Analysis of time course and magnitude of lung inflation effects on airway tone: Relation to airway reactivity

Lung inflation transiently reverses methacholine constriction of airways in normal subjects, whereas this capacity is diminished in subjects with airway hyperreactivity. To explore the mechanisms underlying these differences, we examined the magnitude and time course of the effects of lung inflation in subjects with varying degrees of methacholine responsiveness. Ten subjects were defined as nonreactive (NR) and 9 subjects as reactive (R) on the basis of the FEV₁ decrement evoked during graded methacholine challenge. To examine the effects of inflation, plethysmographic specific airway conductance (SGaw) was first measured before and after an inhaled methacholine dose titrated to produce a 60% fall in SGaw. Subjects then inspired maximally to total lung capacity, and SGaw was remeasured 7, 15, 30, 45, and 60 s after inflation. An increase in SGaw was observed at 7 s and, thereafter, it declined nonlinearly with time toward preinflation values. Measured SGaw values after inflation were fitted to a single exponential function (SG(t) = SG(o)e^-(kt)) using a computerized nonlinear least squares method of analysis. The intercept at time t = 0 (SG(o)) represented the hypothetical maximal SGaw at the completion of lung inflation and described the magnitude of the bronchodilator effect. The time constant (L/k) described the time course of these effects. For equivalent SGaw values before and after methacholine, lung inflation produced significantly higher SG(o) values in the NR group (0.254 ± 0.015) than in the R group (0.155 ± 0.009; p < 0.001). In contrast, mean time constant values were the same in the 2 groups (11.8 ± 1.76 s versus 11.7 ± 1.69 s). We conclude that groups with different methacholine reactivity are distinguished on the basis of the magnitude of bronchodilation achieved by lung inflation rather than by the rate at which bronchomotor tone is reestablished.