Clinical and Biological Heterogeneity in Children with Moderate Asthma

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Abstract
To evaluate the relationship between inflammatory markers and severity of asthma in children, the amount of interleukin-8 (IL-8) and granulocyte/macrophage colony-stimulating factor (GM-CSF) released by peripheral blood mononuclear cells, exhaled nitric oxide (FE NO) levels, p65 nuclear factor-kappaB subunit, and phosphorylated IkBalpha expression by peripheral blood mononuclear cells were assessed in six control subjects, 12 steroid-naives subjects with intermittent asthma, and 17 children with moderate asthma. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18-month follow-up period. We found that GM-CSF release was higher in moderate and intermittent asthmatics than in control subjects, whereas IL-8 release was higher in moderate than in intermittent asthmatics and control subjects. FE NO levels were similar among study groups. In moderate asthmatics, IL-8, GM-CSF, and FE NO significantly correlated with the exacerbation numbers. Moreover, p65 and phosphorylated IkBalpha levels were greater in moderate than in intermittent asthmatics and control subjects. According to GM-CSF, IL-8, and FE NO levels, two distinct subgroups of moderate asthmatics (low and high producers) were identified. High producers experienced more exacerbations than low producers. This study shows ongoing inflammation associated with biological and clinical heterogeneity in moderate asthmatics despite regular treatment and proposes that large prospective studies confirm the importance of biomarkers to assess inflammation and asthma control in children with asthma