Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
Department of Paediatric Otolaryngology, Great North Children's Hospital, Newcastle upon Tyne, UK.
Thorax. 2023 Oct;78(10):1019-1027. doi: 10.1136/thorax-2022-219557. Epub 2023 Feb 20.
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.
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.
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.
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.
儿童气管切开术与显著的发病率、生活质量差、医疗保健费用增加和死亡率增加有关。导致气管切开儿童呼吸不良结局的潜在机制尚未得到很好的理解。我们旨在使用连续的分子分析来描述气管切开儿童的气道宿主防御。
前瞻性收集气管切开儿童和对照组的气管抽吸物、气管细胞学刷和鼻拭子。应用转录组学、蛋白质组学和代谢组学方法来描述气管切开术对宿主免疫反应和气道微生物组的影响。
研究了从气管切开术到术后 3 个月连续随访的儿童(n=9)。还招募了另一组长期气管切开的儿童(n=24)。对照组(n=13)包括未行气管切开术而行支气管镜检查的儿童。与对照组相比,长期气管切开术与气道中性粒细胞炎症、超氧化物产生和蛋白水解证据相关。与对照组相比,在气管切开术前就已经确定了气道微生物多样性减少,并持续存在。
长期儿童气管切开术与炎症性气管表型相关,其特征为中性粒细胞炎症和潜在呼吸道病原体的持续存在。这些发现表明,中性粒细胞募集和激活可能是预防这一脆弱患者群体反复发生气道并发症的潜在探索性目标。