The relationship between bronchial immunopathology and hyperresponsiveness in asthma.
Physiological and Immunopathological parameters were investigated in 15 patients with diagnosed asthma, and 6 non-asthmatics presenting with other chest symptoms. The 15 symptom-free asthmatics expressed bronchohyperresponsiveness with a mean provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of 1 mg histamine. None of the non-asthmatics responded to 16 mg histamine. Twenty four hours later bronchoscopy was performed and endobronchial biopsies were obtained. Histological staining of frozen biopsy sections revealed a mononuclear cell infiltrate in all 15 asthmatics, while only 1 of the 6 non-asthmatics showed mild inflammation. Monoclonal antibodies were used to identify subsets of lymphocytes, activation markers, macrophages, and HLA-DR expression within the peribronchial infiltrates. In all samples, activated T-cells and macrophages were identified and HLA-DR expression was found to be raised, but the CD4: CD8 ratio was highly variable. No clear relationship was found between cellular distribution and measured lung function parameters. A highly significant correlation was found between the level of HLA-DR expression on the infiltrating cells (quantified microdensitometrically) and bronchial hyperresponsiveness. These results show for the first time that a chronic T-cell-mediated immune response is present in the bronchial tissue of asymptomatic asthmatics, and that the HLA-DR expression promoted correlates with the hyperresponsive status. These data promote the hypothesis that a T-cell-mediated response contributes to a predisposition to bronchial hyperresponsiveness in asthmatics.
Poulter
L W
LW
Dept of Immunology, Royal Free Hospital Medical School, London, UK.
Power
C
C
Burke
C
C
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006632:Histamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D006632:Histamine