The phenotypically distinct low-density eosinophil, with its greater inflammatory potential, is increased in asthma. However, the role of hypodense eosinophils in the development of asthma is still unclear. We conducted a double-blind, placebo-controlled study to examine the effect of inhaled corticosteroids on the number of hypodense eosinophils in 27 asthmatic subjects and its relationship with clinical severity. The density profile of eosinophils in the peripheral blood was determined using Percoll density gradient fractionation. Eosinophils recovered from asthmatics were mainly in the lower density fractions (<1.095 g · ml-1) (63 ± 3%; n = 27), significantly different from those of normal subjects (27 ± 2%; n = 7). The proportion of hypodense eosinophils was inversely related to the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) value (r = -0.75). Patients with mild asthma had a lower percentage of hypodense eosinophils (45 ± 4%; n = 14) than those with moderate asthma (67 ± 3%; n = 13). Inhalation of budesonide (800 μg · day-1) (n = 15) for 4 weeks, but not placebo, significantly improved the PC20 values by 0.97 doubling dose, forced expiratory volume in one second (FEV1) % predicted by 17%, and peak expiratory flow rate (PEFR) by 15%, and decreased PEFR diurnal variability by 5.4%. The percentage of hypodense eosinophils was significantly decreased from 68 ± 4 to 47 ± 4% in the budesonide group (n = 15), but not in the placebo group (n = 12) (63 ± 4 to 65 ± 4%). The percentage of lower density eosinophils (1.080-1.085 and 1.085-1.090 g · ml-1) significantly decreased in the budesonide group but not in the placebo group, with a concomitant increase in the highest density (1.095-1.100 g · ml-1). We conclude that hypodense eosinophils are closely related to clinical severity and airway hyperresponsiveness. The clinical efficacy of corticosteroids might be mediated by inhibiting the conversion of eosinophils into hypodense subpopulations.
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