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挑战范式:从笼统分类转向气道疾病的可治疗特征

Challenging the paradigm: moving from umbrella labels to treatable traits in airway disease.

作者信息

Bush Andrew, Pavord Ian D

机构信息

Paediatrics and Paediatric Respirology, Imperial Centre for Paediatrics and Child Health, Imperial College London, London, UK.

Royal Brompton and Harefield NHS Foundation Trust, London, UK.

出版信息

Breathe (Sheff). 2021 Sep;17(3):210053. doi: 10.1183/20734735.0053-2021.

Abstract

UNLABELLED

Airway diseases were initially described by nonspecific patterns of symptoms, for example "dry and wheezy" and "wet and crackly". The model airway disease is cystic fibrosis, which has progressed from nonspecific reactive treatments such as antibiotics for airway infection to molecular sub-endotype, proactive therapies with an unequivocal evidence base, early diagnosis, and biomarkers of treatment efficacy. Unfortunately, other airway diseases lag behind, not least because nonspecific umbrella labels such as "asthma" are considered to be diagnoses not mere descriptions. Pending the delineation of molecular sub-endotypes in other airway disease the concept of treatable traits, and consideration of airway disease in a wider context is preferable. A treatable trait is a characteristic amenable to therapy, with measurable benefits of treatment. This approach determines what pathology is actually present and treatable, rather than using umbrella labels. We determine if airway inflammation is present, and whether there is airway eosinophilia which will likely respond to inhaled corticosteroids; whether there is variable airflow obstruction due to bronchoconstriction which will respond to β-agonists; and whether there is unsuspected underlying airway infection which should be treated with antibiotics unless there is an underlying endotype which can be addressed, as for example an immunodeficiency. The context of airway disease should also be extrapulmonary comorbidities, social and environmental factors, and a developmental perspective, particularly this last aspect if preventive strategies are being contemplated. This approach allows targeted treatment for maximal patient benefit, as well as preventing the discarding of therapies which are useful for appropriate subgroups of patients. Failure to appreciate this almost led to the discarding of valuable treatments such as prednisolone.

EDUCATIONAL AIMS

To use cystic fibrosis as a paradigm to show the benefits of the journey from nonspecific umbrella terms to specific endotypes and sub-endotypes, as a road map for other airway diseases to follow.Demonstrate that nonspecific labels to describe airway disease can and should be abandoned in favour of treatable traits to ensure diagnostic and therapeutic precision.Begin to learn to see airway disease in the context of extrapulmonary comorbidities, and social and environmental factors, as well as with a developmental perspective.

摘要

未标注

气道疾病最初是通过非特异性症状模式来描述的,例如“干咳伴喘鸣”和“湿啰音伴爆裂音”。典型的气道疾病是囊性纤维化,其已从针对气道感染的非特异性反应性治疗(如使用抗生素)发展到基于明确证据基础的分子亚表型、积极治疗、早期诊断以及治疗效果生物标志物。不幸的是,其他气道疾病却滞后了,尤其是因为像“哮喘”这样的非特异性总体标签被视为诊断而非仅仅是描述。在其他气道疾病的分子亚表型得以明确之前,可治疗特征的概念以及在更广泛背景下考虑气道疾病更为可取。可治疗特征是一种适合治疗且治疗具有可测量益处的特征。这种方法确定实际存在且可治疗的病理情况,而非使用总体标签。我们要确定是否存在气道炎症,以及是否存在气道嗜酸性粒细胞增多,后者可能对吸入性糖皮质激素有反应;是否存在因支气管收缩导致的可变气流受限,这会对β受体激动剂有反应;以及是否存在未被怀疑的潜在气道感染,除非存在可解决的潜在表型(如免疫缺陷),否则应使用抗生素进行治疗。气道疾病的背景还应包括肺外合并症、社会和环境因素以及发育视角,特别是如果考虑预防策略时,最后这一方面尤为重要。这种方法允许进行有针对性的治疗以实现患者最大获益,同时防止丢弃对适当患者亚组有用的治疗方法。未能认识到这一点几乎导致丢弃了诸如泼尼松龙等有价值的治疗方法。

教育目标

以囊性纤维化为范例,展示从非特异性总体术语到特定表型和亚表型转变的益处,为其他气道疾病提供可遵循的路线图。证明描述气道疾病的非特异性标签能够且应该被抛弃,转而采用可治疗特征以确保诊断和治疗的精确性。开始学会在肺外合并症、社会和环境因素以及发育视角的背景下看待气道疾病。

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