Cellular and soluble mediators of mucosal inflammation in branchial asthma

The pathological evidence of airways inflammation in asthma has come mainly from studies of asthma deaths and a limited number of studies employing rigid bronchoscopy. I have used fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy to study the role of inflammatory cells in the airways of living asthmatics in relation to the presence of atopy, exposure to allergen leading to natural disease exacerbation, and treatment with inhaled corticosteroids. I have found that bronchoscopy is a safe and generally well tolerated procedure and does not affect airways responsiveness, but may result in a significant immediate reduction in lung function in asthmatics which is related to the level of airways responsiveness. Although arterial haemoglobin oxygen saturation was on average only slightly reduced, in some asthmatics this was more pronounced. My observations suggest that caution is needed when performing bronchoscopy in those asthmatics with very responsive airways and that oximetry is a necessary form of monitoring in these studies. Using immunohistochemistry on endobronchial biopsy samples of atopic asthmatics, atopic nonasthmatics and nonatopic controls, I have found that mast cell numbers in the mucosa are similar in all the groups. Eosinophil numbers were highest in the asthmatics, intermediate in atopic nonasthmatics, and very low in the nonatopic controls, suggesting that bronchial eosinophilia is a general feature of atopy. In both the asthmatics and atopic nonasthmatics both cells were seen by electron microscopy to have features of degranulation, suggesting heightened activation. Analysis of bronchial biopsies by electronmicroscopy showed that the amount of collagen deposited beneath the basement membrane was thickest in atopic asthmatics, intermediate in atopic nonasthmatics, and thinnest in nonatopic controls. This study suggests that atopy is a risk factor for mucosal inflammation in the lower airways, and that the degree of inflammatory changes may determine its clinical expression.