Bush Andrew
National Heart and Lung Institute, Imperial College, London, United Kingdom.
Imperial Centre for Paediatrics and Child Health, London, United Kingdom.
Front Pediatr. 2022 Jun 2;10:902168. doi: 10.3389/fped.2022.902168. eCollection 2022.
When a child with severe asthma (asthma defined clinically for the purposes of this review as wheeze, breathlessness, and chest tightness sometimes with cough) does not respond to treatment, it is important to be sure that an alternative or additional diagnosis is not being missed. In school age children, the next step is a detailed protocolized assessment to determine the nature of the problem, whether within the airway or related to co-morbidities or social/environmental factors, in order to personalize the treatment. For example, those with refractory difficult asthma due to persistent non-adherence may benefit from using budesonide and formoterol combined in a single inhaler [single maintenance and reliever treatment (SMART)] as both a reliever and preventer. For those with steroid-resistant Type 2 airway inflammation, the use of biologicals such as omalizumab and mepolizumab should be considered, but for mepolizumab at least, there is a paucity of pediatric data. Protocols are less well developed in preschool asthma, where steroid insensitive disease is much more common, but the use of two simple measurements, aeroallergen sensitization, and peripheral blood eosinophil count, allows the targeted use of inhaled corticosteroids (ICSs). There is also increasing evidence that chronic airway infection may be important in preschool wheeze, increasing the possibility that targeted antibiotics may be beneficial. Asthma in the first year of life is not driven by Type 2 inflammation, so beyond avoiding prescribing ICSs, no evidence based recommendations can be made. In the future, we urgently need to develop objective biomarkers, especially of risk, so that treatment can be targeted effectively; we need to address the scandal of the lack of data in children compared with adults, precluding making evidence-based therapeutic decisions and move from guiding treatment by phenotypes, which will change as the environment changes, to endotype based therapy.
当患有重度哮喘的儿童(为本综述目的,临床上将哮喘定义为喘息、气促、胸闷,有时伴有咳嗽)对治疗无反应时,务必确保没有遗漏其他诊断或额外诊断。对于学龄儿童,下一步是进行详细的标准化评估,以确定问题的性质,无论是气道内问题还是与合并症或社会/环境因素有关的问题,以便实现个性化治疗。例如,那些因持续不依从导致难治性重度哮喘的患儿,可能会从使用布地奈德和福莫特罗联合在一个吸入器中(单一维持和缓解治疗 [SMART])作为缓解剂和预防剂中获益。对于类固醇抵抗型2型气道炎症的患儿,应考虑使用诸如奥马珠单抗和美泊利珠单抗等生物制剂,但至少对于美泊利珠单抗,儿科数据较少。学龄前哮喘的治疗方案发展不太完善,在学龄前哮喘中类固醇不敏感疾病更为常见,但使用两种简单测量方法,即吸入变应原致敏和外周血嗜酸性粒细胞计数,可实现吸入性糖皮质激素(ICSs)的靶向使用。也有越来越多的证据表明,慢性气道感染可能在学龄前喘息中起重要作用,这增加了靶向使用抗生素可能有益的可能性。出生后第一年的哮喘不是由2型炎症驱动的,因此除了避免开具ICSs外,无法给出基于证据的建议。未来,我们迫切需要开发客观的生物标志物,尤其是风险生物标志物,以便能够有效地进行靶向治疗;我们需要解决与成人相比儿童缺乏数据这一丑闻,因为这使得无法做出基于证据的治疗决策,并从根据表型指导治疗(表型会随着环境变化而改变)转向基于内型的治疗。