The relationship between mast cell-mediator release and bronchial reactivity in allergic asthma

Abstract

The relationship between mast cell-mediator release and nonspecific bronchial reactivity was investigated in allergen-induced asthma. Two groups of subjects with asthma, one group with markedly reactive airways (provocative concentration of methacholine causing a 20% fall in FEV 1, 0.07 mg/ml) and the other group with less reactive airways (provocative concentration of methacholine causing a 20% fall in FEV 1, 3.83 mg/ml), had allergen bronchoprovocation. After challenge, bronchoconstriction was measured as change in specific airway conductance (SG aw), and mast cell-mediator release was measured as change in both plasma histamine and serum neutrophil chemotactic activity (NCA). In the group with more reactive airways, allergen challenge, while it produced a mean fall in SG aw of 58.1%, was not associated with any significant increase in plasma histamine from a mean resting level of 3.69 nmol/L −1. In contrast, a comparable mean fall in SG aw of 52.4% in the group with less reactive airways was associated with a significant ( p < 0.005) increase in plasma histamine from 1.17 to 3.60 nmol/L −1, maximal 5 minutes after allergen challenge. There were, however, significant increments in serum NCA in both groups with asthma after allergen challenge. The changes in NCA in the group with less reactive airways (136.7 ± 38.1% above baseline; p < 0.01; 1% sera dilution) were significantly greater ( p < 0.05) than changes identified in the group with more reactive airways (68.3% above baseline; p < 0.01; 20% sera dilution). These findings directly support the concept that both mast cell-mediator release and nonspecific bronchial reactivity are separate factors that influence the airway response to inhaled allergen in asthma. In addition, the findings identify that increases in serum NCA after allergen challenge are a more sensitive, although they are less precise, index of intrapulmonary mast cell degranulation than increases in plasma histamine.