Daily Ards Research Analysis

Invasive mechanical ventilation remains a cornerstone in the treatment of critically ill patients suffering from acute respiratory failure, providing life-sustaining gas exchange while necessitating careful selection of modes and settings to maximize benefit and minimize harm. This guideline-derived review synthesizes updated, critically appraised and evidence-based recommendations on choosing ventilatory modes and setting key parameters in adults with acute respiratory insufficiency. Building on a systematic GRADE process and presented digitally in the MAGICapp, the 2025 guideline for the German, Austrian and Swiss healthcare context retains a pragmatic taxonomy of ventilatory modes and updates several clinical recommendations. In invasively ventilated patients with moderate-to-severe ARDS, early neuromuscular blockade is no longer favoured; instead, early assisted strategies that allow spontaneous breathing are suggested when clinically appropriate. Pressure-controlled, minute ventilation-supporting modes that enable spontaneous breathing during both inspiration and expiration may be considered in hypoxemic respiratory failure, acknowledging very low certainty of evidence and notable heterogeneity across trials. For the first time, our guideline issues recommendations on adaptive ventilation modes. Some adaptive modes (e.g. ASV/INTELLiVENT-ASV) and neurally adjusted ventilatory assist (NAVA) may be considered on a case-by-case basis, whereas flow- and volume-proportional assist ventilation (e.g. PAV/PAV+) is not recommended given low-certainty evidence and frequent intolerance. Parameter recommendations emphasize lung-protective ventilation with VT ≈6 mL/kg predicted body weight (range 4-8 mL/kg), a plateau pressure ≤30 cmH₂O, and a driving pressure ≤14 cmH₂O. PEEP should be higher in moderate/severe ARDS and individualized using bedside physiology, while oxygen targets of SaO₂/SpO₂ 92-96% or PaO₂ 70-90 mmHg balance hypoxemia and hyperoxia risks. Continuous cardiorespiratory monitoring and capnography for tube placement confirmation and trend assessment are endorsed. Collectively, these recommendations aim to support safe, effective, and implementable ventilatory care while transparently conveying where certainty of evidence remains limited.

OBJECTIVE: Macrophage M1/M2 polarization is essential to mitigate acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Ferroptosis is pivotal in sepsis-induced ALI and interleukin (IL)-35 has been reported to exert anti-inflammatory effects. Therefore, we aimed to investigate the effect of IL-35 on ferroptosis and macrophage polarization in ARDS. METHODS: We constructed an in vitro inflammation model using lipopolysaccharide (LPS) to assess the macrophage polarization, ferroptosis, phagocytosis, and killing effects after IL-35 treatment. A cecal ligation and puncture model was established, and lung injury, ferroptosis, and macrophage polarization were detected following rIL-35 treatment. The indexes showed changes after the use of an NRF2 inhibitor. Additionally, we quantified the injury and apoptosis of MLE-12 cells after co-culture with RAW264.7 cells and detected IL-10 expression. RESULTS: IL-35 blocked LPS-induced polarization of RAW264.7 and bone marrow-derived macrophages to M1 and promoted M2 generation. It up-regulated the NRF2/GPX4 pathway and attenuated ferroptosis in macrophages. When NRF2 was inhibited, the regulatory effects of IL-35 on the macrophage phenotype and ferroptosis were reversed. After co-culture with IL-35-treated RAW264.7, the apoptosis of MLE-12 cells was reduced and IL-10 expression was increased. CONCLUSION: IL-35 alleviates ALI by reducing macrophage ferroptosis and attenuating the activation of proinflammatory macrophages via the NRF2/GPX4 pathway. IL-35-induced macrophages phenotypic remodeling reduce the apoptosis of lung epithelial cells by secreting IL-10.

Gasdermin D (GSDMD) is currently considered the major effector of pyroptosis, a lytic proinflammatory programmed cell death, which mediates pathogenesis in numerous inflammatory lung diseases, such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. When the N-terminal fragment of GSDMD is cleaved by both canonical (caspase-1) and noncanonical (caspase-4/5/11) inflammasome pathways, membrane pores of the protein are formed, which in turn facilitate cell lysis and the release of IL-18 and IL-1B. These events culminate in immune cell infiltration, epithelial endothelial barrier disruption, and tissue remodelling. This is a critical review of GSDMD-mediated pyroptosis as a convergent pathological mediator in a variety of inflammatory pulmonary diseases and synthesizes the findings from the to 2000-2024 literature databases. We also analyzed the mechanism by which GSDMD activation mediates immune cell recruitment, cytokine storm syndrome, and fibrotic remodelling in preclinical disease models. In addition, we performed a systematic evaluation of emerging therapeutic interventions such as direct pore formation inhibitors (disulfiram and necrosulfonamide), upstream caspase inhibitors (VX-765), and anti-inflammatory phytochemicals (andrographolide, emodin, and baicalin). In our analysis, GSDMD was the chosen therapeutic target, allowing precise regulation of terminal pyroptotic signalling without compromising upstream recognition by the immune system. This is a major advantage compared to traditional general immunosuppressants. This review reports that GSDMD is a promising therapeutic target for acute and chronic inflammatory lung disease. This study provides new mechanistic contributions and translational approaches to augment targeted anti-inflammatory interventions in respiratory care by precise pyroptosis modulation.