BAL Fluid Eosinophilia Associates With Chronic Lung Allograft Dysfunction Risk: A Multicenter Study

Area of Science:

• Immunology
• Transplantation Medicine
• Pulmonology

Background:

• Chronic lung allograft dysfunction (CLAD) is a primary cause of mortality in lung transplant recipients.
• Eosinophils, key players in type 2 immunity, are implicated in lung disease pathogenesis and may be linked to rejection or CLAD post-transplant.

Purpose of the Study:

• To investigate the correlation between histologic allograft injury or respiratory microbiology and eosinophils in bronchoalveolar lavage fluid (BALF).
• To determine if early post-transplant BALF eosinophilia predicts future CLAD development, even after accounting for other risk factors.

Main Methods:

• Analysis of BALF cell counts, microbiology, and biopsy data from 531 lung recipients over the first post-transplant year.
• Generalized estimating equation models to assess correlations between histology/microbiology and BALF eosinophils.
• Multivariable Cox regression to evaluate the association between BALF eosinophils (≥1%) and CLAD; quantification of eosinophil-related gene expression in CLAD tissues.

Main Results:

• BALF eosinophils were more frequent with acute rejection, lung injury histologies, and fungal detection.
• Early post-transplant BALF eosinophilia (≥1%) significantly and independently elevated the risk of definite CLAD (aHR=2.04, P=.009).
• Increased expression of eotaxins, IL-13, IL-33, and thymic stromal lymphopoietin was observed in CLAD tissues.

Conclusions:

• BALF eosinophilia serves as an independent predictor of future CLAD risk in lung transplant recipients.
• Type 2 inflammatory pathways are activated in established CLAD.
• Further research is needed to explore type 2 pathway interventions for CLAD prevention and treatment.