The ages of the study cohort at the time of evaluation ranged from 6 to 17 years (mean, 11.2 years), and the mean age of disease onset was 1.8 years. Four of the six patients had been intubated at least once due to a respiratory arrest secondary to a severe asthma exacerbation. All were receiving oral glucocorticoids at the time of admission (mean daily dose, 21 mg) and had required long-term oral glucocorticoid therapy for a mean of 5.2 years (Table 1). All subjects underwent an extensive diagnostic evaluation. Three of the six subjects required an increase in their oral glucocorticoid therapy to optimize lung function and minimize diurnal variability. Four subjects had significant airflow obstruction with hyperinflation and air trapping (Table 2), while two subjects had very little evidence for airflow obstruction or diurnal variability throughout their hospital stay. At the time of discharge, a significant improvement in lung function was noted in every child, with the mean FEV1 increasing from 69.5 to 100.8% of predicted (Table 2).
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Review of the endobronchial specimens revealed evidence for significant structural alterations compatible with the current definition of airway remodeling in every subject studied. Specifically, grossly thickened subbasement membranes, goblet-cell hyperplasia, smooth-muscle hypertrophy and hyperplasia, and varying degrees of both elastin deposition and epithelial desquamation were noted. Of some surprise was the very obvious lack of airway inflammation. In five of the six cases, there was only mild and patchy lymphocytic inflammation immediately below the subbasement membranes, with few to no eosinophils or neutrophils noted.
Case Summaries
Case 1: A 9-year-old boy developed respiratory symptoms at 10 months following an episode of bronchiolitis. He was hospitalized numerous times for acute asthma exacerbations, with one episode requiring intubation. In addition, he had been receiving long-term oral glucocorticoids since 15 months of age. The hospital admission prednisone dose was 10 mg on alternate days in addition to high-dose Viagra 100mg inhaled glucocorticoids, and he required 6 to 10 inhalations of albuterol per day for symptoms. Spirometry initially revealed significant diurnal variability in his lung function, with wheezing and significant airflow obstruction on awakening (Fig 1, top, A).