Increased eosinophil cation protein level in sensitized nonasthmatics is linked to subsequent hyperresponsiveness to methacholine - The Odense schoolchild study

Background: Increased levels of eosinophil cation protein (ECP) in sensitized subjects may reflect early stages of an ongoing inflammatory process and therefore precede asthma and bronchial hyperreactivity. Aim: To study whether nonasthmatic subjects with sensitization to allergens and increased ECP levels are at a higher risk for subsequent increased bronchial reactivity compared with sensitized nonasthmatics with normal ECP levels. Methods: A prospective study of 240 schoolchildren with a mean age of 13.9 years (range: 12.6-15.9) who were followed up after 6.3 years. Bronchial reactivity was assessed by methacholine provocation testing. Sensitization was defined by one or more positive reactions (>3 mm wheal) to 10 common aeroallergens by skin prick testing. Increased ECP was defined as values above 20 mu g/l. This separated the subjects into four categories: group 1: healthy controls without sensitization (n = 147); group 2: sensitized subjects with a serum ECP below 20 mu g/l (n = 55); group 3: sensitized subjects with an ECP level at or above 20 mu g/l (n = 16), and group 4: all asthmatics (n = 22). Results: Bronchial reactivity was similar in subjects of groups 2 and 3 at baseline (p = 0.8). Six years later, subjects from group 3 were more responsive to methacholine compared with subjects from group 2 (median: 12.7 versus 20.5 mu mol; p < 0.05). In a logistic regression with hyperresponsiveness to methacholine at follow-up as dependent variable, the odds ratios (OR) for the groups were, with group 1 as reference: group 2: OR = 2.2 (0.8-6.6: p = 0.2), group 3: 5.9 (1.6-21.7: p <0.01). Conclusion: Subjects with sensitization and increased ECP levels are subsequently more airway-responsive to methacholine compared with sensitized subjects with normal ECP levels. This supports the hypothesis that sensitization is linked to increased bronchial reactivity through a process in which markers of inflammation are involved. Copyright (C) 2000 S. Karger AG, Basel.