Multi-modal data to identify key factors influencing lung injury in ARDS patients undergoing invasive mechanical ventilation: A prospective observational study protocol

Abstract Background Patients with moderate to severe acute respiratory distress syndrome (ARDS) exhibit extremely poor prognoses following mechanical ventilation, with mortality rates as high as 40% to 55%. Despite extensive research into ARDS classification and prognostic assessment, the disease’s pathogenesis remains incompletely understood, and there remains a critical lack of specific biomarkers and effective therapeutic targets for its prevention and management. The core challenges lie in two key areas: First, ARDS demonstrates marked heterogeneity in etiology, pathophysiology, and pathogenesis. Second, current definitions of ARDS phenotypes are often confined to clinical symptoms and routine diagnostic indices, lacking integrated analysis of deeper mechanistic indicators, thereby limiting the stability and clinical utility of existing classification systems. Methods/Design We designed a prospective multicenter cohort study incorporating multi-omics analyses. The study plans to enroll over 200 patients with moderate to severe ARDS receiving mechanical ventilation across 10 medical centers. Peripheral blood and bronchoalveolar lavage fluid (BALF) samples will be collected on the first 24 hours after enrollment and at extubation for metagenomic/meta-transcriptomic sequencing, bulked RNA sequencing, single-cell transcriptomics, proteomics, and metabolomics analyses. Concurrently, comprehensive monitoring of physiological indices, electrical impedance tomography, transpulmonary pressure, pulmonary ultrasound findings, and other relevant parameters will be conducted during the enrollment. Study participants will be stratified by survival and mortality outcomes to analyze the dynamic trends of all measured indices and their underlying molecular mechanisms. Discussion Through comparative analysis of multi-omics data, we aim to identify specific markers and risk factors associated with distinct clinical trajectories of ARDS, further clarifying the key determinants of lung injury. Ultimately, this research will reveal critical immune cell subtypes that govern ARDS onset and prognosis, offering novel insights and therapeutic targets to advance precision medicine for ARDS. Trial registration ClinicalTrials.gov NCT 05922826. Registered on 27 Six 2023.