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Background: Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood. Methods: We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5–18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. Results: In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08–1.35), p <.01, and 1.41 (1.21–1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23–1.69), p <.0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65–0.99), p =.05 (p-interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p-interaction <.01). Further, blood eosinophil count, total-IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children. Conclusion: Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma-associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid as

Vitamin D deficiency and elevated high sensitivity C‐reactive protein (hs‐CRP) have been associated with several health outcomes, but knowledge on early life trajectories and association between 25 hydroxyvitamin D (25(OH)D) and hs‐CRP is lacking. We investigated the association between longitudinal measurements of 25(OH)D and hs‐CRP, respectively, from pregnancy to childhood and throughout childhood in two Danish mother–child cohorts—the COPSAC2010 and COPSAC2000. In COPSAC2010, there was an association between 25(OH)D concentrations at week 24 in pregnancy and at age 6 months in childhood (n = 633): estimate (95% CI); 0.114 (0.041;0.187), p = 0.002, and between 25(OH)D at age 6 months and 6 years (n = 475): 0.155 (0.083;0.228), p < 0.001. This was also demonstrated in the COPSAC2000 cohort between 25(OH)D concentrations in cord blood and at age 4 years (n = 188): 0.294 (0.127;0.461), p < 0.001 and at age 6 months and 4 years (n = 264): 0.260 (0.133;0.388), p < 0.001. In COPSAC2000, we also found an association between hs‐CRP at age 6 months and 12 years in childhood (n = 232): 0.183 (0.076;0.289), p < 0.001. Finally, we found a negative association between the cross‐sectional measurements of 25(OH)D and hs‐CRP at age 6 months (n = 613) in COPSAC2010: −0.004 (−0.008;−0.0004), p = 0.030, but this was not replicated in COPSAC2000. In this study, we found evidence of associations across timepoints of 25(OH)D concentrations from mid‐pregnancy to infancy and through childhood and associations between hs‐CRP levels during childhood, although with weak correlations. We also found a negative cross‐sectional association between 25(OH)D and hs‐CRP concentrations in COPSAC2010 proposing a role of vitamin D in systemic low‐grade inflammation, though this association was not present in COPSAC2000.

BACKGROUND: Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring.METHODS: We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.RESULTS: A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statist

BACKGROUND: Bacterial airway colonization is known to alter the airway mucosa immune response in neonates whereas the impact of viruses is unknown. The objective was therefore to examine the effect of respiratory viruses on the immune signature in the airways of asymptomatic neonates.METHODS: Nasal aspirates from 571 asymptomatic 1-month-old neonates from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort were investigated for respiratory viruses. Simultaneously, unstimulated airway mucosal lining fluid was obtained and quantified for levels of 20 immune mediators related to type 1, type 2, type 17, and regulatory immune paths. The association between immune mediator levels and viruses was tested by conventional statistics and partial least square discriminant analysis.RESULTS: Picornaviruses were detected in 58 neonates (10.2%) and other viruses in 10 (1.8%). A general up-regulation of immune mediators was found in the neonates with picornavirus (P < .0001; partial least square discriminant analysis). The association was pronounced for type 1- and type 2-related markers and was unaffected by comprehensive confounder adjustment. Detection of picornavirus and bacteria was associated with an additive general up-regulating effect.CONCLUSIONS: Asymptomatic presence of picornavirus in the neonatal airway is a potent activator of the topical immune response. This is relevant to understanding the immune potentiating effect of early life exposure to viruses.