A Novel in vivo System to Test Bronchodilators

Abstract

The incidence and severity of asthma continue to rise worldwide. β-agonists are the most commonly prescribed therapeutic for asthma management but have less efficacy for some subsets of asthmatic patients and there are concerns surrounding the side effects from their long-term persistent use. The demand to develop novel asthma therapeutics highlights the need for a standardized approach to effectively screen and test potential bronchoprotective compounds using relevant in vivo animal models. Here we describe a validated method of testing potential therapeutic compounds for their fast-acting efficacy during the midst of an induced bronchoconstriction in a house dust mite challenged animal model.

Keywords: Asthma; Bronchodilators; in vivo.

Figure 1

A) Mice were challenged with HDM on days 0, 7 and 14. On day 16, all HDM challenged mice were divided into two groups B): Control group (left panel); nebulized with saline, and Albuterol group (right panel); nebulized with Albuterol Sulfate (0.083% in saline). C) Immediately after, both groups received an aerosolized methacholine bronchoconstrictor challenge (10, 30, 100 mg/ml) and lung function was recorded using the forced oscillation technique. Arrows indicated when saline or albuterol and methacholine were administered.

Figure 2

Respiratory mechanics parameters from HDM-sensitized and challenged mice that were either given vehicle (saline-solid line) or albuterol (0.083%–dotted line) immediately before each methacholine challenges. Results are shown as mean ± SEM with n=11–15 mice per group. Statistical significance is shown for each parameter as a comparison between albuterol and saline at the respective challenge. ^*p<0.05, ^**p<0.01.