ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target.

Background: Acute Respiratory Distress Syndrome (ARDS) is a common condition in the intensive care unit (ICU) with a high mortality rate, yet the diagnosis rate remains low. Recent studies have increasingly highlighted the role of aging in the occurrence and progression of ARDS. This study is committed to investigating the pathogenic mechanisms of cellular and genetic changes in elderly ARDS patients, providing theoretical support for the precise treatment of ARDS. Methods: Gene expression profiles for control and ARDS samples were obtained from the Gene Expression Omnibus (GEO) database, while aging-related genes (ARGs) were sourced from the Human Aging Genomic Resources (HAGR) database. Differentially expressed genes (DEGs) were subjected to functional enrichment analysis to understand their roles in ARDS and aging. The Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning pinpointed key modules and marker genes, with ROC curves illustrating their significance. The expression of four ARDS-ARDEGs was validated in lung samples from aged mice with ARDS using qRT-PCR. Gene set enrichment analysis (GSEA) investigated the signaling pathways and immune cell infiltration associated with TYMS expression. Single-nucleus RNA sequencing (snRNA-Seq) explored gene-level differences among cells to investigate intercellular communication during ARDS onset and progression. Results: ARDEGs are involved in cellular responses to DNA damage stimuli, inflammatory reactions, and cellular senescence pathways. The MEmagenta module exhibited a significant correlation with elderly ARDS patients. The LASSO, RRF, and XGBoost algorithms were employed to screen for signature genes, including CKAP2, P2RY14, RBP2, and TYMS. Further validation emphasized the potential role of TYMS in the onset and progression of ARDS. Immune cell infiltration indicated differential proportion and correlations with TYMS expression. SnRNA-Seq and cell-cell communication analysis revealed that TYMS is highly expressed in endothelial cells, and the SEMA3 signaling pathway primarily mediates cell communication between endothelial cells and other cells. Conclusion: Endothelial cell damage associated with aging could contribute to ARDS progression by triggering inflammation. TYMS emerges as a promising diagnostic biomarker and potential therapeutic target for ARDS.

The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS.

INTRODUCTION: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. METHODS: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. RESULTS: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. CONCLUSIONS: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.

A case of severe Plasmodium ovale malaria with acute respiratory distress syndrome and splenic infarction in a male traveller presenting in Italy.

BACKGROUND: Plasmodium ovale malaria is usually considered a tropical infectious disease associated with low morbidity and mortality. However, severe disease and death have previously been reported. CASE PRESENTATION: A case of severe P. ovale malaria in a healthy Caucasian man with a triangle splenic infarction and clinical progression towards Acute Respiratory Distress Syndrome was reported despite a rapid response to oral chloroquine treatment with 24-h parasitaemia clearance. CONCLUSION: Plasmodium ovale malaria is generally considered as a benign disease, with low parasitaemia. However, severe disease and death have occasionally been reported. It is important to be aware that occasionally it can progress to serious illness and death even in immunocompetent individuals.

[New 2023 global definition of acute respiratory distress syndrome: progress and limitation].

Acute respiratory distress syndrome (ARDS) presents a challenge in clinical diagnosis as it lacks a definitive gold standard. Over the past 55 years, there have been several revisions to the definition of ARDS. With the progress of clinical practice and scientific research, the limitations of the "Berlin definition" have become increasingly evident. In response to these changes, the 2023 global definition of ARDS aims to address these issues by expanding the diagnostic targets, chest imaging, and methods for assessing hypoxia. Additionally, the new definition increases the diagnostic criteria to accommodate resource-constrained settings. The expansion facilitates early identification and treatment interventions for ARDS, thereby advancing epidemiological and clinically related research. Nevertheless, the broad nature of this revision may include patients who do not actually have ARDS, thus raising the risk of false-positive diagnoses. Therefore, additional verification is crucial to ascertain the validity and accuracy of the 2023 global definition of ARDS.

[Pulse oximetric saturation/fraction of inspired oxygen and partial pressure of oxygen/fraction of inspired oxygen in diagnosing acute respiratory distress syndrome: which is better?]

Acute Respiratory Distress Syndrome (ARDS) is distinguished by hypoxemia, contributing to heightened morbidity, elevated mortality rates, and substantial healthcare expenses, thereby imposing a significant burden on patients and society. Presently, effective treatments for ARDS are lacking, emphasizing the pivotal role of early diagnosis and timely intervention in its successful management. The partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, P/F) has traditionally served as a crucial metric for assessing patient hypoxemia and disease severity. While relatively accurate, its reliance on advanced technical expertise and specific medical equipment conditions constrains its implementation in areas with underdeveloped medical standards, resulting in missed diagnoses and treatments for ARDS patients. Conversely, the Pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2, S/F) has garnered increasing attention owing to its straightforward, non-invasive, and sustainable monitoring attributes. This article seeks to meticulously compare the correlation, accuracy, and clinical feasibility of S/F with P/F in ARDS diagnosis, so as to propose diagnostic indicators for more quickly and accurately assessing the oxygenation status of ARDS patients.

Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.

Breath metabolomics for diagnosis of acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS: This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS: A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION: An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.

Lung tissue expression of epithelial injury markers is associated with acute lung injury severity but does not discriminate sepsis from ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. METHODS: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. RESULTS: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. CONCLUSIONS: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.

A pretrain-finetune approach for improving model generalizability in outcome prediction of acute respiratory distress syndrome patients.

BACKGROUND: Early prediction of acute respiratory distress syndrome (ARDS) of critically ill patients in intensive care units (ICUs) has been intensively studied in the past years. Yet a prediction model trained on data from one hospital might not be well generalized to other hospitals. It is therefore essential to develop an accurate and generalizable ARDS prediction model adaptive to different hospital or medical centers. METHODS: We analyzed electronic medical records of 200,859 and 50,920 hospitalized patients within 24 h after being diagnosed with ARDS from the Philips eICU Institute (eICU-CRD) and the Medical Information Mart for Intensive Care (MIMIC-IV) dataset, respectively. Patients were sorted into three groups, including rapid death, long stay, and recovery, based on their condition or outcome between 24 and 72 h after ARDS diagnosis. To improve prediction performance and generalizability, a "pretrain-finetune" approach was applied, where we pretrained models on the eICU-CRD dataset and performed model finetuning using only a part (35%) of the MIMIC-IV dataset, and then tested the finetuned models on the remaining data from the MIMIC-IV dataset. Well-known machine-learning algorithms, including logistic regression, random forest, extreme gradient boosting, and multilayer perceptron neural networks, were employed to predict ARDS outcomes. Prediction performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Results show that, in general, multilayer perceptron neural networks outperformed the other models. The use of pretrain-finetune yielded improved performance in predicting ARDS outcomes achieving a micro-AUC of 0.870 for the MIMIC-IV dataset, an improvement of 0.046 over the pretrain model. CONCLUSIONS: The proposed pretrain-finetune approach can effectively improve model generalizability from one to another dataset in ARDS prediction.

Diagnosis and Epidemiology of Acute Respiratory Failure.

Acute respiratory failure is a common clinical finding caused by insufficient oxygenation (hypoxemia) or ventilation (hypocapnia). Understanding the pathophysiology of acute respiratory failure can help to facilitate recognition, diagnosis, and treatment. The cause of acute respiratory failure can be identified through utilization of physical examination findings, laboratory analysis, and chest imaging.

Acute Respiratory Distress Syndrome: Definition, Diagnosis, and Routine Management.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by severe hypoxemic respiratory failure, bilateral opacities on chest imaging, and low lung compliance. ARDS is a heterogeneous syndrome that is the common end point of a wide variety of predisposing conditions, with complex pathophysiology and underlying mechanisms. Routine management of ARDS is centered on lung-protective ventilation strategies such as low tidal volume ventilation and targeting low airway pressures to avoid exacerbation of lung injury, as well as a conservative fluid management strategy.

Impact of Virtual Reality Simulation on New Nurses' Assessment of Pediatric Respiratory Distress.

BACKGROUND: Children often experience respiratory illnesses requiring bedside nurses skilled in recognizing respiratory decompensation. Historically, recognizing respiratory distress has relied on teaching during direct patient care. Virtual reality simulation may accelerate such recognition among novice nurses. OBJECTIVE: To determine whether a virtual reality curriculum improved new nurses' recognition of respiratory distress and impending respiratory failure in pediatric patients based on assessment of physical examination findings and appropriate escalation of care. METHODS: New nurses (n = 168) were randomly assigned to complete either an immersive virtual reality curriculum on recognition of respiratory distress (intervention) or the usual orientation curriculum (control). Group differences and changes from 3 months to 6 months after the intervention were examined. RESULTS: Nurses in the intervention group were significantly more likely to correctly recognize impending respiratory failure at both 3 months (23.4% vs 3.0%, P < .001) and 6 months (31.9% vs 2.6%, P < .001), identify respiratory distress without impending respiratory failure at 3 months (57.8% vs 29.6%, P = .002) and 6 months (57.9% vs 17.8%, P < .001), and recognize patients' altered mental status at 3 months (51.4% vs 18.2%, P < .001) and 6 months (46.8% vs 18.4%, P = .006). CONCLUSIONS: Implementation of a virtual reality-based training curriculum was associated with improved recognition of pediatric respiratory distress, impending respiratory failure, and altered mental status at 3 and 6 months compared with standard training approaches. Virtual reality may offer a new approach to nurse orientation to enhance training in pediatrics-specific assessment skills.

[Acute respiratory distress due to tracheostomy tube migration]. / Détresse respiratoire aiguë par migration d'une canule de trachéotomie.

Tracheostomy cannula care is of paramount importance in the daily management of tracheotomized patients. While some complications are commonplace, specific events can occur, often according to type of cannula. We herein report the case of a 71-year-old patient; following a lengthy stay in the intensive care unit, she had received a Safe T-Tube cannula designed to provide support in a stenotic trachea. At home, while suctioning her tracheal secretions, she suddenly experienced respiratory distress requiring a rapid intervention. On arrival, no seeable cannula was found, either in the tracheostomy or in the patient's immediate surroundings. Following her transfer to intensive care, a new cannula was inserted into the tracheostomy opening, enabling mechanical ventilation to begin and achieving rapid relief of dyspnea and improvement of the patient's overall condition. Bronchial fibroscopy was then performed, during which the Safe T-Tube cannula was found folded on itself in a supra-carinal intra-tracheal position. It was extracted and replaced by a cannula of the same model, which was sewn to the skin. Although rare and usually limited to flexible cannulas, this complication is potentially fatal. Generally speaking, when cannula obstruction is suspected, bronchial endoscopy in an intensive care setting is a vital necessity. It is not only the cornerstone of the diagnosis, but also of paramount importance in treatment taking into full account the mechanism of obstruction.

Presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients than for young sepsis patients in ICUs: a pilot study.

OBJECTIVE: Sepsis is a syndrome of life-threatening organ dysfunction. This study aimed to determine whether presepsin is a useful predictor of septic acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and shock in very-old sepsis patients aged 75 years in intensive care units (ICUs). RESULTS: A total of 83 adult patients diagnosed with sepsis were prospectively examined and divided into two groups: those aged 75 years and older (over 75 group) and those aged younger than 75 years (under 75 group). Presepsin values were measured after ICU admission. Inflammation-based prognostic scores were also examined. For category classification, total scores ("inflammation-presepsin scores [iPS]") were calculated. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with septic AKI, ARDS, DIC, or shock and those without these disorders in the over 75 and under 75 groups. Areas under the curve of presepsin for predicting septic AKI and ARDS in the over 75 group were both > 0.7, which were significantly higher than those in the under 75 group. In conclusion, presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients (over 75 years) than for younger sepsis patients (under 75 years).