Bingham Karina, Zahrani Yousef Al, Stewart Iain, Portelli Michael A, Fogarty Andrew, McKeever Tricia M, Singapuri Ananga, Heaney Liam G, Mansur Adel H, Chaudhuri Rekha, Thomson Neil C, Holloway John W, Howarth Peter H, Djukanovic Ratko, Blakey John D, Chauhan Anoop, Brightling Christopher E, Pogson Zara E K, Hall Ian P, Martinez-Pomares Luisa, Shaw Dominick, Sayers Ian
Centre for Respiratory Research, NIHR Nottingham Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK.
Respiratory Care Department, Prince Sultan Military College of Health Sciences, Dhahran, Saudi Arabia.
Immun Inflamm Dis. 2025 Mar;13(3):e70116. doi: 10.1002/iid3.70116.
Asthma is a heterogeneous disease characterized by overlapping clinical and inflammatory features.
This study aimed to provide insight into the systemic inflammatory profile in asthma, greater understanding of asthma endotypes and the contribution of genetic risk factors to both.
4205 patients with asthma aged 16-60 were recruited from UK centers; serum cytokines were quantified from 708, including cytokines associated with Type 1, 2 and 17 inflammation. 3037 patients were genotyped for 25 single nucleotide polymorphisms associated with moderate-severe asthma.
Serum cytokines associated with Th2 inflammation showed high coordinated expression for example, IL-4/IL-5 (R = 0.513). The upper quartile of the serum cytokine data identified 43.7% of patients had high levels for multiple Th2 cytokines. However, the groups defined by serum cytokine profile were not clinically different. Childhood-onset asthma was characterized by elevated total IgE, allergic rhinitis and dermatitis. Exacerbation prone patients had a higher BMI, smoking pack-years, asthma control questionnaire score and reduced lung function. Patients with blood eosinophils of > 300 cells/µL had elevated total IgE and lower smoking pack-years. None of these groups had a differential serum cytokine profile. Asthma risk alleles for; rs61816764 (FLG) and rs9303277 (IKFZ3) were associated with childhood onset disease (p = 2.67 × 10 and 2.20 × 10 ; retrospectively). No genetic variant was associated with cytokine levels.
Systemic inflammation in asthma is complex. Patients had multiple overlapping inflammatory profiles suggesting several disease mechanisms. Genetic risk factors for moderate-severe asthma confirmed previous associations with childhood onset of asthma.
哮喘是一种具有重叠临床和炎症特征的异质性疾病。
本研究旨在深入了解哮喘的全身炎症特征，加深对哮喘内型的理解以及遗传风险因素对两者的影响。
从英国各中心招募了4205名年龄在16 - 60岁的哮喘患者；对708名患者的血清细胞因子进行定量分析，包括与1型、2型和17型炎症相关的细胞因子。对3037名患者进行了与中度至重度哮喘相关的25个单核苷酸多态性的基因分型。
与Th2炎症相关的血清细胞因子表现出高度的协同表达，例如IL-4/IL-5（R = 0.513）。血清细胞因子数据的上四分位数表明，43.7%的患者多种Th2细胞因子水平较高。然而，由血清细胞因子谱定义的组在临床上并无差异。儿童期发病的哮喘以总IgE升高、过敏性鼻炎和皮炎为特征。易加重患者的BMI、吸烟包年数、哮喘控制问卷评分较高，肺功能降低。血液嗜酸性粒细胞>300个/μL的患者总IgE升高，吸烟包年数较少。这些组均无差异血清细胞因子谱。哮喘风险等位基因rs61816764（FLG）和rs9303277（IKFZ3）与儿童期发病疾病相关（回顾性分析，p = 2.67×10 和2.20×10）。没有基因变异与细胞因子水平相关。
哮喘中的全身炎症很复杂。患者具有多种重叠的炎症特征，提示存在多种疾病机制。中度至重度哮喘的遗传风险因素证实了先前与儿童期哮喘发病的关联。
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