Influence of low temperature on bronchodilatation induced by terbutaline administered by metered dose or dry powder inhalers in asthmatics

Low temperatures may affect dose delivery efficacy and clinical effectivene ss of medication aerosols. In this study we examine the effect of cold ambi ent temperature on the bronchodilatation produced by terbutaline delivered from a chlorofluorocarbon pressurized metered dose inhaler (pMDI) compared to a multi-dose dry powder inhaler (DPI). Fourteen stable asthmatics were s tudied on two consecutive days. On day 1, after measuring FEV, at room temp erature (22 degrees C), each patient was randomized to receive 500 mu g of terbutaline delivered from pMDI or DPI stored for 24 h at 22 degrees C with FEV1 recorded 20 min post-dose; then, patients were placed in a chamber at - 10 degrees C, and after obtaining FEV1, each patient received 500 mu g o f terbutaline delivered from pMDI or DPI (same formulation as previously ad ministered) stored for 24 h at - 10 degrees C, and FEV1 was obtained 20 min post-dose. On day 2, a similar protocol was followed but each patient rece ived terbutaline as the alternative to the formulation administered on day 1. Pairwise comparisons of the FEV1 (% predicted) values obtained on day 1 and day 2 at 22 degrees C and - 10 degrees C (pre-dose) showed no significa nt differences. Similar bronchodilatations were observed for terbutaline DP I administration at 22 degrees C and - 10 degrees C (24.85 +/- 11.72 and 20 .08 +/- 6.27 % increase of FEV1; P > 0.05). By contrast, the bronchodilatat ion obtained for terbutaline pMDI at 22 degrees C (21.07 +/- 8.55 % increas e in FEV1) was not reproduced at - 10 degrees C (0.72 +/- 2.84 %; P < 0.05 from 22 degrees C). In five asthmatics a cumulative dose-response curve for terbutaline pMDI was obtained. This part of the study showed that a higher dose of terbutaline pMDI was necessary at - 10 degrees C to obtain a bronc hodilator response (10.04 +/- 6.75 % increase of FEV1 after 2 000 mu g) tha t remained lower than the bronchodilatation for 500 mu g terbutaline pMDI a t -10 degrees C. In conclusion, the clinical effectiveness of terbutaline d elivered from chlorofluorocarbon pMDIs is compromised by cold storage while DPIs are not affected. (C) 2000 Editions scientifiques et medicales Elsevi er SAS.