The development of drug tolerance during long-term beta2-agonist bronchodilator therapy.

the beginning, mid-point and end of study values respectively. There is an apparent tendency or trend for the mean values to progressively decline during the study in the Thllffia group, suggesting the development of resistance. However, when these data are subjected to paired t-testing, a statistical manipulation which tends to find signi6cance in even small deviations, statistical s i g d canoe is not shown. I believe it is important that we, as scientists, insist upon statistical signi6cance to msider a hrpothesis proven rather than accepting trends which may be misleading. Moreover, there remains an important distinction between scientific signi6caoce and clinical sigdcance. Even if we had demonstrated statistical signi6cance. I doubt that a loss of responsiveness by only a few milliliters of FEV, is signi6cant to the health of the patient. The ephedrine group showed a greater variance. The super6cial trend is hyporesponsiveness at six weeks with a tendency for improved nqonsiveners at three month. The only statistically sigdcant points on this graph are the six-week values at four, five and six hours (P < .05). With ephedrine, the magnitude of the merences in means suggests the possibility of clinical significance. If one considers only the best FEV, achieved on test days at the end and beginning of the study, 18 subjects had a lower FEV, and ten a higher FEV,. Possibly some patients develop tolerance, and others do not. Figure 2 represents our study in progress with at present only h e subjects in each group. The total duration of this study is six weeks rather than three months, and Tbllffia is compared to terbutaline. With such small numbers of patients in this preliminary examination of the data, I am hesitant to make any interpretations except perhaps that both Thllffia and terbutaline retain an apparent bronchodilator action of unspecified degree after six weeh of continuous administration three or four times daily. In summary, our studies largely hint at the develop ment of mild tolerance to beta agonists which is likely of little consequence in practical patient management.