Distribution of immunocompetent cells in the bronchial wall of clinically healthy subjects showing bronchial hyperresponsiveness.

C Power, S Sreenan, B Hurson, C Burke, L W Poulter

Department of Respiratory Medicine, James Connolly Memorial Hospital, Dublin.

BACKGROUND--Nearly all asthmatic subjects show bronchial hyperresponsiveness, in that the provocative concentration of histamine reducing forced expiratory volume in one second (FEV1) by 20% (PC20FEV1) is < or = 8 mg/ml histamine, and have underlying chronic inflammation of the bronchial wall mediated by T cells. The possible cause and effect relationship between these phenomena remains an enigma. As a proportion of clinically healthy subjects show bronchial hyperresponsiveness, this study was undertaken to determine whether they also show evidence of bronchial inflammation. METHODS--Bronchial biopsy specimens were obtained from 27 clinically healthy subjects with no history of lung disease. Samples were taken perioperatively before elective knee arthroscopy for sports injuries. Specimens were frozen and cryostat sections analysed immunocytochemically with monoclonal antibodies to identify the presence of T lymphocytes, antigen presenting cells, and the expression of HLA-DR. Double immunofluorescence studies were performed with monoclonal antibodies RFD1 and RFD7 to show the relative proportions of RFD1+ RFD7- antigen presenting cells, RFD1- RFD7+ mature phagocytes, and RFD1+ RFD7+ suppressor macrophages. Histological stains were performed to show the presence of eosinophils and mast cells. Three to four weeks after bronchoscopy spirometry was performed on these subjects to record FEV1, forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75). Bronchial hyperreactivity was recorded by determining PC20FEV1 to histamine. RESULTS--Nine of the 27 subjects showed bronchial hyperresponsiveness as defined by a PC20FEV1 of < or = 8 mg/ml histamine. Segregated subjects with and without bronchial hyperresponsiveness showed no difference in spirometric results. Immunohistological analysis showed no evidence of inflammation in either group. Numbers of T cells, eosinophils, and mast cells were the same in both groups as was the expression of HLA-DR antigen. No neutrophils were observed in any tissues. Interestingly, reduced numbers of macrophages with the phenotype of antigen presenting cells (monoclonal antibodies RFD1+ RFD7-) were recorded in the subjects with bronchial hyperresponsiveness, who also had a significant increase in the proportion of RFD1+ RFD7+ suppressor macrophages. CONCLUSIONS--Up to 30% of selected clinically healthy subjects may have a PC20FEV1 of < or = 8 mg/ml histamine. This physiological trait can exist in the absence of bronchial inflammation. This suggests that bronchial hyperresponsiveness as currently defined is not dependent on immunopathological changes in the bronchial wall and does not necessarily promote even subclinical inflammation.

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