Sputum eosinophilia is more closely associated with airway responsiveness to bradykinin than methacholine in asthma.

Abstract

Hyperresponsiveness of the airways to various spasmogenic stimuli is a characteristic feature of bronchial asthma. However, the association between the different stimuli to which asthmatic airways are hyperresponsive and airways inflammation is not completely understood. We have investigated the relationship between airway inflammation and airway hyperresponsiveness in asthma, as assessed by bronchoprovocation tests to methacholine and bradykinin, two well defined bronchoconstrictor agonists. Sputum induction by hypertonic saline and methacholine and bradykinin challenges were performed in 14 nonsmoking subjects with mild-to-moderate asthma. Airway responsiveness to either agonist did not correlate with sputum neutrophils, lymphocytes, and macrophages. Whilst the absolute number of eosinophilia failed to be significantly related to methacholine responsiveness (r=-0.47; p=0.09), it correlated markedly and significantly with provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (r=0.72; p<0.01). When expressed as % of total cell counts, sputum eosinophils correlated with both types of responsiveness (r=-056; p=0.04 and r=-0.76, p<0.001, respectively). Although the concentration of eosinophil cationic protein (ECP) in the sputum correlated with the absolute numbers of eosinophils (r=0.62; p<0.02), no correlation was found between ECP levels and the airway responsiveness to any of the agonists tested. In subjects with mild-to-moderate asthma, airway responsiveness to bradykinin is more strongly associated with the magnitude of eosinophilic inflammation in the airways than methacholine. This finding underlines the selectivity of diverse agonists in assessing airway hyperresponsiveness and cellular inflammation in asthma.