We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1, 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 micrograms, two puffs four times daily; n = 5) or inhaled budesonide (200 micrograms, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine greater than 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p less than 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p less than 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p less than 0.01) and eosinophils (p less than 0.05) in Group A and of eosinophils (p less than 0.01) and histiocytes (p less than 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p less than 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p less than 0.05). But for the percentage of lymphocytes, which increased (p less than 0.05), terbutaline was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Remodeling of the airway wall occurs in adults with asthma, and reticular basement membrane (RBM) thickening is pathognomonic of the asthma process. To investigate whether RBM thickening is present in children with difficult asthma and comparable to that seen in adults with asthma, we used light microscopy to measure RBM thickness in plastic-embedded endobronchial biopsy sections from 19 children with difficult asthma who were prescribed 1,600 microg/day or more of inhaled steroids (age range, 6-16 years), 10 children without asthma (7-16 years), and three adult groups: 8 healthy control subjects (21-42 years), 10 mild steroid-naive subjects with asthma (18-41 years), and 6 adults (3 steroid naive and 3 on inhaled steroids) intubated after a life-threatening attack of asthma (20-64 years). RBM thickness in the children with asthma was similar to that in adults with either mild or life-threatening asthma (median 8.2 [range 5.4-11.1] versus 8.1 [5.8-10.0] and 7.2 [2.8-10.0] microm, respectively) and greater than either adult or pediatric control subjects (8.2 [5.4-11.1] versus 4.4 [3.2-6.3] microm, p < 0.01, and 4.9 [3.7-8.3] microm, p < 0.01). We conclude that RBM thickening is already present in children with difficult asthma and to a similar extent to that seen in adults with asthma. In addition, we find no association with age, symptom duration, lung function, or concurrent eosinophilic airway inflammation.

No abstract

We undertook a detailed cellular and ultrastructural examination of bronchial biopsies from seven allergic asthmatic patients and 10 nonasthmatic control subjects (five atopic and five nonatopic) to determine the nature of the inflammation that occurs during allergen-induced late-phase responses (LPRs). The asthmatic subjects had mild asthma (FEV1 = 94 +/- 9% predicted; mean +/- SEM) and required only intermittent use of beta 2-agonists. Airway mucosal biopsy specimens were obtained on a single occasion from the nonasthmatic controls and on two occasions from the asthmatic subjects, at 24 h after diluent challenge and 24 h after challenge with allergen 3 wk later. The mean maximal decrease in FEV1 during the late response after allergen challenge was 30%, and that after administration of diluent was 4%. In coded plastic sections, subepithelial cells were counted with both light and electron microscopy, and the numbers present were expressed per 0.1 mm2 of tissue. Light microscopy revealed statistically significant increases in the total number of inflammatory cells (P < 0.02) and in "activated fibroblasts" after allergen challenge (P < 0.05). Electron microscopy showed significant increases after allergen challenge in the total number of eosinophils (P < 0.05) and cells with the ultrastructural features of myofibroblasts. The latter cells constituted 1.5% of cells after administration of diluent, and this increased to 15.5% after allergen challenge (P < 0.05). Mast cells were significantly more abundant in the atopic nonasthmatic controls than in the asthmatic subjects after allergen challenge. The study demonstrates that the profile of inflammatory cells in asthma at 24 h after allergen challenge is distinct from that in stable asthma and in nonasthmatic controls, and that migratory cells with a contractile phenotype appear in greater numbers in the late response. We propose that subjects who repeatedly develop a late response have increased numbers of migrating, contractile cells that may contribute to formation of the increased bronchial smooth-muscle mass observed in fatal asthma.