The use of β₂ agonists for the control of symptoms is central to the treatment of patients with asthma. However, there is controversy surrounding the regular use of this drug class as numerous studies have demonstrated a variety of changes that can be considered unwanted attributes, particularly when these drugs are used regularly as monotherapy. These include increased bronchial hyper-responsiveness (BHR) to inhaled contractile agents1 and an increase in the allergen-induced early2 and late asthmatic response3 following regular treatment with short-acting β₂ agonists (SABAs). Furthermore, a number of studies have suggested that regular treatment with inhaled SABAs and long-acting β₂ agonists (LABAs) by inhalation leads to a loss of bronchoprotection4 5 and with salmeterol treatment an excess mortality in patients with asthma,6 a trend also observed with regular treatment with formoterol.7 This has led the Food and Drug Administration (FDA) to post black-box warnings on all medicines containing these LABAs.

Christian Virchow and colleagues from Rostock have provided data (see page 763) on a potential mechanism as to how regular treatment with salmeterol can paradoxically increase BHR. …