During this first reporting period, activities performed per work package are as follows:
WP1: Three General Assembly meetings were held. Pre-financing of €2,799,993.30 was distributed, the Consortium Agreement executed, and a risk management plan delivered (D1.1). The Nantes Health Ethics Group was appointed as Ethics Advisory Board. Eight deliverables and four milestones were submitted.
WP2: The HomiLung-CAP protocol was finalized (28 March 2024) and registered (NCT06601998). The HomiLung-HAP protocol was authorized by ANSM (17 July 2024), approved by the Ethics Committee (29 August 2024), and registered (NCT06602934). The Healthy Lungs protocol was finalized on 1 July 2024. Clinical Project Managers were appointed to support HISS, CHU-NANTES, and sites. CAP was approved in 13 hospitals in Greece, with monitoring in line with GCP. Enrollment began 8 November 2024, with 61 participants recruited in Greece and Spain, assigned to four groups and undergoing assessments. For the HAP study, first patient inclusion was 2 January 2025; by 20 June 2025, 42 patients were enrolled across 4 of 10 sites, with satisfactory recruitment. Follow-up lasts 30 months with scheduled evaluations. Progress: at M3, 11/20 patients and 13/20 relatives recruited; at M6, 8/20 patients and 8/20 relatives. Patient adaptation impact: Advanced Response Shift methodology shows how patients adapt post-pneumonia, informing patient-centered care.
WP3: Samples are stored at Nantes CRB; import authorization for Greek samples approved; first shipments completed. Lipidomic analysis identified differences between HAP and non-HAP patients (notably HDL-related components). Two patient clusters linked to HAP/ARDS showed distinct temporal patterns but lacked external validation. Stable lipidomic signatures distinguishing septic vs. non-septic and HAP vs. non-HAP patients were observed; future work will focus on MACE risk. ImmunoSep dataset analysis identified two reproducible immune endotypes in sepsis survivors, linked to post-recovery complications, consistent across timepoints, validated in an independent cohort, and outperforming individual predictors. Impact: Poster presented at Nanjing conference showcasing machine learning for incomplete clinical data.
WP4: A PhD student established methodologies and SOPs for cryopreserved PBMC analysis, including flow cytometry, PBMC-PIE for rare HSPCs, and metabolic profiling (CENCAT/SCENITH). New computational frameworks for RNA-seq, proteomics, and metabolomics were developed, integrating external datasets via meta-/transfer learning, improving rare subtype detection and to be applied in Homi-Lung. Proteomic data identified reproducible two-protein marker combinations predicting survival across subgroups, validated in independent cohorts. To address missing data, a new inductive logic programming method was developed, published in IJCLR 2024, integrated into LFIT, and will support biomarker identification for HAP.
WP5: The PEACE study launched in 2024 to compare CVD and respiratory disease incidence post-pneumonia using France’s SND database. Protocol developed, ethical approval obtained, >2.7M pneumonia cases identified. Cardiovascular protocol submission to ClinicalTrials.gov planned for July 2025, with expansion to respiratory outcomes thereafter.
WP6:
Mice models: Validation achieved for weight and cholesterol; histology ongoing. Single-cell and flow cytometry analyses of pneumonia response ongoing. Atherosclerosis’ impact on pneumonia: samples collected, analysis in progress. Immunologic targeting: single-cell, flow cytometry, and transcriptomics underway. Deleterious effect of atherosclerosis on remission validated via survival assays at acute infection phase.
Pig model: Protocol revised to focus on long-term CVD effects of corticosteroids+antibiotics (96h groups removed). Submitted for ethics/biosecurity approval. Strict infection control in place. Team of 7 accredited researchers equipped with EIT and anesthesia monitors for real-time lung monitoring and VILI studies.
Objectives & hypotheses: Investigate causal links between gut/respiratory microbiome and alveolar epithelial repair. Hypothesis 1: Gut dysbiosis during sepsis/influenza drives systemic effects influencing lung repair. Findings support a gut–lung axis, explaining adverse antibiotic effects. Hypothesis 2: Injured alveoli alter metabolism, promoting pathogen growth (e.g. P. aeruginosa, S. aureus). The alveolus acts as an ecological niche, suggesting new targets for pneumonia prevention.
WP7: Objective: maximize impact through visibility, stakeholder engagement, FAIR data, and gender balance. A secure Homi-Lung Data Hub is in development (test Q4 2025) ensuring GDPR compliance and interoperability. Web platform, active social media, >100 stakeholders engaged, toolkit deployed, outreach ongoing, gender balance promoted, FAIR/open-science guidance delivered. Impact: Communication infrastructure operational, dissemination accelerating, societal engagement underway. Exploitation: optimized social channels, GA4 dashboards, press release planned, consortium presence at events, secondary-school kit finalized; milestones unchanged.
WP8 (Ethics): All human studies approved by IRBs with informed consent. Animal studies (~2000 mice) authorized under EU/French law (APAFIS #50096), applying 3Rs principles. Non-lethal pneumonia models used under anesthesia with continuous welfare monitoring.
