Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

Affiliations

¹ Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia. Electronic address: Luke.Garratt@telethonkids.org.au.
² 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.
³ Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Australia; Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
⁹ 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.
¹⁰ 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.

PMID: 33461938
DOI: 10.1016/j.jcf.2020.12.015

Free article

Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

Luke W Garratt et al. J Cyst Fibros. 2021 Nov.

Free article

. 2021 Nov;20(6):941-948.

doi: 10.1016/j.jcf.2020.12.015. Epub 2021 Jan 15.

Affiliations

¹ Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia. Electronic address: Luke.Garratt@telethonkids.org.au.
² 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.
³ Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Australia; Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
⁹ 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.
¹⁰ 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.

PMID: 33461938
DOI: 10.1016/j.jcf.2020.12.015

Abstract

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.

Keywords: Bronchiectasis; CT; Inflammation; Neutrophil elastase; P. aeruginosa.

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Conflict of interest statement

Declaration of Competing Interest There are no conflicts of interest for the authors in regard to the work presented in this publication.

Comment in

Achieving respiratory excellence in pre-school children with cystic fibrosis.
Southern KW. Southern KW. J Cyst Fibros. 2021 Nov;20(6):904-905. doi: 10.1016/j.jcf.2021.09.016. Epub 2021 Oct 21. J Cyst Fibros. 2021. PMID: 34688556 No abstract available.

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Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

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Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

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Abstract

Conflict of interest statement

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