PERCEPTION OF BRONCHIAL OBSTRUCTION IN ASTHMATIC-PATIENTS - RELATIONSHIP WITH BRONCHIAL EOSINOPHILIC INFLAMMATION AND EPITHELIAL DAMAGE AND EFFECT OF CORTICOSTEROID TREATMENT

We studied the perception of bronchoconstriction in asthmatic subjects who were randomly treated with inhaled pt agonist given either alone (n = 9) or associated with inhaled corticosteroids (n = 9). Methacholine and bradykinin challenges, bronchoalveolar lavage, and bronchial biopsies were performed in all subjects. After each dose of agonist, breathlessness was assessed using a visual analog scale (VAS) and the forced expiratory volume in 1 s (FEV(1)) was measured. The relationship between VAS scores and FEV(1) and the slope of the regression line of VAS scores on the corresponding FEV(1) (VAS/FEV(1) slope) were analyzed for each agonist. Subjects without corticosteroids had good perception of methacholine but poor perception of bradykinin-induced bronchoconstriction. In subjects with corticosteroids, bronchoconstriction was well perceived whatever the agonist. VAS/FEV(1) slopes for bradgkinin but not for methacholine correlated negatively with the magnitude of eosinophilic inflammation in airway mucosa. VAS/FEV(1) slopes for each agonist correlated positively with the percentage of basement membrane covered by airway epithelium. We conclude that in asthmatic patients perception of bronchoconstriction is related to eosinophilic inflammation and to epithelial damage in airways and that corticosteroid treatment is associated with improved perception of bronchoconstriction induced by bradykinin, a mediator endogenously produced in asthma.