The Appearance of Hypodense Eosinophils in Antigen-dependent Late Phase Asthma

Abstract

Although peripheral blood eosinophils (EOS) of low density are increased in patients with asthma, the mechanisms contributing to their presence are not well established. The following study evaluated the effect of an antigen bronchoprovocation (BP) on the percentage of circulating hypodense eosinophils (HE) in asthma. EOS density was measured by centrifugation of peripheral blood granulocytes over multiple discontinuous density Percoll gradients in samples taken immediately before and 24 h after antigen BP. We found that the percentage of peripheral blood HE (density < 1.095 g/ml) increased significantly (p < 0.02) over baseline values (78.9 .+-. 4.8% versus 53.3 .+-. 8.2%, mean .+-. SEM, n = 11) when evaluated 24 h after antigen BP but only in patients who experienced both an immediate (IAR) and late phase asthma reaction (LAR). No siginficant change in the percentage of HE was observed in asthma subjects who had only an early asthma response to inhaled antigen (n = 6). In an expanded population of allergic asthmatics (n = 38), a significant correlation was found between the percent peripheral blood HE and disease severity as represented by the percent predicted FEV1 (r = -0.56, p = 0.003). These data sugget that in vivo activation of asthma by inhaled antigen increases the proportion of peripheral blood EOS that are hypodense but only in those patients with both an IAR and LAR. Furthermore, we also conclude that the percentage of HE better reflects the severity of asthma than the concentration of total peripheral blood eosinophils. Because the HE may be metabolically more active and proinflammatory than its normal dense counterpart, we have speculated that the HE may be an important participant in the cascade of events causing LARs and possibly asthma severity.