Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is an innate defence protein that acts as an anti-microbial agent and regulates airway surface liquid volume through inhibition of the epithelial sodium channel (ENaC). SPLUNC1 levels were found to be reduced in airway secretions of adults with cystic fibrosis (CF). The potential of SPLUNC1 as a biomarker in children with CF is unknown. We quantified SPLUNC1, interleukin-8 (IL-8) and neutrophil elastase (NE) in sputum of CF children treated with either intravenous antibiotics or oral antibiotics for a pulmonary exacerbation (PEx)s, and in participants of a prospective cohort of CF children with preserved lung function on spirometry, followed over a period of two years. Sputum SPLUNC1 levels were significantly lower before compared to after intravenous and oral antibiotic therapy for PEx. In the longitudinal cohort, SPLUNC1 levels were found to be decreased at PEx visits compared to both previous and subsequent stable visits. Higher SPLUNC1 levels at stable visits were associated with longer PEx-free time (hazard ratio 0.85, = 0.04). SPLUNC1 at PEx visits did not correlate with IL-8 or NE levels in sputum or forced expiratory volume in one second (FEV) but did correlate with the lung clearance index (LCI) (=-0.53, < 0.001). SPLUNC1 demonstrates promising clinometric properties as a biomarker of PEx in children with CF.

中文翻译：

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SPLUNC1 作为囊性纤维化儿童肺部病情加重的生物标志物

短腭、肺和鼻上皮克隆 1 (SPLUNC1) 是一种先天防御蛋白，可充当抗菌剂，并通过抑制上皮钠通道 (ENaC) 来调节气道表面液体容量。研究发现患有囊性纤维化 (CF) 的成人气道分泌物中的 SPLUNC1 水平降低。SPLUNC1 作为 CF 儿童生物标志物的潜力尚不清楚。我们对接受静脉抗生素或口服抗生素治疗肺部病情加重 (PEx) 的 CF 儿童以及前瞻性 CF 儿童队列参与者的痰液中的 SPLUNC1、白细胞介素 8 (IL-8) 和中性粒细胞弹性蛋白酶 (NE) 进行了定量肺活量测定显示肺功能保留，随访时间为两年。与 PEx 静脉内和口服抗生素治疗后相比，治疗前痰液 SPLUNC1 水平显着降低。在纵向队列中，与之前和随后的稳定就诊相比，PEx 就诊时的 SPLUNC1 水平被发现有所下降。稳定就诊时较高的 SPLUNC1 水平与较长的无 PEx 时间相关（风险比 0.85，= 0.04）。PEx 就诊时的 SPLUNC1 与痰中的 IL-8 或 NE 水平或一秒用力呼气量 (FEV) 无关，但与肺清除指数 (LCI) 相关（=-0.53，< 0.001）。SPLUNC1 表现出作为 CF 儿童 PEx 生物标志物的良好临床测量特性。