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Ugeskrift For Laeger Mar 2024Swimming-induced pulmonary oedema (SIPE) is a rare but potentially life-threatening condition which occurs in otherwise healthy swimmers. This is a case report of a...
Swimming-induced pulmonary oedema (SIPE) is a rare but potentially life-threatening condition which occurs in otherwise healthy swimmers. This is a case report of a 62-year-old female developing severe dyspnoea, haemoptysis and hypoxia during open-water swimming. The report provides the current perspectives of SIPE regarding clinical presentation and treatment and presents theories on the pathophysiology of the condition.
Topics: Female; Humans; Middle Aged; Pulmonary Edema; Swimming; Deafness; Health Status; Hemoptysis
PubMed: 38445342
DOI: 10.61409/V10230642 -
Antioxidants (Basel, Switzerland) Nov 2023Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by the sudden onset of respiratory failure, pulmonary edema,... (Review)
Review
Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by the sudden onset of respiratory failure, pulmonary edema, dysfunction of endothelial and epithelial barriers, and the activation of inflammatory cascades. Despite the increasing number of deaths attributed to ARDS, a comprehensive therapeutic approach for managing patients with ARDS remains elusive. To elucidate the pathological mechanisms underlying ARDS, numerous studies have employed various preclinical models, often utilizing lipopolysaccharide as the ARDS inducer. Accumulating evidence emphasizes the pivotal role of reactive oxygen species (ROS) in the pathophysiology of ARDS. Both preclinical and clinical investigations have asserted the potential of antioxidants in ameliorating ARDS. This review focuses on various sources of ROS, including NADPH oxidase, uncoupled endothelial nitric oxide synthase, cytochrome P450, and xanthine oxidase, and provides a comprehensive overview of their roles in ARDS. Additionally, we discuss the potential of using antioxidants as a strategy for treating ARDS.
PubMed: 38001869
DOI: 10.3390/antiox12112016 -
Frontiers in Physiology 2023This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary... (Review)
Review
This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary relationships. Extracorporeal therapy significantly influences cardiovascular and pulmonary physiology, highlighting the necessity for clinicians to understand these interactions for improved patient care. Veno-arterial extracorporeal membrane oxygenation (veno-arterial ECMO) unloads the right ventricle and increases left ventricular (LV) afterload, potentially exacerbating LV failure and pulmonary edema. Veno-venous (VV) ECMO presents different challenges, where optimal device and ventilator settings remain unknown. Influences on right heart function and native gas exchange as well as end-expiratory lung volumes are important concepts that should be incorporated into daily practice. Future studies should not be limited to large clinical trials focused on mortality but rather address physiological questions to advance the understanding of extracorporeal therapies. This includes exploring optimal device and ventilator settings in VV ECMO, standardizing cardiopulmonary function monitoring strategies, and developing better strategies for device management throughout their use. In this regard, small human or animal studies and computational physiological modeling may contribute valuable insights into optimizing the management of extracorporeal therapies.
PubMed: 37772062
DOI: 10.3389/fphys.2023.1231016 -
APL Bioengineering Sep 2023We present a microvascular model of fluid transport in the alveolar septa related to pulmonary edema. It consists of a two-dimensional capillary sheet coursing by...
We present a microvascular model of fluid transport in the alveolar septa related to pulmonary edema. It consists of a two-dimensional capillary sheet coursing by several alveoli. The alveolar epithelial membrane runs parallel to the capillary endothelial membrane with an interstitial layer in between, making one long septal tract. A coupled system of equations uses lubrication theory for the capillary blood, Darcy flow for the porous media of the interstitium, a passive alveolus, and the Starling equation at both membranes. Case examples include normal physiology, cardiogenic pulmonary edema, acute respiratory distress syndrome (ARDS), hypoalbuminemia, and effects of PEEP. COVID-19 has dramatically increased ARDS in the world population, raising the urgency for such a model to create an analytical framework. Under normal conditions fluid exits the alveolus, crosses the interstitium, and enters the capillary. For edema, this crossflow is reversed with fluid leaving the capillary and entering the alveolus. Because both the interstitial and capillary pressures decrease downstream, the reversal can occur within a single septal tract, with edema upstream and clearance downstream. Clinically useful solution forms are provided allowing calculation of interstitial fluid pressure, crossflows, and critical capillary pressures. Overall, the interstitial pressures are found to be significantly more positive than values used in the traditional physiological literature. That creates steep gradients near the upstream and downstream end outlets, driving significant flows toward the distant lymphatics. This new physiological flow provides an explanation to the puzzle, noted since 1896, of how pulmonary lymphatics can function so far from the alveoli: the interstitium is self-clearing.
PubMed: 37426383
DOI: 10.1063/5.0158324 -
Frontiers in Physiology 2023
PubMed: 37731539
DOI: 10.3389/fphys.2023.1278192 -
International Journal of Molecular... Mar 2024Pulmonary fibrosis results from the deposition and proliferation of extracellular matrix components in the lungs. Despite being an airway disorder, pulmonary fibrosis... (Review)
Review
Pulmonary fibrosis results from the deposition and proliferation of extracellular matrix components in the lungs. Despite being an airway disorder, pulmonary fibrosis also has notable effects on the pulmonary vasculature, with the development and severity of pulmonary hypertension tied closely to patient mortality. Furthermore, the anatomical proximity of blood vessels, the alveolar epithelium, lymphatic tissue, and airway spaces highlights the need to identify shared pathogenic mechanisms and pleiotropic signaling across various cell types. Sensory nerves and their transmitters have a variety of effects on the various cell types within the lungs; however, their effects on many cell types and functions during pulmonary fibrosis have not yet been investigated. This review highlights the importance of gaining a new understanding of sensory nerve function in the context of pulmonary fibrosis as a potential tool to limit airway and vascular dysfunction.
Topics: Humans; Pulmonary Fibrosis; Lung; Afferent Pathways; Hypertension, Pulmonary; Respiratory Mucosa
PubMed: 38542511
DOI: 10.3390/ijms25063538 -
Respiratory Research Jul 2023Alveolar epithelial barrier is a potential therapeutic target for acute respiratory distress syndrome (ARDS). However, an effective intervention against alveolar...
Alveolar epithelial barrier is a potential therapeutic target for acute respiratory distress syndrome (ARDS). However, an effective intervention against alveolar epithelial barrier has not been developed. Here, based on single-cell RNA and mRNA sequencing results, death receptor 3 (DR3) and its only known ligand tumor necrosis factor ligand-associated molecule 1A (TL1A) were significantly reduced in epithelium from an ARDS mice and cell models. The apparent reduction in the TL1A/DR3 axis in lungs from septic-ARDS patients was correlated with the severity of the disease. The examination of knockout (KO) and alveolar epithelium conditional KO (CKO) mice showed that TL1A deficiency exacerbated alveolar inflammation and permeability in lipopolysaccharide (LPS)-induced ARDS. Mechanistically, TL1A deficiency decreased glycocalyx syndecan-1 and tight junction-associated zonula occludens 3 by increasing cathepsin E level for strengthening cell-to-cell permeability. Additionally, DR3 deletion aggravated barrier dysfunction and pulmonary edema in LPS-induced ARDS through the above mechanisms based on the analyses of DR3 CKO mice and DR3 overexpression cells. Therefore, the TL1A/DR3 axis has a potential value as a key therapeutic signaling for the protection of alveolar epithelial barrier.
Topics: Animals; Mice; Epithelium; Ligands; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha; Receptors, Tumor Necrosis Factor, Member 25; Tumor Necrosis Factor Ligand Superfamily Member 15
PubMed: 37434162
DOI: 10.1186/s12931-023-02488-1 -
Journal of Advanced Research Jun 2024High-altitude pulmonary edema (HAPE) is a severe and potentially fatal condition with limited treatment options. Although ceramide kinase (CERK)-derived...
INTRODUCTION
High-altitude pulmonary edema (HAPE) is a severe and potentially fatal condition with limited treatment options. Although ceramide kinase (CERK)-derived ceramide-1-phosphate (C1P) has been demonstrated to offer protection against various pulmonary diseases, its effects on HAPE remain unclear.
OBJECTIVES
Our study aimed to investigate the potential role of CERK-derived C1P in the development of HAPE and to reveal the molecular mechanisms underlying its protective effects. We hypothesized that CERK-derived C1P could protect against HAPE by stabilizing circadian rhythms and maintaining mitochondrial dynamics.
METHODS
To test our hypothesis, we used CERK-knockout mice and established HAPE mouse models using a FLYDWC50-1C hypobaric hypoxic cabin. We utilized a range of methods, including lipidomics, transcriptomics, immunofluorescence, Western blotting, and transmission electron microscopy, to identify the mechanisms of regulation.
RESULTS
Our findings demonstrated that CERK-derived C1P played a protective role against HAPE. Inhibition of CERK exacerbated HAPE induced by the hypobaric hypoxic environment. Specifically, we identified a novel mechanism in which CERK inhibition induced aryl hydrocarbon receptor nuclear translocator-like (ARNTL) autophagic degradation, inducing the circadian rhythm and triggering mitochondrial damage by controlling the expression of proteins required for mitochondrial fission and fusion. The decreased ARNTL caused by CERK inhibition impaired mitochondrial dynamics, induced oxidative stress damage, and resulted in defects in mitophagy, particularly under hypoxia. Exogenous C1P prevented ARNTL degradation, alleviated mitochondrial damage, neutralized oxidative stress induced by CERK inhibition, and ultimately relieved HAPE.
CONCLUSIONS
This study provides evidence for the protective effect of C1P against HAPE, specifically, through stabilizing circadian rhythms and maintaining mitochondrial dynamics. Exogenous C1P therapy may be a promising strategy for treating HAPE. Our findings also highlight the importance of the circadian rhythm and mitochondrial dynamics in the pathogenesis of HAPE, suggesting that targeting these pathways may be a potential therapeutic approach for this condition.
Topics: Animals; Mitochondrial Dynamics; Mice; Ceramides; Mice, Knockout; Altitude Sickness; ARNTL Transcription Factors; Circadian Rhythm; Phosphotransferases (Alcohol Group Acceptor); Male; Disease Models, Animal; Pulmonary Edema; Mitochondria; Altitude; Hypoxia; Mice, Inbred C57BL
PubMed: 37479181
DOI: 10.1016/j.jare.2023.07.008