Potential masking of airway eosinophilic inflammation by combination therapy in asthma

Abstract

Purpose: Long-acting β2 agonists (LABA) may mask ongoing bronchial inflammation, leaving asthmatic patients at greater risk of severe complications. The aim of this study was to compare the effect of combination therapy using low-dose inhaled corticosteroids (ICS) plus LABA on airway inflammation in asthma to the effect of medium-dose ICS alone.

Methods: Twenty-four patients with asthma not controlled by low-dose (400 µg per day) budesonide alone were enrolled in this prospective crossover study. Patients were randomized into 2 treatment phases: one receiving medium-dose (800 µg per day) budesonide (ICS phase), and the other receiving a combination therapy of low-dose budesonide/formoterol (360 µg/9 µg per day) delivered by a single inhaler (LABA phase). Each treatment phase lasted for 6 week, after which patients were crossed over. Asthma symptoms, lung function, and airway inflammation were compared between the 2 phases.

Results: Twenty-three patients completed the study; adequate sputum samples were collected from 17 patients. Asthma symptoms and lung function remained similar between the 2 phases. However, the mean sputum eosinophil percentage was higher in the LABA phase than in the ICS phase (5.07±3.82% vs. 1.02±1.70%; P<0.01). Sputum eosinophilia (≥3%) was more frequently observed in the LABA phase than in the ICS phase (six vs. two).

Conclusion: Addition of LABA may mask airway eosinophilic inflammation in asthmatic patients whose symptoms are not controlled with low-dose ICS.

Keywords: Airway; asthma; beta2-agonists; corticosteroids; inflammation.

Fig. 1

Study design. Following completion of the run-in period, patients began receiving either 800 µg budesonide per day (ICS phase) or 320 µg budesonide plus 9 µg formoterol per day (LABA phase) for 6 weeks, followed by a 1 week washout period, after which patients were crossed over. FEV1, forced expiratory volume in one second; PEFR, peak expiratory flow rate; ACT, asthma control test; ISE, induced sputum eosinophil.

Fig. 2

Comparison of induced sputum eosinophil percentile between two phases. ICS phase, 800 µg budesonide per day; LABA phase, 320 µg budesonide plus 9 µg formoterol per day; ISE, induced sputum eosinophil.