Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role of sensory nerves

Abstract Background : It has recently been suggested that regular treatment with racemic β 2 -adrenoceptor agonists might result in bronchial hyperresponsiveness (BHR) to a range of spasmogens, and this might be due to adverse effects of the distomer. Objective : We sought to determine whether BHR induced by means of continuous exposure to racemic and S-albuterol was mediated by sensory nerves. Methods : Naive or ovalbumin-sensitized guinea pigs were treated for 10 days with RS-, R-, or S-albuterol (1 mg·kg −1 ·d −1 ) through subcutaneously implanted minipumps. Lung function was then determined in response to a number of spasmogens and assessed on the basis of an increase in total airway resistance. A separate group of animals were chronically treated with capsaicin (80 mg/kg) before the albuterol treatment. Results : Treatment with RS- or S-albuterol increased airway responsiveness to bradykinin, leukotriene C 4 , and capsaicin in naive guinea pigs ( P P Conclusion : We have provided evidence demonstrating that continuous exposure to RS- and S-albuterol increases bronchial responsiveness to a range of stimuli, an effect not attributed to β-adrenoceptor occupancy or desensitization. Furthermore, capsaicin-sensitive sensory nerves mediate the development of BHR, at least in part. (J Allergy Clin Immunol 2002;110:388-94.)