外周血炎症表型与成人哮喘不同临床表现之间的关系：基于一项大型人群的队列研究
2022/04/19
摘要
背景：哮喘是一种炎症异质性疾病。基于血嗜酸性粒细胞和中性粒细胞计数的哮喘炎症表型从未在大型人群的队列中得到认证。
方法：将法国CONSTANCES人群队列中患有哮喘且有血嗜酸粒细胞和中性粒细胞数据的成年人作为研究对象。根据过去12个月有哮喘发作史、哮喘症状或治疗的报告来定义哮喘。炎症表型基于低（L）和高（H）血（B）嗜酸性粒细胞（E）（LBE/HBE：</⩾0.25*109/L）和中性粒细胞（LBN/HBN：</⩾5*109/L）来分类。在调整年龄、性别、吸烟状况、体重指数、教育水平、收入水平和治疗后使用Logistic回归分析炎症表型与哮喘临床表现之间的关联。其他区分临界值也被使用。根据年龄或性别进行分层分析。
结果：在15019名哮喘成人中（56%为女性，59%≥40岁），LBE/LBN（参考对象）、LBE/HBN、HBE/LBN和HBE/HBN表型分别占57%、6%、33%和4%。LBE/HBN表型与因咳嗽、慢性支气管炎或呼吸困难醒来（调整后的OR值从1.21-1.42）相关。HBE/LBN和HBE/HBN表型与哮喘发作（调整后的OR值分别为1.31[1.20-1.42],1 .25[1.02-1.53]）和哮喘症状评分相关（p分别<0.0001，p=0.001）。HBE/LBN表型还与因胸闷醒来相关（调整后的OR值为1.30[1.20-1.40]）。无论使用何种临界值，结果都没有变化。根据年龄或性别分层分析，并未观察到统计学上有显著差异。
结论：在不同的炎症表型之间发现了哮喘临床表现的差异，无论使用何种临界值都是可重现的，且与病例对照和临床研究中观察到的相似。这些表型对于改善哮喘管理和研究其环境风险因素很有意义。
Blood inflammatory phenotypes were associated with distinct clinical expressions of asthma in adults from a large population-based cohort
Tajidine Tsiavia, Joseph Henny
Abstrast
BACKGROUND：Asthma is an inflammatory heterogeneous disease. Asthma inflammatory phenotypes based on blood eosinophil and neutrophil counts have never been identified and characterized in population-based studies.
METHODS：Adults with current asthma and available blood eosinophil and neutrophil counts from the French population-based CONSTANCES cohort were included. Current asthma was defined by reports of asthma attacks, symptoms or treatments in the last 12 months. Inflammatory phenotypes were based on low (L) and high (H) blood (B) eosinophil (E) (LBE/HBE: </⩾0.25*109/L, respectively) and neutrophil (N) (LBN/HBN: </⩾5*109/L, respectively) cut-offs. Associations between inflammatory phenotypes and the clinical expressions of asthma were studied using logistic models adjusted for age, sex, smoking status, body mass index, education level, French deprivation index and treatment. Other cut-offs were applied. Stratified analyses according to age or sex were performed.
RESULTS：Among 15,019 adults with asthma (56% women, 59%≥40 years), the LBE/LBN (reference), LBE/HBN, HBE/LBN and HBE/HBN phenotypes accounted for 57%, 6%, 33% and 4% respectively. The LBE/HBN phenotype was associated with being awaken by an attack of coughing, chronic bronchitis, and dyspnoea (adjusted(a)OR ranging from 1·21 to 1·42). The HBE/LBN and HBE/HBN phenotypes were associated with asthma attacks (aOR=1·31[1·20-1·42], 1·25[1·02-1·53]) and asthma symptom score (p for trend<0·0001, p for trend=0·001, respectively). The HBE/LBN phenotype was also associated with being awaken with chest tightness (aOR=1·30[1·20-1·40]). Results were unchanged whatever the cut-offs used. No statistically significant heterogeneity was observed according to age or sex.
CONCLUSION：Differences in the clinical expressions of asthma were found between the phenotypes, reproducible whatever the cut-offs used, and similar to those observed in case-control and clinical studies. Such phenotypes are of interest to improve asthma management and study its environmental risk factors.
背景：哮喘是一种炎症异质性疾病。基于血嗜酸性粒细胞和中性粒细胞计数的哮喘炎症表型从未在大型人群的队列中得到认证。
方法：将法国CONSTANCES人群队列中患有哮喘且有血嗜酸粒细胞和中性粒细胞数据的成年人作为研究对象。根据过去12个月有哮喘发作史、哮喘症状或治疗的报告来定义哮喘。炎症表型基于低（L）和高（H）血（B）嗜酸性粒细胞（E）（LBE/HBE：</⩾0.25*109/L）和中性粒细胞（LBN/HBN：</⩾5*109/L）来分类。在调整年龄、性别、吸烟状况、体重指数、教育水平、收入水平和治疗后使用Logistic回归分析炎症表型与哮喘临床表现之间的关联。其他区分临界值也被使用。根据年龄或性别进行分层分析。
结果：在15019名哮喘成人中（56%为女性，59%≥40岁），LBE/LBN（参考对象）、LBE/HBN、HBE/LBN和HBE/HBN表型分别占57%、6%、33%和4%。LBE/HBN表型与因咳嗽、慢性支气管炎或呼吸困难醒来（调整后的OR值从1.21-1.42）相关。HBE/LBN和HBE/HBN表型与哮喘发作（调整后的OR值分别为1.31[1.20-1.42],1 .25[1.02-1.53]）和哮喘症状评分相关（p分别<0.0001，p=0.001）。HBE/LBN表型还与因胸闷醒来相关（调整后的OR值为1.30[1.20-1.40]）。无论使用何种临界值，结果都没有变化。根据年龄或性别分层分析，并未观察到统计学上有显著差异。
结论：在不同的炎症表型之间发现了哮喘临床表现的差异，无论使用何种临界值都是可重现的，且与病例对照和临床研究中观察到的相似。这些表型对于改善哮喘管理和研究其环境风险因素很有意义。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(EBioMedicine. 2022, Feb;76:103875.doi: 10.1016/j.ebiom.2022.103875. IF: 8.143)
(EBioMedicine. 2022, Feb;76:103875.doi: 10.1016/j.ebiom.2022.103875. IF: 8.143)
Blood inflammatory phenotypes were associated with distinct clinical expressions of asthma in adults from a large population-based cohort
Tajidine Tsiavia, Joseph Henny
Abstrast
BACKGROUND：Asthma is an inflammatory heterogeneous disease. Asthma inflammatory phenotypes based on blood eosinophil and neutrophil counts have never been identified and characterized in population-based studies.
METHODS：Adults with current asthma and available blood eosinophil and neutrophil counts from the French population-based CONSTANCES cohort were included. Current asthma was defined by reports of asthma attacks, symptoms or treatments in the last 12 months. Inflammatory phenotypes were based on low (L) and high (H) blood (B) eosinophil (E) (LBE/HBE: </⩾0.25*109/L, respectively) and neutrophil (N) (LBN/HBN: </⩾5*109/L, respectively) cut-offs. Associations between inflammatory phenotypes and the clinical expressions of asthma were studied using logistic models adjusted for age, sex, smoking status, body mass index, education level, French deprivation index and treatment. Other cut-offs were applied. Stratified analyses according to age or sex were performed.
RESULTS：Among 15,019 adults with asthma (56% women, 59%≥40 years), the LBE/LBN (reference), LBE/HBN, HBE/LBN and HBE/HBN phenotypes accounted for 57%, 6%, 33% and 4% respectively. The LBE/HBN phenotype was associated with being awaken by an attack of coughing, chronic bronchitis, and dyspnoea (adjusted(a)OR ranging from 1·21 to 1·42). The HBE/LBN and HBE/HBN phenotypes were associated with asthma attacks (aOR=1·31[1·20-1·42], 1·25[1·02-1·53]) and asthma symptom score (p for trend<0·0001, p for trend=0·001, respectively). The HBE/LBN phenotype was also associated with being awaken with chest tightness (aOR=1·30[1·20-1·40]). Results were unchanged whatever the cut-offs used. No statistically significant heterogeneity was observed according to age or sex.
CONCLUSION：Differences in the clinical expressions of asthma were found between the phenotypes, reproducible whatever the cut-offs used, and similar to those observed in case-control and clinical studies. Such phenotypes are of interest to improve asthma management and study its environmental risk factors.
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支气管活检中哮喘相关microRNA的鉴定
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