Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Équipe d'Épidémiologie Respiratoire Int´grative, CESP, 94807, Villejuif, France.
Université Paris-Saclay, UVSQ, Inserm, Cohortes Epidémiologiques en population, 94807, Villejuif, France.
EBioMedicine. 2022 Feb;76:103875. doi: 10.1016/j.ebiom.2022.103875. Epub 2022 Feb 10.
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.
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 × 10/L, respectively) and neutrophil (N) (LBN/HBN: </⩾5 × 10/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.
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.
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.
The CONSTANCES cohort receives grants from ANR (ANR-11-INBS-0002), the Caisse nationale d'assurance maladie-CNAM and the Ministry of research. CONSTANCES also receives funding from MSD, AstraZeneca, Lundbeck and L'Oréal, managed by INSERM-Transfert. T.Tsiavia is supported by a PhD grant from the Fondation pour le Recherche Médicale (ECO202006011654).
哮喘是一种炎症性异质性疾病。以血液嗜酸性粒细胞和中性粒细胞计数为基础的哮喘炎症表型在基于人群的研究中从未得到过确定和描述。
纳入了法国基于人群的 CONSTANCES 队列中目前患有哮喘且有可用血液嗜酸性粒细胞和中性粒细胞计数的成年人。目前的哮喘通过过去 12 个月的哮喘发作、症状或治疗报告来定义。炎症表型基于低（L）和高（H）血液（B）嗜酸性粒细胞（E）（LBE/HBE：分别为</⩾0·25×10/L）和中性粒细胞（N）（LBN/HBN：分别为</⩾5×10/L）截断值。使用调整了年龄、性别、吸烟状况、体重指数、教育程度、法国贫困指数和治疗的逻辑模型研究了炎症表型与哮喘临床表现之间的关联。应用了其他截断值。根据年龄或性别进行分层分析。
在 15019 名患有哮喘的成年人（56%为女性，59%≥40 岁）中，LBE/LBN（参考）、LBE/HBN、HBE/LBN 和 HBE/HBN 表型分别占 57%、6%、33%和 4%。LBE/HBN 表型与因咳嗽而惊醒、慢性支气管炎和呼吸困难有关（调整后的比值比范围为 1·21 至 1·42）。HBE/LBN 和 HBE/HBN 表型与哮喘发作（比值比=1·31[1·20-1·42]，1·25[1·02-1·53]）和哮喘症状评分（趋势检验 P<0·0001，趋势检验 P=0·001）有关。HBE/LBN 表型还与因胸闷而惊醒有关（比值比=1·30[1·20-1·40]）。无论使用何种截断值，结果均无显著差异。根据年龄或性别，未观察到统计学上显著的异质性。
在哮喘的临床表现方面发现了不同的表型，无论使用何种截断值，结果均具有可重复性，且与病例对照和临床研究中观察到的相似。这些表型有助于改善哮喘管理并研究其环境危险因素。
CONSTANCES 队列得到了法国国家健康与医学研究院（ANR）（ANR-11-INBS-0002）、法国国家医疗保险中心和研究部的资助。CONSTANCES 还得到了默沙东、阿斯利康、灵北和欧莱雅的资助，由法国国家健康与医学研究院转让管理。TTsiavia 得到了法国医学研究基金会（ECO202006011654）博士奖学金的支持。
