Fungal colonization and CLAD in lung transplant recipients: Implications for antifungal prophylaxis and graft...

Fungal colonization is common after lung transplantation, but its relationship with chronic lung allograft dysfunction (CLAD) remains uncertain.

We conducted a retrospective cohort study of 220 adult lung transplant recipients between 2018 and 2022 at a high-volume transplant center. Colonization was defined by positive respiratory cultures without evidence of invasive fungal infection. The primary outcome was development of bronchiolitis obliterans syndrome (BOS), the predominant phenotype of CLAD. The analytic cohort comprised consecutive recipients meeting inclusion criteria, with exclusions for multiorgan or redo transplant, insufficient follow-up data, and clinically relevant pulmonary infections during follow-up, specifically invasive fungal infection and bacterial pneumonia. Multivariable cox regression models were used to examine associations between colonization and BOS-CLAD.

Fungal colonization occurred in 121 of 220 recipients (55%), most commonly Candida species (95/220, 43%), Penicillium species (34/220, 15%), and Aspergillus species (21/220, 10%). BOS-CLAD developed in 35 recipients (16%) during a median follow-up of 881 days (IQR 603-1011). The median time to BOS-CLAD was shorter in colonized versus non-colonized recipients (527 vs 682 days). In adjusted models, Aspergillus colonization (aHR 2.14, 95% CI 1.06-4.67) and Pseudomonas colonization (aHR 2.13, 95% CI 1.04-4.36) were associated with BOS-CLAD. Age was inversely associated with BOS-CLAD risk (aHR 0.94, 95% CI 0.92-0.97). No clear associations were observed with Candida or Penicillium colonization. Recipient-derived colonization was more frequent (83/121, 69%) and associated with increased BOS-CLAD risk compared with donor-derived colonization.

In this single-center cohort, fungal colonization-particularly with Aspergillus-was associated with earlier onset of BOS-CLAD despite universal antifungal prophylaxis; although colonization may reflect disruption of airway microbiology or heightened clinical acuity rather than a direct causal pathway. These findings underscore the importance of fungal colonization and need for prospective studies to clarify mechanisms, refine prophylaxis strategies, and evaluate targeted interventions.