Association of post-transplant lung microbiome and cytokine profiles with CLAD

Results from a prospective, longitudinal, cohort study evaluating the association of post-transplant lung microbiome and cytokine profiles with chronic lung allograft dysfunction (CLAD) in 186 lung transplant recipients (excluding those with cystic fibrosis [CF]) were published in the American Journal of Transplantation by Merenstein et al. Patients were followed for a median of 6.04 years, with bronchoalveolar lavage (BAL) samples collected over the first post-transplant year. 

Key data: CLAD developed in 38% of patients, with a median time to CLAD of 3.04 years. Higher lung bacterial burden at 6 months was associated with earlier CLAD onset (hazard ratio [HR], 1.34; p = 0.0025). A higher Streptococcus/Prevotella ratio at 6 weeks was associated with delayed CLAD (HR, 0.68; p = 0.00065). Elevated interferon γ-induced protein 10/C-X-C motif chemokine ligand 10 (IP10/CXCL10) immediately post implantation was associated with earlier CLAD onset (HR, 1.81; p = 0.0016). Combined modeling of all three factors, together with previously recognized clinical features, stratified patients into high- and low-risk groups, with a >3-fold difference in CLAD risk (HR, 3.08; p < 0.0001). 

Key learning: These findings show that increased lung bacteria and altered composition during the first-year post-transplant and of IP10/CXCL10 immediately after implantation are associated with CLAD development, potentially enabling CLAD risk stratification in non-CF lung transplant recipients.