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

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.