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

干扰素-λ1和干扰素-λ3在非中性粒细胞减少症侵袭性肺曲霉病患者的支气管肺泡灌洗液和血浆中的诊断和预后作用

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Abstract

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, P < 0.0001; IFN-λ3: 189.70 [94.94, 271.79] pg/mL vs. 78.15 [36.54, 149.14] pg/mL, P < 0.0001). However, no significant differences were observed in plasma IFN-λ1 and IFN-λ3 levels between IPA and non-IPA patients (P > 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.IMPORTANCEInvasive 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.

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