Bronchodilator Testing “Confidence Intervals” Based on the Level of Bronchial Responsiveness

Abstract

"Confidence intervals" based upon inhalation of placebo have been proposed as criteria for defining a significant response to an inhaled bronchodilator. The published intervals were derived from a clinically heterogeneous population. We calculated the difference (delta) between spirometric data before and after placebo in 109 consecutive patients referred for methacholine bronchoprovocation challenge testing. The mean delta, expressed both as a percent change and as actual volume change for both the FVC and FEV1, was not significantly different in patients with bronchial hyperresponsiveness, as compared to subjects with a negative methacholine challenge test; however, the variance of measurements in hyperresponsive subjects was significantly greater than that of the normal population. In addition, as the category of responsiveness increased from mild to moderate to severe hyperresponsiveness, so did the variance within these groups. A negative correlation between the measured PC20FEV1 and the volume and percent change was noted. We conclude that patients with hyperresponsive airways may display increased spirometric variation before and after placebo. This general approach for establishing normal limits for defining a significant response appears to be valid, but the actual values used may vary, depending on the composition of the population tested and the goals of the study. Also, the use of the term, "confidence intervals," in this context is inappropriate; and we propose, instead, the use of percentiles and the simpler terms, upper 90th or 95th percentiles.