Functional location of airway inflammation in eosinophilic asthma

嗜酸性粒细胞性哮喘气道炎症的功能定位

• 批准号: EP/R042160/1
• 负责人: Grant Ritchie
• 金额: $ 60.12万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR042160%2F1
• 关键词: Functional; location; airway; inflammation; eosinophilic

Asthma is a prevalent, complex and highly heterogeneous chronic airways disease, whose treatment is guided by its classification according to levels of type 2 inflammation, namely into 'TH-2 high' and 'TH-2 low' subtypes (commonly called endotypes), with TH-2 high asthma being responsive to treatment with inhaled corticosteroids, while TH-2 low asthma is not. Despite the success of endotyping, there remains the important issue that while TH-2 high asthma is generally responsive to treatment with inhaled corticosteroids, a substantial subgroup of patients with this endotype have persistent symptoms and uncontrolled asthma despite such treatment. There may be several reasons for this failure to respond, one of which is if the location of the inflammation within the airway tree renders it inaccessible to inhaled therapy, i.e. is the inflammation in the proximal or distal airways. This proposal seeks to address this outstanding question in the treatment of TH-2 high asthma by developing a world-leading instrument capable of functionally locating airways inflammation. The instrument will combine highly time-resolved measurements of the fraction of exhaled nitric oxide, FeNO, with highly precise measurements of respiratory gas exchange to assess functional inhomogeneity in the lung, and thereby help ascertain which TH-2 patients, which constitute more than 50% of all asthmatics, are most likely to be unresponsive to inhaled steroid therapy. A key feature of asthma is the variability of symptoms over time - between attacks patients may display apparently normal lung function and, when attacks occur, a number of treatments may be used to reverse airway inflammation. Measurement of FeNO is already a reliable NICE approved method of detecting the presence of eosinophilic airway inflammation, however current methods provide a single FeNO value from sustained expiration at constant flow. This is an important limitation as it is not possible to determine the site of NO production and hence the location of the inflammation within the airways. Furthermore, even if a time-resolved FeNO measurement were obtained, there is no recognition of the fact that the asthmatic lung is highly inhomogeneous and therefore any such time-resolved FeNO can only be interpreted in terms of the person-specific lung inhomogeneity. This research will provide a sea-change in the location and quantification of inflammation by linking for the first time, quantitative and individualised measures of lung inhomogeneity and structure with time-resolved measurements of FeNO.

哮喘是一种普遍，复杂且高度异质性的慢性气道疾病，其治疗是根据2型炎症水平的分类来指导其对“ Th-2高”和“ Th-2高”和“ TH-2低”亚型（通常称为内型）的指导，而TH-2高哮喘对使用inshaled cororticasterics的侵入性抗毒液响应，而th-2 sma asma asma asma asma asma asma asma asma asma asma asma asma asma asma asma asma asma asma th-2-2-2-2-2-2。尽管内型成功取得了成功，但仍然存在一个重要的问题：尽管Th-2高哮喘通常对吸入皮质类固醇的治疗有反应，但尽管这种治疗，但具有这种内型的大量患者具有持久的症状和不受控制的哮喘。这种未能做出反应的原因可能有几个原因，其中之一是，如果气道树内炎症的位置使吸入疗法无法接近，即，即近端或远端气道的炎症。该提案旨在通过开发能够在功能上定位气道炎症的世界领先的工具来处理TH-2高哮喘的杰出问题。该仪器将结合高度时间分辨的一氧化氮（Feno）的分数，并高度精确地测量呼吸气交换，以评估肺部功能性不均匀性，从而有助于确定哪些TH-2患者，哪些TH-2患者构成了所有哮喘的50％以上，最可能是统一的。哮喘的一个关键特征是随着时间的流逝症状的变异性 - 在攻击患者之间可能表现出正常的肺功能，当发生攻击时，可以使用多种治疗方法来逆转气道炎症。 FENO的测量已经是一种可靠的批准方法，可以检测出存在嗜酸性气道炎症的存在，但是当前的方法可从恒定流动时持续到期的持续过期提供单个Feno值。这是一个重要的限制，因为无法确定无生产的部位，因此无法确定炎症在气道中的位置。此外，即使获得了时间分辨的Feno测量，也没有认识到哮喘肺高度不均匀的事实，因此只能以人特异性的肺不中等症来解释任何此类时间分辨的Feno。这项研究将通过首次与FENO的时间分辨测量值连接，对肺部不均匀性和结构进行定量和个性化测量，在炎症的位置和量化炎症的位置和定量。