Sun Chao, Zhong Huanhuan, Lu Yajie, Cai Yuchen, Li Yuanyuan, Wang Yujie, Zhao Tingting, Wang Li, Feng Chunlai, Sun Wenkui, Chen Cheng, Tao Yujian, Ma Guoer, He Binchan, Wang Xinyu, Zhong Jinjin, Lu Xin, Li Yuanqin, Su Xin
Department of Respiratory and Critical Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Department of Respiratory and Critical Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Microbiol Spectr. 2025 Sep 9:e0154925. doi: 10.1128/spectrum.01549-25.
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, < 0.0001; IFN-λ3: 189.70 [94.94, 271.79] pg/mL vs. 78.15 [36.54, 149.14] pg/mL, < 0.0001). However, no significant differences were observed in plasma IFN-λ1 and IFN-λ3 levels between IPA and non-IPA patients ( > 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.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.
本研究旨在评估支气管肺泡灌洗液（BALF）和血浆中干扰素（IFN）-λ1及IFN-λ3水平在非中性粒细胞减少的侵袭性肺曲霉病（IPA）患者中的诊断和预后价值。本研究共纳入481例疑似IPA患者（169例IPA病例和312例非IPA病例）。收集BALF和血浆样本，采用酶联免疫吸附测定法检测IFN-λ1和IFN-λ3水平。在IPA患者中，BALF中IFN-λ1和IFN-λ3水平显著高于非IPA患者（IFN-λ1：284.60[229.12，357.99]pg/mL对189.50[140.00，233.69]pg/mL，<0.0001；IFN-λ3：189.70[94.94，271.79]pg/mL对78.15[36.54，149.14]pg/mL，<0.0001）。然而，IPA患者与非IPA患者血浆中IFN-λ1和IFN-λ3水平未见显著差异（>0.05）。诊断IPA的最佳临界值为BALF中IFN-λ1为238.7 pg/mL，IFN-λ3为133.9 pg/mL，敏感性分别为73.04%和62.61%，特异性分别为78.35%和73.16%。此外，入住重症监护病房的IPA患者BALF中IFN-λ1和IFN-λ3水平高于普通病房患者。BALF中IFN-λ1和IFN-λ3水平升高与30天不良预后相关。BALF中IFN-λ1≥341.6 pg/ml是IPA患者30天不良预后的独立危险因素。总之，IPA患者BALF中较高的IFN-λ1和IFN-λ3水平提示了它们的诊断潜力。这些升高的水平与疾病严重程度和不良预后相关，BALF中高IFN-λ1水平是IPA患者30天不良预后的独立预测因素。侵袭性肺曲霉病（IPA）是一种严重的真菌感染。本研究表明，支气管肺泡灌洗液（BALF）中IFN-λ1和IFN-λ3水平对非中性粒细胞减少的IPA患者具有重要的诊断和预后价值。我们的研究结果表明，与非IPA患者相比，IPA患者BALF中IFN-λ1和IFN-λ3水平显著升高。受试者工作特征曲线分析确定IPA的最佳诊断临界值为BALF中IFN-λ1为238.7 pg/mL，BALF中IFN-λ3为133.9 pg/mL。此外，我们观察到需要入住重症监护病房的IPA患者和30天预后不良的患者BALF中IFN-λ1和IFN-λ3水平较高。值得注意的是，IFN-λ1≥341.6 pg/mL被确定为IPA患者30天预后不良的独立危险因素。这一发现可能有助于改善风险分层并制定更个性化的治疗策略。
