Periodic Reporting for period 1 - Homi-lung (Long-term alterations of host-microbiome interactions and cardiovascular and respiratory diseases progression after pneumonia)
Période du rapport: 2024-01-01 au 2025-06-30
The Homi-lung project aims to (i) define medical, societal, and patient needs; (ii) expand doctors’ knowledge of links between pneumonia and CVD; (iii) enable early identification of patients at risk; and (iv) preclinically develop treatments. We will compare CVD rates in pneumonia survivors vs. matched controls over 3 years, analyze longitudinal samples, and develop AI algorithms linking host-microbiome interactions with CVD progression, validated in preclinical models. Bringing together 8 partners from 5 EU countries, the project will deliver biomarkers, evidence, and TRL4 treatments to improve recovery, reduce infection burden, and strengthen pandemic preparedness.
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.
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.
For this first reporting period, there is no result and potential impact to report yet.