Physiologic factors affecting the discriminant ability of provocation doses to histamine

The discriminant ability of six provocation doses of histamine, PD10, PD15, PD20, PD10T, PD20C, and PD40 has been reported. The subscript connotes -%delta SGaw (PD40), -%delta FEV1 > or = 10% (PD10T), -%delta measured with the lowest (PD20C) or the best FEV1 (PD10, PD15). To explain the differing discriminant ability of the six provocation doses (PD20 = PD15 > PD10T = PD40 > PD20C > PD10), this study analyzed the role of % delta/variability, log dose-response curve, airway hysteresis and the test itself in the original group of 20 normal and 20 asthmatic subjects. For provocation doses measured with the best FEV1, the discriminant ability was related to the ratio %delta/variability and the frequency with which various provocation doses were located on the steep portion of the log dose-response curve; these two parameters and the steepness of the latter were similar in normal and asthmatic subjects. The low discriminant ability of PD20C did not depend on %delta/variability or steepness of the log dose-response curve but on its high rate of false positive results. The lower discriminant ability of PD40 than PD20 or PD15 could not be related to any of the factors analyzed. In conclusion, the factors influencing the calculation of provocation doses affect differently the discriminant ability of these endpoints: (1) %delta/variability and steepness of log dose-response curve influence the provocation doses based on best FEV1. (2) Airway hysteresis reduced the proportion of normals with asthmatic provocation doses, increasing the rate of false positive results with PD20C, based on the smallest FEV1. (3) The nature of the tes, SGaw versus FEV1, affects the discriminant ability of PD40 in a still obscure way.