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Advances in Respiratory Medicine Oct 2023Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar... (Review)
Review
Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.
Topics: Humans; Pulmonary Edema; Lung; Heart Failure; Oxygen; Vasodilator Agents; Emergency Medicine
PubMed: 37887077
DOI: 10.3390/arm91050034 -
Intensive Care Medicine Oct 2022In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful.... (Review)
Review
In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.
Topics: Cardiac Output; Critical Illness; Fluid Therapy; Hemodynamics; Humans; Pulmonary Edema; Thermodilution
PubMed: 35945344
DOI: 10.1007/s00134-022-06808-9 -
British Journal of Haematology Oct 2019Acute promyelocytic leukaemia differentiation syndrome (APL DS) is seen when patients with APL are treated with all-trans retinoic acid (ATRA) and/or arsenic trioxide... (Review)
Review
Acute promyelocytic leukaemia differentiation syndrome (APL DS) is seen when patients with APL are treated with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). Presenting symptoms are varied but frequently include dyspnoea, unexplained fever, weight gain >5 kg, unexplained hypotension, acute renal failure and a chest radiograph demonstrating pulmonary infiltrates or pleural or pericardial effusion. Immediate treatment with steroids at the first clinical suspicion is recommended and ATRA/ATO should be stopped in severe cases or if there is no response to treatment. The utility of steroid prophylaxis in order to prevent APL DS is less certain. Here we provide a detailed review of the pathogenesis, clinical signs and symptoms as well as management and prophylaxis strategies of APL DS.
Topics: Acute Kidney Injury; Arsenic Trioxide; Cell Differentiation; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Pulmonary Edema; Steroids; Syndrome; Tretinoin
PubMed: 31410848
DOI: 10.1111/bjh.16151 -
International Journal of Molecular... Oct 2022Exposure to high altitudes generates a decrease in the partial pressure of oxygen, triggering a hypobaric hypoxic condition. This condition produces pathophysiologic... (Review)
Review
Exposure to high altitudes generates a decrease in the partial pressure of oxygen, triggering a hypobaric hypoxic condition. This condition produces pathophysiologic alterations in an organism. In the lung, one of the principal responses to hypoxia is the development of hypoxic pulmonary vasoconstriction (HPV), which improves gas exchange. However, when HPV is exacerbated, it induces high-altitude pulmonary hypertension (HAPH). Another important illness in hypobaric hypoxia is high-altitude pulmonary edema (HAPE), which occurs under acute exposure. Several studies have shown that inflammatory processes are activated in high-altitude illnesses, highlighting the importance of the crosstalk between hypoxia and inflammation. The aim of this review is to determine the inflammatory pathways involved in hypobaric hypoxia, to investigate the key role of inflammation in lung pathologies, such as HAPH and HAPE, and to summarize different anti-inflammatory treatment approaches for these high-altitude illnesses. In conclusion, both HAPE and HAPH show an increase in inflammatory cell infiltration (macrophages and neutrophils), cytokine levels (IL-6, TNF-α and IL-1β), chemokine levels (MCP-1), and cell adhesion molecule levels (ICAM-1 and VCAM-1), and anti-inflammatory treatments (decreasing all inflammatory components mentioned above) seem to be promising mitigation strategies for treating lung pathologies associated with high-altitude exposure.
Topics: Humans; Hypertension, Pulmonary; Intercellular Adhesion Molecule-1; Altitude; Pulmonary Edema; Vascular Cell Adhesion Molecule-1; Tumor Necrosis Factor-alpha; Interleukin-6; Papillomavirus Infections; Altitude Sickness; Hypoxia; Edema; Cytokines; Inflammation; Oxygen
PubMed: 36293512
DOI: 10.3390/ijms232012656 -
International Journal of Environmental... Feb 2021Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of... (Review)
Review
Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.
Topics: Altitude; Altitude Sickness; Humans; Hypertension, Pulmonary; Hypoxia; Pulmonary Edema
PubMed: 33578749
DOI: 10.3390/ijerph18041692 -
Frontiers in Immunology 2023Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary... (Review)
Review
Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It is mainly manifested by non-cardiogenic pulmonary edema, resulting from intrapulmonary and extrapulmonary risk factors. ARDS is often accompanied by immune system disturbance, both locally in the lungs and systemically. As a common heterogeneous disease in critical care medicine, researchers are often faced with the failure of clinical trials. Latent class analysis had been used to compensate for poor outcomes and found that targeted treatment after subgrouping contribute to ARDS therapy. The subphenotype of ARDS caused by sepsis has garnered attention due to its refractory nature and detrimental consequences. Sepsis stands as the most predominant extrapulmonary cause of ARDS, accounting for approximately 32% of ARDS cases. Studies indicate that sepsis-induced ARDS tends to be more severe than ARDS caused by other factors, leading to poorer prognosis and higher mortality rate. This comprehensive review delves into the immunological mechanisms of sepsis-ARDS, the heterogeneity of ARDS and existing research on targeted treatments, aiming to providing mechanism understanding and exploring ideas for accurate treatment of ARDS or sepsis-ARDS.
Topics: Humans; Endothelial Cells; Respiratory Distress Syndrome; Lung; Sepsis; Pulmonary Edema
PubMed: 38035100
DOI: 10.3389/fimmu.2023.1277161 -
Circulating BMP9 Protects the Pulmonary Endothelium during Inflammation-induced Lung Injury in Mice.American Journal of Respiratory and... Jun 2021Pulmonary endothelial permeability contributes to the high-permeability pulmonary edema that characterizes acute respiratory distress syndrome. Circulating BMP9 (bone...
Pulmonary endothelial permeability contributes to the high-permeability pulmonary edema that characterizes acute respiratory distress syndrome. Circulating BMP9 (bone morphogenetic protein 9) is emerging as an important regulator of pulmonary vascular homeostasis. To determine whether endogenous BMP9 plays a role in preserving pulmonary endothelial integrity and whether loss of endogenous BMP9 occurs during LPS challenge. A BMP9-neutralizing antibody was administrated to healthy adult mice, and lung vasculature was examined. Potential mechanisms were delineated by transcript analysis in human lung endothelial cells. The impact of BMP9 administration was evaluated in a murine acute lung injury model induced by inhaled LPS. Levels of BMP9 were measured in plasma from patients with sepsis and from endotoxemic mice. Subacute neutralization of endogenous BMP9 in mice ( = 12) resulted in increased lung vascular permeability ( = 0.022), interstitial edema ( = 0.0047), and neutrophil extravasation ( = 0.029) compared with IgG control treatment ( = 6). In pulmonary endothelial cells, BMP9 regulated transcriptome pathways implicated in vascular permeability and cell-membrane integrity. Augmentation of BMP9 signaling in mice ( = 8) prevented inhaled LPS-induced lung injury ( = 0.0027) and edema ( < 0.0001). In endotoxemic mice ( = 12), endogenous circulating BMP9 concentrations were markedly reduced, the causes of which include a transient reduction in hepatic BMP9 mRNA expression and increased elastase activity in plasma. In human patients with sepsis ( = 10), circulating concentratons of BMP9 were also markedly reduced ( < 0.0001). Endogenous circulating BMP9 is a pulmonary endothelial-protective factor, downregulated during inflammation. Exogenous BMP9 offers a potential therapy to prevent increased pulmonary endothelial permeability in lung injury.
Topics: Acute Lung Injury; Animals; Case-Control Studies; Endothelial Cells; Endothelium; Endotoxemia; Female; Growth Differentiation Factor 2; Humans; Male; Mice; Pulmonary Edema; Sepsis
PubMed: 33320799
DOI: 10.1164/rccm.202005-1761OC -
Frontiers in Immunology 2023Transfusion-related acute lung injury (TRALI) is a severe adverse event and a leading cause of transfusion-associated death. Its poor associated prognosis is due, in... (Review)
Review
Transfusion-related acute lung injury (TRALI) is a severe adverse event and a leading cause of transfusion-associated death. Its poor associated prognosis is due, in large part, to the current dearth of effective therapeutic strategies. Hence, an urgent need exists for effective management strategies for the prevention and treatment of associated lung edema. Recently, various preclinical and clinical studies have advanced the current knowledge regarding TRALI pathogenesis. In fact, the application of this knowledge to patient management has successfully decreased TRALI-associated morbidity. This article reviews the most relevant data and recent progress related to TRALI pathogenesis. Based on the existing two-hit theory, a novel three-step pathogenesis model composed of a priming step, pulmonary reaction, and effector phase is postulated to explain the process of TRALI. TRALI pathogenesis stage-specific management strategies based on clinical studies and preclinical models are summarized with an explication of their models of prevention and experimental drugs. The primary aim of this review is to provide useful insights regarding the underlying pathogenesis of TRALI to inform the development of preventive or therapeutic alternatives.
Topics: Humans; Transfusion-Related Acute Lung Injury; Transfusion Reaction; Blood Transfusion; Lung; Pulmonary Edema
PubMed: 37251400
DOI: 10.3389/fimmu.2023.1175387 -
Proceedings of the National Academy of... Jun 2019Increased pulmonary microvessel pressure experienced in left heart failure, head trauma, or high altitude can lead to endothelial barrier disruption referred to as...
Increased pulmonary microvessel pressure experienced in left heart failure, head trauma, or high altitude can lead to endothelial barrier disruption referred to as capillary "stress failure" that causes leakage of protein-rich plasma and pulmonary edema. However, little is known about vascular endothelial sensing and transduction of mechanical stimuli inducing endothelial barrier disruption. Piezo1, a mechanosensing ion channel expressed in endothelial cells (ECs), is activated by elevated pressure and other mechanical stimuli. Here, we demonstrate the involvement of Piezo1 in sensing increased lung microvessel pressure and mediating endothelial barrier disruption. Studies were made in mice in which Piezo1 was deleted conditionally in ECs ( ), and lung microvessel pressure was increased either by raising left atrial pressure or by aortic constriction. We observed that lung endothelial barrier leakiness and edema induced by raising pulmonary microvessel pressure were abrogated in mice. Piezo1 signaled lung vascular hyperpermeability by promoting the internalization and degradation of the endothelial adherens junction (AJ) protein VE-cadherin. Breakdown of AJs was the result of activation of the calcium-dependent protease calpain and degradation of the AJ proteins VE-cadherin, β-catenin, and p120-catenin. Deletion of Piezo1 in ECs or inhibition of calpain similarly prevented reduction in the AJ proteins. Thus, Piezo1 activation in ECs induced by elevated lung microvessel pressure mediates capillary stress failure and edema formation secondary to calpain-induced disruption of VE-cadherin adhesion. Inhibiting Piezo1 signaling may be a useful strategy to limit lung capillary stress failure injury in response to elevated vascular pressures.
Topics: Adherens Junctions; Animals; Antigens, CD; Arterial Pressure; Blood Pressure; Cadherins; Capillary Permeability; Cells, Cultured; Disease Models, Animal; Endothelial Cells; Endothelium, Vascular; Female; Gene Knock-In Techniques; Humans; Hydrostatic Pressure; Intercellular Signaling Peptides and Proteins; Ion Channels; Lung; Male; Mechanotransduction, Cellular; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Microvessels; Primary Cell Culture; Pulmonary Edema; Respiratory Insufficiency; Spider Venoms
PubMed: 31186359
DOI: 10.1073/pnas.1902165116 -
Transfusion Jul 2019Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and...
BACKGROUND
Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life-threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI.
STUDY DESIGN AND METHODS
An international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases.
RESULTS
In the redefinition, the term "possible TRALI" has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies.
CONCLUSIONS
Clinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion-associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.
Topics: Blood Transfusion; Consensus; Female; Humans; Male; Pulmonary Edema; Risk Factors; Transfusion-Related Acute Lung Injury
PubMed: 30993745
DOI: 10.1111/trf.15311