Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis

Abstract

Amphiregulin, a member of the epidermal growth factor family, has been shown to promote the growth of fibroblasts, to be associated with the T-helper type 2 cell adaptive immune response, and to up-regulate mucin gene expression. We aimed to determine whether sputum amphiregulin is expressed at elevated levels in patients with asthma or eosinophilic bronchitis (EB), and whether it is associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. A total of 117 children with asthma, 77 with EB, and 84 control subjects were enrolled in this study. Amphiregulin and eosinophil cationic protein (ECP) levels were measured in sputum supernatants. We performed pulmonary function and methacholine challenge tests while measuring total eosinophil count, and serum levels of total IgE and ECP in all children. The children with asthma had significantly higher levels of sputum amphiregulin (mean, 10.80 pg/mL; range, 4.07 to 38.75 pg/mL) than both the children with EB (mean, 5.76 pg/mL; range, 0.61 to 21.65 pg/mL; p = 0.013) and the control subjects (mean, 6.56 pg/mL; range, 0.51 to 17.98 pg/mL; p = 0.003). Sputum amphiregulin levels positively correlated with levels of sputum eosinophils (gamma = 0.221; p = 0.007) and sputum ECP (gamma = 0.601; p < 0.0001). Negative significant correlations were found between sputum amphiregulin and FEV(1) (gamma = -0.181; p = 0.006) or post-bronchodilator therapy FEV(1) (gamma = -0.233; p = 0.002). In children with asthma who were not receiving any controller medications, sputum amphiregulin level was negatively correlated with the provocative concentration of methacholine causing a 20% fall in FEV(1) (r = -0.398; p = 0.008). Our findings suggest that childhood asthma is associated with sputum amphiregulin, whereas EB is not, and that sputum amphiregulin would be a supportive marker of airway inflammation in asthma.