Project description:Background: Acute respiratory distress syndrome (ARDS) is an unresolved challenge in the field of respiratory and critical care, and the changes in the lung microbiome during the development of ARDS and their clinical diagnostic value remain unclear. This study aimed to explore the role of the lung microbiome in disease progression in patients with sepsis-induced ARDS and potential therapeutic targets. Methods: Patients with ARDS were divided into two groups according to the initial site of infection, intrapulmonary infection (ARDSp, 111 cases) and extrapulmonary infection (ARDSexp, 45 cases), and a total of 28 patients with mild pulmonary infections were enrolled as the control group. In this study, we sequenced the DNA in the bronchoalveolar lavage fluid collected from patients using metagenomic next-generation sequencing (mNGS) to analyze the changes in the lung microbiome in patients with different infectious site and prognosis and before and after antibiotic treatment. Results: The Shannon–Wiener index indicated a statistically significant reduction in microbial diversity in the ARDSp group compared with the ARDSexp and control groups. The ARDSp group was characterized by a reduction in microbiome diversity, mainly in the normal microbes of the lung, whereas the ARDSexp group was characterized by an increase in microbiome diversity, mainly in conditionally pathogenic bacteria and intestinal microbes. Further analysis showed that an increase in Bilophila is a potential risk factor for death in ARDSexp. An increase in Escherichia coli, Staphylococcus aureus, Candida albicans, enteric microbes, or conditional pathogens may be risk factors for death in ARDSp. In contrast, Hydrobacter may be a protective factor in ARDSp. Conclusion: Different initial sites of infection and prognoses are likely to affect the composition and diversity of the pulmonary microbiome in patients with septic ARDS. This study provides insights into disease development and exploration of potential therapeutic targets.
Project description:Acute respiratory distress syndrome (ARDS) is an acute respiratory illness characterised by bilateral chest radiographical opacities with severe hypoxaemia due to non-cardiogenic pulmonary oedema. The COVID-19 pandemic has caused an increase in ARDS and highlighted challenges associated with this syndrome, including its unacceptably high mortality and the lack of effective pharmacotherapy. In this Seminar, we summarise current knowledge regarding ARDS epidemiology and risk factors, differential diagnosis, and evidence-based clinical management of both mechanical ventilation and supportive care, and discuss areas of controversy and ongoing research. Although the Seminar focuses on ARDS due to any cause, we also consider commonalities and distinctions of COVID-19-associated ARDS compared with ARDS from other causes.
Project description:The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary oedema, hypoxaemia and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma and is present in ~10% of all patients in intensive care units worldwide. Despite some improvements, mortality remains high at 30-40% in most studies. Pathological specimens from patients with ARDS frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory oedematous fluid in the alveolar space. Diagnosis is based on consensus syndromic criteria, with modifications for under-resourced settings and in paediatric patients. Treatment focuses on lung-protective ventilation; no specific pharmacotherapies have been identified. Long-term outcomes of patients with ARDS are increasingly recognized as important research targets, as many patients survive ARDS only to have ongoing functional and/or psychological sequelae. Future directions include efforts to facilitate earlier recognition of ARDS, identifying responsive subsets of patients and ongoing efforts to understand fundamental mechanisms of lung injury to design specific treatments.
Project description:Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. The objective of this study is to understand the differences in disease biology between survivors and non-survivors by characterizing BALF protein expression profiles in individual ARDS subjects.
Project description:Bronchoalveolar Lavage Fluid protein profile was characterized in ARDS subjects. Patients were divided into three groups: 1) Early phase survivors 2) Early phase non-survivors and 3) Late phase survivors. Bronchoalveolar lavage fluid was pooled within each group for sample preparation and mass spectrometry
Project description:The acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure that is often associated with multiple organ failure. Several clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair.
Project description:Rat model of ARDS was induced by saline lavage and mechanical ventilation. Total RNA from rat lungs were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2. Two-condition experiment, CON vs. ARDS lung tissues. replicates: 5 control, 7 ARDS. One replicate per array.
Project description:Rat model of ARDS was induced by saline lavage and mechanical ventilation. miRNA from rat lungs were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2. Two-condition experiment, CON vs. ARDS lung tissues. replicates: 6 control, 6 ARDS. One replicate per array.
Project description:The rationale for the use of recruitment maneuvers (RMs) in acute respiratory distress syndrome (ARDS) is to promote alveolar recruitment, leading to an increased end-expiratory lung volume and thus decreased ventilator-induced lung injury (VILI). RMs consists of a transient increase in transpulmonary pressure that can re-open previously collapsed alveoli. RMs represents a physiological response to lung aggression in different conditions by re-opening the collapsed part of the lung and decreasing lung oedema. This process can be accomplished through a variety of methods. The RM that has probably been used most commonly is sustained inflation, but recruitment can be achieved by a prolonged sigh, leading to a lesser increase in transpulmonary pressure for a longer period of time. This extended sigh seems to be more efficient, with less haemodynamic compromise. Knowledge of physiological determinants is crucial to selecting good levels of pressure and time required to perform an efficient and well-tolerated RM. Identifying ARDS patients who may benefit from RMs is a major issue, depending essentially on the amount of recruitable lung involved. In any case, however, RMs should be done at the early phase of ARDS.
Project description:The defining features of acute respiratory distress syndrome (ARDS) are an excessive inflammatory respiratory response associated with high morbidity and mortality. Treatment consists mainly of measures to avoid worsening lung injury and cannot reverse the underlying pathophysiological process. New pharmacological agents have shown promising results in preclinical studies; however, they have not been successfully translated to patients with ARDS. The lack of effective therapeutic interventions has resulted in a recent interest in strategies to prevent ARDS with treatments delivering medications directly to the lungs by inhalation and nebulization, hopefully minimizing systemic adverse events. We analyzed the effect of different aerosolized drugs such as bronchodilators, corticosteroids, pulmonary vasodilators, anticoagulants, mucolytics and surfactant. New therapeutic strategies and ongoing trials using carbon monoxide (CO) and AP301 peptide are also briefly reviewed.