Fleming Louise, Heaney Liam
National Heart and Lung Institute, Imperial College, London and Royal Brompton Hospital, London, United Kingdom.
Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Institute for Health Sciences, Queens University Belfast, Belfast, United Kingdom.
Front Pediatr. 2019 Oct 9;7:389. doi: 10.3389/fped.2019.00389. eCollection 2019.
Both adults and children with severe asthma represent a small proportion of the asthma population; however, they consume disproportionate resources. For both groups it is important to confirm the diagnosis of severe asthma and ensure that modifiable factors such as adherence have, as far as possible, been addressed. Most children can be controlled on inhaled corticosteroids and long term oral corticosteroid use is rare, in contrast to adults where steroid related morbidity accounts for a large proportion of the costs of severe asthma. Atopic sensitization is very common in children with severe asthma as are other atopic conditions such as allergic rhinitis and hay fever which can impact on asthma control. In adults, the role of allergic driven disease, even in those with co-existent evidence of sensitization, is unclear. There is currently an exciting pipeline of novel biologicals, particularly directed at Type 2 inflammation, which afford the possibility of improved asthma control and reduced treatment side effects for people with asthma. However, not all drugs will work for all patients and accurate phenotyping is essential. In adults the terms T2 high and T2 low asthma have been coined to describe groups of patients based on the presence/absence of eosinophilic inflammation and T-helper 2 (TH) cytokines. Bronchoscopic studies in children with severe asthma have demonstrated that these children are predominantly eosinophilic but the cytokine patterns do not fit the T2 high paradigm suggesting other steroid resistant pathways are driving the eosinophilic inflammation. It remains to be seen whether treatments developed for adult severe asthma will be effective in children and which biomarkers will predict response.
患有重度哮喘的成人和儿童在哮喘人群中占比很小;然而,他们消耗的资源却不成比例。对于这两类人群而言,确诊重度哮喘并确保尽可能解决诸如依从性等可改变因素非常重要。与成人不同,大多数儿童使用吸入性糖皮质激素即可得到控制,很少需要长期口服糖皮质激素,在成人中,与类固醇相关的发病率在重度哮喘的成本中占很大比例。特应性致敏在重度哮喘儿童中非常常见,其他特应性疾病如过敏性鼻炎和花粉症也很常见,这些疾病会影响哮喘控制。在成人中,即使在那些有致敏证据的患者中,过敏性驱动疾病的作用也不清楚。目前有一系列令人兴奋的新型生物制剂,特别是针对2型炎症的制剂,这为改善哮喘控制和减少哮喘患者的治疗副作用提供了可能性。然而,并非所有药物都对所有患者有效,准确的表型分析至关重要。在成人中,“T2高”和“T2低”哮喘这两个术语已被创造出来,用于根据嗜酸性粒细胞炎症和辅助性T细胞2(TH)细胞因子的有无来描述患者群体。对重度哮喘儿童的支气管镜研究表明,这些儿童主要是嗜酸性粒细胞性的,但细胞因子模式不符合T2高模式,这表明其他类固醇抵抗途径在驱动嗜酸性粒细胞炎症。针对成人重度哮喘开发的治疗方法对儿童是否有效,以及哪些生物标志物可以预测反应,仍有待观察。