Comparison of the effects of budesonide/formoterol maintenance and reliever therapy with fluticasone/salmeterol fixed-dose treatment on airway inflammation and small airway impairment in patients who need to step-up from inhaled corticosteroid monotherapy

Pulm Pharmacol Ther. 2014 Apr;27(2):190-6. doi: 10.1016/j.pupt.2013.12.003. Epub 2014 Jan 2.


Background: If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, adding a long-acting β2 agonist (LABA) is the preferred treatment. We aimed to compare the effect of two widely available ICS/LABA combinations in these patients in real-life conditions: budesonide/formoterol (BUD/FM; Symbicort(®)) for maintenance and reliever therapy (SMART) and a fixed dose of fluticasone propionate/salmeterol (FP/SM).

Methods: Inadequately controlled asthma patients treated with a medium dose of ICS alone, with an Asthma Control Questionnaire (ACQ) score >0.75 and using a short-acting β2-agonist (SABA) 2-6 occasions/week, were enrolled. Patients were randomized into two groups and treated with two inhalation twice-daily BUD/FM 160/4.5 μg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation twice-daily FP/SM 250/50 μg plus as-needed procaterol (FP/SM group, n = 15) for 8 weeks.

Results: Both groups showed significant improvement in airway inflammation, pulmonary functions and symptoms from baseline. The SMART group showed significant improvement in the fraction of nitric oxide, ACQ score, rescue medication use and small airway parameter R5-R20 measured by impulse oscillometry compared with the FP/SM group.

Conclusion: For stepping up treatment from ICS alone to an ICS/LABA combination, SMART is preferable for controlling asthma symptoms by suppressing airway inflammation and improving small airway impairment compared with a fixed dose of FP/SM. It may be achieved by the property of BUD/FM itself and as-needed use, but the degree of each contribution must be investigated further.

Keywords: Budesonide/formoterol; Fluticasone propionate/salmeterol; Fractional exhaled nitric oxide; Impulse oscillometry; Small airways; Symbicort maintenance and reliever therapy (SMART).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Androstadienes / therapeutic use*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Budesonide / therapeutic use*
  • Budesonide, Formoterol Fumarate Drug Combination
  • Drug Combinations
  • Ethanolamines / therapeutic use*
  • Female
  • Fluticasone-Salmeterol Drug Combination
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Androstadienes
  • Anti-Asthmatic Agents
  • Budesonide, Formoterol Fumarate Drug Combination
  • Drug Combinations
  • Ethanolamines
  • Fluticasone-Salmeterol Drug Combination
  • Glucocorticoids
  • Nitric Oxide
  • Budesonide
  • Albuterol