Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

被引：11
|
作者：
Garratt, Luke W. [1 ]
Breuer, Oded [1 ,2 ,3 ]
Schofield, Craig J. [1 ]
McLean, Samantha A. [1 ]
Laucirica, Daniel R. [1 ,4 ]
Tirouvanziam, Rabindra [5 ,6 ]
Clements, Barry S. [1 ,3 ]
Kicic, Anthony [1 ,3 ,4 ,7 ,8 ]
Ranganathan, Sarath [9 ,10 ,11 ]
Stick, Stephen M. [1 ,3 ,4 ]
机构：
[1] Univ Western Australia, Wal Yan Resp Res Ctr, Telethon Kids Inst, Nedlands, WA, Australia
[2] Hadassah Hebrew Univ, Dept Pediat, Pediat Pulm Unit, Med Ctr, Jerusalem, Israel
[3] Perth Childrens Hosp, Dept Resp & Sleep Med, Nedlands, WA, Australia
[4] Univ Western Australia, Fac Hlth & Med Sci, Nedlands, WA, Australia
[5] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA
[6] Childrens Healthcare Atlanta, Ctr CF & Airways Dis Res, Atlanta, GA USA
[7] Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Sch Med & Pharmacol, Subiaco, WA, Australia
[8] CurtinUniv, Sch Publ Hlth, Occupat & Environm, Bentley, WA, Australia
[9] Royal Childrens Hosp, Dept Resp Med, Parkville, Vic, Australia
[10] Murdoch Childrens Res Inst, Parkville, Vic, Australia
[11] Univ Melbourne, Dept Paediat, Parkville, Vic, Australia
来源：
JOURNAL OF CYSTIC FIBROSIS | 2021年 / 20卷 / 06期
基金：
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词：
P; aeruginosa; Inflammation; Neutrophil elastase; CT; Bronchiectasis; YOUNG-CHILDREN; NEUTROPHIL ELASTASE; AERUGINOSA INFECTION; PULMONARY-FUNCTION; SPUTUM BIOMARKERS; RISK-FACTORS; THERAPY; DISEASE; BRONCHIECTASIS; EXACERBATIONS;
D O I：
10.1016/j.jcf.2020.12.015
中图分类号：
R56 [呼吸系及胸部疾病];
学科分类号：
摘要：
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 20 0 0 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, R 2 = 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. (c) 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：941 / 948
页数：8
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