Brustad Nicklas, Thorsen Jonathan, Pedersen Casper Emil Tingskov, Ali Mina, Kyvsgaard Julie, Brandt Sarah, Lehtimäki Jenni, Prince Nicole, Følsgaard Nilofar V, Lasky-Su Jessica, Stokholm Jakob, Bønnelykke Klaus, Chawes Bo
Copenhagen Prospective Studies on Asthma in Childhood, Gentofte, Denmark.
University of Copenhagen, Kobenhavn, Denmark.
Thorax. 2024 Sep 18;79(10):943-952. doi: 10.1136/thorax-2024-221460.
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.
Children (n=633) from the COPSAC 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.
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 (p<0.001).
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.
儿童期感染仍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程度是否与感染风险相关，并探索了潜在机制。
对来自COPSAC母婴队列的633名儿童在出生后的前3年每天用感染发作症状日记进行监测，并前瞻性地诊断哮喘直至6岁。农村和城市环境基于CORINE土地覆盖数据库。在4周龄时测量儿童气道免疫谱。分别在妊娠第24周和出生时评估母婴代谢组学谱。
我们观察到，到3岁时，感染的平均（标准差）总数为16.3（8.4），主要为上呼吸道感染。城市生活与农村生活相比增加了感染风险（17.1（8.7）对15.2（7.9），调整后的发病率比；1.15（1.05 - 1.26），p = 0.002），并改变了儿童气道免疫谱，这增加了感染风险（主成分1（PC1）：1.03（1.00 - 1.06），p = 0.038；PC2：1.04（1.01 - 1.07），p = 0.022）。城市生活还改变了母婴代谢组学谱，这也增加了感染风险。城市化与感染风险之间的关联部分通过母亲代谢组学和儿童气道免疫谱介导。最后，城市化增加了6岁时患哮喘的风险，这是通过早期感染负荷介导的（p < 0.001）。
本研究表明，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，这对后期哮喘风险有影响。
