Daily Ards Research Analysis

BACKGROUND: The "Personalized Mechanical Ventilation Guided by Lung UltraSound in Patients with Acute Respiratory Distress Syndrome" (PEGASUS) study aims to evaluate personalized mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) compared to the standard of care. However, misclassification and misaligned MV strategies were shown to be harmful. We therefore aimed to assess the interobserver agreement of lung ultrasound (LUS) between the local investigator and an expert panel in classifying ARDS subphenotypes alongside protocol adherence and safety endpoints, as a pilot phase of the ongoing PEGASUS study. METHODS: The first 80 mechanically ventilated patients with moderate-to-severe ARDS were enrolled in the ongoing PEGASUS study, a randomized clinical trial (RCT), and were included in the pilot phase. Focal or non-focal subphenotypes were classified using a LUS. Positive end-expiratory pressures (PEEP), tidal volumes (VT), the application of recruitment manoeuvres, and proning were performed according to randomization arm and subphenotype. Safety limits for MV followed current guidelines. Agreement in subphenotype classification between local investigators and a panel of three experts was evaluated using Cohen's κ coefficient. RESULTS: In 68 out of 80 exams, the images were of sufficient quality for assessment. The interobserver agreement for the lung morphology had a Cohen's kappa of 0.72 (95% CI 0.53-0.9) and accuracy of 88% between local investigator and the expert panel. Misclassification occurred in 8/68 exams (11.8%). Among these 8 misclassified cases, 6 (75%) also showed disagreement between experts due to different LUS scores of the anterior regions. Tidal volume and PEEP were generally set according to the protocol. An exception was the TV in the non-focal ARDS patients randomized to personalized MV, where the median (6.2 ml/kg/PBW) was above the target range (4-6 ml/kg/PBW). Patients exceeding safety limits of MV were low. CONCLUSION: In the pilot phase of an ongoing international subphenotype-targeted RCT, we found that local investigators' assessments agreed with expert panel consensus assessments in the large majority of cases, and nearly always when the expert panel assessment was unanimous. Protocol adherence was sufficient, but tidal volume in the non-focal subphenotype deserves attention during continuation of the study. TRIAL REGISTRATION: The study was registered on clinicaltrial.gov (ID: NCT05492344, date 2022-08-05).

BACKGROUND: Severe COVID-19 is frequently associated with acute respiratory distress syndrome (ARDS) and prolonged pulmonary sequelae. Persistent immune activation, including dysregulated B cell responses and increased proinflammatory chemokines, has been linked to the post-acute sequelae of SARS-CoV-2 infection. However, the mechanisms linking these factors remain poorly defined. METHODS: Sixty patients were studied four months after acute COVID-19, including 34 who developed ARDS, 26 who did not develop ARDS, and 12 healthy controls. Clinical, computed tomography scan (CT), and diffusion capacity of the lungs for carbon monoxide (DLCOc) assessments were performed. Anti-SARS-CoV-2 IgM/IgG levels were quantified, circulating B cell subsets were characterized, and circulating cytokines and chemokines were measured. CXCR3 expression on B cells was analyzed by spectral flow cytometry. RESULTS: IgG, but not IgM, levels were significantly higher in patients with ARDS than in patients without ARDS. Both COVID-19 groups showed a reduction in CD19 CONCLUSION: Four months after COVID-19, patients with prior ARDS and persistent pulmonary sequelae exhibit sustained elevations of anti-SARS-CoV-2 IgG and chemokines CXCL9 and CXCL10. Both chemokines directly enhance B cell differentiation into IgG-secreting plasma cells

Despite advancements in bedside monitoring and paradigm shifts in standard ventilatory practice, mortality from acute respiratory distress syndrome (ARDS) remains high. The recent Global ARDS definition adopts a more pragmatic approach enabling earlier identification across a broader patient spectrum, independent of the interventions being administered. Meanwhile, our understanding of managing this heterogeneous syndrome has shifted towards defining precise subgroups with shared therapeutic targets. Physiological, biological, and radiological phenotypes may modify the response to interventions previously showing indeterminate benefit, making them potentially central to future personalised ARDS management. This narrative review summarises core evidence for the medical and ventilatory management of ARDS, explores emerging concepts, and offers clinicians a framework for current best practice and a roadmap for possible future directions.