Is there a problem with inhaled long-acting β-adrenergic agonists?

The absolute response to albuterol before and after 28 days of treatment with either 42 μg of salmeterol (SAL) twice daily (upper panel) or placebo (PBO; lower panel) in a crossover study with 20 subjects not using (No ICS) and 20 subjects using (ICS) inhaled corticosteroids. Reprinted with permission from Nelson et al.⁵⁷

The effect of β-adrenergic receptor genotypes on morning PEF during 6 months of treatment with placebo, albuterol 4 times daily, or salmeterol twice daily. Whereas the trend is for morning PEF to be lower in the Arg:Arg-16 subjects while receiving regular albuterol, 400 μg twice daily, these same subjects tended to have higher morning PEFs while receiving salmeterol, 50 μg twice daily. Similar differences were observed in the rate of asthma exacerbations. Reprinted from Taylor et al³⁸ with permission from the BMJ Publishing Group.

The effect on the rate of asthma exacerbations of 2 doses of budesonide (BUD) with or without the addition of formoterol (F) in patients previously treated with low doses of inhaled corticosteroids. Reprinted with permission from O'Byrne et al.⁴⁴

Onset and recovery from asthma exacerbations in patients receiving 88 μg of fluticasone twice daily plus salmeterol twice daily or receiving 220 μg of fluticasone twice daily. At the time the exacerbation was diagnosed, the subjects were started on prednisone. The improvement was faster in subjects receiving low-dose fluticasone plus salmeterol than in those receiving the higher dose of fluticasone alone. The differences were statistically significant at several time points, as indicated by asterisks. Reprinted with permission from Matz et al.⁸⁹