Dissertations / Theses on the topic 'Syndrome de détresse respiratoire aiguë de l'adulte – Thérapeutique'
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Jabaudon, Gandet Matthieu. "Approche translationnelle de la voie RAGE au cours du syndrôme de détresse respiratoire aiguë : implications diagnostiques, physiopathologiques et thérapeutiques." Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM09.
Full textThe acute respiratory distress syndrome (ARDS) is associated with diffuse alveolarinjury leading to increased permeability pulmonary edema and hypoxemic respiratory failure. Despite recent improvements in intensive care, ARDS is still frequent and associated with high mortality and morbidity. Two major features of ARDS may contribute to mortality and response to treatment: impaired alveolar fluid clearance (AFC), i.e. altered capacity of the alveolar epithelium to remove edema fluid from distal lung airspaces, and phenotypes of severe inflammation. Pharmacological approaches of ARDS treatment are limited and further mechanistic explorations are needed to develop innovative diagnostic and therapeutic approaches. The receptor for advanced glycation endproducts (RAGE) is a multiligand pattern recognition receptor that is abundantly expressed by lung alveolar epithelial cells andmodulates several cellular signaling pathways. There is growing evidence supporting sRAGE (the main soluble isoform of RAGE) as a marker of epithelial cell injury, and RAGE may be pivotal in ARDS pathophysiology through the initiation and perpetuation of inflammatory responses. Our objectives were to characterize the roles of RAGE in ARDS through a translational approach combining preclinical and clinical studies. First, observational and interventional clinical studies were conducted to test sRAGE as a biomarker during ARDS.Then, cultures of epithelial cells, macrophages and a mouse model of acidinduced lung injury were used to describe the effects of RAGE pathway on AFC and inflammation, with special emphasis on a macrophage activation through NodLikeReceptor family, Pyrindomain containing 3 (NLRP3) inflammasome. Acidinjured mice were treated with an antiRAGE monoclonal antibody or recombinant sRAGE to test the impact of RAGE inhibition on criteria of experimental ARDS. Results from clinical studies support a role of sRAGE as a biomarker of ARDS, withdiagnostic, prognostic and predictive values. In addition, plasma sRAGE is correlated with a lung imaging phenotype of nonfocal ARDS and could inform on therapeutic response. Herein, we also describe in vivo and in vitro effects of RAGE activation on transepithelial fluid transport and expression levels of epithelial channels (aquaporin 5, αNa,KATPaseandαENaC) and on macrophage activation through NLRP3 inflammasome. Finally, RAGE inhibition improves AFC and decreases lung injury in vivo. Taken together, our findings support a role of RAGE pathway in the regulation of lung injury, AFC and macrophage activation during ARDS, albeit precise regulatory mechanisms remain uncertain. sRAGE has most features of a validated biomarker that could be used in clinical medicine, but whether it may help to identify subgroups (or phenotypes) of patients that would benefit from tailored therapy remains underinvestigated. Modulation ofRAGE pathway may be a promising therapeutic target, and though validation studies are warranted, such findings may ultimately open novel diagnostic and therapeutic perspectivesin patients with ARDS
Zhai, Ruoyang. "Effects of sevoflurane in the treatment of Acute Respiratory Distress Syndrome : a translational approach." Electronic Thesis or Diss., Université Clermont Auvergne (2021-...), 2023. http://www.theses.fr/2023UCFA0077.
Full textAcute respiratory distress syndrome (ARDS) is a major cause of respiratory failurewith a high mortality rate. It is characterized by diffuse alveolar damage, alveolar edema, and hypoxemic respiratory loss which cause heavy healthcare costs. Currently, available treatments for ARDS remain primarily supportive, and no pharmacological approach is successfully translated into clinical application. There are two major processes during the physiopathological development of ARDS that lead to the formation of lung edema:alveolar barrier dysfunction and the impairment of alveolar fluid clearance following alveolar epithelial injury and inflammation. The receptor for advanced glycation end products (RAGE) was indicated to be involved during those processes, with the high potential of its soluble form as a biomarker for ARDS diagnostic and prognostic. Volatile halogenated agents, such as sevoflurane or isoflurane, are increasingly used in intensive care units as sedative agents with their ideal intrinsic characteristics as a sedative. Furthermore, numerous pre-clinical and clinical studies indicate its lung protective effects for ARDS patients.However, its mechanisms of such beneficial effects remain to be clarified.The main objectives of this thesis work are multiple, through experimental andtranslational in vivo and in vitro models of ARDS, to1) Asses the beneficial lung protective effects of sevoflurane in ARDS, including its effects on ARDS physiological features, lung fluid clearance, and alveolar permeability.2) Investigate the precise mechanism of observed effects of sevoflurane, including mechanistic studies and involved proteins' function and expression.3) Explore the role of RAGE in lung epithelial injury and repair and its eventualmediation role of the beneficial effects of sevoflurane.During this thesis work, we advanced from many angles: First, our work found in ourA549 cells wound healing model, the important role of RAGE in the lung injury repairprocess, as its ligand, HMGB1, and AGEs promoted RAGE-dependent wound healing oflung alveolar epithelial cells, which is possible through enhanced cell migration and proliferation.Secondly, our work in murine in vitro and in vivo ARDS models, animprovement of experimental features, with decreased indices of permeability and preserved epithelial structures in cells and mice, by at least in a part, increasing expression of ZO-1 and the inhibition of RhoA activity and pMLC as well as actin cytoskeleton rearrangement following lung epithelial injury. Additionally, RAGE may play a mediating role in the effects of sevoflurane on acute lung injury. Furthermore, our work in porcine in vivo ARDS models confirmed the lung protective effects of sevoflurane on ARDS features, with improved oxygenation, restored alveolar permeability, and improved AFC. Our study suggests theprotective effect of sevoflurane on AFC may be explained by the restoration of impaired lung expression of epithelial channels AQP-5, Na, K, ATPase, and ENaC during ARDS.Taken together, this thesis work explained more precisely the protective effects ofhalogenated agents and the new revelation of its potential mechanism, and hence supports the high interest in the use of inhaled sedation in intensive care for ARDS patients. This work may give some new insights for research on the effects of sevoflurane on ARDS and its resolution.Keywords: Acute respiratory distress syndrome; Sevoflurane; Lung epithelial barrierfunction; Lung wound repair; Alveolar fluid clearance; Epithelial channels: Junction proteins;Intracellular pathways; Receptor for advanced glycation end-products
Delclaux, Christophe. "Rôle du polynucléaire neutrophile dans la physiopathologie du syndrome de détresse respiratoire aiguë." Paris 12, 1998. http://www.theses.fr/1998PA120016.
Full textRichard, Jean-Christophe M. "Recrutement alvéolaire au cours du syndrome de détresse respiratoire aigue͏̈ : influence de la ventilation." Paris 12, 2003. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990003948900204611&vid=upec.
Full textAim: To assess influence of ventilatory pattern on alveolar recruitment measured by pressure volume curves (PV Curve) in acute respiratory distress syndrome (ARDS). Methods: We tested : PEEP, tidal volume (\/t), plateau pressure (Pplat) and respiratorv rate (RR). Results: (I) linear compliance on the zero end expiratory (ZEEP) PV curve reflected continuous alveolar recruitment. Recruitrnent induced by PEEP was associated with compliance reduction. (2) Pulmonary closing pressure that theoretically indicates a maximal PEEP was not tound for PEEP below 20 cmH2O. Potential for recruitment vas positively correlated with linear compliance measured on the ZEEP PV curve. (3) Vt reduction induced significant alveolar derecruitment. (4) Increasing RR resulted in gas trapping. Conclusions: Alveolar recruirnient is a continuous process. High compliance measured on the ZEEP PV curve, indicates that the lung is highly recruitable. Both, Pplat and PEEP may affect recruitment
Constantin, Jean-Michel. "Recrutement alvéolaire dans le syndrome de détresse respiratoire aigüe : approche morphométrique et biochimique." Clermont-Ferrand 1, 2007. http://www.theses.fr/2007CLF1MM21.
Full textAcute respiratory distress syndrome (ARDS) is a very frequent cause of respiratory failure in intensive care units with a poor outcome. Alveolar derecruitment (i. E atelectasis and lung oedema) is a major concept in ARDS. In the first part of the manuscript, we describe the pathophysiological aspect of alveolar derecruitment, the ways to avoid it and how to increase alveolar recruitment. In the second part, we tried to propose answers to 3 questions : How could we assess alveolar recruitment with CT-Scan and at bedside ; how could we increase alveolar recruitment and what happened in the lung when we performed recruitment maneuvers (RM) ? We have described a new method of CT-scan assessment of alveolar recruitment, we have compared this method usable at bedside. We have compared 2 RM and our data suggested that an extended sigh, ventilatory mechanics-based pressure level is more efficient that one CPAP performed at the same pressure level for the same time in all patients with ARDS. We have shown that response to RM influences net alveolar fluid clearance. CT-scan analysis of RM-induced changes in lung has been described. The prospects were presented
Maggiore, Salvatore Maurizio. "Le dérecrutement alvéolaire au cours du syndrome de détresse respiratoire aigue͏̈ : mécanismes physiopathologiques et prévention." Paris 12, 2003. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002111190204611&vid=upec.
Full textIntroduction. The acute respiratory distress syndrome is characterized by alveolar instability and tendency for derecruitment. Aims. To study the influence of ventilatory settings and diagnostic and therapeutic procedures on derecruitment, and its prevention. Interventions. 1) Reduced tidal volume (Vt) ; 2) decreasing positive end-expiratory pressure (PEEP) ; 3 ) endotracheal suctioning ; 4) fiberoptic bronchoscopy. Results. 1)Vt reduction induces a derecruitment, prenvented by PEEP. 2) Alveolar closure is a continuous process, starting at high pressures. 3) Endotracheal suctioning induces a massive derecruitment, prevented by recruitment maneuvers during the procedure. 4) Fiberoptic bronchoscopy induces oxygenation disturbances, prevented by the application of continuous airway pressure during the procedure. Conclusions. Alveolar derecruitment is influenced by ventilatory settings and diagnostic and therapeutic procedures, and may be prevented by PEEP and recruitment maneuvers during such procedures
Le, Bouffant Gildas. "Administration prolongee d'isoflurane au cours du syndrome de détresse respiratoire aigue de l'adulte : à propos de deux observations." Amiens, 1990. http://www.theses.fr/1990AMIEM055.
Full textDuboucher, Christophe. "Contribution à l'étude des trichomonoses pulmonaires." Lille 2, 2007. http://www.theses.fr/2007LIL2S034.
Full textLe, Tulzo Yves. "Réponses immunitaires locales et systémiques au cours de l'agression aigue͏̈." Rennes 1, 2002. http://www.theses.fr/2002REN1B067.
Full textBrethes, Christophe Benjamin. "Place du surfactant exogène dans le traitement du syndrome de détresse respiratoire aiguë (SDRA) : à propos de trois cas pédiatriques." Bordeaux 2, 2000. http://www.theses.fr/2000BOR2M074.
Full textRoux, Jérémie. "Function of the epithelial sodium channel ENaC in acute lung injury." Nice, 2005. http://www.theses.fr/2005NICE4010.
Full textThe objective of this thesis is to investigate the role of abnormalities in alveolar epithelial ion channel function in the pathogenesis of acute lung injury. Clinical studies have demonstrated that impaired alveolar fluid clearance associated with the release of inflammatory mediators within the distal airspace of the lung is a characteristic feature of acute lung injury. Therefore, we examined the potential effect of these mediators on ion transport across the alveolar epithelium. In the first study, we demonstrated that increased transforming growth factor -b1 (TGF-b1) activity in distal airspaces during acute lung injury promoted pulmonary edema by reducing alveolar epithelial sodium and fluid transport. In the second study we showed that in alveolar epithelial cells, interleukin -1b (IL-1b) activated TGF-b1 via an integrin avb6-dependent mechanism. Finally in the last study, we demonstrated that IL-1b could also directly and independently reduce the alveolar epithelial sodium and fluid transport. The reduction in fluid transport was shown to be attributable in large part to a decrease in apical membrane expression of the epithelial sodium channel (ENaC) in lung epithelial cells. The decreased cell surface expression of ENaC was mediated through a MAP kinase-dependent inhibition of ENaC promoter activity. In summary, the studies presented here demonstrate that IL-1b and TGF-b1 down-regulate ENaC biosynthesis and indicate a critical role for these mediators in the impaired fluid clearance of patients with acute lung injury
Briot, Raphaël. "Mesures répétées de la perméabilité capillaro-alvéolaire à une macromolécule au cours de modèles de lésion pulmonaire inflammatoire chez le chien." Université Joseph Fourier (Grenoble), 2005. http://www.theses.fr/2005GRE10067.
Full textWe developed a new modality of broncho-alveolar lavage technique to measure repeatedly in vivo (every 15 min. During 3. 5 h), the capillary-alveolar permeability to a macromolecule (FlTC-dextran). Following a pre-clinical model of oleic acid lung injury, capillary-alveolar permeability to FlTC-dextran reaches a peak within 30 minutes. Thereafter the permeability decreases slowly until the end of the experiment. We assessed the effects of terbutaline, a β2-agonist assumed to reduce in vitro the microvascular permeability in acute lung injury. Terbutaline infusion started 10 min. After oleic acid injury did not change the time course of permeability. Terbutaline infusion started 90 min. After injury interrupted the recovery with an aggravation in permeability. As cardia index and pulmonary capillary pressure increased with terbutaline infusion, we speculate that terbutaline recruits leaky capillaries and increases FlTC-dextran permeability during late recovery from oleic acid injury
Tariket, Sofiane. "Investigation de la pathogenèse du syndrome de détresse respiratoire aiguë post-transfusionnel (TRALI) dans un modèle murin." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSES059/document.
Full textBlood transfusion saves lives and reduces morbidity for many diseases and clinical conditions, but it is not without complications. A transfusion-related adverse event, also known as the Adverse Reaction (AR), is an incident occurring in a patient during or after a blood transfusion. Among them, TRALI is considered as one of the most critical inflammatory reactions. This pathology usually occurs within 6 hours after transfusion. Two types are recognized: immune TRALI and non-immune TRALI. In France, the first is almost completely prevented by a blood product safety policy, while the frequency of the second increases. The pathophysiology of TRALI remains poorly understood. While some scientists give an important function of patient blood platelets, others consider them dispensable. The aim of this thesis was, first, to investigate the inflammatory potential of blood platelets stored in platelet concentrates and its impact on the general vascular endothelium. Next, the role of patient blood platelets, including their secretory products, in the pathogenesis of this transfusion complication will be evaluated. For it, an ALI (mimicking a TRALI) was triggered, in an in vivo model, by an injection of anti-MHC I antibody in mice previously stimulated with LPS. Our results confirm the inflammatory potential of blood platelets in platelet concentrates, which can probably assume the entire responsibility for triggering a non-immune TRALI, and a secondary role for patient blood platelets in the amplification of the severity of this pathology. This thesis is the continuity of studies conducted in the laboratory GIMAP-EA3064, investigating the function of blood platelets in inflammation, thus opening up new perspectives in transfusion safety
Farenc, Christine. "Pharmacocinétique et pharmacodynamie de l'atracurium, du cisatracurium et du rocuronium chez le patient de réanimation atteint d'un syndrome de détresse respiratoire aiguë." Montpellier 1, 2000. http://www.theses.fr/2000MON13518.
Full textKumar, Gaurav. "Infections humaines et molécules de costimulation lymphocytaires T." Nice, 2012. http://www.theses.fr/2012NICE4057.
Full textInfectious diseases, caused by various microorganisms are the major cause of death worldwide. T-lymphocytes are a diverse population of cells that participate in both innate and adaptive immunity. We are defining human T lymphocyte responses to viral and bacterial infection and their role on protective immunity and disease pathogenesis. Our research focuses on chronic and acute bacterial and viral infection in Osteomyelities, Acute respiratory distress syndrome (ARDS) and human Immunodeficiency virus (HIV). Our research is largely clinically based because these diseases do not have good experimental animal models. We report increased T-cell activation and decreased proliferation along with the alteration of its costimulatory pathways as hallmarks of bacterial bone infections in humans. A remarkable decrease in the CD28 expression on CD4 T cells was observed in infected bone tissues along with increased CTLA4 expression. On further analysis of CD28 negative CD4 T cell population, it seemed that it has enhanced cytotoxic capabilities in comparison to their CD28 positive counterparts, being obvious by increased perforine secretion. In ARDS we observed increased activated and proliferating T cell phenotype with increased CTLA4 expression, suggesting that increased CTLA4 seems to play a suppressive role in order to achieve normal T cell homeostasis after going through the active phase of activation. Also we observed IL-17 secretion in ARDS, which may suggest the role of IL-17 as a chemoattractant for neutrophils at the site of infection. In AIDS, the included patients had a stable HAART treatment with undetectable viral load for at least six months. In our study we did not observed major alteration in T cell phenotype and its costimulatory molecules after Raltegravir introduction, but we observed a decrease in viral load in CD4 T cells. In conclusion, alteration of the costimulatory molecules appeared to be disease-related but not pathogen specific
Preira, Pascal. "Etude microfluidique de la rigidité leucocytaire liée au syndrome de détresse respiratoire aigue (SDRA)." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4020/document.
Full textThe project consists in using microfluidic devices to test human leukocyte behavior in microcirculation. Adult Respiratory Distress Syndrome (ARDS) is a disease that affects numerous patients in intense care services with a rate of death 50%. It is triggered to the sequestration of neutrophils within the lung microvasculature. There is neither diagnostic nor efficient treatment now. We study the properties of the passage of THP-1, and real neutrophils in micro-channels of width 6µm. In order to improve the understanding of SDRA, we also incubate models cells in patient's serums who are suffering from ARDS and diagnostic tools are being developed in collaboration with the hospitals of Marseille
Roch, Antoine. "Monoxyde d'azote inhalé et vasoconstricteurs au cours du SDRA [Syndrome de Détresse Respiratoire Aigue͏̈] et de l'ischémie-reperfusion pulmonaire : effets sur l'oxygénation et l'oedème pulmonaire." Aix-Marseille 2, 2004. http://www.theses.fr/2004AIX20655.
Full textSchortgen, Frédérique. "Prévention de l’insuffisance rénale aiguë ischémique chez le patient ventilé." Thesis, Paris Est, 2011. http://www.theses.fr/2011PEST0102/document.
Full textCritically ill patients needing mechanical ventilation are particularly exposed to ischemic renal injury leading for acute kidney injury (AKI) occurrence is associated and poor outcome. The aim of this work was to optimize AKI prevention. We evaluated protective measures for renal oxygen delivery on one hand and the performance of usual tools for the detection and characterization of renal injury on the other hand.The main measure in preventing AKI is the correction and the preservation of blood volume; fluid resuscitation is, however, associated with an increased risk of pulmonary oedema. Our results show that renal outcome depends on the type of fluid used with an increased risk of AKI using hydroxyethylstarches and/or hyper-oncotic colloids while pulmonary function is not influenced by the type of fluids used but depends on the volume infused. Pulmonary worsening seems to occure for a lower volume of colloids than crystalloids, probably because of a higher efficiency to increase intravascular volume.In addition to the restoration of renal perfusion, arterial oxygenation is a potential determinant of renal oxygenation. Because the use of a low FiO2 level is recommended to avoid oxygen related pulmonary lesions, we assessed the renal response to a moderate hypoxemia, usually applied in patient with acute respiratory distress syndrome. Two hours of mechanical ventilation with a SaO2 between 88% and 92% induces renal diuretic and vascular response identified by Doppler. This response is independent from ventilator and hemodynamic changes. Renal response is rapidly reversible with the correction of hypoxemia. In addition to the ability in detecting changes of intra-renal vascular resistances, we found that Doppler resistive index is helpful in predicting the persistence of AKI, better than most of the usual urinary indices.Our works allow a better approach of the intricate mechanisms in preventing renal and pulmonary functions. Fluid resuscitation can be optimized preferring hypo-oncotic fluids for reducing AKI incidence without apparent negative impact on pulmonary function. Renal response to a moderate hypoxemia suggests that arterial oxygen preservation might be essential for renal function preservation. Renal Doppler is a promising tool for the selection and the evaluation of AKI preventive measures
Scherpereel, Arnaud. "Endothélium et agressions pulmonaires aigue͏̈s." Lille 2, 2002. http://www.theses.fr/2002LIL2MT03.
Full textMonsel, Antoine. "Inflammation aiguë pulmonaire en réanimation : développement d'axes diagnostiques, préventifs et de thérapies immunomodulatrices." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066248/document.
Full textPneumonia and acute respiratory distress syndrome (ARDS) are two facets of severe acute lunginflammation, often met in intensive care unit (ICU). Rapid diagnosis of pneumonia remains essential inorder to optimize their management. We worked on setting up a quick test diagnosis based on theintensity of alveolar neutrophils autofluorescence. The validation of this test in a multicenter cohort isunderway. Preventing microaspiration across the cuff remains a priority to prevent pneumonia inmechanically ventilated patients. Based on the results of an ex vivo study followed by a clinicalrandomized trial, we showed that tapered-cuff endotracheal tube prevented microaspiration in the exvivo model, without lowering intraoperative microaspirations and postoperative pneumonia rate aftermajor vascular surgery. Both studies yielded similar results concerning the higher variation of cuffpressureover time, which leads to the question of their safety of use in terms of potential resultingtracheal wall ischemia.Pneumonia represents 80% of the cause of ARDS, which can be viewed as lung uncontrolledinflammatory response. Cell-based therapy using mesenchymal stem cells (MSC) is a growing field ofresearch in ARDS therapy. Despite numerous beneficial effects in ARDS, their capacity of self-renewalpoints them out as a potential cancer inducer in the mid-long term. In this context, evaluating thetherapeutic effects of extracellular vesicles-released from MSC (EV-MSC) represents a novel approach.We showed therapeutic effects of EC-CSM in two murine model of ARDS induced by endotoxin or liveEscherichia coli bacteria, and in another ex vivo human lung preparation.We then focused our research on temporal and compartmental dynamics of regulatory T cells(Treg) phenotypes in ARDS patients. This prospective observational clinical study showed that Early ARDSwas characterized with an alveolar compartment fully polarized towards pro-inflammatory state andneutrophils chemotaxis. In lung compartment, and compared to control patients, ARDS patients showeda quantitative Tregs deficiency, which partially recovered over time, while activation markers wereoverexpressed in both Tregs and effectors T cells (Teff). Conversely, patients with ARDS had a higherproportion of systemic Tregs compared to controls. Significant increased proportion in circulating Th1,Th22, and ILC1 subsets, and decreased proportion in ILC3 subsets were also found in ARDS patientscompared to controls.In conclusion, we developed novel strategies to diagnose and prevent pneumonia in ICU, whichremains essential to improve patients’ outcomes. Therapeutic effects of MSC and EV-MSC, as well asTreg phenotype alterations pave the way for development of novel immunoregulatory therapies
Friggeri, Arnaud. "Rôle extranucléaire de HMGB1 (High Mobility Group Box 1) au cours de l'efferocytose (phagocytose de cellules apoptotiques)." Amiens, 2012. http://www.theses.fr/2012AMIED004.
Full textGaudet, Alexandre. "Biological role of endocan and of its major catabolite p14 in the regulation of acute lung inflammation : from physiopathology to prediction of ARDS." Thesis, Lille, 2018. http://www.theses.fr/2018LILUS059.
Full textARDS is defined as an acute diffuse, inflammatory lung injury associated with increased vascular permeability and leading to life-threatening respiratory failure. ARDS is still a severe and common condition in ICU patients, resulting from lung epithelial injuries (as observed in pneumonia) as well as systemic acute inflammatory states, such as septic shock, in which endothelial injury and excessive cellular recruitment play a major role. This condition is characterized by an increase in the migration of leukocytes and especially neutrophils from blood compartment into the lung. Following a firm adherence step depending on the interaction between the integrin LFA-1 and its endothelial ligand ICAM-1, transendothelial migration is based on complex molecular mechanisms involving on one hand endothelial adhesion molecules (E-selectine, ICAMs), and their leukocyte ligands (PSGL-1, LFA-1, Mac-1) and on the other hand chemotactic activators of leukocyte diapedesis (CXCL-12, CCL-2, IL-8) or inhibitors such as endocan.Endocan is a circulating proteoglycan mainly synthesized and secreted by lung endothelium. This molecule has been reported as a functional inhibitor of the LFA-1 / ICAM-1 interaction, explaining its ability to inhibit leukocyte recruitment. Consistently, low levels of endocan have been reported to be associated with high occurrence of respiratory failure in patients admitted in ICU with severe sepsis. This association could result from a lack of secretion of endocan leading to an insufficient protection against excessive lung inflammation in these patients. Another explanation could be advanced, based on the results from De Freitas Caires et al, who have reported the existence of a major catabolite of endocan produced under the proteolytic effect of neutrophil cathepsin G. This endocan fragment, named p14, devoid of the glycanic chain required for the anti-inflammatory activity of endocan, could be involved in the restoration of high levels of lung inflammation. Indeed, it could compete with endocan’s ability to interact with LFA-1, and then could reverse its biological anti-migratory effect. Thus, endocan and p14 could constitute an interesting innovative pathway integrating in much larger models that could finally improve the management of ARDS.During my PhD, we first investigated the effects of human endocan on transendothelial migration, then assessed the potential involvement of the LFA-1 / ICAM-1 interaction in those effects and finally evaluated the hypothetical anti-inflammatory effect of human endocan in a mouse LPS-induced ALI model. We also explored the effects of p14 on the endocan / LFA-1 / ICAM-1 interaction and its consequence on the recruitment of human leukocytes. Then, to assess whether those results concerning the effects of endocan and p14 in the field of basic science could be extrapolated for clinical investigations, we described the conditions of reliability of measurement of blood endocan in ICU patients. Finally, we aimed to comfort the prognostic value of blood endocan measured at ICU admission as a predictor of ARDS, thus supporting the hypothesis emitted by Palud et al, in an independent and larger cohort of patients
Voiriot, Guillaume. "Etude de déterminants de la dysfonction vasculaire pulmonaire au cours du syndrome de détresse respiratoire aigue." Thesis, Paris Est, 2014. http://www.theses.fr/2014PEST0023/document.
Full textStudy of factors determining the pulmonary vascular dysfunction during acute respiratory distress syndrome.The pathophysiology of the acute respiratory distress syndrome (ARDS) includes a pulmonary vascular dysfunction, which is attributable to thrombosis, endothelial hyperpermeability, dysregulation of the pulmonary vasomotor tone and remodeling. Positive pressure ventilation is an exacerbating factor. The result is an increase in the pulmonary vascular resistances, which lead to an acute pulmonary hypertension and may cause acute cor pulmonale, both associated with an altered prognosis during ARDS. But the factors determining the pulmonary vascular dysfunction are poorly known. A murine model of two hit acute lung injury, combining an orotracheal aspiration of bacterial lipopolysaccharide to a protective mechanical ventilation, with physiological respiratory and invasive hemodynamic monitoring. Three factors which might determine pulmonary vascular dysfunction were studied. In the first work, we established that the use of alveolar recruitment maneuvers, consisting in a transient and repetitive application of high positive pressure level, minimized the alteration of lung mechanics but induced a pulmonary hypertension. A transcriptomic lung analysis showed a dysregulation of many genes involved in main endothelial functions. In the second work, a interleukin-6 deficiency was shown to be associated with higher pulmonary inflammation and edema. An increase in total pulmonary resistances was also observed, but prevented with a human recombinant interleukin-6 treatment and at least partially attributed to a nitric oxide synthase-dependent dysregulation of the pulmonary vasoreactivity. In the third work, we compared young adult and mature adult mice and we observed an age-dependent severity, including a higher systemic and pulmonary inflammation, a higher alveolocapillary leak and a higher bronchoalveolar angiopoietin 2, suggestive for a severe endothelial injury. Our results might contribute to identify new therapeutic pathways targeting pulmonary microvessels during ARDS.Key words: acute respiratory distress syndrome, mechanical ventilation, pulmonary hypertension, pulmonary vascular dysfunction, aging, interleukin-6, recruitment maneuvers
Vaillant, Pierre. "Régulation par les phagocytes mononuclées de l'accumulation des cellules mésenchymateuses au cours de la fibrogenèse pulmonaire." Nancy 1, 1995. http://www.theses.fr/1995NAN10433.
Full textTogbe, Dieudonnée. "Récepteurs Toll (TLRs) et leurs voies de signalisation : rôles dans les réponses innée et acquise aux antigènes de la tuberculose et du paludisme (malaria)." Orléans, 2007. http://www.theses.fr/2007ORLE2047.
Full textGarnier, Marc. "Influence de l'environnement alvéolaire sur les monocytes/macrophages au cours du Syndrome de Détresse Respiratoire Aigüe : rôle sur la réparation alvéolaire." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC137/document.
Full textAcute Respiratory Distress Syndrome (ARDS) is the most severe form of acute lung injury. ARDS is characterized bydiffuse alveolar damage followed by a phase of alveolar repair necessary to recovery. Althoughmonocytes/macrophages are key actors of pathogenicity and resolution of ARDS, little is known about theirpolarization and role on alveolar repair during human ARDS. The hypothesis of our studies was that ARDS alveolarenvironment modulates differentiation and polarization of monocytes and macrophages, and that polarizedmacrophages are involved in alveolar repair and its regulation. The main results of our work have shown that: 1)ARDS alveolar environment inhibited monocytes differentiation into fibrocytes (mesenchymal progenitorsassociated with fibroprolifération and a poor prognosis), mainly through its Serum Amyloid P (SAP) content,originating, at least in part, from the release of SAP associated with lung connective tissue during ARDS; 2) ARDSalveolar environment drove an anti-inflammatory macrophage polarization, close to that induced by IL-10 in vitro;3) anti-inflammatory macrophages polarized by broncho-alveolar lavage (BAL) from ARDS patients favored alveolarepithelial repair through a polarization-dependent production of Hepatocyte Growth Factor (HGF). This HGFproduction is amplified by an autocrine PTGS2/PGE2 dependent loop in human macrophages; 4) these results mayhave clinical relevance, since sCD163 (a marker of anti-inflammatory polarization) and HGF concentrations,expressed relatively to BAL macrophage count, were higher in ARDS survivors than non-survivors. Taken together,our works demonstrate for the first time the beneficial role of the ARDS alveolar environment onmonocytes/macrophages, inhibiting their differentiation into fibrocytes, thus limiting excessive lungfibroproliferation, and inducing an anti-inflammatory macrophage polarization, thus limiting the inflammationgenerated by the initial alveolar damage and favoring epithelial repair through HGF production. The datapresented in this thesis may allow considering anti-inflammatory macrophage repolarization as a potential newtherapeutic target of ARDS with excessive inflammation or fibro-proliferation with aberrant repair
Kitsiouli, Eirini. "Etudes biochimique et immunochimique du liquide bronchoalvéolaire de patients atteints du syndrome de détresse respiratoire aigue͏̈. Développement d'une méthode fluorimétrique pour le dosage des activités phospholipase A2 et PAF-acétylhydrolase dans les fluides biologiques." Bordeaux 2, 2000. http://www.theses.fr/2000BOR28720.
Full textDarmon, Michaël. "Outils d'évaluation de la réponse rénale aux agressions chez le patient de réanimation." Thesis, Paris Est, 2010. http://www.theses.fr/2010PEST0038.
Full textMorales, Pinzon Alfredo. "Lung segmentation and airway tree matching : application to aeration quantification in CT images of subjects with ARDS." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1019/document.
Full textAcute Respiratory Distress Syndrome (ARDS) is a life threatening disease presenting a high mortality of about 40% in intensive care units. It is the consequence of different pulmonary aggressions generating hypoxemia and pulmonary edema, which are radiologically expressed as infiltrations observable as opaque regions in the lung. The treatment of ARDS requires mechanical ventilation, which may deteriorate the state of the patient if the ventilation parameters, namely volume and pressure, are not correctly adjusted. To adjust the parameter settings to each individual case, lung aeration - in response to ventilation - needs to be assessed. This assessment can be done using computed tomography (CT) images. However, it requires the segmentation of the lung-parenchymal tissue, which is a challenging task in ARDS images due the opacities that hinder the image contrast. In this thesis we aim to provide the required tools for the experts to analyze the aeration in the images acquired within an ARDS project using an animal model
Uzunhan, Yurdagül. "Effet des cellules souches mésenchymateuses dans les altérations épithéliales alvéolaires induites par l'hypoxie." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCD103/document.
Full textNon communiqué
Dridi, Haikel. "Mécanismes cellulaires précoces impliqués dans la dysfonction diaphragmatique induite par la ventilation mécanique." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONT4005/document.
Full textMechanical ventilation (MV) is the first treatment in intensive care for acute respiratory distress syndrome to maintain adequate tissue oxygenation. However, it induces an impairment of the contractile function of the respiratory muscles, particularly the diaphragm, thereby increasing the patient's dependence on his ventilator. This acquired muscle disease have been termed ventilator induced diaphragmatic dysfunction (VIDD). The aim of this thesis is to propose, from a mouse model of mechanical ventilation, early pathophysiologic mechanisms involved in this dysfunction, to identify new therapeutic targets in preventing VIDD.We observed after 6 hours of mechanical ventilation, a mitochondrial oxidative stress which induces ryanodine receptor (RyR1) oxidation, the main calcium channel involved in the ECC. We also showed the presence after an equivalent time of mechanical ventilation, phosphorylation of RyR1, due to protein kinase activation, secondary to an adrenergic stress. Then, we have demonstrated that these post-translational modifications of RyR1 should be necessarily associated to trigger a functional impairment of RyR1 with calcium leakage from the sarcoplasmic reticulum to the cytosol, due to the loss of connection between RyR1 and the stabilizing protein KBP12. In his thesis, we also showed that these calcium homeostasis disorders, induced by 12 hours of ventilation, secondary activates the dependent proteolysis calcium and atrophy.Thus, these results show the benefit of all therapy stabilizing the connection between the RyR1 channel and the FKBP12 protein to prevent VIDD. Indeed, were observed in mice, that a specific mitochondrial anti-oxidant treatment (SS-31), or a specific beta-blocker treatment of beta2 adrenergic pathway (ICI-118551 ) or a treatment that stabilizes directly FKBP12- binding RyR1 (S107 ) prevent early disorders of calcium homeostasis and secondary appearance of proteolysis and atrophy induced by mechanical ventilation.Finally, in the last part of my work thesis, I suggest that mitochondrial ROS production may be associated with remodeling of the mitochondrial network with a preponderance of mitochondrial fission phenomenon. This remodeling could be seen as an adaptation of the mitochondria due to a sudden mismatch between energy production and consumption. Indeed, we showed that an inhibitor of the mitochondrial fission (P110), which blocks the connection between the DRP1 protein and its receptor in our animal model of mechanical ventilation, could prevent the appearance of VIDD. Thus the continuity of this last work of my thesis is to make the link between mitochondrial fission and oxidative stress underlying the disorders of calcium homeostasis. Indeed, I hope to show that this treatment during mechanical ventilation, may decrease mitochondrial ROS production, oxidation of RyR1 channel and calcium leak through the RyR1. This last work will emphasis any therapeutic which limit mitochondrial fission and its consequences, to prevent VIDD.Keywords: RyR1, mitochondria, contractile dysfunction, VIDD, oxidative stress
Creusat, Florent. "Etude et origine des neutrophiles régulateurs dans l'infection pulmonaire." Thesis, Tours, 2019. http://www.theses.fr/2019TOUR3304.
Full textNeutrophils are key innate effector cells during infections, mostly described as single footsoldiers of innate immunity that eliminate pathogens through multiple mechanisms. However, emerging evidences tend to reposition neutrophils as cells endowed with relevant immunomodulatory functions in various immune responses including auto-immunity, cancer and viral infections. Thus, it is now admitted that neutrophils can play multiple (sometimes opposite) functions in relation to the environment or the existence of preset functional subsets. In this context, neutrophil(s) can play either protective or deleterious role according to the disease and the inflammatory stage of the disease. This paradigm can be further exemplified during experimental Influenza A virus (IAV) infection, a model of lung immunopathology, in which neutrophils have been shown to play either pro- or anti-inflammatory functions. It is usually conceded that neutrophils play a critical role in IAV-dependent immunopathology and its complications such as acute respiratory distress syndrome. Thus, its presence in airways is correlated to disease severity in experimental model and clinical studies. However, some studies indicate a protective role for neutrophils during IAV infection. While the differences in the model used may somehow explain these contradictory results, we hypothesized that this discrepancy may arise from the existence of functional subsets that play opposite roles during IAV infection.During IAV infection, we observed the emergence of a subset of mature neutrophils expressing the hematopoietic stem cell marker Sca-1 (Ly6A). This subset could be observed under steady-state and preferentially populated non lymphoid tissues. During flu infection, Sca-1+ neutrophils displayed a phenotypic and functional profile of cells endowed with immunoregulatory functions. Specifically, they expressed the regulatory surface makers PD-L1 and MHC-II and secreted anti-inflammatory molecules such as IL-10 and arginase-1. These functions appeared to be acquired in the bone marrow during neutrophil development in an IFN-γ-dependent manner. Interestingly, depletion of Sca-1+ neutrophils culminated in increased susceptibility to IAV infection and IAV-dependent inflammation. In sum, our work suggest a new immunological concept in which a distant viral infection can remote the functional development of neutrophils in the bone marrow
Pouzot-Névoret, Céline. "Imagerie fonctionnelle de la ventilation et de l’inflammation pulmonaires lors d'agression pulmonaire aiguë expérimentale." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10234/document.
Full textAcute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage andresulting from an increased permeability of the alveolar-capillary membrane. Of notice, thereis an intense lung inflammation. Positron emission tomography (PET) and electricalimpedance tomography (EIT) allow noninvasive assessment of pulmonary ventilation,perfusion and inflammation. We use these techniques to decipher the impairments ofventilation and inflammation throughout the lungs in an experimental model of acute lunginjury by hydrochloric acid inhalation in pigs.In a first study, we compared EIT to PET in quantifying pulmonary aerated volume andventilation, using PET as a gold standard. We found that lung ventilation and volume wereaccurately measured with EIT over a wide range of lung volume and minute ventilation. Wehave then described and validated a new model to obtain lung aerated volume and ventilationwith PET, without the requirement of gas sampling in the respiratory circuit. Finally, weconducted a controlled study with PET to evaluate the effects of positive end-expiratorypressure and body position on regional lung inflammation, ventilation and perfusion.Inflammation was significantly higher in injured groups than in control. However, there wasno significant change in inflammation across ALI groups despite significant differencebetween ventilation and perfusion repartition.We have developed in this work a stable experimental model of acute lung injury andvalidated noninvasive imaging tools allowing studying of important physiologic parametersthat could help setting up mechanical ventilation
Pham, Tai Olivier. "Utilisation de données observationnelles en réanimation." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC280/document.
Full textIntroduction: Intensive care is a recent medical specialty which has the particularity to provide a close monitoring and traceability of patients and their treatments. Thus, a huge amount of data is daily collected on characteristics, management and evolution of patients. Evidence based medicine usually confronts observational and interventional studies confers to the latters, particularly randomized controlled trials, a higher scientific quality.Objective: To describe the benefit of observational data for intensive care through recent works using different analysis methods. To discuss respective benefits of observational and interventional studies for scientific knowledge in intensive care.Methods: Four prospective observational multicenter studies conducted in intensive care units and published in peer reviewed journals. Detail of the spectrum of available tools to design observational studies presenting different methods such as real time data use, cohort description and propensity matched analysis to estimate a treatment effect. Results: The studies presented in this thesis describe the different contributions of observational data for intensive care. As we demonstrated during the Influenza A H1N1 pandemics, observational data can be used for a real-time monitoring of epidemics. They are necessary to conduct epidemiological studies such as the acute respiratory distress syndrome study presented. We also show how observational data lead to question the definition of weaning from mechanical ventilation groups initially proposed by a consensus conference. Finally, innovative statistics techniques as propensity score allowed the evaluation of extracorporeal membrane oxygenation for the most severe cases of respiratory failure due the Influenza A H1N1. Conclusion: Observational studies should not be opposed to interventional studies as they provide additional results and give alternative options when an interventional cannot be tested. One must know the benefits and limits of each methods in order to optimize studies design and results interpretation. Observational data are fully part of the knowledge progress of intensive care specialty
Mokart, Djamel. "Pronostic du patient neutropénique admis en réanimation." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC317/document.
Full textThe short-term prognosis of patients with onco-hematological diseases and neutropenia admitted to intensive care has significantly improved over the last two decades. This progress is the fact of a significant diversification of the armamentarium on oncology and hematology but also a better management of these patients in the ICUs. Our research has focused on the outcome of these patients and its prognostic factors. In this context, we have conducted several prognostic observational studies of neutropenic patients admitted to intensive care units. We showed that factors independently associated with hospital mortality were the bone marrow transplantation, the use of invasive mechanical ventilation, the use of renal replacement therapy and a positive microbiological documentation. Moreover, in neutropenic patients admitted to intensive care for severe sepsis / septic shock, factors independently associated with ICU mortality were inappropriate initial antibiotic therapy, a delay of antibiotic treatment > 1h, a positive microbiological documentation with non-fermenting gram negative bacilli, a high SOFA score on admission in ICU. The de-escalation of initial antibiotic treatment feasible in 44% of cases had no significant impact on the short and long-term outcomes. Otherwise, in neutropenic patients admitted to intensive care for acute respiratory failure, the only independent factor associated with hospital mortality was the need for mechanical ventilation, while the use of corticosteroids in the days before ICU admission and a admission during neutropenia recovery period were protective. Finally, we have shown in a recent review of the literature that the outcome of hematology-oncology patient admitted to intensive care had improved over time and that neutropenia did not seem to be a prognostic factor in this context. In conclusion, we have shown that the neutropenic patient is at high risk of severe infectious,respiratory and immunological complications. These complications significantly impact the outcome of these patients. Our results could lead to the planning of several randomized trials in neutropenic patients admitted to intensive care in particular about the escalation antibiotic in sepsis and oxygentherapy strategies for respiratory distress
Quesnel, Christophe. "Participation des fibroblastes et des fibrocytes aux mécanismes de réparation pulmonaire au cours des agressions alvéolaires aiguës." Thesis, Paris Est, 2009. http://www.theses.fr/2009PEST0055.
Full textAcute Respiratory Distress Syndrome (ARDS) is the most severe form of Acute Lung Injury (ALI) and is characterized by diffuse alveolar damage followed by a phase of alveolar repair necessary to recovery. Although lung fibroblasts are key players in this repair process, their characteristics and functions remain poorly understood in humans during ALI/ARDS. The hypothesis of our studies was that effective alveolar repair requires a regulated recruitment of fibroblasts and fibrocytes (circulating mesenchymal precursors of hematopoietic origin) to the lung, as well as a tight regulation of their functions by the alveolar inflammatory environment. The main results of our works have shown that: 1) The alveolar lavage fluid (BAL) from ALI/ARDS patients stimulated the production of Hepatocyte Growth Factor (HGF) and Keratinocyte Growth Factor (KGF) by fibroblasts, both of which were involved in epithelial repair. This production was mainly induced by IL-1ß via an autocrine COX2/PGE2 dependant loop. 2) The alveolar fibroblasts cultured from BAL fluids of ALI/ARDS patients demonstrated an activated phenotype, characterized by an increase of both collagen 1 production and ability to migrate. A positive BAL fibroblast cell culture was associated with reduced markers of inflammation and reduced ventilation duration of ALI/ARDS patients. 3) BAL fluids from ALI/ARDS patients modulated fibroblast migration. This effect was related to a balance between activation and inhibition of migration involving the PDGF signaling pathway. The soluble form of the PDGF a receptor (PDGF-sRa) participated in the BAL inhibitory chemotactic activity. An increased chemotactic ability of BAL from ALI/ARDS patients was associated with higher mortality. 4) Excessive recruitment of fibrocytes is associated with poor prognosis. After adjustment of clinical and biological covariates (Cox model), a percentage of fibrocytes higher than 6% of total BAL cells is associated with a prolonged ventilation duration and an increased mortality. Taken together, our works demonstrate for the first time that fibroblasts and fibrocytes are directly associated with prognosis in ALI/ARDS. Fibroblasts are essential to lung healing, but their excessive recruitment may have a negative impact on prognosis. The data presented in this thesis may help identify new therapeutic targets and suggest new biomarkers to consider in the management of ALI/ARDS
Bernard, Olivier. "Caractérisation de l'effet cytoprotecteur des cellules souches mésenchymateuses sur l'apoptose et sur les altérations phénotypiques des cellules épithèliales alvéolaires soumises à l'hypoxie." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCD072/document.
Full textAcute or chronic alveolar injuries provoke massive apoptosis of alveolar epithelial cells (AEC) that compromises an efficient repair of the alveolar epithelium and leads to lung diseases such as ARDS or IPF. These disorders are commonly associated with local alveolar hypoxia aggravating their progression through the stimulation of AEC apoptosis. Administration of allogenic mesenchymal stem cells (MSCs) has been shown to limit lung inflammation and fibrosis in murine models of alveolar injury, through a still poorly understood paracrine mechanism. In a first study, we showed that long term exposure of AEC in hypoxia leads to phenotypic alterations which looks like epithelio-mesenchymal transition (EMT). Co-culture with MSCs prevent hypoxia-induced EMT.In a second work, we studied whether MSC could protect AEC from hypoxia-induced apoptosis and the mechanisms involved. hMSC-conditioned media (hMSC-CM) significantly reduced hypoxia-induced apoptosis of AEC. Such a anti-apoptotic effect was also obtained with ROS scavenger N-acetylcystein or HIF1a inhibitor YC-1. hMSC-CM decreased the protein expression of HIF1α and HIF2α and of their pro-apoptotic target Bnip3 in hypoxic AEC. hMSC-CM also reduced ROS accumulation in hypoxic AEC by enhancing the activity of anti-oxidant enzymes and prevented the induction of CHOP, a pro-apoptotic factor induced by ROS signaling. The paracrine effect of hMSC was partly dependent on KGF and HGF secretion. hMSC prevent via a paracrine effect hypoxia-induced apoptosis of AEC by modulating hypoxic and ROS signaling.These two studies show that MSCs exert cytoprotective effects in vitro against hypoxia-induced apoptosis and EMT in AEC