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Elevated blood levels of thymus and activation-regulated chemokine (TARC)/CCL17 have been observed in atopic dermatitis (AD) and may serve as a new biomarker for AD. However, the normal levels, especially in children, have not been well determined. We sought to establish an efficient enzyme-linked immunosorbent assay (ELISA) with a wide range of detection that would be suitable for measurement of serum TARC/CCL17 and to determine the normal ranges of this chemokine in different age groups and its diagnostic usefulness for AD. A sensitive specific ELISA for TARC/CCL17, which we previously reported, was modified to accommodate the wide range of TARC/CCL17 values often found in sera. Twenty-seven children with AD under 6 yr of age and 25 age-matched normal non-atopic controls, and 18 patients with AD and 27 controls who were 6 yr and older were enrolled. The severity of AD was evaluated using the SCORAD index. The serum levels of TARC/CCL17 were measured with the ELISA, and the serum levels of IP-10/CXCL10 were also measured. With the novel ELISA system, the assayable range of TARC/CCL17 was 14-8000 pg/ml, and the coefficient of variation at various concentrations ranged from 2.3% to 5.0%. The serum levels of TARC/CCL17 in normal individuals were significantly higher in young children, especially in the age group of 0-1 yr. The cut-off values of TARC/CCL17 for the diagnosis of AD were 1431 pg/ml for 0-1 yr group, 803 pg/ml for 2-5 yr group and 510 pg/ml for the 6 yr and older group, with high sensitivity and specificity of 0.83 and 0.93, 0.83 and 0.92, 0.85 and 0.96, respectively. The magnitude of the decrease in the SCORAD index after treatment with topical steroids correlated significantly with the decrease in serum TARC/CCL17. There was no difference in the serum levels of IP-10/CXCL10 between AD and the controls. The TARC/CCL17:IP-10/CXCL10 ratio tended to be higher in the control children aged 0-1 yr than in those aged 2-5 yr. The serum level of TARC/CCL17 reflects the severity and therapeutic response in AD. The high normal levels in infants should be taken into account when assaying TARC/CCL17.

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Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV(1) and ENO were measured before and at 0, 5, 10, and 15 min after exercise performed on a treadmill for 6 min. EIB was defined as a decrease in FEV(1) of more than 15% after the exercise. Normal children (control group) did not have EIB. Twenty-one patients with asthma had EIB (EIB group) whereas the remaining 18 patients did not (non-EIB group). The baseline ENO value was significantly higher in the asthmatic children than in the normal children, and there was a positive correlation between the maximal percent decrease in FEV(1) and the baseline ENO value (r = 0.501, p = 0.012). At the end of the exercise, ENO had decreased in all the subjects. In the non-EIB and control groups, ENO rebounded to above the baseline at 5 min after the exercise and thereafter. In contrast, ENO remained at a decreased level in the EIB group. The change in ENO did not correlate with the change in minute ventilation, and beta-agonist inhalation at the peak of EIB that accelerated the recovery of FEV(1) did not affect the depressed level of ENO, demonstrating that the reduction of ENO is not a simple consequence of increased ventilation nor airway obstruction. Among the EIB group, steroid-treated patients showed sooner recovery in ENO after the exercise than steroid-naive patients. Our study suggests that NO production in response to exercise may be impaired in patients with EIB, and that ENO represents not only airway inflammation but also a protective function of NO in EIB.