Sharma Varun, Ricketts Helen Clare, Steffensen Femke, Goodfellow Anna, Cowan Douglas C
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Glasgow Clinical Research Facility, Glasgow Royal Infirmary, Glasgow, UK.
J Asthma. 2023 Feb;60(2):385-392. doi: 10.1080/02770903.2022.2051548. Epub 2022 Mar 17.
Type 2 (T2) inflammation offers a therapeutic target for biologics. Previous trials suggest obesity influences T2-biomarker levels in asthma, though have not accounted for key variables, e.g. inhaled (ICS)/oral corticosteroid (OCS) use. We hypothesized that body mass index (BMI) would affect T2-biomarker levels, after adjusting for covariates.
A retrospective analysis of data from two recent local trials of 153 participants with asthma (102 difficult-to-treat, 51 mild). Measurements included BMI, fractional exhaled nitric oxide (FeNO) and eosinophils. Correlation and regression analysis were performed for each biomarker to describe their relationship with BMI. Data was analyzed overall, and by asthma severity, T2-status and BMI tertile.
Increasing BMI was associated with reduction in FeNO when stratified by BMI tertile (25 ppb lowest tertile, 18 ppb highest tertile; = 0.014). Spearmans rank showed a negative correlation between BMI and FeNO in difficult-to-treat asthma (ρ= -0.309, = 0.002). Linear regression adjusting for sex, age, smoking, atopy, allergic/perennial rhinitis, ICS and OCS confirmed BMI as a predictor of FeNO overall (β= -2.848, = 0.019). Eosinophils were reduced in the highest BMI tertile versus lowest in difficult-to-treat asthma (0.2x10/L, 0.3x10/L respectively; = 0.02).
Increasing BMI is associated with lower FeNO in asthma when adjusted for relevant covariates, including steroid use. There also appears to be an effect on eosinophil levels. Obesity, therefore, affects T2 biomarker levels with implications for disease endotyping and determination of eligibility for biologic therapy. Whether this is due to masking of underlying T2-high status or development of a truly T2-low endotype requires further research.
2型(T2)炎症为生物制剂提供了一个治疗靶点。先前的试验表明肥胖会影响哮喘中T2生物标志物水平,但未考虑关键变量,如吸入性(ICS)/口服糖皮质激素(OCS)的使用情况。我们假设在调整协变量后,体重指数(BMI)会影响T2生物标志物水平。
对最近两项针对153名哮喘患者(102名难治性患者,51名轻度患者)的本地试验数据进行回顾性分析。测量指标包括BMI、呼出一氧化氮分数(FeNO)和嗜酸性粒细胞。对每个生物标志物进行相关性和回归分析,以描述它们与BMI的关系。数据整体进行分析,并按哮喘严重程度、T2状态和BMI三分位数进行分析。
按BMI三分位数分层时,BMI升高与FeNO降低相关(最低三分位数为25 ppb,最高三分位数为18 ppb;P = 0.014)。斯皮尔曼等级相关显示,在难治性哮喘中,BMI与FeNO呈负相关(ρ = -0.309,P = 0.002)。在调整性别、年龄、吸烟、特应性、过敏性/常年性鼻炎、ICS和OCS后进行的线性回归分析证实,BMI总体上是FeNO的一个预测指标(β = -2.848,P = 0.019)。在难治性哮喘中,最高BMI三分位数组的嗜酸性粒细胞低于最低三分位数组(分别为0.2×10⁹/L和0.3×10⁹/L;P = 0.02)。
在调整包括类固醇使用在内的相关协变量后,BMI升高与哮喘患者较低的FeNO相关。对嗜酸性粒细胞水平似乎也有影响。因此,肥胖会影响T2生物标志物水平,对疾病的内型分类和生物治疗资格的判定有影响。这是由于掩盖了潜在的T2高状态还是真正发展为T2低内型,需要进一步研究。