Non-invasive markers of airway inflammation and remodeling in childhood asthma

To evaluate the relationship between pro-inflammatory and pro-remodeling mediators and severity and control of asthma in children, the levels of IL-8, MMP-9, TIMP-1 in induced sputum supernatants, the number of sputum eosinophils, as well as FeNO, were investigated in 35 asthmatic children, 12 with intermittent (IA) and 23 with moderate asthma (MA), and 9 controls (C). The patients with asthma were followed for 1 yr and sputum was obtained twice during the follow-up. Biomarker levels were correlated with the number of exacerbations. We found that IL-8, MMP-9, TIMP-1 and the numbers of eosinophils in induced sputum, as well as FeNO, were increased in children with IA and MA in comparison to C. The ongoing inflammation was confirmed by increased nuclear p65 NF-kappaB subunit localization in sputum cells. In MA, FeNO measurements, sputum eosinophils and IL-8 levels, positively correlated with the occurrence of disease exacerbations during a 1-yr follow-up. According to FeNO, sputum eosinophils and IL-8 sputum concentrations, and the number of exacerbations, two distinct phenotypes of MA were identified. This study shows that the presence of bronchial inflammation is detectable in the airways of some IA, as well as in the airways of MA, despite the regular ICS treatment. This study also proposes the need to perform large prospective studies to confirm the importance of measuring specific biomarkers in induced sputum, concomitantly to FeNO analyses, to assess sub-clinical airway inflammation and disease control in children with asthma.