The use of sequential doses of inhaled histamine in the measurement of bronchial responsiveness: cumulative effect and distortion produced by shortening the test protocol.

We have evaluated a shortened protocol for measuring bronchial responsiveness to histamine. This safely eliminates unnecessarily low doses from a standard doubling dose sequence (i.e., full protocol) so that the dose provoking the definitive 20% decrement in FEV1 (PD20) is usually reached within two or three dose increments. In 20 subjects with asthma tested with both protocols, the ratio of geometric mean PD20 short protocol (86.8 micrograms) to PD20 full protocol (45.7 micrograms) was significantly greater than 1 when the results were expressed on a noncumulative scale (1.90 versus 1; p less than 0.001). When PD20 was expressed on a cumulative scale, the discordance was less striking (123.7 versus 89.2 micrograms, respectively), but this ratio (1.39) was still significantly greater than 1 (p = 0.007). By contrast, duplicated measurements of PD20 with the full protocol and the cumulative scale elicited a ratio of geometric mean PD20 day 1 (63.0 micrograms) to PD20 day 2 (67.0 micrograms) of 0.94, which was not significantly different from 1. Thus, the bronchoconstrictor effect of histamine depends on both the cumulative dose and the number of component doses. We conclude (1) that PD20 histamine is more nearly accurately expressed on a cumulative than on a noncumulative scale and (2) that histamine is less suitable for shortened protocols than methacholine because a reduction in the number of component doses produces significant distortion of the PD20 result.