Editorial: Acute respiratory distress syndrome: Lung protective strategy

The acute respiratory distress syndrome (ARDS) is a severe acute hypoxemic respiratory failure caused by the inflammatory response involving alveolar epithelium (inflammatory edema) and capillary endothelial (microvascular thrombosis), which induced by various etiologies (1) . In the intensive care unit, mechanical ventilation, combined with auxiliary management, is one of the most important supportive therapies for ARDS patients (2). The traditional goal of mechanical ventilation is to maintain oxygenation and ensure cardon dioxide removal through adequate alveolar ventilation (3). However, in the last 3 decades, raising evidence indicates that mechanical ventilation may itself be harmful through the occurrence of ventilatorinduced lung injury (VILI), which activates (or worsens) systemic inflammation and induces multi-organ failure. VILI is the leading cause of death in ARDS patients (4).Current evidence and clinical guidelines have shown that a lung-protective strategy including low tidal volume (<6-8 ml/kg of predicted body weight), plateau (<28-30 cmH2O) and driving pressure (<14 cmH2O), and prone position for at least 12-16 hours per day may alleviate VILI and improve clinical outcome (2). The respective effects of positive end-expiratory pressure and extra-corporeal membrane oxygenation (ECMO) or carbon dioxide removal are still under investigation (5,6). In this Research Topic collection "Acute Respiratory Distress Syndrome: novel insights in strategies to enhance lung protection", five related articles are published to provide further insights in this field.Up to now, only low tidal volume and prone position have been supported by high-level clinical evidence [7,8]. Studies in mechanically ventilated ARDS patients have shown that the population that most benefit from prone position is those with severe ARDS, which was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the inspired oxygen fraction (FiO2) of less than 150 mm Hg, measured with a positive end-expiratory pressure (PEEP) of at least 5 cmH2O [8]. After the outbreak of COVID-19 pneumonia in 2020, medical resources limitation had become an issue worthy of attention. Several centers have tried to conduct prone position in non-intubated patients undergoing oxygen therapy, especially during high-flow nasal oxygen.In our collection in the Journal, Huang et al. conducted a systematic review and metaanalysis to evaluate the efficacy and safety of awake prone position in COVID-19 patients. Among 1,686 patients from ten randomized controlled trials, awake prone position significantly reduced intubation requirement (risk ratio: 0.84; 95% confidence interval [CI]: 0.74-0.96, P=0.007). However, the study also revealed poor adherence to awake prone position protocols in real clinical practice, which represents a call for the establishment of standardized procedures that can be applied worldwide.Not all ARDS patients respond positively to prone position. Improvement of oxygenation is usually used as a marker for the response of the prone position. However, the improvement of oxygenation is not the sole parameter indicating less-injurious ventilation in the prone position. Wang et al. performed a retrospective analysis in ARDS patients undergoing prone position to evaluate the association of ventilatory ratio, which is a surrogate of alveolar dead space, with ventilator weaning endpoints.Study results showed the ventilatory ratio decreased more significantly within 4 hours after prone positioning in patients with successful weaning, and that ventilatory ratioimprovement induced by prone position was independently associated with liberation from mechanical ventilation on day 28. Prone position-induced improvement in ventilatory ratio may represent a tool to identify patients in whom this prone position maximize its benefits.ARDS is a syndrome caused by multiple etiologies, and heterogeneity is one of the important clinical manifestations. Classification of patients, either by biological markers or clinical markers, is a research prioritu for ARDS patients. In this Research Topic, three articles focused on this domain.Studies have shown that baseline mechanical ventilation intensity parameters, such as airway driving pressure and mechanical power, are associated with clinical outcomes in ARDS patients. In Hu et al. study, a secondary analysis was performed in 1,000Trials (FACTT). The results showed that the 28-day mortality was significantly lower in patients with early negative fluid balance (15%) than those with persistent-positive fluid balance (50%), with the latter group requiring higher tidal volumes, driving pressure and mechanical power. The hazard ratio of 28-day mortality for time-varying static driving pressure and mechanical was significant lower in patients with negative fluid balance, but not in persistent-positive fluid balance patients. These results show that persistent-positive fluid balance was characterized by a higher intensity of mechanical ventilation, which suggests further research is warranted in this phenotype.In Cheng et al. retrospective study, immunocompromised ARDS patients undergoing ECMO. Study results suggested that immunocompromised status was not an independent risk factor for unsuccessful weaning from ECMO. Importantly, for patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as a bridge therapy.In Wang et al. study, the China Critical Care Sepsis Trial (CCCST) database was used, and clinical outcomes in various patients with ARDS were analyzed according to different etiologies. The study enrolled a total of 2,138 patients with ARDS, and found that hospital mortality in pulmonary ARDS is higher compared with extrapulmonary ARDS; however, if ARDS coexist with sepsis (multi-organ failure), mortality is increased. The study recommended that sepsis-induced pulmonary ARDS should attract 5 more attention from ICU physicians and be cautiously treated.ARDS is a heterogeneous diseases: future research on lung-protective strategies should focus on personalizing intervention based on patients' individual mechanical or inflammatory phenotype (7)(8)(9)(10).