Daily Ards Research Analysis

BACKGROUND: Acute Lung Injury (ALI) and its most severe form, Acute Respiratory Distress Syndrome (ARDS), are critical pulmonary conditions characterized by life-threatening acute hypoxic respiratory failure, affecting over three million individuals globally each year. ALI involves alveolar inflammation and disruption of the alveolar-capillary barrier, primarily driven by neutrophil infiltration and the release of inflammatory mediators. In our previous study using a lipopolysaccharide (LPS)-induced mouse model of ALI, we demonstrated that C6, a peptide inhibitor of voltage-gated proton channels (Hv1), ameliorates lung injury, identifying Hv1 as a potential therapeutic target. However, (i) whether the anti-inflammatory effects of C6 are translatable to a clinically relevant live bacterial infection model, and (ii) the molecular mechanisms underlying these anti-inflammatory effects, remain unknown, and are a crucial next step towards targeted rational drug development. METHODS: To induce ALI, we used an intratracheal RESULTS: C6 mitigates P. aeruginosa-induced ALI in mice by reducing neutrophil infiltration into the alveolar space by ~ 86%, improving lung injury scores, decreasing BAL fluid proinflammatory cytokine levels, and suppressing neutrophil ROS production and intracellular calcium levels. RNA sequencing of BAL neutrophils revealed 51 downregulated genes, including key regulators of neutrophil migration, cytokine release, and ROS production; only three genes were upregulated and they also have roles in neutrophil immune defense. In human neutrophils, C6 similarly inhibited chemotaxis and reduced ROS and cytokine release, and calcium influx. CONCLUSIONS: Targeting Hv1 with C6 effectively protects against P. aeruginosa-induced ALI by limiting neutrophil recruitment and activation. These findings establish C6 as a promising therapeutic candidate against infectious ALI and provide important mechanistic insights into its immunomodulatory effects on neutrophils. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-025-03409-0.

Ventilatory management of acute respiratory distress syndrome (ARDS) requires a careful balance between achieving adequate gas exchange and minimizing ventilator-induced lung injury (VILI). Recent advances in bedside monitoring of respiratory mechanics have created new opportunities to individualize mechanical ventilation by aligning ventilator settings with the patient's dynamic pathophysiology. This review synthesizes current evidence on key respiratory mechanics parameters - such as driving pressure, respiratory system compliance, airway resistance, mechanical power - and examines how they can guide titration of tidal volume, positive end-expiratory pressure (PEEP), and respiratory rate. By integrating real-time assessments of respiratory mechanics, clinicians can reduce stress and strain, limit alveolar overdistension and collapse, and optimize oxygenation and ventilation. Moreover, practical strategies are discussed for implementing physiology-guided ventilation in the intensive care unit, with attention to patient-specific characteristics and the heterogeneity of ARDS subphenotypes. Respiratory mechanics-guided ventilation represents a pragmatic, individualized strategy that enhances lung protection, complements established protocols and may contribute to improve survival. Further experimental and clinical studies are required to validate these approaches and translate them into precision medicine for ARDS.

INTRODUCTION: Determining whether chronic exposure to air pollution contributes to observed disparities in COVID-19 outcomes requires integrating multiple determinants of patient vulnerability to COVID-19, given the complex interactions that contribute to health disparities. Exposure to adverse social and structural factors heightens vulnerability to environmental exposures, potentially resulting in increased risk of unfavorable COVID-19 outcomes. Additionally, as populations are often exposed to various co-occurring adverse factors in the setting of disinvested neighborhoods and communities, examining such factors individually may not be sufficient to fully understand how they may modify the effects of air pollutant exposures. In an effort to explain COVID-19-related disparities observed in New York City (NYC METHODS: We used harmonized electronic health record (EHR) data from five healthcare systems in NYC to derive a study population of hospitalized or emergency department (ED) patients diagnosed with COVID-19 from March 1, 2020, through February 28, 2021, who had a NYC zip code of residence. To reduce potential selection bias, we also constructed a subset of the study population restricted to patients with residential zip codes in the typical catchment area of the hospitals affiliated with the EHR data repository. We estimated air pollutant concentrations for fine particulate matter (PM RESULTS: Exposures to NO CONCLUSIONS: When limiting to individuals in the hospital's typical catchment areas, the observed positive associations between air pollutant exposures and COVID-19-related morbidities such as ARDS, pneumonia, and use of dialysis were strongest in areas with higher neighborhood-level environmental vulnerability. Inverse associations between air pollutant exposures and severe outcomes like death and use of mechanical ventilation were unexpected findings that highlighted challenges in examining such associations at the population level in NYC.