补体C3与过敏性哮喘：一项针对一般人群的队列研究
2021/01/20
摘要
补体C3在哮喘的发展和严重程度中发挥作用。我们检验了以下假设：血浆补体C3高浓度与哮喘住院治疗和急性发作的高风险有关。
我们通过血浆补体C3的基线测量值，对来自哥本哈根一般人群的101 029例哮喘受试者住院治疗的风险进行前瞻性评估，并根据rs1065489，rs429608和rs448260进行了基因分型，从而确定补体C3的水平。在2248例过敏性哮喘患者中进一步评估了哮喘急性发作的风险。
血浆补体C3三分位数最高（>1.19 g/L）的个体相对于三分位数最低（<1.03 g/L）的个体，哮喘住院治疗的多变量调整风险比为1.23（95%CI：1.04-1.45）。C3 rs448260基因型与哮喘住院治疗的风险具有相关性：与AA基因型相比，CC基因型的危险比为1.17（1.06-1.28）。高水平血浆补体C3与血液嗜酸性粒细胞和IgE的高水平相关（p≤6·10-9），但只有SKIV2L rs429608基因型与血液嗜酸性粒细胞计数（p=3·10-4）和IgE水平（p=3·10-4）呈正相关。在过敏性哮喘中，血浆补体C3三分位数最高（>1.24 g/L）相比三分位数最低（<1.06 g/L）的个体，急性发作风险的多变量调整发生率比为1.69（1.06-2.72）。
总之，血浆补体C3高浓度与一般人群中哮喘住院治疗的高风险相关，并且与过敏性哮喘患者中哮喘急性发作的高风险相关。我们这一发现支持补体系统在哮喘严重程度中的因果作用。
Complement C3 and allergic asthma: A cohort study of the general population.
Vedel-Krogh S, Rasmussen KL, Nordestgaard BG, Nielsen SF.
Eur Respir J. 2020. pii: 2000645.
ABSTRACT
Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration was associated with high risk of asthma hospitalisations and exacerbations.
We prospectively assessed the risk of asthma hospitalisations in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608, and rs448260 determining levels of complement C3. Risk of asthma exacerbations was further assessed in 2248 individuals with allergic asthma.
The multivariable adjusted hazard ratio of asthma hospitalisations was 1.23 (95% confidence interval 1.04-1.45) for individuals in the highest tertile (>1.19 g/L) of plasma complement C3 compared with those in the lowest tertile (<1.03 g/L). The C3 rs448260 genotype was associated with risk of asthma hospitalisations with an observed hazard ratio of 1.17 (1.06-1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE (p for trends ≤6·10-9), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count (p=3·10-4) and level of IgE (p=3·10-4). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbations was 1.69 (1.06-2.72) for individuals in the highest plasma complement C3 tertile (>1.24 g/L) versus the lowest (<1.06 g/L).
In conclusion, high concentration of plasma complement C3 was associated with high risk of asthma hospitalisations in the general population and with high risk of asthma exacerbations in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity.
补体C3在哮喘的发展和严重程度中发挥作用。我们检验了以下假设：血浆补体C3高浓度与哮喘住院治疗和急性发作的高风险有关。
我们通过血浆补体C3的基线测量值，对来自哥本哈根一般人群的101 029例哮喘受试者住院治疗的风险进行前瞻性评估，并根据rs1065489，rs429608和rs448260进行了基因分型，从而确定补体C3的水平。在2248例过敏性哮喘患者中进一步评估了哮喘急性发作的风险。
血浆补体C3三分位数最高（>1.19 g/L）的个体相对于三分位数最低（<1.03 g/L）的个体，哮喘住院治疗的多变量调整风险比为1.23（95%CI：1.04-1.45）。C3 rs448260基因型与哮喘住院治疗的风险具有相关性：与AA基因型相比，CC基因型的危险比为1.17（1.06-1.28）。高水平血浆补体C3与血液嗜酸性粒细胞和IgE的高水平相关（p≤6·10-9），但只有SKIV2L rs429608基因型与血液嗜酸性粒细胞计数（p=3·10-4）和IgE水平（p=3·10-4）呈正相关。在过敏性哮喘中，血浆补体C3三分位数最高（>1.24 g/L）相比三分位数最低（<1.06 g/L）的个体，急性发作风险的多变量调整发生率比为1.69（1.06-2.72）。
总之，血浆补体C3高浓度与一般人群中哮喘住院治疗的高风险相关，并且与过敏性哮喘患者中哮喘急性发作的高风险相关。我们这一发现支持补体系统在哮喘严重程度中的因果作用。
(王昌勇1 张红萍2 王刚1 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Eur Respir J. 2020. pii: 2000645.）
（Eur Respir J. 2020. pii: 2000645.）
Complement C3 and allergic asthma: A cohort study of the general population.
Vedel-Krogh S, Rasmussen KL, Nordestgaard BG, Nielsen SF.
Eur Respir J. 2020. pii: 2000645.
ABSTRACT
Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration was associated with high risk of asthma hospitalisations and exacerbations.
We prospectively assessed the risk of asthma hospitalisations in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608, and rs448260 determining levels of complement C3. Risk of asthma exacerbations was further assessed in 2248 individuals with allergic asthma.
The multivariable adjusted hazard ratio of asthma hospitalisations was 1.23 (95% confidence interval 1.04-1.45) for individuals in the highest tertile (>1.19 g/L) of plasma complement C3 compared with those in the lowest tertile (<1.03 g/L). The C3 rs448260 genotype was associated with risk of asthma hospitalisations with an observed hazard ratio of 1.17 (1.06-1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE (p for trends ≤6·10-9), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count (p=3·10-4) and level of IgE (p=3·10-4). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbations was 1.69 (1.06-2.72) for individuals in the highest plasma complement C3 tertile (>1.24 g/L) versus the lowest (<1.06 g/L).
In conclusion, high concentration of plasma complement C3 was associated with high risk of asthma hospitalisations in the general population and with high risk of asthma exacerbations in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity.
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儿童哮喘严重程度的相关因素：来自法国COBRAPed队列的数据
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重症哮喘患者的辣椒素敏感性增加与临床结果恶化相关
