Daily Ards Research Analysis

This study evaluated the therapeutic effects of fecal microbiota transplantation (FMT) on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in rats. The study focused on the balance of T-helper 17 (Th17) and regulatory T (Treg) cells, as well as the modulation of the JAK/STAT pathway. This study established a rat ARDS model using intranasal LPS instillation, administering interventions such as FMT, Treg cell depletion, and JAK inhibitors. Assessments included histopathological examination of lung and intestinal tissues, flow cytometry for Th17 and Treg cell proportions, qPCR and Western blot for gene and protein expression, ELISA for inflammatory cytokines, and correlation analysis using Spearman's method for cytokine-immune cell interactions. Results indicated that FMT and JAK inhibitors significantly reduce lung damage induced by LPS, reduced alveolar destruction and inflammation, restored Th17/Treg balance, and inhibited JAK/STAT pathway activity. Notably, FMT decreased pro-inflammatory cytokines (IL-2, IL-6, IL-8, IL-17A, IL-23, TGF-β1) and increased anti-inflammatory cytokines (IL-10, IL-35) in serum. Spearman correlation analysis indicated that FMT restored immune balance by modulating the interactions between cytokines and immune cells. In conclusion, FMT effectively alleviates lung and intestinal injury in LPS-induced ARDS rat models by modulating Th17/Treg balance and inhibiting JAK/STAT pathway activity, demonstrating promising therapeutic potential for ARDS treatment.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is associated with significant mortality and long-term morbidity, often preventing survivors from returning to work. This poses particular challenges in the military, where maintaining combat-ready forces depends on the health and readiness of service members. This study investigates ARDS in active duty U.S. military personnel to estimate its broader impact on the military. MATERIALS AND METHODS: A retrospective cohort study was conducted with Institutional Review Board (IRB) approval, utilizing the U.S. Military Data Repository, which contains health data from all active duty service members. Acute respiratory distress syndrome was identified using Current Procedural Terminology (CPT) codes and confirmed with chart review. Data were collected on demographics, clinical course, underlying ARDS etiology, survival, and military separation. Statistical analyses included univariate comparisons to identify demographic and clinical factors associated with mortality. RESULTS: The overall incidence of ARDS in active duty personnel was 1.01 per 100,000 person-years, with a 2-fold increase in the post-COVID period (1.55 per 100,000 person-years) compared to the pre-COVID period (0.76 per 100,000 person-years). The most common cause of ARDS was infection (53%), followed by trauma (16%). The mean age of affected servicemembers was 32 years, with a mortality rate of 20%. Among those who survived, 43% failed to return to active duty and were medically separated; 70% of these separations were directly attributable to ARDS or related complications, while 30% were because of other etiologies. CONCLUSIONS: Acute respiratory distress syndrome poses significant risks to active duty military personnel, with notable short-term mortality and long-term morbidity, including high rates of medical separation and failure to return to duty. These complications could impact the military overall by decreasing the workforce, impairing military readiness, and introducing financial burdens. Further studies are needed to fully assess functional limitations following ARDS and to optimize management strategies that enhance recovery outcomes for military service members affected by the condition.

Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the world that have resulted in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in some of those infected. Ad14p1 is the predominant circulating strain of Ad14 worldwide that has caused ARDS. An explanation for the severity of illness caused by Ad14p1 infection in immunocompetent patients is unknown. Previously, we have shown that A549 cells infected with Ad14 repress macrophage pro-inflammatory responses, whereas cells infected with Ad14p1 fail to repress macrophages and instead can increase pro-inflammatory responses. Adenoviral infection has been shown to modulate host miRNA expression, and we hypothesized that differences in miRNA expression between Ad14- and Ad14p1-infected cells might explain the differential responses of macrophages to Ad14- and Ad14p1-infected cells. Analysis of host miRNA showed that 98 miRNAs are differentially expressed when infection reaches full cytopathic effect (CPE), the same point at which Ad14 and Ad14p1 CPE corpses induce differential inflammatory responses in macrophages. Only 10 of the miRNAs that were enriched in Ad14 CPE corpses were expressed at levels that are potentially biologically relevant. Pathway enrichment analysis showed that the differentially expressed miRNAs might explain the increased pathogenesis of Ad14p1 through strain-related loss of modulation of cytokine expression when compared with prototype Ad14. Overall, the data suggest a role for viral regulation of host miRNA expression in pathogenesis by regulating host inflammatory responses through the delivery of de-regulated miRNAs by viral CPE corpses to macrophages.