Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Pediatric Endocrinology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
JAMA Netw Open. 2020 Mar 2;3(3):e200834. doi: 10.1001/jamanetworkopen.2020.0834.
The association between atopic and autoimmune disease, particularly asthma and type 1 diabetes, has been debated. Further understanding of the underlying factors associated with the comorbidity in children is warranted.
To assess the bidirectional association between asthma and type 1 diabetes and examine the possibility of a shared risk for the diseases by studying their pattern of familial coaggregation.
DESIGN, SETTING, AND PARTICIPANTS: A birth cohort study of children born from January 1, 2001, and followed up until December 31, 2015, was performed. Population data were obtained from multiple national Swedish registers. A total of 1 347 901 singleton children, live-born in Sweden between January 1, 2001, and December 31, 2013, were identified, and children with incomplete data were excluded. The remaining 1 284 748 children were linked to their biological full siblings, maternal and paternal half-siblings, cousins, and half-cousins. Data analysis was conducted from April 1, 2019, to January 17, 2020.
Cases of asthma and type 1 diabetes were defined using a combination of diagnoses and medication prescriptions found in the registers.
In the cohort of 1 284 748 children, 660 738 children (51.4%) were boys; 121 809 children (9.5%) had asthma, 3812 children (0.3%) had type 1 diabetes, and 494 children had both asthma and type 1 diabetes, representing 0.4% of all asthma or 13% of all type 1 diabetes. Mean (SD) age at diagnosis was 3.0 (2.8) years for children with asthma, and 5.9 (3.3) years for those with type 1 diabetes. Asthma and type 1 diabetes were associated within individuals (odds ratio, 1.15; 95% CI, 1.05-1.27). Children with asthma had an increased risk of subsequent type 1 diabetes (hazard ratio, 1.16; 95% CI, 1.06-1.27); however, subsequent asthma risk did not differ substantially among children with type 1 diabetes (hazard ratio, 0.92; 95% CI, 0.75-1.12). Siblings of individuals with asthma were at an increased risk of type 1 diabetes (odds ratio, 1.27; 95% CI, 1.13-1.42) and vice versa. The results remained positive after controlling for the direct association of one disease with the other.
This study appears to provide evidence for co-occurrence, importance of sequential appearance, and coaggregation of asthma and type 1 diabetes in children and their siblings. The findings may suggest shared familial factors contributing to the associations. Knowledge of the nature of the association could be of importance in future clinical practice.
特应性和自身免疫性疾病之间的关联，特别是哮喘和 1 型糖尿病之间的关联，一直存在争议。需要进一步了解与儿童共病相关的潜在因素。
通过研究哮喘和 1 型糖尿病的家族聚集模式，评估它们之间的双向关联，并探讨这两种疾病存在共同风险的可能性。
设计、地点和参与者：对 2001 年 1 月 1 日至 2015 年 12 月 31 日出生的儿童进行了一项出生队列研究，并进行了随访。人群数据来自多个瑞典国家登记处。共确定了 2001 年 1 月 1 日至 2013 年 12 月 31 日期间在瑞典出生的 1347901 名单胎活产儿童，并排除了数据不完整的儿童。其余 1284748 名儿童与他们的生物学全兄弟姐妹、母亲和父亲的半兄弟姐妹、表兄弟姐妹和堂兄弟姐妹相关联。数据分析于 2019 年 4 月 1 日至 2020 年 1 月 17 日进行。
哮喘和 1 型糖尿病的病例通过在登记处发现的诊断和药物处方的组合来定义。
在 1284748 名儿童队列中，660738 名儿童（51.4%）为男孩；121809 名儿童（9.5%）患有哮喘，3812 名儿童（0.3%）患有 1 型糖尿病，494 名儿童同时患有哮喘和 1 型糖尿病，占所有哮喘的 0.4%或所有 1 型糖尿病的 13%。哮喘儿童的平均（SD）诊断年龄为 3.0（2.8）岁，1 型糖尿病儿童为 5.9（3.3）岁。个体内哮喘和 1 型糖尿病之间存在关联（优势比，1.15；95%CI，1.05-1.27）。患有哮喘的儿童随后发生 1 型糖尿病的风险增加（风险比，1.16；95%CI，1.06-1.27）；然而，患有 1 型糖尿病的儿童随后发生哮喘的风险并没有显著差异（风险比，0.92；95%CI，0.75-1.12）。患有哮喘的个体的兄弟姐妹患 1 型糖尿病的风险增加（优势比，1.27；95%CI，1.13-1.42），反之亦然。在控制了一种疾病与另一种疾病的直接关联后，结果仍然为阳性。
本研究似乎为儿童及其兄弟姐妹中哮喘和 1 型糖尿病的同时发生、重要的先后出现和聚集提供了证据。这些发现可能表明存在共同的家族因素导致了这些关联。了解关联的性质可能对未来的临床实践具有重要意义。
