Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study

Area of Science:

• Pulmonary Medicine
• Microbiology
• Immunology

Background:

• Bronchiectasis pathogenesis involves inflammation and infection, but integrating host inflammatory and microbiome data for precision medicine is limited.
• Few studies have explored the relationship between distinct inflammatory profiles (endotypes) and the lung microbiome in bronchiectasis.

Purpose of the Study:

• To classify bronchiectasis patients into clusters based on inflammatory markers.
• To investigate the association between these inflammatory endotypes, lung microbiome characteristics, and the risk of future exacerbations.

Main Methods:

• Cluster analysis of 33 sputum and serum inflammatory markers in 199 stable bronchiectasis patients from three European centers.
• 16S ribosomal RNA sequencing to analyze lung microbiome composition.
• 12-month follow-up to assess exacerbation risk in relation to inflammatory clusters and microbiome profiles.

Main Results:

• Four distinct inflammatory clusters were identified: milder neutrophilic, mixed-neutrophilic/type 2, severe neutrophilic, and mixed-epithelial/type 2.
• Lower microbiome diversity correlated with more severe inflammatory clusters.
• Specific microbiome profiles, including enrichment of Proteobacteria and Pseudomonas, were associated with distinct inflammatory clusters and higher exacerbation risk in clusters 2 and 3.

Conclusions:

• Inflammatory endotypes in bronchiectasis are linked to specific lung microbiome compositions.
• These associations predict future exacerbation risk, offering potential for precision medicine approaches in bronchiectasis management.