The determinants of airway hyperresponsiveness to hypertonic saline in atopic asthma in vivo. Relationship with sub-populations of peripheral blood leucocytes

In patients with asthma there is only a weak relationship between airway responsiveness to hypertonic saline and methacholine. We tested the hypothesis that airway responsiveness to hypertonic saline in asthma is related to the presence and activity of inflammatory cells in the peripheral blood. Nineteen atopic asthmatic adults (19-28 yr; PC20 0.06-12.4 mg/ml), not receiving steroid treatment, entered a metacholine and hypertonic saline period in random order. Dose-response curves to doubling doses of inhaled methacholine (0.03-256 mg/ml) or hypertonic saline (0.9-14.4% NaCl) were obtained twice in each period, 7 days apart. The response was measured by FEV1. Methacholine responsiveness was measured by PC20 METH of FEV1 and responsiveness to hypertonic saline was expressed as the percentage fall in FEV1 after 14.4% NaCl (HYP14.4%). Peripheral blood was collected before the second challenge test of each period. Apart from leucocyte counts and serum eosinophilic cationic protein (ECP) level, sub-sets of lymphocytes (CD4+/CD3+, CD8+/CD3+, CD25+/CD4+ and VLA-1+/CD4+) were determined using flow cytometry. HYP14.4% was positively correlated to basophil, eosinophil and monocyte counts (r = 0.64, 0.54 and 0.44, respectively; P <0.05). The basophil count remained positively related to HYP14.4% when PC20METH or FEV1%pred were entered in multiple linear regression analyses (r = 0.66 and 0.75, respectively; P <0.05). There were no significant relationships between HYP14.4% or PC20METH on one side and ECP level or T-lymphocyte subsets on the other (P > 0.05). We conclude that airway responsiveness to hypertonic saline is positively related to the number of peripheral blood basophils, eosinophils and monocytes. Basophil count is an independent correlate of responsiveness to hypertonic saline, after correction for methacholine responsiveness and baseline lung function. This fits in with active involvement of basophils in airway narrowing to hypertonic saline in vivo