Immunohistology and remodeling in fatal pediatric and adolescent asthma
BACKGROUND Difficult asthma in children displays distinct clinical patterns, and its physiopathology remains poorly understood. OBJECTIVE To determine the characteristics of the bronchial inflammatory profile in children with difficult asthma. METHODS We performed endobronchial biopsy and bronchoalveolar lavage in 28 children with persistent bronchial obstruction despite high doses of inhaled corticosteroids and regular treatment with long-acting beta(2)-agonists: 13 had persistent symptoms and 15 had few or no symptoms. RESULTS The number of eosinophils (P =.03) and neutrophils (P =.04) in the epithelium was significantly higher in symptomatic children than in children with few symptoms. Reticular basement membrane thicknening was similar in both groups. IFNgamma levels (P =.03) and IFNgamma/IL-4 ratio (P =.01) were significantly higher in children with few symptoms. CONCLUSIONS In symptomatic children, T(H)2-type inflammation was associated with the presence of activated eosinophils in the epithelium, whereas asthma in children with few symptoms was associated with an increase in T(H)1 cytokine levels. The high levels of IFNgamma suggest that this T(H)1 cytokine may modulate the local inflammatory response.