Diagnostic value of galactomannan in tracheobronchial aspirate for Aspergillus infection in lung transplant recipients (the GALACTBAS study).

Lung transplant recipients (LTR) are highly susceptible to Aspergillus infection (AI), but diagnosis may be limited by the invasiveness of bronchoalveolar lavage fluid (BALF) collection. Proximal airway samples may provide a less invasive alternative. We conducted a retrospective single-center study including all adult LTR (March 2018-March 2022) who underwent bronchoscopy with tracheobronchial aspirate (TBA) and BALF galactomannan (GM) testing in the same procedure. They were processed for mycological culture and EIA-based GM (Bio-Rad) after cysteine homogenization. AI was defined according to ISHLT consensus. A ROC curve for TBA GM and its diagnostic performance were assessed. A total of 545 paired TBA-BALF samples from 282 LTR were analyzed. Proven or probable AI was diagnosed in 22 samples (4%). The optimal TBA GM cut-off was ≥0.54 optical density index (ODI), yielding 95.2% sensitivity, 92% specificity, and an AUC of 0.97 (95% CI, 0.95-0.99). In comparison, BALF GM at ≥1.0 ODI showed 33.3% sensitivity and 99.6% specificity (AUC 0.88, 95% CI, 0.80-0.95) although BALF GM values were significantly higher in invasive infections compared with non-invasive infections (1.49 vs 0.14; P-value = 0.007). TBA cultures were more frequently positive than BALF (24% vs 9.9%). Finally, TBA and BALF GM values demonstrated moderate correlation (r = 0.54), and combined testing with concordant results improved accuracy to 99.6%. TBA GM demonstrated higher sensitivity than BALF GM for detecting AI in LTR, while maintaining high specificity. Proximal airway samples could complement BALF in future diagnostic strategies.IMPORTANCEThis study provides evidence that galactomannan antigen testing (GM) in tracheobronchial aspirate (TBA) is a highly sensitive, reliable, and less invasive diagnostic tool for detecting Aspergillus infection in lung transplant recipients under universal antifungal prophylaxis, compared to the current standard bronchoalveolar lavage fluid (BALF) GM. These findings highlight the diagnostic value of proximal airway specimens, consistent with the pathophysiology of post-transplant aspergillosis, which often originates in the bronchial tree and may not be adequately captured by BALF early in the disease course. Importantly, the study shows that combining TBA and BALF GM results yields near-perfect diagnostic accuracy, supporting a complementary diagnostic strategy rather than a replacement approach. Although this is a proof-of-concept study, it fills a critical evidence gap in transplant infectious diseases and lays the groundwork for safer, more accurate, and earlier diagnosis of Aspergillus infection, with potential implications for clinical practice, antifungal stewardship, and future guideline development.