Discussion
Airway remodeling is a distinctive pathologic feature of asthma, and is thought to be the result of an aberrant reparative process associated with ongoing allergic inflammation. The histopathologic changes that occur within the airways of asthmatics include epithelial desquamation and regeneration, gobletcell hyperplasia, submucosal gland hypertrophy, subepithelial fibrosis or thickening of the basement membrane, inflammatory cell infiltration, hyperplasia and hypertrophy of the bronchial smooth muscle, and vascular changes. What role these changes have on asthma severity and disease course remains to be determined.
This case series is among the first to combine historical and clinical features, pulmonary physiology, and endobronchial biopsy results in a group of children with severe asthma. All of the subjects studied had long, if not lifelong Generic Cialis, histories of severe, persistent, high-risk asthma, with the majority having been intubated at least once for a severe asthma exacerbation. In addition, all required long-term oral and inhaled glucocorticoid therapy, yet adequate asthma control had been difficult to achieve.
During their evaluation, all of the subjects displayed improvement in lung function, with the mean FEV1 increasing from 69.5 to 100.8% of predicted (Table 1). Despite structural alterations of the airways, compatible with airway remodeling, normalization of lung function was nonetheless achievable in nearly every subject. In addition, there was a noticeable lack of airway inflammation noted on endobronchial biopsy, perhaps the result of aggressive glucocorticoid therapy. However, the absence of inflammation may indicate that airway inflammation need not be a prominent feature of refractory asthma.
The observations from this cohort of children provide insight into the pathophysiology of severe childhood asthma. First, significant airway remodeling can occur in children with severe asthma as young as 6 years old. Second, airway remodeling occurred despite aggressive, long-term treatment with both systemic and inhaled glucocorticoids. Third, in five of the six patients studied, there was little to no airway inflammation.
