吸入甘露醇的气道高反应性确定了一组高症状负担的非嗜酸性哮喘患者
2021/08/24
摘要
背景：哮喘患者的临床表现和对治疗的反应各不相同。尽管如此，指导治疗的工具有限，主要包括嗜酸性炎症和症状的监测。对甘露醇的气道高反应性(AHR)存在于不同炎症表型的患者中，经吸入皮质类固醇后得到改善。
目的：探讨除了嗜酸性炎症和症状外，测定甘露醇的AHR是否能增加哮喘患者表型特征的信息。
方法：总共纳入来自6个不同队列的317例哮喘患者进行分析。所有患者均进行甘露醇AHR、血嗜酸性粒细胞和ACQ-5测定。采用Wards最小方差法进行聚类分析。比较各集群间FeNO、IgE、肺功能、诱导痰炎性细胞计数、发病年龄和病情严重程度的分布。
结果：共鉴定出四个集群。其中三个集群具有相称的 AHR、嗜酸性粒细胞炎症和症状水平，但一个集群呈现低水平的嗜酸性粒细胞炎症和显著的症状负担。该集群中一半受试者出现吸入甘露醇后出现了AHR。肺功能、呼出一氧化氮分数、体重指数和IgE均正常。
结论：除血嗜酸性粒细胞和症状外，有关甘露醇的AHR信息确定了一个有症状的非嗜酸性粒细胞的哮喘患者亚群。甘露醇的 AHR 可能在非嗜酸性粒细胞哮喘患者的亚群中提供了一种可治疗的特征。
Airway hyperresponsiveness to inhaled mannitol identifies a cluster of non-eosinophilic asthma patients with high symptom burden
Asger Sverrild, Anne H Andreasen, Christian G Westergaard, Anna von Bülow, Pernille B Udesen, Simon F Thomsen, Kristine H Allin, Vibeke Backer, Celeste Porsbjerg
Abstract
BACKGROUND: Patients with asthma are heterogeneous in clinical presentation and in response to treatment. Despite this, tools to guide treatment are limited and include mainly measures of eosinophilic inflammation and symptoms. Airway hyperresponsiveness (AHR) to mannitol is present in patients across inflammatory phenotypes and improve with inhaled cortico-steroids.
OBJECTIVE: To investigate whether measuring AHR to mannitol in addition to eosinophilic inflammation and symptoms add information to the phenotypic characterization of patients with asthma.
METHODS: A total of 317 patients with asthma from six different cohorts were included in the analysis. All patients had measures of AHR to mannitol, blood eosinophils and ACQ-5 available. A cluster analysis using Wards minimum variance method was performed. The distribution of FeNO, IgE, lung function, induced sputum inflammatory cell count, age of onset and severity of disease was compared between clusters.
RESULTS: Four clusters were identified. Three of the clusters had proportionate levels of AHR, eosinophilic inflammation and symptoms, but one cluster presented with low levels of eosinophilic inflammation and a significant symptom burden. Half of the subjects in this cluster presented with AHR to inhaled mannitol. Lung function, fractional exhaled nitric oxide, Body Mass Index and IgE were normal.
CONCLUSION: Information on AHR to mannitol in addition to blood eosinophils and symptoms identifies a subgroup of asthma patients with symptomatic, non-eosinophilic disease. AHR to mannitol may provide a treatable trait in a subgroup of patients with non-eosinophilic asthma.
背景：哮喘患者的临床表现和对治疗的反应各不相同。尽管如此，指导治疗的工具有限，主要包括嗜酸性炎症和症状的监测。对甘露醇的气道高反应性(AHR)存在于不同炎症表型的患者中，经吸入皮质类固醇后得到改善。
目的：探讨除了嗜酸性炎症和症状外，测定甘露醇的AHR是否能增加哮喘患者表型特征的信息。
方法：总共纳入来自6个不同队列的317例哮喘患者进行分析。所有患者均进行甘露醇AHR、血嗜酸性粒细胞和ACQ-5测定。采用Wards最小方差法进行聚类分析。比较各集群间FeNO、IgE、肺功能、诱导痰炎性细胞计数、发病年龄和病情严重程度的分布。
结果：共鉴定出四个集群。其中三个集群具有相称的 AHR、嗜酸性粒细胞炎症和症状水平，但一个集群呈现低水平的嗜酸性粒细胞炎症和显著的症状负担。该集群中一半受试者出现吸入甘露醇后出现了AHR。肺功能、呼出一氧化氮分数、体重指数和IgE均正常。
结论：除血嗜酸性粒细胞和症状外，有关甘露醇的AHR信息确定了一个有症状的非嗜酸性粒细胞的哮喘患者亚群。甘露醇的 AHR 可能在非嗜酸性粒细胞哮喘患者的亚群中提供了一种可治疗的特征。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(J Allergy Clin Immunol Pract. 2021 Jul 28;S2213-2198(21)00823-0. doi: 10.1016/j.jaip.2021.07.021.)
(J Allergy Clin Immunol Pract. 2021 Jul 28;S2213-2198(21)00823-0. doi: 10.1016/j.jaip.2021.07.021.)
Airway hyperresponsiveness to inhaled mannitol identifies a cluster of non-eosinophilic asthma patients with high symptom burden
Asger Sverrild, Anne H Andreasen, Christian G Westergaard, Anna von Bülow, Pernille B Udesen, Simon F Thomsen, Kristine H Allin, Vibeke Backer, Celeste Porsbjerg
Abstract
BACKGROUND: Patients with asthma are heterogeneous in clinical presentation and in response to treatment. Despite this, tools to guide treatment are limited and include mainly measures of eosinophilic inflammation and symptoms. Airway hyperresponsiveness (AHR) to mannitol is present in patients across inflammatory phenotypes and improve with inhaled cortico-steroids.
OBJECTIVE: To investigate whether measuring AHR to mannitol in addition to eosinophilic inflammation and symptoms add information to the phenotypic characterization of patients with asthma.
METHODS: A total of 317 patients with asthma from six different cohorts were included in the analysis. All patients had measures of AHR to mannitol, blood eosinophils and ACQ-5 available. A cluster analysis using Wards minimum variance method was performed. The distribution of FeNO, IgE, lung function, induced sputum inflammatory cell count, age of onset and severity of disease was compared between clusters.
RESULTS: Four clusters were identified. Three of the clusters had proportionate levels of AHR, eosinophilic inflammation and symptoms, but one cluster presented with low levels of eosinophilic inflammation and a significant symptom burden. Half of the subjects in this cluster presented with AHR to inhaled mannitol. Lung function, fractional exhaled nitric oxide, Body Mass Index and IgE were normal.
CONCLUSION: Information on AHR to mannitol in addition to blood eosinophils and symptoms identifies a subgroup of asthma patients with symptomatic, non-eosinophilic disease. AHR to mannitol may provide a treatable trait in a subgroup of patients with non-eosinophilic asthma.
