Lung transplant for CF: Low lung bacterial burden and immune mediators in year one associate with clad development.

Abstract

Background: Lung transplantation is commonly required for advanced lung disease in cystic fibrosis (CF). Long-term lung allograft survival is limited primarily by chronic lung allograft dysfunction (CLAD), and microbial factors have been implicated in CLAD development. However studies have not specifically investigated CF patients despite the unique microbe-rich nature of the CF respiratory tract. We investigated whether early post-transplantation lung microbiome features associate with CLAD development.

Methods: We investigated a longitudinal cohort of 23 CF patients undergoing lung transplantation. Lung lavage was collected from donor lungs, and from recipient allografts serially during the first year post-transplantation. Patients were followed for a median of 4.9 years. This was complemented by a case-control study of 8 CF patients sampled at incident CLAD along with non-CLAD CF transplant controls. Lung bacteria were enumerated by 16S rRNA gene sequencing and quantified by qPCR, and immune mediators investigated by multiplex assay.

Results: Cohort patients who developed CLAD had lower lung bacterial burden, lower relative abundances of classic CF lung microbiota, and lower mediator levels during the first-year post-transplantation than those remaining CLAD-free. In contrast, incident CLAD showed elevated lung immune mediators but no microbiome differences.

Conclusions: Low lung bacterial content and immune mediators during the first year post-transplantation for CF associate CLAD, whereas CLAD onset is characterized by elevated immune mediators but no lung microbiome differences. Whether airway bacteria early after transplantation for CF may protect against CLAD or serve as a biomarker merits further study.