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.

No abstract

We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a doubleblind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Thl-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance. (J. Clin. Invest. 1993. 92:644-651.)

Immunotherapy is effective in patients with severe summer hay fever, but immediate anaphylactic reactions limit its use to specialised centres. Patient selection is extremely important, and chronic perennial asthma should be specifically excluded. As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary.