Eosinophils play a key role in airway remodeling

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 F'EV_X (r = —0.398; p = 0.008). Conclusions: 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.

Abbreviations: AHR = airway hyperresponsiveness; BD = bronchodilator; EB = eosinophilic bronchitis; ECP = eosinophil cationic protein; FEF_25-75% = forced expiratory flow, midexpiratory phase; ICS = inhaled corticosteroid; IQR = interquartile range; PC₂₀ = provocative concentration of methacholine causing a 20% fall in FEV₁

Airway remodeling and eosinophilic airway inflammation, which are characteristic features of asthma in adults, are already present in children with asthma and even in pre-school-aged children who wheeze. There is evidence that eosinophils play a key role in airway remodeling, which produces a wide range of proteins in fibrogenesis and angiogenesis, particularly transforming growth factor-P and other cytokines. Eosinophils also are increased within the airways in patients with nonasthmatic eosinophilic bronchitis (EB) to levels similar to those found in patients with asthma. EB has emerged from the study of chronic cough, and is characterized by eosinophilic inflammation, increased exhaled nitric oxide levels, increased basement membrane thickening, and normal spirometry findings, without airway hyperresponsiveness (AHR). Although the pathogenesis of EB is still unclear, especially in children, its immunopathologic features are distinct from those of asthma in that EB shows no evidence of the overexpression of interleukin-4 or interleukin-13 by mast cells or mast cell colonization to airway smooth muscle.

Amphiregulin was originally classified as a member of the epidermal growth factor family, which plays important roles in cell proliferation, survival, and differentiation.

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