Tracheostomy in children is associated with neutrophilic airway inflammation

Abstract

BackgroundTracheostomies 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.MethodsTracheal 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.ResultsChildren 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.ConclusionsLong-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.

A systematic review of antimicrobial therapy in children with tracheostomies

“…Comprehensive profiling of microbial communities will help us better understand the dynamic interplay between the tracheal microbiome and host–immune system 49,50 . In turn, improved understanding of what factors predispose individuals to microbial dysfunction and subsequent infection could provide alternatives to antimicrobial therapy to break the cycle of recurrent infections 28 …”

“…Studies of children with tracheostomies frequently demonstrate airway bacterial colonization, often with drug‐resistant Pseudomonas aeruginosa and Methicillin‐resistant Staphylococcus aureus 27 . The microbiology and antimicrobial resistance patterns of tracheostomy‐associated infections have been summarized in recent reviews 19,21,28 . This review aims to summarize the current evidence for the use of antimicrobial therapies in the management of tracheostomy‐dependent children and identify core areas of need for further research.…”

“…27 The microbiology and antimicrobial resistance patterns of tracheostomy-associated infections have been summarized in recent reviews. 19,21,28 This review aims to summarize the current evidence for the use of antimicrobial therapies in the management of tracheostomydependent children and identify core areas of need for further research.…”

“…The increasing uptake of nextgeneration sequencing techniques, which are currently mainly limited to the research environment, may offer hope for the future. Comprehensive profiling of microbial communities will help us better understand the dynamic interplay between the tracheal microbiome and host-immune system.49,50 In turn, improved understanding of what factors predispose individuals to microbial dysfunction and subsequent infection could provide alternatives to antimicrobial therapy to break the cycle of recurrent infections 28. The data summarized here have four main overriding limitations.…”