Little is known of the structural changes in mild asthma. We have studied the light and electron microscopic structure of lobar bronchial biopsies taken at fiberoptic bronchoscopy from 11 atopic asthmatics, four of whom were symptomatic and seven of whom were asymptomatic. The former and three of the latter had bronchial hyperresponsiveness to methacholine (PC20 less than 4 mg/ml). Quantitative comparisons were made with biopsies from ten control subjects with normal airway reactivity; five had hay fever and five were nonatopic healthy volunteers. Complete absence of surface epithelium was found in three cases of symptomatic asthma, and stratified squamous epithelium was present in the fourth. A biopsy from one of the healthy control subjects had also lost its surface epithelium. The degree of epithelial loss in all subjects correlated with the degree of airway reactivity (rs = 0.67, p less than 0.001). The reticular lamina of the epithelial basement membrane showed a trend toward thickening in the seven hyperreactive asthmatics (p less than 0.001: median test). There was a tendency to high numbers of inflammatory cells in the lamina propria, but not in the submucosa, of asthmatics, but the differences between groups did not achieve statistical significance. There were significant alterations (px2 less than 0.001) in the proportions of each type of inflammatory cell found in the lamina propria and submucosa of symptomatic asthmatics: an increase of irregularly shaped lymphocytes contributed most to the observed alteration. Where surface epithelium was present, intraepithelial lymphocytes formed the major proportion of intraepithelial "migratory" cells: 64% in normal control subjects, 78% in subjects with hay fever, and 87% in asymptomatic asthmatics.(ABSTRACT TRUNCATED AT 250 WORDS)

We have performed bronchoalveolar lavage (BAL) on 17 subjects with mild atopic asthma (9 symptomatic, 8 asymptomatic) and 14 nonasthmatic control subjects (6 hay fever, 8 nonatopic). There was a significant increase in the percentage of mast cells in both groups of asthmatics although the counts were no different from those previously reported for a number of other respiratory diseases. Asthmatics with airway hyperreactivity (PC20 less than 4 mg/ml) had significant increases in spontaneous histamine release. There was a significant elevation in the eosinophil count and the concentration of major basic protein (MBP) in BAL fluid in the symptomatic asthmatics. Furthermore, there was a significant correlation between the amounts of MBP recovered and the percentage of eosinophils in the BAL. These changes were even more marked when asthmatics with airway hyperreactivity were compared with subjects with normoreactive airways. In addition, there was a significant increase in the percentage of epithelial cells in the hyperreactive asthmatics. There was an inverse correlation between the PC20 and the percentage of mast cells (p less than 0.01), eosinophils (p less than 0.05), and epithelial cells (p less than 0.05) and amount of MBP in BAL (p less than 0.01). This study supports the hypothesis that bronchial hyperresponsiveness is secondary to epithelial cell damage mediated through eosinophil-derived granule products.

We have attempted to identify mRNA for IL-5 in endobronchial mucosal biopsies from asthmatics and controls, using the technique of in situ hybridization. Bronchial biopsies were obtained from 10 asthmatics and 9 nonatopic normal controls. A radio-labeled cRNA probe was prepared from an IL-5 cDNA and hybridized to permeabilized sections. These were washed extensively before processing for autoradiography. An IL-5-producing T cell clone derived from a patient with the hyperIgE syndrome was used as a positive control. As a negative control, sections were also treated with a "sense" IL-5 probe. Specific hybridization signals for IL-5 mRNA were demonstrated within the bronchial mucosa in 6 out ofthe 10 asthmatic subjects. Cells exhibiting hybridization signals were located beneath the epithelial basement membrane. In contrast, there was no hybridization in the control group. No hybridization was observed with the sense probe.The six IL-5 mRNA-positive asthmatics tended to have more severe disease than the negative asthmatics, as assessed by symptoms and lung function, and showed a significant increase in the degree of infiltration of the bronchial mucosa by secreting (EG2+) eosinophils and activated (CD25+) T lymphocytes. Within the subjects who showed positive IL-5 mRNA, there was a correlation between IL-5 mRNA expression and the number of CD25+ and EG2+ cells and total eosinophil count.This study provides evidence for the cellular localization of IL-5 mRNA in the bronchial mucosa of asthmatics and supports the concept that this cytokine regulates eosinophil function in bronchial asthma. (J. Clin. Invest. 1991. 87:1541-1546

Most of the studies linking chronic obstructive pulmonary disease (COPD) with oxidative stress are in vitro, using invasive techniques, or measuring systemic oxidative stress. The aim of this study was to quantify oxidative stress in the lungs in patients with COPD and in healthy smokers, as reflected by 8-isoprostane concentrations in breath condensate. This is a noninvasive method to collect airway secretions. 8-Isoprostane is a prostaglandin-F(2alpha) isomer that is formed in vivo by free radical-catalyzed peroxidation of arachidonic acid. We also studied the acute effect of smoking on exhaled 8-isoprostane in healthy smokers. Exhaled 8-isoprostane was measured by a specific enzyme immunoassay in 10 healthy nonsmokers and 12 smokers, 25 COPD ex-smokers, and 15 COPD current smokers. 8-Isoprostane concentrations were similar in COPD ex-smokers (40 +/- 3.1 pg/ml) and current smokers (45 +/- 3.6 pg/ ml) and were increased about 1.8-fold compared with healthy smokers (24 +/- 2.6 pg/ml, p < 0.001), who had 2.2-fold higher 8-isoprostane than healthy nonsmokers (10.8 +/- 0.8 pg/ml, p < 0.05). Smoking caused an acute increase in exhaled 8-isoprostane by about 50%. Our study shows that free radical production is increased in patients with COPD and that smoking causes an acute increase in oxidative stress.

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