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BACKGROUND: Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting. OBJECTIVES: To investigate in situ virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma. METHODS: We included 493 episodes of acute respiratory illnesses in 277 children aged 0-3 years from the COPSAC2010 mother-child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high-sensitivity MesoScale Discovery kits and compared between children with and without viral PCR-identification in nasopharyngeal samples. Finally, we investigated whether the virus-specific immune response was associated with asthma by age 6 years. RESULTS: Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-É£, TNF-α, CCL4, CXCL10 and IL-10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL-10 (FDR <0.05) during viral episodes compared to children not developing asthma. CONCLUSION: We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL-10) immune mediator level. This provides insight into the interplay between early-life viral infections, airway immunity and asthma development.
RESUMEN
BACKGROUND: We previously reported that children of mothers who received fish oil supplementation during pregnancy had higher body mass index [BMI (in kg/m2)] at 6 y of age as well as a concomitant increase in fat-, muscle, and bone mass, but no difference in fat percentage. OBJECTIVES: Here, we report follow-up at age 10 y including assessment of metabolic health. METHODS: This is a follow-up analysis of a randomized clinical trial conducted among 736 pregnant females and their offspring participating in the Copenhagen Prospective Studies on Asthma in Childhood mother-child cohort. The intervention was 2.4 g n-3 (ω-3) Long-Chain PolyUnsaturated Fatty Acid (n-3 LCPUFA) or control daily from pregnancy week 24 until 1 wk after birth. Outcomes were anthropometric measurements, body composition from Bioelectrical Impedance Analysis, blood pressure, concentrations of triglycerides, cholesterol, glucose, and C-peptide from fasting blood samples, and a metabolic syndrome score was calculated. Anthropometric measurements and body composition were prespecified secondary endpoints of the n-3 LCPUFA trial, and others were exploratory. RESULTS: Children in the n-3 LCPUFA group had a higher mean BMI at age 10 year compared to the control group: 17.4 (SD: 2.44) compared with 16.9 (2.28); P = 0.020 and a higher odds ratio of having overweight (odds ratio: 1.53; 95% CI: 1.01, 2.33; P = 0.047). This corresponded to differences in body composition in terms of increased lean mass (0.49 kg; 95% CI: -0.20, 1.14; P = 0.17), fat mass (0.49 kg; 95% CI: -0.03, 1.01; P = 0.06), and fat percent (0.74%; 95% CI: -0.01, 1.49; P = 0.053) compared to the control group. Children in the n-3 LCPUFA group had a higher metabolic syndrome score compared to the control (mean difference: 0.19; 95% CI: -0.02, 0.39; P = 0.053). CONCLUSIONS: In this randomized clinical trial, children of mothers receiving n-3 LCPUFA supplementation had increased BMI at age 10 y, increased risk of being overweight, and a tendency of increased fat percentage and higher metabolic syndrome score. These findings suggest potential adverse health effects from n-3 LCPUFA supplementation during pregnancy and need to be replicated in future independent studies. This trial was registered at clinicaltrials.gov as NCT00798226.