Potential masking of airway inflammation by combination therapy in asthma

Background: There is a concern about safety of long-acting beta2 agonists (LABA), because LABA might mask ongoing bronchial inflammation and thereby leave the asthmatic patient at risk for more severe exacerbations. We compared the effect of combination therapy including low dose of inhaled corticosteroids (ICS) and LABA with the effect of medium dose of ICS alone on airway inflammation in asthma. Methods: Twenty-four patients whose asthma is not controlled by low dose ICS (400 ug a day of budesonide) were enrolled in this prospective crossover study. Participating patients were randomized into two treatment phases: one receiving higher dose (800 ug a day) budesonide (ICS phase), and the other receiving a combination therapy of budesonide/formoterol (360 ug/9 mg a day) delivered by a single inhaler (LABA phase). Each treatment phase was lasted for 6 weeks then crossed over. Asthma symptoms, lung function, and airway inflammation were compared between the two phases. Results: Among 23 patients who completed the study, adequate sputum for the analysis was available in 17 patients. Asthma symptoms and lung function remained similar in the two phases. By contrary, the mean sputum eosinophil percentile was significantly higher in LABA phase than ICS phase (5.07 ± 3.82 % vs. 1.02 ± 1.70 %, p < 0.01). Sputum eosinophilia (≥3 %) remained in six subjects during the LABA phase, but in two subjects during the ICS period. Conclusion: Combination therapy of low dose ICS and LABA may mask airway eosinophilic inflammation in asthmatic patients compared to medium dose ICS alone.