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Journal of the... 2020The purpose of the study was to investigate the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of the study was to investigate the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema.
METHODS
A systematic search for relevant literature was performed in MEDLINE, CNKI, and EMBASE. The pooled odds ratios and their corresponding 95% confidence intervals were calculated in STATA 12.0 software.
RESULTS
Seven studies, with a total of 304 patients and 564 controls, qualified for the inclusion in the analysis. There was no significant association between angiotensin-converting enzyme insertion/deletion polymorphism and high-altitude pulmonary edema risk in the total population (DD vs II: odds ratio=1.07, 95% confidence interval 0.52-2.24; DI vs II: odds ratio=1.12, 0.85-1.49; dominant model: odds ratio=1.07, 0.83-1.40; recessive model: odds ratio=0.96, 0.53-1.77). Subgroup analysis according to race also revealed no significant correlation between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema.
CONCLUSIONS
Our findings suggest that angiotensin-converting enzyme insertion/deletion polymorphism does not contribute to the risk of high-altitude pulmonary edema. Larger, well-designed studies are required to further validate these results.
Topics: Altitude; Confidence Intervals; Genetic Association Studies; Genetic Predisposition to Disease; Humans; INDEL Mutation; Odds Ratio; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Publication Bias; Pulmonary Edema
PubMed: 32106754
DOI: 10.1177/1470320319900039 -
Submersion and hypoxia inhibit alveolar epithelial Na transport through ERK/NF-κB signaling pathway.Respiratory Research Apr 2023Hypoxia is associated with many respiratory diseases, partly due to the accumulation of edema fluid and mucus on the surface of alveolar epithelial cell (AEC), which...
BACKGROUND
Hypoxia is associated with many respiratory diseases, partly due to the accumulation of edema fluid and mucus on the surface of alveolar epithelial cell (AEC), which forms oxygen delivery barriers and is responsible for the disruption of ion transport. Epithelial sodium channel (ENaC) on the apical side of AEC plays a crucial role to maintain the electrochemical gradient of Na and water reabsorption, thus becomes the key point for edema fluid removal under hypoxia. Here we sought to explore the effects of hypoxia on ENaC expression and the further mechanism related, which may provide a possible treatment strategy in edema related pulmonary diseases.
METHODS
Excess volume of culture medium was added on the surface of AEC to simulate the hypoxic environment of alveoli in the state of pulmonary edema, supported by the evidence of increased hypoxia-inducible factor-1 expression. The protein/mRNA expressions of ENaC were detected, and extracellular signal-regulated kinase (ERK)/nuclear factor κB (NF-κB) inhibitor was applied to explore the detailed mechanism about the effects of hypoxia on epithelial ion transport in AEC. Meanwhile, mice were placed in chambers with normoxic or hypoxic (8%) condition for 24 h, respectively. The effects of hypoxia and NF-κB were assessed through alveolar fluid clearance and ENaC function by Ussing chamber assay.
RESULTS
Hypoxia (submersion culture mode) induced the reduction of protein/mRNA expression of ENaC, whereas increased the activation of ERK/NF-κB signaling pathway in parallel experiments using human A549 and mouse alveolar type 2 cells, respectively. Moreover, the inhibition of ERK (PD98059, 10 µM) alleviated the phosphorylation of IκB and p65, implying NF-κB as a downstream pathway involved with ERK regulation. Intriguingly, the expression of α-ENaC could be reversed by either ERK or NF-κB inhibitor (QNZ, 100 nM) under hypoxia. The alleviation of pulmonary edema was evidenced by the administration of NF-κB inhibitor, and enhancement of ENaC function was supported by recording amiloride-sensitive short-circuit currents.
CONCLUSIONS
The expression of ENaC was downregulated under hypoxia induced by submersion culture, which may be mediated by ERK/NF-κB signaling pathway.
Topics: Mice; Humans; Animals; NF-kappa B; Pulmonary Edema; Extracellular Signal-Regulated MAP Kinases; Immersion; Pulmonary Alveoli; Hypoxia; Signal Transduction; Epithelial Sodium Channels; Sodium; RNA, Messenger; Epithelial Cells
PubMed: 37095538
DOI: 10.1186/s12931-023-02428-z -
American Journal of Physiology. Lung... Jun 2021A significant number of patients with coronavirus disease 2019 (COVID-19) develop acute respiratory distress syndrome (ARDS) that is associated with a poor outcome. The...
A significant number of patients with coronavirus disease 2019 (COVID-19) develop acute respiratory distress syndrome (ARDS) that is associated with a poor outcome. The molecular mechanisms driving failure of the alveolar barrier upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain incompletely understood. The Na,K-ATPase is an adhesion molecule and a plasma membrane transporter that is critically required for proper alveolar epithelial function by both promoting barrier integrity and resolution of excess alveolar fluid, thus enabling appropriate gas exchange. However, numerous SARS-CoV-2-mediated and COVID-19-related signals directly or indirectly impair the function of the Na,K-ATPase, thereby potentially contributing to disease progression. In this Perspective, we highlight some of the putative mechanisms of SARS-CoV-2-driven dysfunction of the Na,K-ATPase, focusing on expression, maturation, and trafficking of the transporter. A therapeutic mean to selectively inhibit the maladaptive signals that impair the Na,K-ATPase upon SARS-CoV-2 infection might be effective in reestablishing the alveolar epithelial barrier and promoting alveolar fluid clearance and thus advantageous in patients with COVID-19-associated ARDS.
Topics: Biological Transport; COVID-19; Humans; Pulmonary Alveoli; Pulmonary Edema; SARS-CoV-2; Severe Acute Respiratory Syndrome; Sodium-Potassium-Exchanging ATPase; Tight Junctions
PubMed: 33689516
DOI: 10.1152/ajplung.00056.2021 -
Minerva Anestesiologica Oct 2023Adequate fluid therapy in the acute brain injured (ABI) patient is essential for maintaining an adequate brain and systemic physiology and preventing intra- and...
Adequate fluid therapy in the acute brain injured (ABI) patient is essential for maintaining an adequate brain and systemic physiology and preventing intra- and extracranial complications. The target of euvolemia, implying avoidance of both hypovolemia and fluid overloading (or "hypervolemia," by definition associated with fluid extravasation leading to tissue edema) is of key importance. Primary brain injury can be aggravated by secondary brain injury and systemic deterioration through diverse pathways which can challenge appropriate fluid management, e.g. neuroendocrine and electrolyte disorders, stress cardiomyopathy (also known as cardiac stunning) and neurogenic pulmonary edema. This is an updated expert opinion aiming to provide a practical overview on fluid therapy in the ABI patient, partly based on more recent work and stressing the fact that intravenous fluids should be regarded as drugs, with their inherent potential for both benefit and (unintended) harm.
Topics: Humans; Fluid Therapy; Hypovolemia; Pulmonary Edema; Brain Injuries; Heart Failure; Brain
PubMed: 37822149
DOI: 10.23736/S0375-9393.23.17328-7 -
European Review For Medical and... Aug 2023Pulmonary embolism and acute pulmonary edema can often be confused. The aim of this study is to investigate the role of clinical and laboratory parameters in the...
OBJECTIVE
Pulmonary embolism and acute pulmonary edema can often be confused. The aim of this study is to investigate the role of clinical and laboratory parameters in the differentiation of these two pathologies.
PATIENTS AND METHODS
Between March 2017 and December 2021, a total of 114 patients (51 patients with acute hypertensive pulmonary edema and 63 patients with pulmonary embolism) were included in the study. The medical history, hemodynamic findings, main echocardiographic data, and routine laboratory markers were recorded, retrospectively.
RESULTS
Coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and recent operation histories were found as more common concomitant disorders in the pulmonary embolism group (p = 0.001, p = 0.011, p = 0.001, respectively). In addition, patients with pulmonary embolism had a higher heart rate (p = 0.001) and systolic pulmonary artery pressure (SPAP) (p = 0.001) compared to those with hypertensive pulmonary edema, while patients with hypertensive pulmonary edema had higher blood pressure (p = 0.001). While significantly low albumin levels (p = 0.001) were found among blood parameters in the pulmonary embolism group, D-Dimer, fibrinogen, troponin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), red blood cell distribution width (RDW), and creatinine values were found to be higher (p < 0.001). The most sensitive (95%) and specific (92%) clinical parameter was the SPAP with a 19.00 mmHg cut-off level. Additionally, the most sensitive (98%) and specific (97%) laboratory parameter was the D-Dimer, with a 260.5 ng/mL cut-off level.
CONCLUSIONS
Especially simple blood parameters such as D-dimer and echocardiographic evaluation of SPAP seem to be quite effective in distinguishing pulmonary embolism from hypertensive pulmonary edema.
Topics: Humans; Pulmonary Edema; Retrospective Studies; Hypertension; Coronary Artery Disease; Acute Disease; Pulmonary Embolism
PubMed: 37606134
DOI: 10.26355/eurrev_202308_33297 -
Critical Care (London, England) May 2023A quantitative assessment of pulmonary edema is important because the clinical severity can range from mild impairment to life threatening. A quantitative surrogate...
BACKGROUND
A quantitative assessment of pulmonary edema is important because the clinical severity can range from mild impairment to life threatening. A quantitative surrogate measure, although invasive, for pulmonary edema is the extravascular lung water index (EVLWI) extracted from the transpulmonary thermodilution (TPTD). Severity of edema from chest X-rays, to date is based on the subjective classification of radiologists. In this work, we use machine learning to quantitatively predict the severity of pulmonary edema from chest radiography.
METHODS
We retrospectively included 471 X-rays from 431 patients who underwent chest radiography and TPTD measurement within 24 h at our intensive care unit. The EVLWI extracted from the TPTD was used as a quantitative measure for pulmonary edema. We used a deep learning approach and binned the data into two, three, four and five classes increasing the resolution of the EVLWI prediction from the X-rays.
RESULTS
The accuracy, area under the receiver operating characteristic curve (AUROC) and Mathews correlation coefficient (MCC) in the binary classification models (EVLWI < 15, ≥ 15) were 0.93 (accuracy), 0.98 (AUROC) and 0.86(MCC). In the three multiclass models, the accuracy ranged between 0.90 and 0.95, the AUROC between 0.97 and 0.99 and the MCC between 0.86 and 0.92.
CONCLUSION
Deep learning can quantify pulmonary edema as measured by EVLWI with high accuracy.
Topics: Humans; Pulmonary Edema; X-Rays; Retrospective Studies; Deep Learning; Extravascular Lung Water; Radiography; Thermodilution
PubMed: 37237287
DOI: 10.1186/s13054-023-04426-5 -
The International Journal of... Dec 2022B-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in...
BACKGROUND
B-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in patients with hypertrophic cardiomyopathy (HCM).
AIM
To assess the clinical, anatomical and functional correlates of pulmonary congestion elicited by exercise in HCM.
METHODS
We enrolled 128 HCM patients (age 52 ± 15 years, 72 males) consecutively referred for ESE (treadmill in 46, bicycle in 82 patients) in 10 quality-controlled centers from 7 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Serbia, Spain). ESE assessment at rest and peak stress included: mitral regurgitation (MR, score from 0 to 3); E/e'; systolic pulmonary arterial pressure (SPAP) and end-diastolic volume (EDV). Change from rest to stress was calculated for each variable. Reduced preload reserve was defined by a decrease in EDV during exercise. B-lines at rest and at peak exercise were assessed by lung ultrasound with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was ≥ 2.
RESULTS
LUS was feasible in all subjects. B-lines were present in 13 patients at rest and in 38 during stress (10 vs 30%, p < 0.0001). When compared to patients without stress B-lines (n = 90), patients with B-lines (n = 38) had higher resting E/e' (14 ± 6 vs. 11 ± 4, p = 0.016) and SPAP (33 ± 10 vs. 27 ± 7 mm Hg p = 0.002). At peak exercise, patients with B-lines had higher peak E/e' (17 ± 6 vs. 13 ± 5 p = 0.003) and stress SPAP (55 ± 18 vs. 40 ± 12 mm Hg p < 0.0001), reduced preload reserve (68 vs. 30%, p = 0.001) and an increase in MR (42 vs. 17%, p = 0.013) compared to patients without congestion. Among baseline parameters, the number of B-lines and SPAP were the only independent predictors of exercise pulmonary congestion.
CONCLUSIONS
Two-thirds of HCM patients who develop pulmonary congestion on exercise had no evidence of B-lines at rest. Diastolic impairment and mitral regurgitation were key determinants of pulmonary congestion during ESE. These findings underscore the importance of evaluating hemodynamic stability by physiological stress in HCM, particularly in the presence of unexplained symptoms and functional limitation.
Topics: Male; Humans; Adult; Middle Aged; Aged; Echocardiography, Stress; Echocardiography, Doppler; Mitral Valve Insufficiency; Predictive Value of Tests; Cardiomyopathy, Hypertrophic; Exercise Test; Pulmonary Edema; Lung
PubMed: 36322266
DOI: 10.1007/s10554-022-02620-0 -
Cell and Tissue Research May 2020Traditionally, the lung has been excluded from the ultrasound organ repertoire and, hence, the application of lung ultrasound (LUS) was largely limited to a few... (Review)
Review
Traditionally, the lung has been excluded from the ultrasound organ repertoire and, hence, the application of lung ultrasound (LUS) was largely limited to a few enthusiastic clinicians. Yet, in the last decades, the recognition of the previously untapped diagnostic potential of LUS in intensive care medicine has fueled its widespread use as a rapid, non-invasive and radiation-free bedside approach with excellent diagnostic accuracy for many of the most common causes of acute respiratory failure, e.g., cardiogenic pulmonary edema, pneumonia, pleural effusion and pneumothorax. Its increased clinical use has also incited attention for the potential usefulness of LUS in preclinical studies with small animal models mimicking lung congestion and pulmonary edema formation. Application of LUS to small animal models of pulmonary edema may save time, is cost-effective, and may reduce the number of experimental animals due to the possibility of serial evaluations in the same animal as compared with traditional end-point measurements. This review provides an overview of the emerging field of LUS with a specific focus on its application in animal models and highlights future perspectives for LUS in preclinical research.
Topics: Animals; Disease Models, Animal; Humans; Lung; Pulmonary Edema; Ultrasonography
PubMed: 32009189
DOI: 10.1007/s00441-020-03172-2 -
Clinical Cardiology Nov 2021Chronic heart failure is one of the common causes of hospitalization and death. Pulmonary congestion is the common disease feature of patients with chronic heart... (Review)
Review
Chronic heart failure is one of the common causes of hospitalization and death. Pulmonary congestion is the common disease feature of patients with chronic heart failure, which could be correctly diagnosed by lung ultrasound. Efficacy of lung ultrasound-guided pulmonary congestion management for patients with acute heart failure is well documented, however, more evidence is needed to establish the clinical value of pulmonary congestion detection by lung ultrasound examination in patients with chronic heart failure. This review summarized current evidence related to the use and clinical value of pulmonary congestion assessment by lung ultrasound in patients with chronic heart failure, aiming to provide new suggestions on promoting the widespread use of lung ultrasound in patients with chronic heart failure to improve the quality of life and outcome of patients with chronic heart failure.
Topics: Heart Failure; Humans; Lung; Prognosis; Pulmonary Edema; Quality of Life; Ultrasonography
PubMed: 34599512
DOI: 10.1002/clc.23738 -
Pflugers Archiv : European Journal of... Oct 2022Acute hypoxia impairs left ventricular (LV) inotropic function and induces development of pulmonary edema (PE). Enhanced and uneven hypoxic pulmonary vasoconstriction is...
Acute hypoxia impairs left ventricular (LV) inotropic function and induces development of pulmonary edema (PE). Enhanced and uneven hypoxic pulmonary vasoconstriction is an important pathogenic factor of hypoxic PE. We hypothesized that the potent vasodilator relaxin might reduce hypoxic pulmonary vasoconstriction and prevent PE formation. Furthermore, as relaxin has shown beneficial effects in acute heart failure, we expected that relaxin might also improve LV inotropic function in hypoxia. Forty-two rats were exposed over 24 h to normoxia or hypoxia (10% N in O). They were infused with either 0.9% NaCl solution (normoxic/hypoxic controls) or relaxin at two doses (15 and 75 μg kg day). After 24 h, hemodynamic measurements and bronchoalveolar lavage were performed. Lung tissue was obtained for histological and immunohistochemical analyses. Hypoxic control rats presented significant depression of LV systolic pressure by 19% and of left and right ventricular contractility by about 40%. Relaxin did not prevent the hypoxic decrease in LV inotropic function, but re-increased right ventricular contractility. Moreover, hypoxia induced moderate interstitial PE and inflammation in the lung. Contrasting to our hypothesis, relaxin did not prevent hypoxia-induced pulmonary edema and inflammation. In hypoxic control rats, PE was similarly distributed in the apical and basal lung lobes. In relaxin-treated rats, PE index was 35-40% higher in the apical than in the basal lobe, which is probably due to gravity effects. We suggest that relaxin induced exaggerated vasodilation, and hence pulmonary overperfusion. In conclusion, the results show that relaxin does not prevent but rather may aggravate PE formation.
Topics: Animals; Hypoxia; Pneumonia; Pulmonary Artery; Pulmonary Edema; Rats; Relaxin; Saline Solution; Vasodilator Agents
PubMed: 35778581
DOI: 10.1007/s00424-022-02720-9