Bronchoalveolar Lavage Metagenomic Sequencing in the Early Post-Lung Transplantation Period: A Pilot Comparison with Microbiologic Culture

Conventional bronchoalveolar lavage (BAL) culture has limited sensitivity in lung transplant recipients. Metagenomic sequencing of BAL offers culture-independent pathogen identification. A study compared conventional culture with metagenomic sequencing (Karius Focus BAL and Oxford Nanopore) in 19 adult lung transplant recipients, analyzing 33 BAL samples. Karius detected pathogens in 19 out of 33 episodes (58%), whereas conventional culture found them in only 8 out of 33 episodes (24%). In 16 episodes where Karius detected a pathogen not recovered by culture, 8 were predictive, meaning the same organism was later confirmed as causing invasive infection, including fatal Pseudomonas pneumonia. Quantitative microbial cell-free DNA (mcfDNA) burden positively correlated with alveolar inflammatory biomarkers such as total protein, IL-6, and sST2. In conclusion, BAL mcfDNA metagenomics identified clinically relevant pathogens not recovered by conventional culture, and its quantitative signal correlated with inflammatory mediators.