Development Of Acute Respiratory Distress Syndrome Research Articles

Effects of ozone exposure on lung injury, inflammation, and oxidative stress in a murine model of non-pneumonic endotoxemia.

Recent studies have identified exposure to environmental levels of ozone as a risk factor for the development of acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI) that can develop in humans with sepsis. The aim of this study was to develop a murine model of ALI to mechanistically explore the impact of ozone exposure on ARDS development. Mice were exposed to ozone (0.8 ppm, 3 hr) or air control followed 24 hr later by intravenous administration of 3 mg/kg lipopolysaccharide (LPS) or PBS. Exposure of mice to ozone + LPS caused alveolar hyperplasia; increased BAL levels of albumin, IgM, phospholipids, and proinflammatory mediators including surfactant protein D and soluble receptor for advanced glycation end products were also detected in BAL, along with markers of oxidative and nitrosative stress. Administration of ozone + LPS resulted in an increase in neutrophils and anti-inflammatory macrophages in the lung, with no effects on proinflammatory macrophages. Conversely, numbers of resident alveolar macrophages decreased after ozone + LPS; however, expression of Nos2, Arg1, Cxcl1, Cxcl2, Ccl2 by these cells increased, indicating that they are activated. These findings demonstrate that ozone sensitizes the lung to respond to endotoxin, resulting in ALI, oxidative stress and exacerbated pulmonary inflammation, and provide support for the epidemiologic association between ozone exposure and ARDS incidence.

Elevated Hemoglobin A1c and the Risk of Developing Acute Respiratory Distress Syndrome in Two Cohort Studies

BackgroundOnly a subset of patients at risk for acute respiratory distress syndrome (ARDS) go on to develop it, and the contribution of preexisting comorbidities, such as diabetes, to ARDS risk is not well understood. Prior studies of the association between diabetes and ARDS yielded conflicting results. Research QuestionDoes assessing ARDS risk based on hemoglobin A1c (HbA1c) as a marker of long-term blood glucose levels, rather than a charted diagnosis of diabetes, clarify the relationship between diabetes and ARDS? Study Design and MethodsUsing data from two prospective observational cohorts of critically ill adults (VALID and EARLI), we analyzed the association between clinical HbA1c category and development of ARDS in patients with a risk factor for ARDS and at least one clinical HbA1c measurement within the 180 days prior through 14 days after enrollment. Results599 patients in VALID and 276 in EARLI met inclusion criteria, of whom 164 and 58 developed ARDS, respectively. Patients with a charted diagnosis of diabetes were not more likely to develop ARDS (VALID: 24.6% ARDS in non-diabetics vs. 30.0% in diabetics, p=0.14; EARLI: 19.6% vs. 22.8%, p=0.55). However, in VALID, patients categorized as diabetic with inadequate glycemic control based on their HbA1c had an increased risk of developing ARDS compared to those with a non-diabetic HbA1c (20.9% vs. 34.0%; p=0.0073), a finding that persisted in multivariable analysis (OR for diabetic with inadequate glycemic control vs. non-diabetic range HbA1c = 1.25, 95% CI 1.01-1.57). These findings were not reproduced in the smaller EARLI cohort, but were appreciated when the cohorts were combined for analysis. InterpretationElevated HbA1c may be associated with risk of developing ARDS, independent of clinical diagnosis of diabetes, but prospective validation is needed. If confirmed, these findings suggest that inadequate glycemic control could be an unrecognized risk factor for ARDS.

The Role of Pericytes in Lipopolysaccharide-Induced Murine Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome that is most commonly triggered by infection-related inflammation. Lung pericytes can respond to infection and act as immune and proangiogenic cells; moreover, these cells can differentiate into myofibroblasts in non-resolving ARDS and contribute to the development of pulmonary fibrosis. Here, we aimed to characterize the role of lung cells which present characteristic of pericytes, such as peri-endothelial location and expression of panel of specific markers. To study their role in ARDS we used a murine model of lipopolysaccharide induced (LPS) resolving ARDS. We confirmed the development of ARDS after LPS instillation which was resolved 14 days after onset. Using immunofluorescence and flow cytometry we observed early expansion of NG2+PDGFRβ+ pericytes in murine lungs with loss of CD31+ PDGFRβ+ endothelial cells. These changes were accompanied by specific changes in lung structure and loss of vascular integrity. On day 14 after ARDS onset the composition of pericytes and endothelial cells returned to baseline values. LPS-induced ARDS activated NOTCH signaling in lung pericytes, the inhibition of which during LPS stimulation reduced the expression of its downstream target genes, pericyte markers and angiogenic factors. Together, lung pericytes in response to inflammatory injury activate NOTCH signaling that supports their maintenance and in turn can contribute to recovery of the microvascular endothelium.

Hospital Outcomes in Patients Who Developed Acute Respiratory Distress Syndrome After Community-Acquired Pneumonia.

Purpose: To identify risk factors for and outcomes in acute respiratory distress syndrome (ARDS) in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a retrospective study using the Premier Healthcare Database between 2016 and 2020. Patients diagnosed with pneumonia, requiring mechanical ventilation (MV), antimicrobial therapy, and hospital admission ≥2 days were included. Multivariable regression models were used for outcomes including in-hospital mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, and days on MV. Results: 1924 (2.7%) of 72 107 patients with CAP developed ARDS. ARDS was associated with higher mortality (33.7% vs 18.9%; adjusted odds ratio 2.4; 95% confidence interval [CI] 2.16-2.66), longer hospital LOS (13 vs 9 days; adjusted incidence risk ratio (aIRR) 1.24; 95% CI 1.20-1.27), ICU LOS (9 vs 5 days; aIRR 1.51; 95% CI 1.46-1.56), more MV days (8 vs 5; aIRR 1.54; 95% CI 1.48-1.59), and increased hospitalization cost ($46 459 vs $29 441; aIRR 1.50; 95% CI 1.45-1.55). Conclusion: In CAP, ARDS was associated with worse in-patient outcomes in terms of mortality, LOS, and hospitalization cost. Future studies are needed to explore outcomes in patients with CAP with ARDS and explore risk factors for development of ARDS after CAP.

TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis.

Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically disease patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI. TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome through LPS+adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death was preformed to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern (mtDAMP) led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. TSPO may be the key regulatory of cellular pyroptosis, it plays a vital protective role in ARDS occurrence and development.

449 Does incorporation of plasma biomarkers to the Lung Injury Prediction Score improve the predictive value for development of acute respiratory distress syndrome?

OBJECTIVES/GOALS: To determine if incorporating specific laboratory values and plasma biomarkers (club cell secretory protein (CC16), matrix metalloproteinase 3 (MMP3), interleukin 8 (IL-8), protein C) to the Lung Injury Prediction (LIP) Score improves the predictive value for development of acute respiratory distress syndrome (ARDS) in ICU patients. METHODS/STUDY POPULATION: Adult patients admitted to the ICU on supplemental oxygen over baseline requirement with a LIP Score ≥6 will be included. Patients admitted to the ICU >24 hours, end-stage renal disease, decompensated heart failure, or <100 µL plasma available will be excluded. Whole blood will be collected from the core lab, centrifuged, and plasma will be stored at -80°C. Protein biomarkers will be measured using enzyme-linked immunosorbent assay. Baseline characteristics, laboratory values, ventilator parameters, and clinical outcomes will be collected from the medical record. ARDS will be defined by the Berlin criteria. Machine learning methods will be used to identify the model with the highest predictive accuracy. Area under the receiver operating characteristic curve of each model will be compared to the LIP Score. RESULTS/ANTICIPATED RESULTS: Research is in progress. Plasma samples and clinical data have been collected for 148 of the 160 samples required to achieve power. Biomarker analysis will take place after sample collection is complete. We anticipate a machine learning model incorporating laboratory values and one or more plasma biomarkers into the LIP Score will outperform the baseline LIP Score for prediction of ARDS development. DISCUSSION/SIGNIFICANCE: Delayed diagnosis and intervention contribute to poor ARDS outcomes. Current predictive models for ARDS have low accuracy and enriching these models with plasma biomarkers may increase their predictive value. Development of accurate models may facilitate earlier ARDS diagnosis and intervention as well as enrichment strategies for ARDS trials.

Blood group O is associated with ARDS development but exhibits lower mortality in the intensive care unit – A retrospective multicentre study

ABSTRACT Background Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in the intensive care unit (ICU). Previous studies have suggested that blood group A increases the risk of developing ARDS following sepsis and major trauma. This study investigated the association between ABO and Rh blood groups and ARDS development and mortality in ARDS. Methods Patients admitted to the ICUs at Skåne University Hospital in Lund and Malmö, Sweden, in 2016 were retrospectively screened for ARDS according to the Berlin definition. Clinical data, patient characteristics, lab results, and survival data were collected from medical records and registry data. In addition, chest radiographs were reviewed by radiologists. ARDS development and 30-day mortality were analysed using multivariable logistic regression. Results A total of 1439 ICU patients were included. Of these, 10% had ARDS. Blood group O was associated with an increased risk of having or developing ARDS compared to blood group A (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.13–2.84, p = 0.014). Among ARDS patients, blood group O had decreased 30-day mortality compared to blood group A (OR 0.25, 95% CI 0.09–0.67, p = 0.007). The Rh blood group was not associated with ARDS development or mortality. Conclusion In this study of ICU patients, blood group O was associated with an increased risk of having or developing ARDS but a decreased mortality in ARDS compared to blood group A. Further studies are needed to clarify the relationship and underlying mechanisms of the ABO blood group and ARDS.

Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS.

Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA(cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.

ELUCIDATING THE MECHANISMS OF NEUTROPHIL EXTRACELLULAR TRAPS IN ACUTE RESPIRATORY DISTRESS SYNDROME PATHOGENESIS

This article critically examines the scientific literature related to the formation of neutrophil extracellular traps and their impact on the pathogenesis and clinical course of acute respiratory distress syndrome (ARDS). The available evidence indicates that the formation and accumulation of neutrophil extracellular traps in the lung tissue are implicated in the development and progression of ARDS. Moreover, recent studies have shed light on the potential mechanisms by which neutrophil extracellular traps contribute to impaired ventilationperfusion relationships in ARDS. The findings presented in this review suggest that further research into the phenomenon of neutrophil extracellular traps may lead to new insights into the pathophysiology of ARDS and inform the development of novel therapeutic strategies. Specifically, targeting neutrophil extracellular traps may offer a promising approach to attenuate the severity of ARDS and improve clinical outcomes. However, the complexity of the underlying mechanisms and the heterogeneity of ARDS patients necessitate further investigation to identify optimal therapeutic targets and treatment strategies.

Repurposing Disulfiram to Combat Acute Respiratory Distress Syndrome with Targeted Delivery by LET-Functionalized Nanoplatforms.

Acute respiratory distress syndrome (ARDS) is a serious respiratory condition characterized by a damaged pulmonary endothelial barrier that causes protein-rich lung edema, an influx of proinflammatory cells, and treatment-resistant hypoxemia. Damage to pulmonary endothelial cells and inflammation are pivotal in ARDS development with a key role played by endothelial cell pyroptosis. Disulfiram (DSF), a drug that has long been used to treat alcohol addiction, has recently been identified as a potent inhibitor of gasdermin D (GSDMD)-induced pore formation and can thus prevent pyroptosis and inflammatory cytokine release. These findings indicate that DSF is a promising treatment for inflammatory disorders. However, addressing the challenge posed by its intrinsic physicochemical properties, which hinder intravenous administration, and effective delivery to pulmonary vascular endothelial cells are crucial. Herein, we used biocompatible liposomes incorporating a lung endothelial cell-targeted peptide (CGSPGWVRC) to produce DSF-loaded nanoparticles (DTP-LET@DSF NPs) for targeted delivery and reactive oxygen species-responsive release facilitated by the inclusion of thioketal (TK) within the liposomal structure. After intravenous administration, DTP-LET@DSF NPs exhibited excellent cytocompatibility and minor systemic toxicity, effectively inhibited pyroptosis, mitigated lipopolysaccharide (LPS)-induced ARDS, and prevented cytokine storms resulting from excessive immune reactions in ARDS mice. This study presents a straightforward nanoplatform for ARDS treatment that potentially paves the way for the clinical use of this nanomedicine.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

LncRNA HOTTIP as a diagnostic biomarker for acute respiratory distress syndrome in patients with sepsis and to predict the short-term clinical outcome: a case-control study

BackgroundThe present research aims to investigate the clinical diagnostic value of LncRNA HOXA distal transcript antisense RNA (HOTTIP) in acute respiratory distress syndrome (ARDS) of sepsis and its predictive significance for mortality.MethodsOne hundred eighteenth patients with sepsis and 96 healthy individuals were enrolled. RT-qPCR to examine HOTTIP levels. The incidence of ARDS and death was recorded. The diagnostic significance of HOTTIP in sepsis ARDS was examined using ROC and logistic regression analysis. The correlation between HOTTIP and disease severity was evaluated using Pearson’s coefficients. Kaplan-Meier analysis and COX regression were employed to examine the predictive significance of mortality. Validation of HOTTIP target miRNA by dual-luciferase assay.ResultsHOTTIP was persistently up-regulated in patients with ARDS sepsis than in patients without ARDS patients (P < 0.05). HOTTIP was a risk factor for the development of ARDS, which could be diagnosed in ARDS patients from non-ARDS patients (AUC = 0.847). Both the SOFA score (r = 0.6793) and the APACHE II score (r = 0.6384) were positively correlated with the HOTTIP levels. Furthermore, serum HOTTIP was an independent predictor of short-term mortality (HR = 4.813. 95%CI: 1.471–15.750, P = 0.009) and noticeably predicted the occurrence of short-term death (log rank = 0.020). miR-574-5p, a target miRNA for HOTTIP, was reduced in patients with sepsis ARDS and negatively correlated with HOTTIP.ConclusionsThe presence of HOTTIP serves as a diagnostic biomarker for the occurrence of ARDS, exhibits correlation with disease severity, and provides predictive value of short-term mortality in sepsis patients. HOTTIP may be involved in ARDS progression by targeting miR-574-5p.

Retrospectively gated ultrashort-echo-time MRI T1 mapping reveals compromised pulmonary microvascular NO-dependent function in a murine model of acute lung injury.

This study sought to develop noninvasive, in vivo imaging schemes that allow for quantitative assessment of pulmonary microvascular functional status based on the combination of pulmonary T1 mapping and dynamic contrast-enhanced (DynCE) imaging. Ultrashort-echo-time (UTE) imaging at 9.4 T of lung parenchyma was performed. Retrospective gating was based on modulation of the first point in each recorded spoke. T1 maps were obtained using a series of five consecutive images with varying RF angles and analyzed with the variable flip angle approach. The obtained mean T1 lung value of 1078 ± 38 ms correlated well with previous reports. Improved intersession variability was observed, as evident from a decreased standard deviation of motion-resolved T1 mapping (F-test = 0.051). Animals received lipopolysaccharide (LPS) and were imaged at t= 2, 6, and 12 h after administration. The nitric oxide (NO)-dependent function was assessed according to changes in lung T1 after L-NAME injection, while microvascular perfusion and oxidant stress were assessed with contrast-enhanced imaging after injection of gadolinium or 3-carbamoyl-proxyl nitroxide radical, respectively. Retrospectivel gated UTE allowed robust, motion-compensated imaging that could be used for T1 mapping of lung parenchyma. Changes in lung T1 after L-NAME injection indicated that LPS induced overproduction of NO at t= 2 and 6 h after LPS, but NO-dependent microvascular function was impaired at t= 12 h after LPS. DynCE imaging at t= 6 h after LPS injection revealed decreased microvascular perfusion, with increased vascular permeability and oxidant stress. MRI allows to visualize and quantify lung microvascular NO-dependent function and its concomitant impairment during acute respiratory distress syndrome development with high sensitivity. UTE T1 mapping appears to be sensitive and useful in probing pulmonary microvascular functional status.

Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19.

Patients with coronavirus disease-2019 (COVID-19) have an increased risk of thrombosis and acute respiratory distress syndrome (ARDS). Thrombosis is often attributed to increases in plasminogen activator inhibitor-1 (PAI-1) and a shut-down of fibrinolysis (blood clot dissolution). Decreased urokinase-type plasminogen activator (uPA), a protease necessary for cell-associated plasmin generation, and increased tissue-type plasminogen activator (tPA) and PAI-1 levels have been reported in COVID-19 patients. Because these factors can occur in free and complexed forms with differences in their biological functions, we examined the predictive impact of uPA, tPA, and PAI-1 in their free forms and complexes as a biomarker for COVID-19 severity and the development of ARDS. In this retrospective study of 69 Japanese adults hospitalized with COVID-19 and 20 healthy donors, we found elevated free, non-complexed PAI-1 antigen, low circulating uPA, and uPA/PAI-1 but not tPA/PAI-1 complex levels to be associated with COVID-19 severity and ARDS development. This biomarker profile was typical for patients in the complicated phase. Lack of PAI-1 activity in circulation despite free, non-complexed PAI-1 protein and plasmin/α2anti-plasmin complex correlated with suPAR and sVCAM levels, markers indicating endothelial dysfunction. Furthermore, uPA/PAI-1 complex levels positively correlated with TNFα, a cytokine reported to trigger inflammatory cell death and tissue damage. Those levels also positively correlated with lymphopenia and the pro-inflammatory factors interleukin1β (IL1β), IL6, and C-reactive protein, markers associated with the anti-viral inflammatory response. These findings argue for using uPA and uPA/PAI-1 as novel biomarkers to detect patients at risk of developing severe COVID-19, including ARDS.

Advances and Applications of Lung Organoids in the Research on Acute Respiratory Distress Syndrome (ARDS).

Acute Respiratory Distress Syndrome (ARDS) is a sudden onset of lung injury characterized by bilateral pulmonary edema, diffuse inflammation, hypoxemia, and a low P/F ratio. Epithelial injury and endothelial injury are notable in the development of ARDS, which is more severe under mechanical stress. This review explains the role of alveolar epithelial cells and endothelial cells under physiological and pathological conditions during the progression of ARDS. Mechanical injury not only causes ARDS but is also a side effect of ventilator-supporting treatment, which is difficult to model both in vitro and in vivo. The development of lung organoids has seen rapid progress in recent years, with numerous promising achievements made. Multiple types of cells and construction strategies are emerging in the lung organoid culture system. Additionally, the lung-on-a-chip system presents a new idea for simulating lung diseases. This review summarizes the basic features and critical problems in the research on ARDS, as well as the progress in lung organoids, particularly in the rapidly developing microfluidic system-based organoids. Overall, this review provides valuable insights into the three major factors that promote the progression of ARDS and how advances in lung organoid technology can be used to further understand ARDS.

Occurrence of COVID-19 in cystic fibrosis patients: a review.

Cystic fibrosis (CF) is a genetic ailment caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This autosomal recessive disorder is characterized by diverse pathobiological abnormalities, such as the disorder of CFTR channels in mucosal surfaces, caused by inadequate clearance of mucus and sputum, in addition to the malfunctioning of mucous organs. However, the primary motive of mortality in CF patients is pulmonary failure, which is attributed to the colonization of opportunistic microorganisms, formation of resistant biofilms, and a subsequent decline in lung characteristics. In December 2019, the World Health Organization (WHO) declared the outbreak of the radical coronavirus disease 2019 (COVID-19) as a worldwide public health crisis, which unexpectedly spread not only within China but also globally. Given that the respiration system is the primary target of the COVID-19 virus, it is crucial to investigate the impact of COVID-19 on the pathogenesis and mortality of CF patients, mainly in the context of acute respiratory distress syndrome (ARDS). Therefore, the goal of this review is to comprehensively review the present literature on the relationship between cystic fibrosis, COVID-19 contamination, and development of ARDS. Several investigations performed during the early stages of the virus outbreak have discovered unexpected findings regarding the occurrence and effectiveness of COVID-19 in individuals with CF. Contrary to initial expectancies, the rate of infection and the effectiveness of the virus in CF patients are lower than those in the overall population. This finding may be attributed to different factors, including the presence of thick mucus, social avoidance, using remedies that include azithromycin, the fairly younger age of CF patients, decreased presence of ACE-2 receptors, and the effect of CFTR channel disorder on the replication cycle and infectivity of the virus. However, it is important to notice that certain situations, which include undergoing a transplant, can also doubtlessly boost the susceptibility of CF patients to COVID-19. Furthermore, with an increase in age in CF patients, it is vital to take into account the prevalence of the SARS-CoV-2 virus in this population. Therefore, ordinary surveillance of CF patients is vital to evaluate and save the population from the capability of transmission of the virus given the various factors that contribute to the spread of the SARS-CoV-2 outbreak in this precise organization.

Diagnostic and Predictive Significance of Serum MiR-141-3p in Acute Respiratory Distress Syndrome Patients with Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is the major complication and death-related factor of acute respiratory distress syndrome (ARDS). This study evaluated the significance of miR-141-3p in ARDS and its complication of PF aiming to identify a potential biomarker for screening ARDS and predicting the occurrence of PF. A total of 137 ARDS patients and 69 healthy individuals were enrolled in this study and the serum samples were collected from all participants. The serum miR-141-3p levels were analyzed by polymerase chain reaction. The significance of miR-141-3p in the diagnosis and development of ARDS, and the occurrence of PF was evaluated by receiver operating curve, Chi-square test, and logistic regression analysis. MiR-141-3p was downregulated in ARDS patients and showed significant potential in its diagnosis. Reduced miR-141-3p was significantly associated with the increasing Murray and APACHEII score and the occurrence of PF in ARDS patients. MiR-141-3p, Murray score, and APACHEII score were identified as risk factors for the occurrence of PF in ARDS, and miR-141-3p was also found to be downregulated in ARDS patients with PF. Additionally, miR-141-3p could discriminate ARDS patients with PF and without PF, and was closely associated with the decreased total lung capacity, carbon monoxide diffusing capacity, and forced vital capacity of ARDS patients with PF. Downregulated miR-141-3p served as a biomarker for ARDS screening disease onset and indicating the severity. Reduced miR-141-3p was also identified as a risk factor for PF in ARDS patients and was associated with the severe progression of PF.

H3N2 Influenza Virus Pathogenesis, Transmission and Complications: A Narrative Review

The recent outbreak of the influenza virus has grown to be a significant issue and a matter of great concern in terms of controlling the impending influenza pandemic. The influenza virus poses a serious threat as it directly infects and impairs the immune system reaction and the respiratory tract. The virus effectively produces infectious viral particles when haemagglutinin molecules are properly cleaved at the respiratory epithelium. The mode of transmission is via droplets from an affected case. The lungs, responsible for the vital exchange of gases, can fail due to various mechanisms, including the destruction of epithelial cells, significant degradation of the extracellular matrix, and airway obstruction. Influenza is a primary cause of severe pneumonia, but it can be accompanied by further bacterial infections, commonly involving bacteria such as Streptococcus pneumoniae and S. aureus. Influenza infection increases the susceptibility to developing Acute Respiratory Distress Syndrome (ARDS) and bacterial sepsis. Both adults and children have a 30-50% chance of experiencing viral infections along with bacterial pneumonia. Notably, Influenza A virus (H3N2) influenza has been associated with a significant increase in admissions to intensive care units. Among the factors contributing to the development of ARDS, individuals between the ages of 36 and 55 years, pregnant women, and obese individuals are at a higher risk. However, infection with influenza viruses A (H3N2) or B, female sex, and influenza vaccination have been identified as protective factors against ARDS. Influenza infection increases the susceptibility to developing ARDS and bacterial sepsis. Disease progression can be limited by spreading awareness among the people about the factors responsible for transmission, clinical manifestations, and preventive methodologies.

Role of gut microbiota and inflammatory factors in acute respiratory distress syndrome: a Mendelian randomization analysis.

Acute respiratory distress syndrome (ARDS) is a serious lung ailment marked by significant inflammation and damage in the alveoli and capillaries of the lungs. Recent research suggests a strong correlation between the onset and advancement of ARDS and an imbalance in the gut microbiota (GM). In this investigation, Mendelian randomization (MR) analysis was utilized, drawing on data from publicly accessible genome-wide association studies. The primary focus was on examining the interplay between GM, inflammatory factors (IFs) and ARDS. Instrumental variables were established through genetic modifications of GM and IFs. Various statistical analysis methods including the inverse-variance weighted model, MR-Egger method and Wald ratio test were applied for comprehensive data analysis. Eight bacterial taxa within the GM demonstrated a potential causal link with development of ARDS. Notably, the phylum Actinobacteria and the genus Intestinibacter exhibited a negative association with the risk of ARDS. However, Erysipelotrichales (id. 2,148), Victivallis (id. 2,256), Ruminococcaceae UCG014 (id. 11,371), Eubacterium ruminantium group (id. 11,340), Erysipelotrichaceae (id. 2,149) and Erysipelotrichia (id. 2,147) demonstrated a positive association with ARDS risk. Additionally, the study identified a potential causal relationship between the inflammatory factors interleukin-16 and C-C motif chemokine 3 with the occurrence of ARDS. This study strongly suggests that the interaction between gut microbiota (GM) and inflammatory factors (IFs) significantly contributes to the pathogenesis of acute respiratory distress syndrome (ARDS). This underscores their crucial involvement in both the initiation and advancement of this severe lung disorder.

Integration of multiomics analysis to reveal the major pathways of vitamin A deficiency aggravates acute respiratory distress syndrome in neonatal rats

Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS. Moreover, the VA levels can be used as a predictor of the development and severity of neonatal ARDS. However, the critical question here is; Does ARDS develop due to VAD in these systemic diseases? Or does ARDS develop because these diseases cause VAD? We hypothesize that VAD may aggravate neonatal ARDS by affecting immunity, metabolism, barriers and other pathways. In this article, we used multiomics analysis to find that VAD may aggravate ARDS mainly through the Fc epsilon RI signaling pathway, the HIF-1 signaling pathway, glutathione metabolism, and valine, leucine and isoleucine degradation signaling pathways, which may provide the molecular pathogenic mechanism behind the pathology of VAD-aggravated ARDS and can also provide potential molecular targets for subsequent research on ARDS.