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

Abstract— Low temperatures may affect dose delivery efficacy and clinical effectiveness of medication aerosols. In this study we examine the effect of cold ambient temperature on the bronchodilatation produced by terbutaline delivered from a chlorofluorocarbon pressurized metered dose inhaler (pMDl) compared to a multi‐dose dry powder inhaler (DPI). Fourteen stable asthmatics were studied on two consecutive days. On day 1, after measuring FEV1 at room temperature (22 °C), each patient was randomized to receive 500 μg of terbutaline delivered from pMDI or DPI stored for 24 h at 22 °C with FEV1 recorded 20 min post‐dose; then, patients were placed in a chamber at − 10 °C, and after obtaining FEV1, each patient received 500 μg of terbutaline delivered from pMDI or DPI (same formulation as previously administered) stored for 24 h at − 10 °C, and FEV1 was obtained 20 min post‐dose. On day 2, a similar protocol was followed but each patient received 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 °C and − 10 °C (pre‐dose) showed no significant differences. Similar bronchodilatations were observed for terbutaline DPI administration at 22 °C and − 10 °C (24.85 ± 11.72 and 20.08 ± 6.27 % increase of FEV1; P>0.05). By contrast, the bronchodilatation obtained for terbutaline pMDI at 22 °C (21.07 ± 8.55% increase in FEV1) was not reproduced at − 10 °C (0.72 ± 2.84%; P < 0.05 from 22 °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 °C to obtain a bronchodilator response (10.04 ± 6.75% increase of FEV1 after 2 000 μg) that remained lower than the bronchodilatation for 500 μg terbutaline pMDI at − 10 °C. In conclusion, the clinical effectiveness of terbutaline delivered from chlorofluorocarbon pMDIs is compromised by cold storage while DPIs are not affected.