INCREASES IN AIRWAY EOSINOPHILS AND INTERLEUKIN-5 WITH MINIMAL BRONCHOCONSTRICTION DURING REPEATED LOW-DOSE ALLERGEN CHALLENGE IN ATOPIC ASTHMATICS

Repeated low-dose allergen challenge increases airway hyperresponsiven ess in atopic asthmatics. However, it is not known whether low-dose al lergen challenge increases airway inflammation. Eight atopic asthmatic s mere enrolled in a controlled, cross-over study to evaluate the effe ct and time course of repeated low-dose allergen challenge on airway i nflammation and hyperresponsiveness. The dose of allergen to reduce fo rced expiratory volume in one second (FEV1) by approximately 5% was se lected in a screening allergen challenge, The subjects then were chall enged for five consecutive days with either diluent or the selected lo w-dose of allergen. Methacholine airway hyperresponsiveness (PC20,meth ) was measured and sputum induced on days 1, 3 and 5 of the repeated c hallenge, and then 1 day and 3 days after the last challenge. Repeated low-dose allergen challenge caused small reductions in FEV1, but incr eased airway eosinophils and interleukin (1L)-5, airway hyperresponsiv eness, asthma symptoms and beta(2)-agonist use, all of which peaked on days 3 or 5 of the challenge. The mean (SEM) percentage sputum eosino phils was 21.2 (0.7)% after allergen versus 3.9 (0.1)% after diluent ( p<0.001); percentage EG2+ cells were 13.4 (0.3)% after allergen versus 1.1 (0.04)% after diluent (p<0.01) and geometric mean (GSEM) eosinoph il cationic protein (ECP) was 1061.8 (1.6) mu g.L-1 after allergen ver sus 447.03 (1.2) mu g.L-1 after diluent (p<0.05). Geometric mean (GSEM ) IL-5 was 71.4 (1.4) pg.mL(-1) after allergen versus 18.4 (1.04) pg.m L(-1) after diluent (p<0.01), All the changes had resolved by 3 days a fter the last challenges, The study demonstrated that repeated inhalat ion of a low-dose of allergen causes airway eosinophilia and increases in interleukin-5, associated with airway hyperresponsiveness, and mil d worsening of asthma control, without the development of marked acute bronchoconstriction or the development of late responses.