Background Infections in childhood remain a leading global cause of child mortality and environmental exposures seem crucial. We investigated whether urbanicity at birth was associated with the risk of infections and explored underlying mechanisms. Methods Children (n=633) from the COPSAC2010 mother–child cohort were monitored daily with symptom diaries of infection episodes during the first 3 years and prospectively diagnosed with asthma until age 6 years. Rural and urban environments were based on the CORINE land cover database. Child airway immune profile was measured at age 4 weeks. Maternal and child metabolomics profiling were assessed at pregnancy week 24 and at birth, respectively. Results We observed a mean (SD) total number of infections of 16.3 (8.4) consisting mainly of upper respiratory infections until age 3 years. Urban versus rural living increased infection risk (17.1 (8.7) vs 15.2 (7.9), adjusted incidence rate ratio; 1.15 (1.05–1.26), p=0.002) and altered the child airway immune profile, which increased infection risk (principal component 1 (PC1): 1.03 (1.00–1.06), p=0.038 and PC2: 1.04 (1.01–1.07), p=0.022). Urban living also altered the maternal and child metabolomic profiles, which also increased infection risk. The association between urbanicity and infection risk was partly mediated through the maternal metabolomic and child airway immune profiles. Finally, urbanicity increased the risk of asthma by age 6 years, which was mediated through early infection load (pACME<0.001). Conclusion This study suggests urbanicity as an independent risk factor for early infections partly explained by changes in the early metabolic and immunological development with implications for later risk of asthma. Data are available upon reasonable request. Data will be available on request by email to nicklas.brustad@dbac.dk.

中文翻译：

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城市代谢和气道免疫特征增加了幼儿感染的风险


背景 儿童感染仍然是全球儿童死亡的主要原因，环境暴露似乎至关重要。我们调查了出生时的城市化是否与感染风险相关，并探讨了潜在的机制。方法 每天​​对 COPSAC2010 母婴队列中的儿童 (n=633) 进行监测，记录头 3 年内感染发作的症状日记，并前瞻性诊断出哮喘直至 6 岁。农村和城市环境基于 CORINE 土地覆盖数据库。儿童气道免疫特征在 4 周大时进行测量。分别在妊娠第 24 周和出生时评估母婴代谢组学分析。结果 我们观察到 3 岁之前的感染总数平均 (SD) 为 16.3 (8.4)，主要为上呼吸道感染。与农村生活相比，城市生活增加了感染风险（17.1 (8.7) vs 15.2 (7.9)，调整后发病率比；1.15 (1.05–1.26)，p=0.002），并改变了儿童气道免疫特征，从而增加了感染风险（主要成分 1） (PC1): 1.03 (1.00–1.06), p=0.038 和 PC2: 1.04 (1.01–1.07), p=0.022)。城市生活还改变了孕产妇和儿童的代谢特征，这也增加了感染风险。城市化与感染风险之间的关联部分是通过母亲代谢组和儿童气道免疫特征介导的。最后，城市化会增加 6 岁时患哮喘的风险，这是通过早期感染负荷介导的 (pACME<0.001)。结论 这项研究表明，城市化是早期感染的独立危险因素，部分原因是早期代谢和免疫发育的变化，并影响后期哮喘的风险。数据可根据合理要求提供。 可通过发送电子邮件至 nicklas.brustad@dbac.dk 索取数据。