac vascular system of neonates in Neonatal Intensive Care Unit (NICU). There are many scales available which are helpful for assessing behavior, pain, and neurological status of neonates but there is no scale available till now which can help to assess cardio-pulmonary status of neonates.
Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)
COVIDARDS3 moreThis protocol proposes to use IC14, a recombinant chimeric monoclonal antibody (mAb) recognizing human CD14, to block CD14-mediated cellular activation in patients early in the development of ARDS. The binding of IC14 to human CD14 prevents CD14 from participating in the recognition of PAMPs and DAMPs due to SARS-CoV-2 infection. The putative mechanism of action of IC14 in ARDS is blockade of PAMP and DAMP interactions with CD14, thus attenuating the inflammatory cascade that leads to increased endothelial and epithelial permeability and injury resulting in alveolar injury and fluid accumulation characteristic of ARDS. IC14 is a chimeric monoclonal antibody that binds to CD14 with high affinity and inhibits signaling via membrane and soluble CD14. Blocking CD14 with IC14 treatment in normal volunteers strongly inhibits systemic inflammation in response to bacterial endotoxin (LPS). University of Washington conducted a small NIH-funded pilot trial of IC14 treatment in 13 patients with ARDS, which suggested that IC14 treatment reduced alveolar inflammation and decreased BAL cytokines. IC14 was also the subject of IND 105803 for a phase 2 study of ARDS from all causes which we propose to revise for the COVID-19 indication. A dosing regimen for IC14 with favorable pharmacokinetics supporting once daily intravenous dosing has been defined, making this an acceptable treatment for hospitalized patients. Two pharmacodynamic biomarkers can be used that are related to CD14, measurements of sCD14 (serum at baseline; urine at baseline and follow up) as well as a CD14 fragment (sCD14-ST; presepsin). A CD14 target engagement assay is available. Therefore, because of the central role of CD14 in the amplification of lung inflammatory responses leading to severe lung injury and the safety record of IC14 in humans, we propose to have an open-label protocol to test the safety and potential efficacy of IC14 treatment in preventing the progression of severe respiratory disease in patients hospitalized with COVID-19.
Acute Kidney Dysfunction in COVID-19 and Non-COVID-19 Related ARDS
COVID-19 Acute Respiratory Distress SyndromeAcute Kidney Injury Due to COVID-19In addition to respiratory involvement, SARS-CoV 2, the virus responsible for coronavirus 2019 or Covid-19, appears to be responsible for renal involvement such as acute renal failure or proteinuria, so the mechanisms are not known at this time. The consequences of Covid-19 on renal function in the short and long term are not known. It is important to be able to better document these renal impairments to understand the mechanisms of this disease. The main objective of this study is to describe the prevalence of Covid-19-related renal damage (acute renal failure, proteinuria, microalbuminuria, hematuria) in a large cohort of patients in intensive care for SARS-CoV 2 infection with severe respiratory impairment. The other objectives will be to evaluate in this cohort the impact of these renal impairments on the severity of the Covid-19 disease, and to compare them to the renal impairments of patients in intensive care for acute respiratory distress syndrome (ARDS) due to other respiratory diseases. Blood and urine samples will be taken at the time of intubation in all critically ill patients with respiratory distress requiring mechanical ventilation for Covid-19 or other cause of respiratory distress with PaO2/FiO2 ratio < 300. Patients will be followed for the duration of their ICU and hospital stay. Data will be collected prospectively in three ICUs in the University Hospitals of Marseille.
Impact of Inflammation Biomarkers on the Acute Respiratory Distress Syndrome (ARDS) Definition
Acute Respiratory Distress SyndromeThe ARDS has a clinical definition with criteria of the American-European Consensus Conference (1994). This definition inconveniently applies to a lot of patients with acute respiratory failure. We know that there are 2 forms of ARDS morphology on CT scan : "lobar attenuation" (loss of aeration with no concomitant excess in lung tissue) predominating in the lower lobes and "non lobar attenuation" with diffuse and massive loss of aeration with excess lung tissue in all the pulmonary parenchyma. Today, plasmatic biomarkers are used as prognostic and diagnostic markers of ARDS. Some of them are characteristics of the different damages in the ARDS (alveolar epithelium and vascular endothelium lesions) : sRAGE, SP-D, PAI 1 and sICAM 1. This study's hypothesis is that patients with ARDS criteria and lobar morphology on CT scan present loss of aeration but no inflammatory pulmonary oedema, whereas patients with non lobar morphology on CT scan present both characteristics. The primary purpose of our protocol is to show that the patients who respond to ARDS criteria and have a lobar morphology on CT scan do not have an elevation of the biomarkers specific to the pulmonary aggression of ARDS.
Intrabronchial Airway Pressures in Intubated Patients During Bronchoscopy
Acute Respiratory Distress SyndromeAcute Lung Injury (ALI)The purpose of this study is to examine changes in ventilation and airway pressures during conventional bronchoscopy of intubated patients.
Observational Study on the Prophylactic Use of Curosurf in Neonatal Respiratory Distress Syndrome...
Respiratory Distress SyndromeNewbornThe aim of Alizé is to describe a population of premature babies (gestational age (GA) < 32 weeks) in real life situation and the management of RDS.
Epidemiology of Respiratory Insufficiency in Critical Care
Acute Respiratory FailureAcute respiratory failure is a common entity in intensive care units nowadays and is associated with significant morbidity and mortality, thus representing a major health problem. Most of the published epidemiological studies on this condition were performed when modern ventilatory strategies and non-invasive ventilation were not available. Therefore, an actual evaluation on the incidence and outcomes of this syndrome is mandatory. We will perform an observational prospective study of patients admitted with acute respiratory insufficiency in several ICUs in Brazil.
Genetic Regulation of Surfactant Deficiency
Respiratory Distress SyndromeNewbornInherited deficiencies in any one of 3 genes (surfactant protein B, surfactant protein C, and ATP-binding cassette transporter A3) can cause neonatal respiratory distress syndrome by disrupting metabolism of the pulmonary surfactant. The investigators will use state of the art methods to link specific changes in the genetic code of each of these genes with disruption of discrete steps in the metabolism of the pulmonary surfactant in human newborn infants. These studies will lead to improved diagnostic capabilities and suggest novel strategies to correct surfactant deficiency in newborn infants.
Estimation of Intrinsic Positive End-Expiratory Pressure (PEEP) in Acute Respiratory Distress Syndrome...
Acute Respiratory Distress SyndromeARDS (Acute Respiratory Distress Syndrome) is a condition of severe inflammation and excess fluids in the lungs that impairs their function of oxygen uptake to the point of needing a ventilator (breathing machine) to help them obtain enough oxygen into the body. Because of the high amounts of gas that the ventilator has to give to these patients, high pressures may develop deep into the lungs and produce complications for the patient. However, physicians sometimes cannot recognize it because it requires special equipment to measure pressure deep in the lungs. The goal of this study is to determine if the amount of this pressure can be calculated using mathematical formulas and the routine numbers provided by ventilators. The study consists on making the conventional measurement of this deep pressure and at the same time calculate this same pressure from other measurements that the ventilator routinely provides, to see if the calculated value can replace the more complicated conventional measurement. The measurements will be done by: placing a small device along the tubing connecting the patient to the ventilator; giving medicines to relax the muscles (if the patient is not already receiving them); and making the ventilator hold the patient's breath for a few seconds to take measurements. This is repeated after the breathing rate of the ventilator is increased or decreased mildly. Risks related to the medicine to be used and the measuring maneuvers are rare but include transient narrowing of windpipes, transiently low heart rate, blood pressure or blood oxygen, and allergic reactions. This is not a treatment. The information obtained during the study will be shared with the treating doctors who may find it useful to make adjustments to the ventilator. The patient may receive no direct benefit from being in this study; however, the findings may contribute to better care for this kind of patients in the future.
Validation of the Percentage of Alveolar Fibrocyte as Biomarker During ARDS
Acute Respiratory Distress Syndrome (ARDS)Mechanical VentilationFibrocyte is a monocyte sub-population involved in fibroproliferation/repair processes and associated with outcome in different diseases. In previous study, we have demonstrated the presence of alveolar fibrocytes during Acute expiratory Distress Syndrome (ARDS) and their association with patient outcome. The purpose of this multicentric observational prospective study is to describe the percentage of alveolar fibrocytes in ICU patients with ARDS (survivors vs. non survivors) and to confirm their association with 28-day mortality.