Regular use of beta agonists like inhaled salbutamol doubles a person's sensitivity to an allergen and creates tolerance to the drug, thus reducing its effectiveness.

In a double blind, random trial of 13 mild asthmatics, researchers from the Royal University Hospital at the University of Saskatchewan in Canada found that patients given the salbutamol reacted to far smaller amounts of allergen than did controls. The protective effects of salbutamol were also significantly reduced.

The Canadian researchers believe that this tolerance could be behind the increasingly severe asthma and increased numbers of asthma deaths now being seen in the general population.

In an editorial, John Britton, of the Respiratory Medicine Unit in Nottingham's City Hospital, summarized: "Regular beta agonist therapy rendered the airways of atopic asthmatics more sensitive to the effects of inhaled allergen and less amenable to protection from this adverse effect by further beta agonist therapy."

Both he and the authors conclude that "regular dose regimens are best avoided". He also believes that doctors should re evaluate the use of long acting beta agonists like salmeterol since the sustained action of the drugs "might increase the likelihood of tolerance".

Britton also argues that regular use of inhalers leads to poor control of symptoms and faster decline of lung function, and that patients tend to improve after regular high dose beta agonist therapy is withdrawn.

Another report published the same month analyzing six case control studies of the relation between beta agonist use and death from asthma. The analysis revealed a significant, "although extremely weak" relation between beta agonist use and death from asthma, and appeared to have something to do with the use of a nebulizer.