Provocation dose and discriminant analysis in histamine bronchoprovocation. Are the current predictive data satisfactory?

In 20 normal subjects (N) and 20 asthmatic patients (A) using bronchodilators as needed, the PD40, PD10, PD15, PD20, PD10T, and PD20C were measured (PD being provocation dose, subscript being -% delta in Gaw/VL for PD40, lowest FEV1 for PD20C, and best FEV1 for the remaining PDs; 10T means delta FEV1 greater than -10 percent). For discriminant analysis we used an ad hoc graphic (best case) method, a ceiling method based on highest PD in A and two methods (logistic and linear) which considered PDs in both N and A (PDN and PDA, respectively). The distribution of PDN and PDA had substantial overlap and appeared log normal. The PD15, PD20, and PD20C displayed the smallest mean misclassification error followed by PD10T, PD40, and PD10. The linear and logistic methods produced balanced sensitivity and specificity but, predictably, a misclassification error higher than that of the graphic method. The ceiling method proved unsatisfactory with 100 percent sensitivity but approximately equal to 60 percent specificity. Using linear and logistic methods, the posttest likelihood of asthma could be expressed as a function of its pretest likelihood and level of PD recorded. We concluded that: (1) the most discriminant PDs are PD20, PD15 and PD20c; and (2) new normative data for diagnostic bronchoprovocation are needed, because: (a) when PDA and PDN overlap, the currently used ceiling method leads to a high misclassification rate, while the linear and logistic method based on mathematical model have a better discriminant ability; (b) to separate PDA from PDN and allow the application of the ceiling method, "as-needed bronchodilators" is not a reproducible criterion.