Comparison of the clinical effects of combined salmeterol/fluticasone delivered by dry powder or pressurized metered dose inhaler Masayuki Hojo a, * , Toshihiro Shirai b , Junko Hirashima a , Motoyasu Iikura a , Haruhito Sugiyama a a Division of Respiratory Medicine, National Center for Global Health and Medicine, Japan b Department of Respiratory Medicine, Shizuoka General Hospital, Japan article info Article history: Received 13 November 2015 Received in revised form 15 January 2016 Accepted 16 February 2016 Available online 17 February 2016 Keywords: Bronchial asthma Salmeterol/fluticasone combination inhaler Dry powder inhaler Pressurized metered dose inhaler Forced oscillation technique abstract The salmeterol/fluticasone combination (SFC) inhaler is currently the most widely used maintenance drug for asthmatics worldwide. Although the effectiveness of SFC as either a dry powder inhaler (DPI) or a pressurized metered dose inhaler (pMDI) is well documented, there is limited data comparing the clinical efficacies of the two devices. To address this issue, we carried out a randomized crossover trial in which asthmatic patients (n ¼ 47; mean age, 62.5 ± 16.5 years old) received a 12-week treatment of SFC DPI (50/250 mg twice daily) or SFC pMDI (four puffs of 25/125 mg daily). After a 4-week washout period, patients received another crossover treatment for 12 weeks. Respiratory resistance and reactance were measured by forced oscillation technique (MostGraph-01), spirometry, fractional exhaled nitric oxide (FeNO), and an asthma control test (ACT) every 4 weeks. The mean forced expiratory volume 1.0 at the baseline was 2.16 ± 0.86 (L). Respiratory system resistance at 5 Hz (R5), the difference between R5 and R at 20 Hz (R5 e R20), and FeNO improved in both treatment groups, while reactance at 5 Hz (X5) and ACT score improved only in the pMDI group. In patients >70 years old (n ¼ 21), R5, R5 e R20, DX5, and FeNO improved only in the pMDI group. These results suggest that SFC by pMDI produces a stronger anti- inflammatory and bronchodilatory effect even in patients whose asthma is well controlled by SFC delivered by DPI. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Asthma is a global public health problem that affects up to 300 million people worldwide [1]. Despite recent advances in phar- macological therapies, under-treatment of asthma remains com- mon, especially in terms of long-term maintenance regimens targeting airway inflammation. Although inhalation is an effective delivery route for bronchodilators as well as inhaled corticosteroids (ICS), many asthmaticsdespecially elderly patientsdstill have difficulty in using the inhaler correctly. This along with poor adherence to treatment programs are thought to be common causes of uncontrolled asthma [2,3]. Available types of inhaler de- vice for ICS and long-acting b 2 agonist (LABA) combination therapy now include the dry powder inhaler (DPI) and pressurized metered-dose inhaler (pMDI). Although device preparation and handling techniques vary among brands, some generalizations can be made with regard to optimal inhalation procedure for each type of device: inhalation should be slow and steady with the pMDI, but sharp and rapid with the DPI [4,5]. Additionally, the particle size of each preparationdi.e., mass median aerodynamic diameterdmay impact treatment outcome [6]. It has been reported that particle sizes are smaller for pMDI than for DPI products, such that the former can be more widely distributed from central to peripheral airways [7]. However, there have been few clinical trials comparing inhalers for licenseeequivalent combinations of ICS/LABA. The salmeterol/fluticasone combination (SFC) inhaler is currently the most widely used product by persistent asthmatics for maintenance therapy. Although the effectiveness of both SFC Abbreviations: ACT, asthma control test; BUD/FM, budenoside/formoterol; DPI, dry powder inhaler; COPD, chronic obstructive pulmonary disease; FeNO, fractional exhaled nitric oxide; FEV, forced expiratory volume; FOT, forced oscillation tech- nique; ICS, inhaled corticosteroids; LABA, long-acting b 2 -agonist; pMDI, pressurized metered dose inhaler; R5 (20), respiratory system resistance at 5 (20) Hz; R5R20, difference between R5 and R20; SFC, salmeterol/fluticasone combination; X5, reactance at 5 Hz. * Corresponding author. Division of Respiratory Medicine, National Center for Global Health and Medicine, Toyama1-21-1, Shinjuku, Tokyo, Japan. E-mail address: houjiyou-ncgm@umin.ac.jp (M. Hojo). Contents lists available at ScienceDirect Pulmonary Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/ypupt http://dx.doi.org/10.1016/j.pupt.2016.02.004 1094-5539/© 2016 Elsevier Ltd. All rights reserved. Pulmonary Pharmacology & Therapeutics 37 (2016) 43e48