BALance: ARDS Deconvolution by Bronchoalveolar Lavage Multiomics and Radiomics (BALance)

Check the BALance: ARDS Deconvolution by Bronchoalveolar Lavage Multiomics Profiling and Radiomics

Acute respiratory distress syndrome (ARDS) is a major contributor to ICU mortality and is characterised by hypoxaemia and pulmonary oedema. Pathomechanisms include barrier breakdown, immunopathology, haemostatic derailment and dysbiosis; however, the actual sequence of events and how they cumulatively lead to lung failure remains unclear. Although ARDS is frequently triggered by pneumonia, it can also occur as a result of trauma, aspiration or non-pulmonary causes. Importantly, ARDS is highly heterogeneous; growing evidence points to aetiology-specific pathomechanisms - a circumstance that explains why attempts to develop specific drugs or timely diagnostic markers have so far failed.

A comprehensive analysis of key microenvironmental and haemostasis-related parameters of the lung, combined with multidimensional quantitative image features derived from chest CT scans (radiomics), will enable us to i) identify ARDS phenotypes with different biological characteristics and ii) generate new hypotheses regarding aetiology- or subgroup-specific mechanisms, molecular markers and therapeutic options.

Our approach is based on ICU management of our patients guided by bronchoalveolar lavage fluid (BALF). Together with previously sampled cases and new samples collected as part of this study, our cohort will consist of patients with i) COVID-19-associated ARDS, ii) ARDS associated with other viral pneumonia, iii) ARDS associated with bacterial pneumonia, and iv) ARDS of non-pulmonary origin. Bacterial and fungal co-infections and superinfections are recorded in all patients and taken into account in the stratification. Patients with pneumonia without ARDS, as well as ventilated patients without underlying lung disease, serve as controls. To characterise the microbial lung microenvironment, the investigators combine data from routine microbiological diagnostics with microbiome sequencing and metabolomics. In addition, the investigators conduct comprehensive and longitudinal immune and haemostatic profiling by regularly analysing immune cells, cytokines and parameters of immune thrombosis in BALF and blood. Multi-omics integration then identifies phenotypic subgroups by merging all multimodal datasets - including radiomics. Selected samples from identified clusters are then further characterised using single-cell sequencing to uncover specific features/markers and pathomechanisms of the respective ARDS subtypes.

Although it is clear that the pathogenesis of ARDS is multifactorial, comprehensive studies that integrate all relevant parameters are rare. Radiomics is increasingly recognised as a powerful tool for capturing the clinical status of ARDS in detail; however, to date, this imaging data has not been systematically linked to other omics readouts. The investigators aim to bridging this gap by conducting a thorough investigation across various ARDS aetiologies in the present study, incorporating all identifiable key factors.

Our interdisciplinary team comprises basic immunologists, infectious disease and computational biologists, as well as clinicians with expertise in ARDS, infectious diseases, immunothrombosis and radiology.

Study Overview

• Status: Not yet recruiting
• Conditions: ARDS (Acute Respiratory Distress Syndrome)
• Intervention / Treatment: Diagnostic test: sampling blood; Diagnostic test: Lavage with physiologic saline solution

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Oliver Robak, Prof. PD Dr.; Phone Number: +43 1 40400 44920; Email: oliver.robak@meduniwien.ac.at
• Study Contact Backup: Name: Riem Gawish, PhD; Phone Number: +43 1 40400 51480; Email: riem.gawish@meduniwien.ac.at

Study Locations

• Austria
  • State of Vienna
    • Vienna, State of Vienna, Austria, 1090
      • General Hospital of Vienna, Medical University of Vienna
      • Contact: Oliver Robak, Ap. Prof. Priv.-Doz. Dr.; Phone Number: +43 1 40400 44920; Email: oliver.robak@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients admitted to the University Hospitals of the Medical University of Vienna at the Vienna General Hospital (AKH Vienna) during the specified study period who meet the inclusion criteria will be enrolled in this study.

Description

Inclusion Criteria:

• male and female
• aged 18 years or over
• signed consent form
• depending on the study group: Confirmed ARDS according to the Berlin criteria (see below, Groups B and D) Confirmed severe CAP requiring mechanical ventilation and intensive care (see below, Groups B and C) Ventilated patients without signs of ARDS (see below, Group E)

Exclusion Criteria:

- under 18 years of age

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 ARDS	Diagnostic test: sampling blood; blood will be drawn from patients on day 1 and once a week until discharge/withdrawal/death; Diagnostic test: Lavage with physiologic saline solution; mini-BALF using a physiologic saline soluation will be performed on day 1 and once a week until discharge/withdrawal/death; Other Names: Mini-BALF
Pneumonia-induced ARDS	Diagnostic test: sampling blood; blood will be drawn from patients on day 1 and once a week until discharge/withdrawal/death; Diagnostic test: Lavage with physiologic saline solution; mini-BALF using a physiologic saline soluation will be performed on day 1 and once a week until discharge/withdrawal/death; Other Names: Mini-BALF
Severe pneumonia but no ARDS	Diagnostic test: sampling blood; blood will be drawn from patients on day 1 and once a week until discharge/withdrawal/death; Diagnostic test: Lavage with physiologic saline solution; mini-BALF using a physiologic saline soluation will be performed on day 1 and once a week until discharge/withdrawal/death; Other Names: Mini-BALF
Non-pulmonary origin ARDS	Diagnostic test: sampling blood; blood will be drawn from patients on day 1 and once a week until discharge/withdrawal/death; Diagnostic test: Lavage with physiologic saline solution; mini-BALF using a physiologic saline soluation will be performed on day 1 and once a week until discharge/withdrawal/death; Other Names: Mini-BALF
No lung pathology	Diagnostic test: sampling blood; blood will be drawn from patients on day 1 and once a week until discharge/withdrawal/death; Diagnostic test: Lavage with physiologic saline solution; mini-BALF using a physiologic saline soluation will be performed on day 1 and once a week until discharge/withdrawal/death; Other Names: Mini-BALF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ARDS phenotypes	The application of multi-omics cluster analysis to reveal any distinct ARDS phenotypes or subgroup-specific characteristics.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Microbiome Composition Analysis via 16S rRNA Gene Sequencing of Bronchoalveolar Lavage (BAL) Fluid	Differences in the microbial community composition (alpha diversity, beta diversity, and taxonomic abundance at phylum/genus level) of the lower respiratory tract microbiome in intensive care patients with ARDS	4 years
Metabolomic Profile of Bronchoalveolar Lavage Fluid and Plasma	Differences in the metabolomic profile (relative concentrations of annotated metabolites and pathway-level scores) in bronchoalveolar lavage (BAL) fluid and plasma between ARDS subgroups (with vs. without bacterial/fungal co-/superinfection). Metabolomic measurements will be performed using the METAB02, AMINO01, and LIPID01 or other appropriate packages. Samples will be analyzed via mass spectrometry to quantify a wide range of analytes, including various amino acids, lipids and their subclasses, and metabolites such as pyruvate, lactate, citrate, and succinate.	4 years
Inflammatory Cytokine Profile in Bronchoalveolar Lavage Fluid and Plasma	Concentrations of predefined pro- and anti-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α, others according to panel) in BAL fluid and plasma of ARDS patients, and detection of differences between ARDS subgroups (with vs. without bacterial/fungal co-/superinfection) by Multiplex bead-based immunoassay or ELISA panels (e.g., Luminex, electrochemiluminescence).	4 years

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Study Director: Oliver Robak, Prof. PD Dr., Medical University of Vienna, Department of Medicine 1; Principal Investigator: Riem Gawish, PhD, Medical University of Vienna, Department of Medicine 1

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pneumonia; Influenza; COVID-19; ARDS; viral; Co-Infection; bacterial; BALF
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Lung Injury; COVID-19; Influenza, Human; Pneumonia; Acute Lung Injury; Coinfection; Investigative Techniques; Therapeutics; Paracentesis; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection; Cordocentesis
• Other Study ID Numbers: 2405/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share de-identified individual participant data (IPD) underlying the results reported in this study, including demographic data, baseline characteristics, and outcome measures. Data will be available following publication of the primary results, upon reasonable request from qualified researchers.
• IPD Sharing Time Frame: 4 years, starting from enrollment
• IPD Sharing Access Criteria: Access will be granted after approval of a methodologically sound proposal and completion of a data sharing agreement, in compliance with institutional and data protection regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR