Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis,Journal of Cystic Fibrosis

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Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis
Journal of Cystic Fibrosis ( IF 5.2 ) Pub Date : 2021-01-15 , DOI: 10.1016/j.jcf.2020.12.015
Luke W Garratt ₁ , Oded Breuer ₂ , Craig J Schofield ₁ , Samantha A McLean ₁ , Daniel R Laucirica ₃ , Rabindra Tirouvanziam ₄ , Barry S Clements ₅ , Anthony Kicic ₆ , Sarath Ranganathan ₇ , Stephen M Stick ₈ , On Behalf Of Arest Cf ₉

Affiliation

Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia.
Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia; Department of Pediatrics, Pediatric Pulmonary Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Australia.
Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, Australia.
Department of Pediatrics, Emory University School of Medicine, Atlanta, United States; Center for CF & Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, United States.
Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia; Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Australia.
Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia; Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Subiaco, Australia; Occupation and Environment, School of Public Health, Curtin University, Bentley, Australia.
Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Australia; Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia; Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, Australia.
Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, Australia; Center for CF & Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, United States; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Subiaco, Australia; Occupation and Environment, School of Public Health, Curtin University, Bentley, Australia.

Background: Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes.

Methods: We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated.

Results: Eighty-eight episodes (3 months to 6 years old) of P. aeruginosa infection were studied. Eradication was successful in 84.1% of episodes. Median activity of NE was significantly reduced post-eradication from 9.15 to 3.4 nM (p = 0.008) but persisted in 33 subjects. High post-eradication NE levels were associated with an increased risk for P. aeruginosa infection in the next annual visit (odds ratio=1.7, 95% confidence interval 1.1–2.7, p = 0.014). Post-eradication NE levels (difference, 0.8; 95% confidence interval, 0.1–1.5) and baseline bronchiectasis computed tomography (CT) score (difference, 0.4; 95% confidence interval, 0.1–0.8) were the best predictors of bronchiectasis progression within 1 year (backward stepwise linear regression model, R²= 0.608, P<0.001), independent of eradication.

Conclusion: In children with CF, NE activity may persist following successful P. aeruginosa eradication and is significantly associated with bronchiectasis progression. Evaluating strategies to diminish neutrophilic inflammation is essential for improving long-term outcomes.

中文翻译：

早期囊性纤维化中假单胞菌根除对气道炎症的改变

背景：中性粒细胞弹性蛋白酶是囊性纤维化中结构性肺病的重要危险因素，而铜绿假单胞菌气道感染与中性粒细胞炎症和大量呼吸道疾病有关。我们旨在评估绿脓杆菌根除后中性粒细胞弹性蛋白酶 (NE) 活性如何变化并影响早期疾病结果。

方法：我们评估了 2000 年至 2018 年间 AREST CF 队列的参与者，他们从常规年度支气管肺泡灌洗 (BAL) 液中培养出铜绿假单胞菌，并接受了根除治疗和根除后 BAL。评估了与持续性铜绿假单胞菌感染、根除后持续性中性粒细胞炎症和根除后一年更严重的结构性肺病相关的因素。

结果：研究了 88 次（3 个月至 6 岁）的铜绿假单胞菌感染。84.1% 的发作成功根除。NE 的中位活性在根除后显着降低，从 9.15 到 3.4 nM ( p = 0.008)，但在 33 名受试者中持续存在。根除后 NE 水平高与下一次年度就诊时铜绿假单胞菌感染风险增加相关（优势比 = 1.7，95% 置信区间 1.1-2.7，p = 0.014)。根除后 NE 水平（差异，0.8；95% 置信区间，0.1-1.5）和基线支气管扩张计算机断层扫描（CT）评分（差异，0.4；95% 置信区间，0.1-0.8）是支气管扩张进展的最佳预测指标。 1 年（向后逐步线性回归模型，R ² = 0.608，P <0.001），与根除无关。

结论：在患有 CF 的儿童中，在成功根除铜绿假单胞菌后，NE 活动可能会持续存在，并且与支气管扩张进展显着相关。评估减少中性粒细胞炎症的策略对于改善长期结果至关重要。

更新日期：2021-01-15

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