Tracheostomy in children is associated with neutrophilic airway inflammation

Powell, Jason, Powell, Steven, Mather, Michael W., Beck, Lauren, Nelson, Andrew, Palmowski, Pawel, Porter, Andrew, Coxhead, Jonathan, Hedley, Ann, Scott, Jonathan, Rostron, Anthony J., Hellyer, Thomas P., Zaidi, Fatima, Davey, Tracey, Garnett, James P., Agbeko, Rachel, Ward, Chris, Stewart, Christopher J., Taggart, Clifford C., Brodlie, Malcolm and Simpson, A. John (2023) Tracheostomy in children is associated with neutrophilic airway inflammation. Thorax. thorax-2022-219557. ISSN 0040-6376 (In Press)

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Official URL: https://doi.org/10.1136/thorax-2022-219557

Abstract

Background Tracheostomies in children are associated with significant morbidity, poor quality of life, excess healthcare costs and excess mortality. The underlying mechanisms facilitating adverse respiratory outcomes in tracheostomised children are poorly understood. We aimed to characterise airway host defence in tracheostomised children using serial molecular analyses.

Methods Tracheal aspirates, tracheal cytology brushings and nasal swabs were prospectively collected from children with a tracheostomy and controls. Transcriptomic, proteomic and metabolomic methods were applied to characterise the impact of tracheostomy on host immune response and the airway microbiome.

Results Children followed up serially from the time of tracheostomy up to 3 months postprocedure (n=9) were studied. A further cohort of children with a long-term tracheostomy were also enrolled (n=24). Controls (n=13) comprised children without a tracheostomy undergoing bronchoscopy. Long-term tracheostomy was associated with airway neutrophilic inflammation, superoxide production and evidence of proteolysis when compared with controls. Reduced airway microbial diversity was established pre-tracheostomy and sustained thereafter.

Conclusions Long-term childhood tracheostomy is associated with a inflammatory tracheal phenotype characterised by neutrophilic inflammation and the ongoing presence of potential respiratory pathogens. These findings suggest neutrophil recruitment and activation as potential exploratory targets in seeking to prevent recurrent airway complications in this vulnerable group of patients.

Item Type: Article
Additional Information: Funding information: Academy of Medical Sciences Grant SGL020\1003; Newcastle University Wellcome Trust Institutional Strategic Support Fund; Newcastle Hospitals Charity; SHIELD consortium; Barbour Foundation.
Subjects: B100 Anatomy, Physiology and Pathology
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 27 Feb 2023 15:48
Last Modified: 27 Feb 2023 16:00
URI: https://nrl.northumbria.ac.uk/id/eprint/51502

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