症状控制不佳的哮喘患者蛋白组学和转录组学特征：U-BIOPRED队列分析
2026/01/15
摘要
背景：哮喘患者症状控制仍具挑战，了解其分子机制可能为哮喘病理生理学提供新的见解。作者旨在探讨血液和痰液转录组和蛋白组与哮喘症状控制间的相关性。
方法：本横断面研究纳入来自U-BIOPRED队列的哮喘患者和健康成人。控制不佳定义为5项哮喘控制问卷的平均分≥1.5分。采用基于LASSO逻辑回归的稳定性选择筛选出与症状控制相关的基因/蛋白，随后采用逻辑回归模型对其关联性进行进一步的评估。分析根据年龄、性别、哮喘发作年龄、吸烟史、体重指数（BMI）、FEV1%预测值、急性发作史、抗IgE治疗史及尿类固醇水平进行调整。采用线性回归将哮喘患者与健康人群进行比较分析，并根据年龄、性别、BMI、吸烟史和尿类固醇水平进行调整。
结果：根据415名哮喘患者（41-61岁，中位年龄52岁；59%女性；64%控制）的蛋白组学数据选取四类血清蛋白。较高的TWEAKR/TNFRSF12A[OR 2.25; 95% CI 1.15-4.77]和MBL/MBP-C[OR 1.6; 95%CI 1.07-2.42]水平增加了哮喘控制不佳概率，而较高的MK08/MAPK8 [OR 0.48; 95%CI 0.29-0.76]和CD5L [OR 0.59; 95%CI 0.41-0.82]水平则降低。重度哮喘患者CD5L水平显著低于健康人群[估计值-0.23；95%CI-0.41- -0.04]。痰液蛋白组学（N=90）、痰液（N=96）和血液（N=360）转录组学数据与哮喘控制间未见显著相关性。
结论：筛选出的四类血清蛋白成功识别控制不佳哮喘患者。且重度哮喘患者CD5L水平较健康人群显著下降，为深入研究其潜在治疗价值提供了理论依据。
关键词：哮喘；患者预后评估；蛋白组学；转录组学
Background: Controlling asthma symptoms remains challenging. Understanding its molecular mechanisms may provide new insights into asthma pathophysiology. We explored the associations between the transcriptome and proteome in blood and sputum and asthma symptom control.
Methods: This cross- sectional study included asthmatic and healthy adults from the U- BIOPRED cohort. Uncontrolled symptoms were defined as a mean ≥ 1.5 points on the 5- item asthma control questionnaire. Stability selection using LASSO logistic regression identified genes/proteins associated with symptom control, followed by logistic regression. Analyses were adjusted for age, sex, age of asthma onset, smoking status, body mass index (BMI), FEV1% predicted, exacerbation history, anti-IgE therapy and urinary steroid levels. The selected variables were compared with healthy controls using linear regression, adjusted for age, sex, BMI, smoking status and urinary steroid levels.
Results: Four serum proteins were selected based on data from 415 asthmatics (median age 52 [41, 61] years; 59% female; 64% uncontrolled). Higher TWEAKR/TNFRSF12A [OR 2.25 (95% CI 1.15, 4.77)] and MBL/MBP- C [1.6 (1.07, 2.42)] levels increased the odds of uncontrolled symptoms, whereas higher MK08/MAPK8 [0.48 (0.29, 0.76)] and CD5L [0.59 (0.41, 0.82)] levels de creased the odds. CD5L levels were significantly lower in severe asthma than in healthy controls [estimate −0.23 (95% CI −0.41, −0.04)]. No associations were found between symptom control and the sputum proteome (N = 90) or the sputum (N = 96) and blood (N = 360) transcriptomes.
Conclusion: Four serum proteins distinguished asthmatics with uncontrolled from controlled symptoms. CD5L levels were also lower in asthmatics with severe disease than in healthy controls, warranting further investigation into its potential therapeutic value.
Keywords: asthma ; patient outcome assessment ; proteomics ;transcriptomic
背景：哮喘患者症状控制仍具挑战，了解其分子机制可能为哮喘病理生理学提供新的见解。作者旨在探讨血液和痰液转录组和蛋白组与哮喘症状控制间的相关性。
方法：本横断面研究纳入来自U-BIOPRED队列的哮喘患者和健康成人。控制不佳定义为5项哮喘控制问卷的平均分≥1.5分。采用基于LASSO逻辑回归的稳定性选择筛选出与症状控制相关的基因/蛋白，随后采用逻辑回归模型对其关联性进行进一步的评估。分析根据年龄、性别、哮喘发作年龄、吸烟史、体重指数（BMI）、FEV1%预测值、急性发作史、抗IgE治疗史及尿类固醇水平进行调整。采用线性回归将哮喘患者与健康人群进行比较分析，并根据年龄、性别、BMI、吸烟史和尿类固醇水平进行调整。
结果：根据415名哮喘患者（41-61岁，中位年龄52岁；59%女性；64%控制）的蛋白组学数据选取四类血清蛋白。较高的TWEAKR/TNFRSF12A[OR 2.25; 95% CI 1.15-4.77]和MBL/MBP-C[OR 1.6; 95%CI 1.07-2.42]水平增加了哮喘控制不佳概率，而较高的MK08/MAPK8 [OR 0.48; 95%CI 0.29-0.76]和CD5L [OR 0.59; 95%CI 0.41-0.82]水平则降低。重度哮喘患者CD5L水平显著低于健康人群[估计值-0.23；95%CI-0.41- -0.04]。痰液蛋白组学（N=90）、痰液（N=96）和血液（N=360）转录组学数据与哮喘控制间未见显著相关性。
结论：筛选出的四类血清蛋白成功识别控制不佳哮喘患者。且重度哮喘患者CD5L水平较健康人群显著下降，为深入研究其潜在治疗价值提供了理论依据。
关键词：哮喘；患者预后评估；蛋白组学；转录组学
（南方医科大学南方医院 倪钰 陈颖 赵海金）
(Joana Antão, Guilherme Rodrigues et al. Proteomic and Transcriptomic Signatures of Poor Asthma Symptom Control in the U- BIOPRED Cohort. 2025 Dec 8. PMID: 41358571.DOI: 10.1111/all.70178)
Abstract(Joana Antão, Guilherme Rodrigues et al. Proteomic and Transcriptomic Signatures of Poor Asthma Symptom Control in the U- BIOPRED Cohort. 2025 Dec 8. PMID: 41358571.DOI: 10.1111/all.70178)
Background: Controlling asthma symptoms remains challenging. Understanding its molecular mechanisms may provide new insights into asthma pathophysiology. We explored the associations between the transcriptome and proteome in blood and sputum and asthma symptom control.
Methods: This cross- sectional study included asthmatic and healthy adults from the U- BIOPRED cohort. Uncontrolled symptoms were defined as a mean ≥ 1.5 points on the 5- item asthma control questionnaire. Stability selection using LASSO logistic regression identified genes/proteins associated with symptom control, followed by logistic regression. Analyses were adjusted for age, sex, age of asthma onset, smoking status, body mass index (BMI), FEV1% predicted, exacerbation history, anti-IgE therapy and urinary steroid levels. The selected variables were compared with healthy controls using linear regression, adjusted for age, sex, BMI, smoking status and urinary steroid levels.
Results: Four serum proteins were selected based on data from 415 asthmatics (median age 52 [41, 61] years; 59% female; 64% uncontrolled). Higher TWEAKR/TNFRSF12A [OR 2.25 (95% CI 1.15, 4.77)] and MBL/MBP- C [1.6 (1.07, 2.42)] levels increased the odds of uncontrolled symptoms, whereas higher MK08/MAPK8 [0.48 (0.29, 0.76)] and CD5L [0.59 (0.41, 0.82)] levels de creased the odds. CD5L levels were significantly lower in severe asthma than in healthy controls [estimate −0.23 (95% CI −0.41, −0.04)]. No associations were found between symptom control and the sputum proteome (N = 90) or the sputum (N = 96) and blood (N = 360) transcriptomes.
Conclusion: Four serum proteins distinguished asthmatics with uncontrolled from controlled symptoms. CD5L levels were also lower in asthmatics with severe disease than in healthy controls, warranting further investigation into its potential therapeutic value.
Keywords: asthma ; patient outcome assessment ; proteomics ;transcriptomic
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