THE USE OF CRITERIA FOR REVERSIBILITY AND OBSTRUCTION TO DEFINE PATIENT GROUPS FOR BRONCHODILATOR TRIALS - INFLUENCE OF CLINICAL-DIAGNOSIS, SPIROMETRIC, AND ANTHROPOMETRIC VARIABLES

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Abstract
Multiple criteria for obstruction and reversibility are being used at present to define patient populations for bronchodilator studies. In order to establish whether the use of different criteria would result in variation in results, we evaluated 4 criteria for obstruction and found that the outcome of a bronchodilator trial, mean response, will depend on the definition of obstruction used. The obstruction criteria evaluated were: (1) FEV < lower 95% confidence limit (CL) of predicted, (2) FEV1/FVC% < lower 95% CL, (3) FEV1 between 500 and 1,500 ml, and (4) FEV1 < 60% of predicted. Patients selected by criterion (1) had 8.9% FEV1 response, whereas those selected by criterion (3) had 14% FEV1 response. This difference resulted mostly from the difference in the degree of obstruction among the groups as well as the effect of regression to the mean compounded by calculating the results as percent of baseline. Also, it appears the use of obstruction criteria based on the absolute value of the FEV1 or on predicted FEV1 may create an age and height bias for bronchodilator response, this being of minimal clinical importance, though. Finally, we found that the conventional reversibility criterion: 15% improvement of the initial FEV1, could be misleading. This criterion could not be used to define disease, and when it was applied to a patient population it resulted in the selection of the most obstructed subjects, which is a contradiction of the very definition of reversibility. The absolute difference of the before and after bronchodilator FEV1 or response as percent of the predicted FEV1 appeared to be more appropriate expressions of reversibility. When comparison of results from one bronchodilator study to another is required, careful attention needs to be paid to the clinical definition of the patient populations, the definitions of obstruction and reversibility, the degree of obstruction present, the method of calculating bronchodilator response, and possibly also age and height.