Daily Ards Research Analysis

BACKGROUND: Dysregulated innate immunity and oxidative stress drive the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), yet master endogenous regulators that orchestrate inflammation resolution remain elusive. METHODS: This study employed public database mining, clinical data investigation, murine disease models, mouse bone marrow-derived macrophages and neutrophils, and human macrophages from healthy donors and ARDS patients, to investigate the dynamic changes of the dopaminergic signaling system in the acute pulmonary inflammatory environment and its role in regulating macrophage metabolism and neutrophil extracellular trap formation (NETosis). RESULTS: Public database mining and experimental data reveal accelerated dopamine (DA) turnover during ALI. DA, signaling via D1-like receptors, reprograms macrophage metabolism by enhancing carnitine palmitoyltransferase 1 A (CPT1A)-dependent fatty acid oxidation (FAO) and mitochondrial fitness, which is coupled with the suppression of MAPK/NF-κB and NLRP3 inflammasome activation. These modulated macrophages restrain neutrophilic inflammation by secreting IL-10 to inhibit the CXCL10-CXCR3 axis, thereby curtailing neutrophil hyperactivation and pathogenic NETosis. Crucially, this protective mechanism is conserved in human macrophages from both healthy donors and ARDS patients. CONCLUSION: Our findings establish DA as a therapeutic target for recalibrating innate immunity in ALI, providing a mechanistically grounded framework for targeting dopaminergic signaling to resolve dysregulated inflammation, with exploratory preclinical translational implications for ALI/ARDS therapy.

Lung surfactant is essential for regulating alveolar surface stresses, reducing the work of breathing, maintaining compliance, and preventing collapse. Under pathological conditions such as acute respiratory distress syndrome (ARDS), this functionality is compromised, yet the underlying physical mechanisms remain incompletely understood. Recent work has shown that surfactant failure cannot be described from surface tension alone, but requires consideration of the interfacial dilatational modulus, which quantifies the ability of the interface to sustain stress under deformation. Mechanical instability arises when this stress-bearing capacity is lost, linking alveolar collapse directly to a reduction in the dilatational modulus. However, this response is typically interpreted in terms of equilibrium adsorption and Gibbs elasticity. Here, we demonstrate instead that it reflects the breakdown of nonequilibrium, microstructure-mediated mechanical surface stresses. By combining freestanding thin-film measurements, cryo-TEM imaging, and dilatational rheology, we isolate the effects of extra compressive stress contributions arising from interfacial microstructure and probe the effects of Albumin and lysophosphatidylcholine (LysoPC) on the clinical surfactant Infasurf. We show that LysoPC-induced structural reorganization disrupts the interfacial architecture, suppressing the development of compressive surface stresses and thereby weakening the mechanical integrity of the interface. These results establish a more subtle link between surfactant microstructure and the interfacial stress response, providing a physically grounded framework for surfactant inactivation and suggesting distinct directions for therapeutic design.

PURPOSE: The role of obesity in sepsis-associated acute respiratory distress syndrome (SA-ARDS) remains uncertain, particularly amid evolving diagnostic criteria. We aimed to assess whether obesity differentially influences SA-ARDS incidence and mortality under the Berlin definition versus an expanded framework incorporating high-flow nasal cannula (HFNC). METHODS: This prospective multicenter cohort study included 1,799 adults with sepsis 3.0 from three ICUs. SA-ARDS was diagnosed using (1) Berlin criteria and (2) a new definition integrating HFNC. The primary outcome was incidence of SA-ARDS. Secondary outcomes included 28- and 90-day mortality in SA-ARDS patients. RESULTS: Obesity was independently associated with elevated SA-ARDS incidence under the new definition (adjusted OR 5.61, 95% CI 4.56-6.92; AUC = 0.700), with even higher risk in ARDS patients under Berlin criteria (OR 6.66, 95% CI 5.01-8.91) and HFNC recipients (OR 5.77, 95% CI 3.85-8.85). These associations remained robust in PSM and IPW analyses. However, in ARDS patients of the new definition (including HFNC patients), no survival differences were observed across BMI categories. However, under the Berlin definition, obesity patients had significantly lower 90-day mortality than underweight and normal-weight patients, particularly in the elderly and those with prolonged hospital stays (P < 0.05). CONCLUSIONS: Obesity independently increased SA-ARDS risk across both diagnostic frameworks. However, the mortality benefit (Berlin definition) was absent when using the expanded criteria incorporating HFNC. This indicates obesity drives susceptibility but confers no universal survival advantage in new ARDS cohorts.