Clinical Research Collaborations (CRCs) at the ERS Congress

Introduction: Antimicrobial resistance (AMR) is a global threat disproportionately affecting people with chronic lung infection, however the epidemiology in bronchiectasis and Cystic Fibrosis (CF) is poorly characterised.

Conclusion: We show significant increasing global AMR burden in bronchiectasis and CF with geographic variation and persistence post CFTR modulator therapy.

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Learn more about AMR-Lung.

Background: Primary ciliary dyskinesia (PCD) is a multisystem genetic disorder causing mucociliary clearance abnormalities. Limited and indirect evidence is available for the care of people with PCD, which is often based on cystic fibrosis and bronchiectasis management guidelines. The European guidelines on the management of PCD (Barbato, A et al. ERJ 2009) are outdated. The aim of this BEAT-PCD project was to update the consensus management guideline based on current evidence and expert opinions.

Conclusion: This updated international consensus statement targets respiratory professionals and aims to improve standards of care for patients with PCD worldwide.

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Learn more about the BEAT-PCD CRC.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) can have its origins in early life, and epigenetic mechanisms may be involved. This study investigates if lung function levels are associated with epigenetic profiles across the lifespan.

CONCLUSIONS: We identified associations between FEV1 across the lifespan and methylation levels at multiple annotated genes. The methylation levels of these genes could serve as potential early biomarkers of abnormal lung function later in life.

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Learn more about CADSET.

Introduction: The transition from paediatric to adult healthcare is a critical period for patients as  it involves complex changes, resulting in additional challenges for those with chronic disease as their healthcare needs evolve. When well-structured, transition enhances quality of life, self-management, treatment adherence, and follow-up. However, if inadequate, it may lead to patients being lost to follow-up. We undertook a literature review that aimed to synthesise the evidence on transitioning adolescents and young adults (AYA) with bronchiectasis from paediatric to adult healthcare.

Conclusion: There is currently a glaring gap in transitioning AYA with bronchiectasis. The development of a structured and effective transition program for AYA with bronchiectasis is needed.

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Learn more about Child-BEAR-Net.

Introduction: Heterozygous variants in the transcription factor NK2 homeobox1 (NKX2-1) can be associated with brain-lung-thyroid syndrome. NKX2-1 partly controls the transcription of surfactant proteins, thyroglobulin (TG) and thyroid peroxidase (TPO). This study aimed to explore the pathogenicity of three variants of NKX2-1 identified in patients with fatal respiratory diseases.

Conclusion: Herein, we confirmed the peculiar pathogenicity of two variants of the NKX2.1 homeodomain, with the newly described Y214C, being associated with the most severe phenotype. We also acknowledge that G147A is probably benign. More genotype-phenotype studies are needed to better understand the pathogenicity of NKX2-1 variants.

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Learn more about ChILD-EU CRC.

AECOPD severity is traditionally graded post facto based on treatment decisions influenced by patients’ symptom perception and healthcare resources. The 2023 GOLD adopted Rome classification relies on clinical variables without accounting for baseline condition, a gap addressed by the novel BAT (Baseline, Acuity, Trigger) Model developed by the CICERO CRC. We compared these severity classifications in their ability to discriminate within a cohort of hospitalised patients.
149 patients hospitalised for an AECOPD in Belgium (Oct2022-Feb2024) were classified by Rome and BAT. Median age was 69y (IQR:64-76), median BMI 24.3 (IQR:20.6-29.1), median FEV1(%pred) 42 (IQR:32-55), 58% were male. Agreement between Rome and BAT was low (Fig.1a, κ=0.23). The BAT model appointed more patients to the high risk group (56%) and fewer to the low risk group (11%) as compared to Rome (13% and 24%, respectively). Severity stratification by BAT was superior to Rome in predicting mortality across the different timepoints (Fig.1b). BAT and Rome categories failed to predict readmission rates at 3 months, although BAT showed non-significant trends for the risk of readmission at 1 year (Fig.1c).

The BAT Model demonstrates superior alignment between severity grading and patient mortality across all timepoints in patients hospitalised for an acute exacerbation.

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Learn more about CICERO CRC.

Background: Implementation of digital healthcare is complex and challenging. Harmonising implementation strategies can promote safe and equitable digital healthcare, but guidance for implementation is lacking.

Conclusion: We identified enablers and barriers for implementation.Findings will inform policy statements to promote a harmonised framework for digital respirtory.

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Learn more about CONNECT CRC.

AATD is a rare monogenic disorder predisposing individuals to liver and lung disease. Yet, even within the same genotype, AATD is very heterogeneous regarding clinical presentation.
To identify clinical phenotypes, we performed a cluster analysis using baseline EARCO data (n=1238) and identified six clusters (C1-6) using K-prototypes. With a Random Forest model, we identified age at diagnosis, lung function and smoking history as most important variables in differentiating the clusters.

C1-3 grouped individuals with normal lung function and low CAT scores. C1 and C2 grouped rare or never-smokers, with a markedly different age at diagnosis, whereas individuals of C3 have a notable smoking history.

C4-6 grouped individuals with COPD diagnosis based on low lung function and high CAT scores. Individuals of C4 were older at diagnosis and reported higher smoking history compared to C5 and C6. Individuals of C6 had the lowest lung function, with ±80% of individuals on AAT augmentation therapy compared to ±30% in C5.

The SS, SZ and ZZ genotype were present in C1-4, but shifted to ZZ in C5-6.

Altogether, we identified six clinical AATD phenotypes mainly differentiated by lung function and smoking history rather than genotype. Longitudinal follow-up of these clusters will help to better understand disease progression and potential benefits of augmentation therapy.

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Learn more about EARCO CRC.

Rationale: We report a randomized, double-blind, placebo-controlled trial of gremubamab, a bispecific mAb targeting Psl exopolysaccharide and PcrV T3SS component, in people with bronchiectasis and P. aeruginosa infection.

Conclusion: Gremubamab treatment significantly reduced P. aeruginosa load, symptoms and exacerbations in bronchiectasis.

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Learn more about EMBARC CRC.

The genioglossus muscle (GG) is critical for diurnal activities such as talking and maintaining open upper airway during sleep. Reduced GG responsiveness during sleep contributes to the development of obstructive sleep apnoea (OSA). While talking, GG is accurately moved to produce various phonemes. Each language includes phonemes that require specific posterior or anterior GG contractions. As a more trained and responsive GG is protective for OSA, we hypothesized that OSA severity might be conditioned by the language spoken. In the European Sleep Apnea Database (ESADA), an ERS supported CRC, we evaluated the association between OSA severity and linguistic strains.

Conclusion: Predominant Germanic language includes more posterior phonemes and is associated with almost 50% less OSA severity. Our data suggests that posterior phonemes may train the GG as a preventive measure for OSA

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Learn more about ESADA.

Background: Cardiopulmonary exercise testing (CPET) is used to assess individuals’ physiological responses to exercise and to identify potential causes of exercise limitation.

Conclusion: Significant heterogeneity in CPET testing methodology and outcomes between sites precluded the development of generalised reference ranges for V’O2peak and Wpeak. Further prospective studies with standardised CPET protocols and analytical methods are needed to reduce variability and establish robust, clinically meaningful interpretation strategies.

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Learn more about GLI CRC.

Introduction: The iDREAM CRC was launched in 2024. Pediatric sleep disordered breathing (SDB) received increasing attention, resulting in advancements in diagnosis and management guidelines, primarily for children aged 2 years and older. However, infants and toddlers below this age have been overlooked, creating a gap in addressing their sleep-related issues.

Conclusion: These pilot data from the first survey of our CRC on sleep-disordered breathing in infants clearly show potential to standardize the diagnosis, work-up and management of obstructive sleep apnea in this vulnerable patient population.

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Learn more about iDREAM CRC.

Background: The field of pleural medicine has developed rapidly, with many publications and guidelines based on high quality evidence.

Conclusions: This survey identified significant variation in clinical practice and highlighted access issues to certain investigations and interventions across WHO regions.

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Learn more about IMPACT CRC.

Introduction: Chest X-ray is a key diagnostic test in the management of chronic cough (CC) while diagnostic value of chest computed tomography (CT) is still a matter of debate. The aim of this study was to analyse the results of chest CT performed in patients participating in the ERS NEuroCOUGH CRC Registry– European CC patient registry.

Conclusion: In Europe, chest CT is performed often in adults with CC. Although pulmonary abnormalities revealed in chest CT are frequent, few of the are unequivocally relevant to CC.

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Learn more about N-EUROCOUGH CRC.

Introduction: The hyperinflammatory and hypoinflammatory ARDS subphenotypes have different outcomes and treatment effects in retrospective analyses of clinical trials. We hypothesised that real-time prospective identification of these biological subphenotypes at the bedside is feasible.
Methods: Patients with ARDS were recruited in 30 ICUs in the UK and Ireland. Fresh plasma IL-6 and sTNFR1 were quantified using a point of-care analyzer (Randox Laboratories Inc.) and input in a validated classifier model with arterial bicarbonate to determine subphenotype. The primary outcome was difference in 60-day mortality between subphenotypes (NCT04009330).
Results: 512 patients were included and 490 (95.7%) were classified to subphenotype. Selected outcomes are shown in Table 1 below:

Conclusion: Our large multicentre study indicates that real-time classification of ARDS subphenotypes is feasible and that the subphenotypes have distinct clinical characteristics and outcomes. Our findings will enable precision medicine trials, such as the PANTHER trial, to test differential treatment effects in these subphenotypes.

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Learn more about PANTHER.

Background: Existing cohort studies suggest infants born preterm (before 37 weeks’ gestation) are vulnerable to lung disease, which may be progressive over their lifespan. However, small sample sizes and high heterogeneity in individual studies have limited a thorough understanding of lung function trajectories, and the factors associated with both resiliant and adverse trajectories.
We aimed to establish the world’s first harmonised global repository for lung health data from cohorts of survivors of preterm birth to generate greater statistical power and enable use of robust methods, expediting our understanding of lung health trajectories after preterm birth.

Conclusions: PELICAN presents a unique opportunity to fill key evidence gaps in the long-term respiratory outcomes of survivors of preterm birth, essential for guiding follow-up and early intervention for those at risk of poorer outcome.

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Learn more about PELICAN CRC.

Background: Real-world responses to biologics were assessed by cigarette smoking exposure.

Conclusion: Former/current smokers respond as well as never smokers to biologics, with AQLQ improving most in current smokers. Management disparities identified across Europe need for inclusive, evidence-based guidelines.

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Learn more about SHARP.