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Cytokine levels in children and adults with wheezing and asthma show specific patterns of variability over time
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-11-17 , DOI: 10.1111/cei.13550 M Weckmann 1, 2 , D Thiele 2, 3 , L Liboschik 1, 2 , T Bahmer 2, 4, 5 , M Pech 1, 2 , A-M Dittrich 6, 7 , O Fuchs 1, 2, 8 , C Happle 6, 7 , B Schaub 9, 10 , I Ricklefs 1, 2 , K F Rabe 2, 4 , E von Mutius 9, 10 , G Hansen 6, 7 , I R König 2, 3 , M V Kopp 1, 2, 8 ,
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-11-17 , DOI: 10.1111/cei.13550 M Weckmann 1, 2 , D Thiele 2, 3 , L Liboschik 1, 2 , T Bahmer 2, 4, 5 , M Pech 1, 2 , A-M Dittrich 6, 7 , O Fuchs 1, 2, 8 , C Happle 6, 7 , B Schaub 9, 10 , I Ricklefs 1, 2 , K F Rabe 2, 4 , E von Mutius 9, 10 , G Hansen 6, 7 , I R König 2, 3 , M V Kopp 1, 2, 8 ,
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Levels of cytokines are used for in‐depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the course of serum cytokines in children, adolescents and adults with asthma and in healthy controls and to propose statistical methods to control for seasonal effects. Of 532 screened subjects, 514 (91·5%) were included in the All Age Asthma Cohort (ALLIANCE). The cohort included 279 children with either recurrent wheezing bronchitis (more than two episodes) or doctor‐diagnosed asthma, 75 healthy controls, 150 adult asthmatics and 31 adult healthy controls. Blood samples were collected and 25 μl serum was used for analysis with the Bio‐Plex Pr human cytokine 27‐Plex assay. Mean age, body mass index and gender in the three groups of wheezers, asthmatic children and adult asthmatics were comparable to healthy controls. Wheezers (34·5%), asthmatic children (78·7%) and adult asthmatics (62·8%) were significantly more often sensitized compared to controls (4·5, 22 and 22·6%, respectively). Considering the entire cohort, interleukin (IL)‐1ra, IL‐4, IL‐9, IL‐17, macrophage inflammatory protein (MIP)‐1‐
and tumor necrosis factor (TNF)‐
showed seasonal variability, whereas IL‐1β, IL‐7, IL‐8, IL‐13, eotaxin, granulocyte colony‐stimulating factor (G‐CSF), interferon gamma‐induced protein (IP)‐10, MIP‐1
and platelet‐derived growth factor (PDGF)‐BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL‐17 and PDGF‐BB, which remained stable after adjustment for the seasonality of IL‐17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient‐tailored therapy, it is important to account for seasonal effects.
中文翻译：
患有喘息和哮喘的儿童和成人的细胞因子水平显示出随时间变化的特定模式
细胞因子水平用于深入描述哮喘患者的特征；然而，随时间的变化可能是一个关键的混杂因素。分析儿童、青少年和成人哮喘患者和健康对照组血清细胞因子的变化过程，并提出控制季节性影响的统计方法。在 532 名筛查对象中，514 名 (91·5%) 被纳入全年龄哮喘队列 (ALLIANCE)。该队列包括 279 名患有复发性喘息性支气管炎（两次以上发作）或医生诊断为哮喘的儿童、75 名健康对照、150 名成人哮喘患者和 31 名成人健康对照。收集血样，使用 Bio-Plex Pr 人细胞因子 27-Plex 测定法分析 25 μl 血清。三组喘息者的平均年龄、体重指数和性别，哮喘儿童和成人哮喘患者与健康对照组相当。与对照组（分别为 4·5、22 和 22·6%）相比，喘息者 (34·5%)、哮喘儿童 (78·7%) 和成人哮喘患者 (62·8%) 的致敏率明显更高。考虑到整个队列，白细胞介素 (IL)-1ra、IL-4、IL-9、IL-17、巨噬细胞炎症蛋白 (MIP)-1-和肿瘤坏死因子 (TNF)-表现出季节性变化，而 IL-1β、IL-7、IL-8、IL-13、eotaxin、粒细胞集落刺激因子 (G-CSF)、干扰素 γ 诱导蛋白 (IP) -10，MIP-1和血小板衍生生长因子 (PDGF)-BB 没有。IL-17 和 PDGF-BB 观察到喘息者/哮喘患者和健康对照组之间的显着差异，在调整 IL-17 的季节性后保持稳定。季节性对哮喘患者的血清细胞因子水平有显着影响。由于内分型在指导个体化患者定制治疗方面具有临床重要性，因此考虑季节性影响非常重要。
更新日期：2020-11-17
and tumor necrosis factor (TNF)‐ showed seasonal variability, whereas IL‐1β, IL‐7, IL‐8, IL‐13, eotaxin, granulocyte colony‐stimulating factor (G‐CSF), interferon gamma‐induced protein (IP)‐10, MIP‐1 and platelet‐derived growth factor (PDGF)‐BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL‐17 and PDGF‐BB, which remained stable after adjustment for the seasonality of IL‐17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient‐tailored therapy, it is important to account for seasonal effects.
中文翻译：
患有喘息和哮喘的儿童和成人的细胞因子水平显示出随时间变化的特定模式
细胞因子水平用于深入描述哮喘患者的特征；然而，随时间的变化可能是一个关键的混杂因素。分析儿童、青少年和成人哮喘患者和健康对照组血清细胞因子的变化过程，并提出控制季节性影响的统计方法。在 532 名筛查对象中，514 名 (91·5%) 被纳入全年龄哮喘队列 (ALLIANCE)。该队列包括 279 名患有复发性喘息性支气管炎（两次以上发作）或医生诊断为哮喘的儿童、75 名健康对照、150 名成人哮喘患者和 31 名成人健康对照。收集血样，使用 Bio-Plex Pr 人细胞因子 27-Plex 测定法分析 25 μl 血清。三组喘息者的平均年龄、体重指数和性别，哮喘儿童和成人哮喘患者与健康对照组相当。与对照组（分别为 4·5、22 和 22·6%）相比，喘息者 (34·5%)、哮喘儿童 (78·7%) 和成人哮喘患者 (62·8%) 的致敏率明显更高。考虑到整个队列，白细胞介素 (IL)-1ra、IL-4、IL-9、IL-17、巨噬细胞炎症蛋白 (MIP)-1-
和肿瘤坏死因子 (TNF)-表现出季节性变化，而 IL-1β、IL-7、IL-8、IL-13、eotaxin、粒细胞集落刺激因子 (G-CSF)、干扰素 γ 诱导蛋白 (IP) -10，MIP-1和血小板衍生生长因子 (PDGF)-BB 没有。IL-17 和 PDGF-BB 观察到喘息者/哮喘患者和健康对照组之间的显着差异，在调整 IL-17 的季节性后保持稳定。季节性对哮喘患者的血清细胞因子水平有显着影响。由于内分型在指导个体化患者定制治疗方面具有临床重要性，因此考虑季节性影响非常重要。
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