Airway associated inflammation in post-transplant cystic fibrosis patients as a predictor of chronic lung allograft dysfunction (CLAD).

Abstract

Aims: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.

Methods: A retrospective, single-centre observational study of cystic fibrosis LTRs between 2002 and 2021 was performed. Data from biopsy slides, pulmonary function testing and bronchoalveolar lavage fluid microbiology tests were collected. The primary outcome was bronchiolitis obliterans syndrome (BOS) or death after transplant, with an 8-year follow-up period.

Results: 40 patients were identified with an average age of 35.3 at first transplantation, including 5 redo lung transplants. Fungal infections were correlated with higher rejection scores (p<0.01) and survival status (p=0.027). Fungal and bacterial infection rates were reduced in later transplants (2014-2021) compared with earlier (2002-2014). Fungal infections were associated with significantly worsened outcomes (p≤0.001). Eosinophils in large airways was associated with worse BOS-free survival (p=0.03).

Conclusions: Subcategorisation of the inflammatory milieu (particularly noting eosinophils) in surveillance biopsies may help detect CLAD earlier and improve long-term outcomes in cystic fibrosis LTRs.