Daily Ards Research Analysis

To assess the efficacy of electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration in improving outcomes for patients with acute respiratory distress syndrome (ARDS). A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials and observational studies with a control group comparing EIT-guided PEEP titration to other strategies were included. Endpoints analysed included mortality, days of mechanical ventilation (MV), intensive care unit (ICU) length of stay (LOS), weaning success rate, barotrauma, driving pressure (∆P), mechanical power (MP), Sequential Organ Failure Assessment (SOFA) score and adverse events. Pooled results were presented as Risk Ratio (RR) for dichotomous outcomes and standardized difference in means (SMD) for continuous outcomes. A total of 4 studies were identified (3 randomized controlled trials and one observational study). All studies were single-center studies (N total = 271 patients). The main limitations were related to potential bias in selecting reported outcomes. EIT-guided PEEP titration was associated with a significant reduction in mortality among critically ill patients with ARDS (RR = 0.64, 95% CI: 0.45-0.91). No significant differences were found in other outcomes. Our findings suggest that EIT may be a valuable tool for PEEP titration in critically ill patients with ARDS. By optimizing lung mechanics, EIT-guided PEEP titration may potentially reduce mortality rates. While larger, multicenter studies are needed to definitively establish the clinical role of EIT in ARDS management, our results provide promising evidence for its potential clinical impact.

As a gatekeeper of the airway epithelial cells, E-cadherin is not only a critical component for the maintenance of epithelial integrity, but also engaged in pathological processes through the release of a soluble form (sE-cadherin). This study was aimed to investigate the role of sE-cadherin in ALI/ARDS. Serum samples from patients with ARDS and healthy volunteers were collected for the detection of sE-cadherin. An LPS-induced mouse model was induced to analyze the expression of sE-cadherin, and a neutralizing antibody against sE-cadherin (DECMA-1) was given to the LPS-exposed mice. The effects of recombinant sE-cadherin were tested both in vitro and in vivo, and VEGFR2 inhibition was used to explore a possible mechanism for sE-cadherin-induced pulmonary inflammation. We observed an increased level of sE-cadherin in ARDS patients as well as in LPS-exposed mice. In vivo treatment of DECMA-1 significantly attenuated LPS-induced inflammation. In vitro, exogenous sE-cadherin can dramatically upregulate the expression of VEGF in THP1-derived macrophages and human primary macrophages. In addition, intratracheal instillation of recombinant sE-cadherin leads to significant increased infiltration of neutrophils as well as overproduction of IL-6 and IL1β, which could be attenuated by inhibition of VEGF/VEGFR2 signaling. While blockade of the VEGF/VEGFR2 pathway inhibited pulmonary inflammatory responses in LPS-exposed mice. Taken together, our data demonstrated that sE-cadherin contributes to lung inflammation in ALI/ARDS, which is related to activation of the VEGF/VEGFR2 pathway.

BACKGROUND: The US Food and Drug Administration (FDA) has raised concerns about a potential link between trimethoprim/sulfamethoxazole (TMP-SMX) and an increased risk of acute respiratory failure/acute respiratory distress syndrome (ARF/ARDS) in healthy adolescents and young adults. OBJECTIVE: To assess the association between TMP-SMX and the risk of ARF/ARDS using data from the FDA Adverse Event Reporting System (FAERS). METHODS: We analyzed adverse drug events (ADEs) reported in FAERS from January 1, 2004, to December 31, 2023. We focused on reports where TMP-SMX, amoxicillin-clavulanic acid, or azithromycin were the primary suspect drugs for ADEs in individuals aged 10 to 24 years. The outcomes of interest-ARF/ARDS-were identified using MedDRA-preferred terms. We used an active comparator-restricted disproportionality analysis (ACR-DA) to estimate the reporting odds ratio (ROR) and 95% confidence interval (CI), adjusting for age, sex, acne, and urinary tract infections. Bayesian Confidence Propagation Neural Networks (BCPNN) were used to calculate the Information Components (IC RESULTS: 3171 ICSRs (810 for TMP-SMX, 1617 for azithromycin, and 744 for amoxicillin-clavulanic acid) were included in the study. ACR-DA showed an unadjusted 8-fold increase in the reports of ARF/ARDS with TMP-SMX compared with azithromycin (unadjusted ROR, 7.98; 95% CI, 4.09 to 15.60) and an adjusted 3-fold increase after adjustment for age, sex, acne, and urinary tract infection (adjusted ROR, 2.80; 95% CI, 1.28 to 6.11). BCPNN analysis confirmed significant disproportionality (IC CONCLUSION AND RELEVANCE: TMP-SMX may increase the risk of ARF/ARDS, requiring further validation in larger pharmacoepidemiological studies. Our findings lay the groundwork for future research to further investigate the safety profile of TMP-SMX in adolescent populations. If confirmed, prescribers should exercise greater caution when prescribing TMP-SMX to adolescents and young adults.