RESUMO
The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.
Assuntos
Asma/patologia , Beclometasona/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Membrana Basal/imunologia , Membrana Basal/metabolismo , Membrana Basal/patologia , Biópsia por Agulha , Brônquios/imunologia , Brônquios/metabolismo , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Colágeno/análise , Método Duplo-Cego , Eosinófilos/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Humanos , Masculino , Mastócitos/patologia , Pessoa de Meia-Idade , Subpopulações de Linfócitos TRESUMO
Ten mild atopic asthmatics on inhaled beta 2-agonists alone were studied in order to determine the repeatability of methacholine inhalation provocation tests at 24 h intervals over a period of 5 days. Such patients are most frequently studied in therapeutic trials of anti-asthmatic medications. There were no significant differences in results obtained on any of the days and no evidence for the development of tolerance to methacholine in this group of patients at one day intervals. The 95% confidence interval for repeatability of the results was +/- 1.05 doubling doses of methacholine, and 95% range +/- 2.36 doubling doses, comparable to the results obtained by other investigators on similar patients. Some investigators have produced more highly repeatable results but these have generally been obtained using highly selected groups of patients.
