Switching from salmeterol/fluticasone to formoterol/budesonide combinations improves peripheral airway/alveolar inflammation in asthma

Pulm Pharmacol Ther. 2014 Feb;27(1):52-6. doi: 10.1016/j.pupt.2013.04.001. Epub 2013 Apr 11.

Abstract

Background: Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in a single inhaler is the mainstay of asthma management. We previously showed that switching from salmeterol/fluticasone combination (SFC) 50/250 μg bid to a fixed-dose formoterol/budesonide combination (FBC) 9/320 μg bid improved asthma control and pulmonary functions, but not fractional exhaled nitric oxide (FeNO), in patients with asthma not adequately controlled under the former treatment regimen.

Objective: To assess whether switching from SFC to FBC improves peripheral airway/alveolar inflammation in asthma (UMIN000009619).

Methods: Subjects included 66 patients with mild to moderate asthma receiving SFC 50/250 μg bid for more than 8 weeks. Patients were randomized into FBC 9/320 μg bid or continued the same dose of SFC for 12 weeks. Asthma Control Questionnaire, 5-item version (ACQ5) score, peak expiratory flow, spirometry, FeNO, alveolar NO concentration (CANO), and maximal NO flux in the conductive airways (J'awNO) were measured.

Results: Sixty-one patients completed the study. The proportion of patients with an improvement in ACQ5 was significantly higher in the FBC group than in the SFC group (51.6% vs 16.7%, respectively, p = 0.003). A significant decrease in CANO was observed in the FBC group (from 8.8 ± 9.2 ppb to 4.0 ± 2.6 ppb; p = 0.007) compared to the SFC group (from 7.4 ± 7.8 ppb to 6.4 ± 5.0 ppb; p = 0.266) although there was no significant difference in the changes in pulmonary functions between the 2 groups. Similar significant differences were found in the CANO corrected for the axial back diffusion of NO (FBC, from 6.5 ± 8.2 ppb to 2.3 ± 2.5 ppb; and SFC, from 4.3 ± 5.3 ppb to 3.9 ± 4.3 ppb). There was no difference in the changes in FeNO or J'awNO between the 2 groups.

Conclusions: Switching therapy from SFC to FBC improves asthma control and peripheral airway/alveolar inflammation even though there is no improvement in pulmonary functions, and FeNO in asthmatic patients.

Keywords: ACQ5; ANOVA; Alveolar nitric oxide; Asthma Control Questionnaire 5-item version; CANO; Exhaled nitric oxide; FBC; FEF50%; FeNO; Formoterol/budesonide; GINA; Global Initiative for Asthma; ICS; J’awNO; LABA; MMADs; Min%Max PEF; PEF; SABA; SFC; Salmeterol/fluticasone; Switching therapy; alveolar NO concentration; analysis of variance; forced expiratory flow at 50% of FVC; formoterol/budesonide combination; fractional exhaled nitric oxide; inhaled corticosteroid; long-acting β2-agonist; lowest PEF expressed as a percentage of the highest PEF; mass median aerodynamic diameters; maximal NO flux in the conductive airways; peak expiratory flow; salmeterol/fluticasone combination; short-acting β2-agonist.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Adult
  • Aged
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Androstadienes / administration & dosage
  • Androstadienes / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use
  • Budesonide / administration & dosage
  • Budesonide / therapeutic use*
  • Drug Combinations
  • Ethanolamines / administration & dosage
  • Ethanolamines / pharmacology*
  • Female
  • Fluticasone-Salmeterol Drug Combination
  • Formoterol Fumarate
  • Humans
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Prospective Studies
  • Pulmonary Alveoli / pathology
  • Severity of Illness Index
  • Spirometry
  • Surveys and Questionnaires
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Androstadienes
  • Bronchodilator Agents
  • Drug Combinations
  • Ethanolamines
  • Fluticasone-Salmeterol Drug Combination
  • Nitric Oxide
  • Budesonide
  • Albuterol
  • Formoterol Fumarate