Daily Ards Research Analysis

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of lung failure with a high mortality rate and no effective pharmacological therapy. Although the cellular and molecular mechanisms involved in ARDS onset have been extensively studied, those governing its resolution remain unclear. Recent human cohort studies have suggested an association between ARDS severity and low blood basophil count. Therefore, in this study, we investigated the roles of basophils in ARDS pathogenesis and resolution. METHODS: We examined the effects of basophil depletion in lipopolysaccharide-induced ARDS model mice and assessed the roles of basophils in ARDS onset and resolution using genetically engineered mice and single-cell RNA-sequencing analysis. RESULTS: Intratracheal administration of lipopolysaccharides induced severe lung inflammation, characterised by extensive neutrophil infiltration, followed by gradual recovery to homeostatic conditions. Basophil depletion impaired the resolution but not the induction of lung inflammation, highlighting the critical role of basophils in the resolution phase of ARDS. Basophils accumulated in the lungs were the primary sources of the cytokine interleukin (IL)-4. Mice with basophil-specific IL-4 deficiency failed to resolve lung inflammation, as did mice with neutrophil-specific IL-4 receptor deficiency. Transcriptomic analysis revealed that basophil-derived IL-4 acted on neutrophils to suppress the anti-apoptotic gene and pro-inflammatory mediator expression. CONCLUSIONS: Overall, our findings revealed that basophils played essential roles in the ARDS resolution phase, primarily by producing IL-4, which acted on neutrophils to alleviate lung inflammation in ARDS model mice.

Research using lower respiratory tract (LRT) sampling may lead to improved understanding and management of patients with acute respiratory failure (ARF). Research bronchoscopy is a valuable tool for sampling the LRT during ARF. However, bronchoscopy may be limited by challenges with repeated sampling, the inability to sample the most severely ill patients, and increased resource utilization. "Noninvasive" sampling strategies, such as nonbronchoscopic bronchoalveolar lavage, endotracheal aspirate collection, and heat moisture exchange filter fluid collection, may expand the opportunity to collect LRT samples for research. Upper respiratory tract and sputum sampling may enable sampling in nonintubated patients with ARF, for whom there is no direct noninvasive access to the LRT. We convened a workshop with 32 experts from diverse continents, scientific backgrounds, and healthcare professions, all with experience in clinical or research practice during ARF. The Workshop goals were to review existing noninvasive sampling methods, evaluate their respective potential benefits and limitations, and identify future research priorities aimed at improving standardization and integration of these approaches into practice. Findings were generated by review of literature, expert presentations, meeting discussions, and electronic surveys using a modified Delphi approach. Participants agreed that each sampling method provides biologically meaningful data during ARF while also acknowledging that each method has benefits and limitations. Various potential advantages to noninvasive methods include reduced cost, enhanced speed, and ease of adoption compared with standard fiberoptic bronchoscopy. Despite the potential advantages, rigorous head-to-head comparisons between noninvasive methods and/or standard bronchoscopy are limited, which is a priority for future research. Additional research priorities include examination of the feasibility and benefit of serial sampling of the LRT and investigation of how LRT biomarkers are related to lung pathophysiology and patient-centered clinical outcomes during ARF. This Workshop Report provides guidance for investigators to integrate LRT sampling into their research and highlights key priorities, such as rigorous head-to-head comparison of sampling methods for research, to improve the standardization of noninvasive sampling methods and use of LRT sampling in research and clinical practice.

PURPOSE: The optimal ventilation strategy in acute respiratory distress syndrome (ARDS) patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO) remains unknown. We aimed to compare the effects of two ultra-protective ventilatory strategies applied to patients with ARDS and VV-ECMO. METHODS: Our study was an observational, retrospective, single-center study with a before-and-after design. All consecutive patients treated with VV-ECMO for severe ARDS between 2016 and 2023 were included. Before 2021, patients received a quasi-apneic ventilation strategy in assist-controlled volume mode with a tidal volume (V RESULTS: 121 patients were enrolled, with 69 receiving the VT1 strategy, and 52 the ∆P8 strategy. Over the first 7 days of ECMO, the ∆P8 strategy was associated with significantly higher ∆P and RR, lower PaCO CONCLUSIONS: In the context of our center, a ventilatory strategy targeting a PEEP of 14 cmH