高BMI的遗传易感性增加了早期呼吸道感染以及严重喘息和哮喘发作的风险
2024/09/29
摘要
背景：高BMI是哮喘的一个确定的危险因素，但其潜在机制尚不清楚。
目的：通过研究儿童时期较高 BMI 的遗传易感性与哮喘、感染和其他哮喘特征之间的关联，增加对 BMI 与哮喘关系的理解。
方法：数据来自两项正在进行的哥本哈根儿童哮喘前瞻性研究 （COPSAC） 母婴队列。计算每个儿童的成人 BMI 的多基因风险评分。在基于注册的大规模综合精神病学研究 （iPSYCH） 队列中使用哮喘和感染住院数据进行复制。
结果：在COPSAC队列中(n=974)，成人BMI多基因风险评分与0-3岁时的下呼吸道感染(IRR 1.20, 95% CI 1.08-1.33，pFDR=0.005)和0-6岁时的严重喘息发作(IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04)显著相关。下呼吸道感染部分介导了成人BMI多基因风险评分与严重喘息之间的关联(比例介导:0.59, 95%CI 0.28-2.24, 值与平均因果中介效应相关(pACME)= 2e-16)。相比之下，这些关联不是通过儿童当前的BMI介导的，多基因风险评分与哮喘诊断或肺功能降低无关，直至18岁。这种关联在iPSYCH中得到了重复(n=114 283)，其中成人BMI多基因风险评分显著增加了儿童期至18岁期间因下呼吸道感染和喘息或哮喘住院的风险。
结论：具有较高 BMI 遗传倾向的儿童患下呼吸道感染和严重喘息的风险增加，这与儿童当前的 BMI 无关。这些结果进一步阐明了体重 BMI 与哮喘之间的复杂关系。
Genetic predisposition to high BMI increases risk of early life respiratory infections and episodes of severe wheeze and asthma.
Signe Kjeldgaard, Jensen; Casper-Emil Tingskov,
Abstrast
Background: High body mass index (BMI) is an established risk factor for asthma, but the underlying mechanisms remain unclear.
Objective: To increase understanding of the BMI-asthma relationship by studying the association between genetic predisposition to higher BMI and asthma, infections and other asthma traits during childhood.
Methods: Data were obtained from the two ongoing Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts. Polygenic risk scores for adult BMI were calculated for each child. Replication was done in the large-scale register-based Integrative Psychiatric Research (iPSYCH) cohort using data on hospitalisation for asthma and infections.
Results：In the COPSAC cohorts (n=974), the adult BMI polygenic risk score was significantly associated with lower respiratory tract infections (incidence rate ratio (IRR) 1.20, 95% CI 1.08-1.33, false discovery rate p-value (pFDR)=0.005) at age 0-3 years and episodes of severe wheeze (IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04) at age 0-6 years. Lower respiratory tract infections partly mediated the association between the adult BMI polygenic risk score and severe wheeze (proportion mediated: 0.59, 95% CI 0.28-2.24, p-value associated with the average causal mediation effect (pACME)=2e-16). In contrast, these associations were not mediated through the child's current BMI and the polygenic risk score was not associated with an asthma diagnosis or reduced lung function up to age 18 years. The associations were replicated in iPSYCH (n=114 283), where the adult BMI polygenic risk score significantly increased the risk of hospitalisations for lower respiratory tract infections and wheeze or asthma throughout childhood to age 18 years.
Conclusions: Children with genetic predisposition to higher BMI had increased risk of lower respiratory tract infections and severe wheeze, independent of the child's current BMI. These results shed further light on the complex relationship between body mass BMI and asthma.
背景：高BMI是哮喘的一个确定的危险因素，但其潜在机制尚不清楚。
目的：通过研究儿童时期较高 BMI 的遗传易感性与哮喘、感染和其他哮喘特征之间的关联，增加对 BMI 与哮喘关系的理解。
方法：数据来自两项正在进行的哥本哈根儿童哮喘前瞻性研究 （COPSAC） 母婴队列。计算每个儿童的成人 BMI 的多基因风险评分。在基于注册的大规模综合精神病学研究 （iPSYCH） 队列中使用哮喘和感染住院数据进行复制。
结果：在COPSAC队列中(n=974)，成人BMI多基因风险评分与0-3岁时的下呼吸道感染(IRR 1.20, 95% CI 1.08-1.33，pFDR=0.005)和0-6岁时的严重喘息发作(IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04)显著相关。下呼吸道感染部分介导了成人BMI多基因风险评分与严重喘息之间的关联(比例介导:0.59, 95%CI 0.28-2.24, 值与平均因果中介效应相关(pACME)= 2e-16)。相比之下，这些关联不是通过儿童当前的BMI介导的，多基因风险评分与哮喘诊断或肺功能降低无关，直至18岁。这种关联在iPSYCH中得到了重复(n=114 283)，其中成人BMI多基因风险评分显著增加了儿童期至18岁期间因下呼吸道感染和喘息或哮喘住院的风险。
结论：具有较高 BMI 遗传倾向的儿童患下呼吸道感染和严重喘息的风险增加，这与儿童当前的 BMI 无关。这些结果进一步阐明了体重 BMI 与哮喘之间的复杂关系。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校 )
(Eur Respir J 2024 Sep;64(3). 10.1183/13993003.00169-2024.IF：12.339)
(Eur Respir J 2024 Sep;64(3). 10.1183/13993003.00169-2024.IF：12.339)
Genetic predisposition to high BMI increases risk of early life respiratory infections and episodes of severe wheeze and asthma.
Signe Kjeldgaard, Jensen; Casper-Emil Tingskov,
Abstrast
Background: High body mass index (BMI) is an established risk factor for asthma, but the underlying mechanisms remain unclear.
Objective: To increase understanding of the BMI-asthma relationship by studying the association between genetic predisposition to higher BMI and asthma, infections and other asthma traits during childhood.
Methods: Data were obtained from the two ongoing Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts. Polygenic risk scores for adult BMI were calculated for each child. Replication was done in the large-scale register-based Integrative Psychiatric Research (iPSYCH) cohort using data on hospitalisation for asthma and infections.
Results：In the COPSAC cohorts (n=974), the adult BMI polygenic risk score was significantly associated with lower respiratory tract infections (incidence rate ratio (IRR) 1.20, 95% CI 1.08-1.33, false discovery rate p-value (pFDR)=0.005) at age 0-3 years and episodes of severe wheeze (IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04) at age 0-6 years. Lower respiratory tract infections partly mediated the association between the adult BMI polygenic risk score and severe wheeze (proportion mediated: 0.59, 95% CI 0.28-2.24, p-value associated with the average causal mediation effect (pACME)=2e-16). In contrast, these associations were not mediated through the child's current BMI and the polygenic risk score was not associated with an asthma diagnosis or reduced lung function up to age 18 years. The associations were replicated in iPSYCH (n=114 283), where the adult BMI polygenic risk score significantly increased the risk of hospitalisations for lower respiratory tract infections and wheeze or asthma throughout childhood to age 18 years.
Conclusions: Children with genetic predisposition to higher BMI had increased risk of lower respiratory tract infections and severe wheeze, independent of the child's current BMI. These results shed further light on the complex relationship between body mass BMI and asthma.
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重度嗜酸性哮喘患者对美泊利珠单抗治疗反应向缓解的不同轨迹
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哮喘和代谢功能障碍与住院新型冠状病毒肺炎患者预后的关系
