Beyond Aspergillus fumigatus: The Clinical Burden of Aspergillus flavus and Aspergillus niger in Chronic Pulmonary Diseases

Background: The clinical burden of pulmonary diseases associated with the genus Aspergillus is increasing, although diagnostic focus remains largely on A. fumigatus. This study evaluated the diagnostic value of testing for A. flavus and A. niger-specific IgG in patients with chronic respiratory conditions. Methods: A retrospective study was conducted on 274 subjects (156 with chronic respiratory diseases, Bronchiectasis, Hypersensitivity Pneumonitis [HP], and Interstitial Lung Disease [ILD] non-HP, and 67 healthy controls). Cut-off values were established at the 97.5th percentile of the control group: 30 mg/L for A. fumigatus, 13 mg/L for A. flavus, and 8 mg/L for A. niger. Results: Among 109 patients who tested negative for A. fumigatus, 49.5% showed positivity to at least one other species, preventing a significant diagnostic gap in exposure detection. Notably, 40.4% of these patients exhibited simultaneous positivity for both A. flavus and A. niger. In the HP subgroup, 100% of patients who were A. fumigatus-positive also showed concurrent positivity to the two other species. Furthermore, the Bronchiectasis group showed the highest rate of isolated A. flavus at 11.8%. Conclusions: Testing solely for A. fumigatus IgG leads to substantial underestimation of Aspergillus exposure. Integrating A. flavus and A. niger into diagnostic panels is essential for a comprehensive immunological assessment of fungal interaction, particularly in HP and ILD, where identifying specific antigenic exposure is crucial for managing chronic inflammation and preventing disease progression.