Daily Ards Research Analysis

RATIONALE: COVID-19-associated acute-respiratory distress syndrome (C-ARDS) results from a direct viral injury associated with host excessive innate immune response mainly affecting the lungs. However, cytokine profile in the lung compartment of C-ARDS patients has not been widely studied, nor compared to non-COVID related ARDS (NC-ARDS). OBJECTIVES: To evaluate caspase-1 activation, IL-1 signature, and other inflammatory cytokine pathways associated with tissue damage using post-mortem lung tissues, bronchoalveolar lavage fluids (BALF), and serum across the spectrum of COVID-19 severity. METHODS: Histological features were described and activated-caspase-1 labeling was performed in 40 post-mortem biopsies. Inflammatory cytokines were quantified in BALF and serum from 19 steroid-treated-C-ARDSand compared to 19 NC-ARDS. Cytokine concentrations were also measured in serum from 128 COVID-19 patients at different severity stages. MEASUREMENTS AND MAIN RESULTS: Typical "diffuse alveolar damage" in lung biopsies were associated with activated caspase-1 expression and vascular lesions. Soluble Caspase-1p20, IL-1β, IL-1Ra, IL-6 and at lower level IFNγ and CXCL-10, were highly elevated in BALF from steroid-treated-C-ARDS as well as in NC-ARDS. IL-1β appeared concentrated in BALF, whereas circulating IL-6 and IL-1Ra concentrations were comparable to those in BALF and correlated with severity. TNFα, TNFR1 and CXCL8 however, were significantly higher in NC-ARDS compared to C-ARDS, treated by steroid. CONCLUSIONS: In the lungs of C-ARDS, both caspase-1 activation with a predominant IL-1β/IL-6 signature and IFNγ -associated chemokines are elevated despite steroid treatment. These pathways may be specifically targeted in ARDS to improve response to treatment and to limit alveolar and vascular lung damage.

Sepsis is a life-threatening condition caused by severe infection and often complicates acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) due to the collapse of the oxidative and inflammatory balance induced by microbial pathogens, including lipopolysaccharides (LPS). In sepsis-related ARDS/ALI, NADPH oxidase (NOX) and toll-like receptors (TLR) in neutrophils and macrophages are key players in initiating oxidative and inflammatory imbalances. Although NOX and TLR activation has been linked to carbon monoxide (CO), the mechanism by which CO affects sepsis-related ARDS/ALI through NOX and TLR remains unknown. Here, we demonstrate that CO reduces sepsis-related ARDS/ALI by inhibiting NOX in neutrophils and macrophages, which in turn suppresses the production of reactive oxygen species (ROS), TLR4-associated inflammatory responses, and macrophage polarization toward M1-like macrophages. CO-bound hemoglobin vesicle (CO-HbV) therapy, a hemoglobin-based CO donor, exerts a protective effect against LPS-induced ALI by suppressing exaggerated oxidative and inflammatory responses and neutrophil and M1-like macrophage infiltration in the bronchoalveolar lavage fluid (BALF). Through suppression of NOX activity, CO decreased ROS generation, the TLR4/NF-κB signaling pathway, and macrophage polarization toward M1-like macrophages, according to cellular experiments conducted with peripheral neutrophils, BALF cells, and Raw264.7 cells. Moreover, ALI was found to be more severe in Hmox1

INTRODUCTION: In high-altitude cities located above 2,500 m, hospitals face a concerning mortality rate of over 50% among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS). This elevated mortality rate is largely due to the absence of altitude-specific medical protocols that consider the unique physiological adaptations of high-altitude residents to hypoxic conditions. This study addresses this critical gap by analyzing demographic, clinical, sex-specific, and preclinical data from ICUs in Bogotá, Colombia (2,650 m) and El Alto, Bolivia (4,150 m). METHODS: A cohort of seventy ARDS patients, aged 18 and older, was evaluated within 24 h of ICU admission. Data collected included demographic information (age, sex), clinical characteristics (primary pathology, weight, height), vital signs, respiratory variables, cardiorespiratory parameters, blood count results, inflammatory markers, severity assessment scores, and comorbidities. Advanced statistical analyses, such as multivariate logistic regression and principal component analysis, were utilized to identify key clinical predictors of ARDS-related mortality. RESULTS: Our findings indicate that in high-altitude ICUs, monitoring inflammatory markers may be more beneficial for improving ARDS survival rates than emphasizing respiratory failure markers. Unexpectedly, we found no significant differences in clinical outcomes between altitudes of 2,650 and 4,150 m or between male and female patients. CONCLUSION: The study concludes that, in high-altitude settings, ARDS patient survival in ICUs is more closely associated with managing inflammatory responses than with focusing solely on respiratory parameters. Further large-scale studies are recommended to validate the impact of inflammatory marker monitoring on survival outcomes in high-altitude ICUs.