Diagnostic and prognostic roles of interferon-λ1 and interferon-λ3 in bronchoalveolar lavage fluid and plasma in non-neutropenic patients with invasive pulmonary aspergillosis

This study aims to evaluate the diagnostic and prognostic value of interferon (IFN)-λ1 and IFN-λ3 levels in bronchoalveolar lavage fluid (BALF) and plasma in non-neutropenic invasive pulmonary aspergillosis (IPA) patients. A total of 481 patients suspected of IPA were enrolled (169 IPA cases and 312 non-IPA cases) in this study. BALF and plasma samples were collected, and IFN-λ1 and IFN-λ3 levels were measured using an enzyme-linked immunosorbent assay. In IPA patients, BALF IFN-λ1 and IFN-λ3 levels were significantly higher than in non-IPA patients (IFN-λ1: 284.60 [229.12, 357.99] pg/mL vs. 189.50 [140.00, 233.69] pg/mL, <i>P</i> < 0.0001; IFN-λ3: 189.70 [94.94, 271.79] pg/mL vs. 78.15 [36.54, 149.14] pg/mL, <i>P</i> < 0.0001). However, no significant differences were observed in plasma IFN-λ1 and IFN-λ3 levels between IPA and non-IPA patients (<i>P</i> > 0.05). The optimal cutoff values for diagnosing IPA were 238.7 pg/mL for BALF IFN-λ1 and 133.9 pg/mL for IFN-λ3, with sensitivities of 73.04% and 62.61%, and specificities of 78.35% and 73.16%, respectively. Additionally, IPA patients admitted to the intensive care unit showed higher BALF IFN-λ1 and IFN-λ3 levels than those in general wards. Elevated BALF IFN-λ1 and IFN-λ3 levels were associated with adverse 30-day outcomes. BALF IFN-λ1 ≥ 341.6 pg/ml was an independent risk factor for 30-day poor outcomes in IPA patients. In conclusion, higher BALF IFN-λ1 and IFN-λ3 levels in IPA patients suggest their diagnostic potential. These elevated levels link to disease severity and poor outcomes, with high BALF IFN-λ1 levels being an independent predictor of 30-day adverse outcomes in IPA patients.<b>IMPORTANCE</b>Invasive pulmonary aspergillosis (IPA) is a severe fungal infection. The present study demonstrates that the levels of IFN-λ1 and IFN-λ3 in bronchoalveolar lavage fluid (BALF) hold significant diagnostic and prognostic value for non-neutropenic IPA patients. Our findings indicate that, compared with non-IPA patients, the levels of BALF IFN-λ1 and IFN-λ3 are significantly elevated in IPA patients. Receiver operating characteristic curve analysis established optimal diagnostic cutoff values for IPA of 238.7 pg/mL for BALF IFN-λ1 and 133.9 pg/mL for BALF IFN-λ3. Furthermore, we observed that IPA patients requiring intensive care unit admission and those with poor 30-day outcomes exhibited higher levels of BALF IFN-λ1 and IFN-λ3. Notably, IFN-λ1 ≥341.6 pg/mL was identified as an independent risk factor for poor 30-day prognosis in IPA patients. This finding may enable improved risk stratification and the development of more personalized treatment strategies.