SPLUNC1: a novel marker of cystic fibrosis exacerbations.
SPLUNC1: a novel marker of cystic fibrosis exacerbations.
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DOI：
10.1183/13993003.00507-2020
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Britto CJ
中科院分区：
文献类型：
--
作者：
Khanal S;Webster M;Niu N;Zielonka J;Nunez M;Chupp G;Slade MD;Cohn L;Sauler M;Gomez JL;Tarran R;Sharma L;Dela Cruz CS;Egan M;Laguna T;Britto CJ
急性肺加重（AE）是囊性纤维化（CF）临床恶化的发作，通常由感染引起。及时检测对于最大限度地减少AE期间与急性炎症相关的发病率和肺功能下降至关重要。基于我们先前的观察，即气道蛋白短腭肺鼻上皮克隆1（SPLUNC 1）受炎症信号调节，我们研究了使用SPLUNC 1波动来诊断和预测CF中的AE。我们从两个独立的队列中招募CF参与者，以测量痰液中炎症的AE标志物，并记录1年随访期的临床结局。SPLUNC 1水平在健康对照组中较高（n=9，10.7μg/mL），在无AE的CF参与者中显著降低（n=30，5.7μg/mL，p=0.016）。在AE期间SPLUNC 1水平降低71.9%（n=14，1.6μg/mL，p=0.0034），与年龄、性别、CF致突变或微生物学结果无关。细胞因子IL-1β和TNFα也在AE中升高，而肺功能并未持续降低。SPLUNC 1水平较低的稳定CF参与者在60天时更有可能发生AE（HR：11.49，标准误：0.83，p=0.0033）。低SPLUNC 1稳定参与者即使在痰液采集后一年仍保持较高的AE风险（HR：3.21，标准误：0.47，p=0.0125）。SPLUNC 1在AE期间被炎性细胞因子下调，并且痰液中的蛋白酶增加。在急性CF护理中，低SPLUNC 1水平可以支持增加气道清除率或开始药物干预的决定。在无症状、稳定的患者中，低SPLUNC 1水平可以告知临床管理的变化，以改善CF的长期疾病控制和临床结局。SPLUNC 1是在呼吸道中发现的丰富的宿主防御蛋白，其随着炎症而减少。经历临床恶化（恶化）的囊性纤维化个体的痰液中SPLUNC 1水平较低。在稳定的囊性纤维化患者中，较低水平的SPLUNC 1可能预示即将发生的呼吸道疾病。因此，SPLUNC 1可作为早期诊断和治疗囊性纤维化恶化的工具。
Acute pulmonary Exacerbations (AE) are episodes of clinical worsening in cystic fibrosis (CF), often precipitated by infection. Timely detection is critical to minimize morbidity and lung function declines associated with acute inflammation during AE. Based on our previous observations that airway protein Short Palate Lung Nasal epithelium Clone 1 (SPLUNC1) is regulated by inflammatory signals, we investigated the use of SPLUNC1 fluctuations to diagnose and predict AE in CF. We enrolled CF participants from two independent cohorts to measure AE markers of inflammation in sputum and recorded clinical outcomes for a 1-year follow-up period. SPLUNC1 levels were high in healthy controls (n=9, 10.7μg/mL), and significantly decreased in CF participants without AE (n=30, 5.7μg/mL, p=0.016). SPLUNC1 levels were 71.9% lower during AE (n=14, 1.6μg/mL, p=0.0034) regardless of age, sex, CF-causing mutation, or microbiology findings. Cytokines Il-1β and TNFα were also increased in AE, whereas lung function did not consistently decrease. Stable CF participants with lower SPLUNC1 levels were much more likely to have an AE at 60 days (HR: 11.49, Standard Error: 0.83, p=0.0033). Low-SPLUNC1 stable participants remained at higher AE risk even one year after sputum collection (HR: 3.21, Standard Error: 0.47, p=0.0125). SPLUNC1 was downregulated by inflammatory cytokines and proteases increased in sputum during AE. In acute CF care, low SPLUNC1 levels could support a decision to increase airway clearance or to initiate pharmacological interventions. In asymptomatic, stable patients, low SPLUNC1 levels could inform changes in clinical management to improve long-term disease control and clinical outcomes in CF. SPLUNC1 is an abundant host defense protein found in the respiratory tract that decreases with inflammation. Individuals with cystic fibrosis experiencing clinical worsening (exacerbation) have lower levels of SPLUNC1 in their sputum. In stable cystic fibrosis patients, lower levels of SPLUNC1 may predict an upcoming respiratory illness. Therefore, SPLUNC1 may serve as a tool for early diagnosis and treatment of cystic fibrosis exacerbations.
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DOI：
10.2147/copd.s144136
发表时间：
2018
影响因子：
2.8
作者：
De Smet EG;Seys LJ;Verhamme FM;Vanaudenaerde BM;Brusselle GG;Bingle CD;Bracke KR
通讯作者：
Bracke KR
影响因子：
7.3
作者：
Bingle, L;Cross, SS;Bingle, CD
通讯作者：
Bingle, CD
DOI：
10.1016/s0167-4781(00)00196-2
发表时间：
2000-10-02
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Bingle, CD;Bingle, L
通讯作者：
Bingle, L
影响因子：
3.2
作者：
Flight, W. G.;Bright-Thomas, R. J.;Jones, A. M.
通讯作者：
Jones, A. M.
影响因子：
4.4
作者：
Chu, Hong Wei;Thaikoottathil, Jyoti;Martin, Richard J.
通讯作者：
Martin, Richard J.