LAUSR

Introduction: Cough is an essential defensive reflex, however excessive/chronic cough is a problematic symptom of respiratory diseases. We have previously shown that inhaled LABA can attenuate cough responses by suppressing airway sensory nerves. As LABAs are commonly prescribed to asthmatic patients where coughing persists, we hypothesised that this beneficial property may be lost due to tachyphylaxis as seen in airway smooth muscle (ASM) (Finney et al, BJP, 2001). Methods: Guinea pigs were treated with inhaled vehicle/formoterol (3μg/ml, 10 min) b.i.d. for 7 days. On day 8 inhaled vehicle/formoterol was administered 1h prior to assessments. Formoterol ASM relaxation was assessed on tracheal segments. Formoterol anti-tussive activity was assessed on capsaicin-evoked cough in vivo, & capsaicin-induced vagus nerve depolarisation in vitro. Results: Formoterol relaxation of ASM was reduced in tissues from animals chronically dosed with LABA, indicating tachyphylaxis of the β2-adrenoreceptor (β2A) (Fig. 1a). Formoterol inhibition of cough and sensory nerve activation was not altered (Fig.1b/c), suggesting β2A on nerves was not desensitised. Conclusions: As reported by others in pre-clinical systems & observed clinically, prolonged LABA dosing can lead to β2A tachyphylaxis on ASM and reduced bronchodilator effectiveness. In this study, it appeared that the impact of LABAs on airway sensory nerves was not altered by chronic treatment.