Bronchial hyperreactivity is correlated with increased baseline airway tone

Abstract

Physiologically, airways are not completely relaxed but maintain a baseline airway tone (BAT). Although not fulfilling the criteria for obstructive airway disease, increased BAT may nevertheless be important because the same amount of airway narrowing can be well tolerated or can cause severe airway obstruction depending on the starting point of the narrowing. In this study, we aimed at studying if BAT is correlated with bronchial hyperreactivity (BHR). For in vitro studies, airways in murine lung slices were digitally recorded and the change in cross-sectional area with time was quantified. BAT was measured by the amount of relaxation induced by permeabilization of the cell membrane with beta-escin in zero external calcium. BHR was induced by incubation of lung slices with interleukin-13 (IL-13). T-bet knock-out mice served as an additional model for BHR. T-bet knock-out mice show a shift towards TH2-lymphocytes and display histological as well as functional characteristics of asthma. In vivo, the specific airway resistance of healthy non-smoking volunteers was assessed before and after inhalation of formoterol and bronchial challenge was performed using methacholin. In murine lung slices that had been cultivated without serum, only a minimal BAT could be observed. But, after cultivation with 10 % new born calve serum, airways showed a BAT of approximately 13 % that could be reduced by incubation with an IL-13 receptor antagonist. Atropine, isoproterenol and indomethacin failed to relax airways regardless of cultivation with serum. Incubation of lung slices without serum but with IL-13 increased BAT as well as airway responsiveness to acetylcholine and both effects were more pronounced in small compared to large airways. In lung slices from T-bet knock-out mice, airways were hyperreactive compared to airways in slices from wild type mice and BAT was found to be increased. Again, both effects were more pronounced in small compared to large airways. In human non-smokers without airway obstruction, increased BAT was correlated with bronchial hyperreactivity. We therefore conclude that although not fulfilling the criteria for obstructive airway disease, increased airway tone may yet be relevant in asthma.