Measurements

Respiratory functions were measured using a dry wedge spirometer (Chestac 8900^TM, Chest Co., Ltd., Tokyo, Japan) to assess the bronchodilatory effect for small airway obstruction of the treatment regimens, in the same manner as previously reported [18, 19, 20, 21]. Respiratory impedance was measured by FOT using another device (MostGraph-01^TM, Chest Co., Ltd.) in accordance with the previously reported recommended techniques [20, 21, 22, 23]. The FeNO level, a surrogate eosinophilic airway inflammatory marker, was measured using a commercially-available device (NIOX MINO^TM, Aerocrine, Stockholm, Sweden) before any forced expiratory maneuvers [24]. To assess and quantify the effect of COPD symptoms on patient health status, patients were asked to complete a CAT, a simple questionnaire that is a reliable and valid tool to examine the impact of COPD symptoms over time [25]. It comprises 8 items scored from 0 to 5 to give a maximum total score of 40. CAT scores of 1 – 10, 11 – 20, 21 – 30, and 31 – 40, respectively, represent categories of mild, moderate, severe, and very severe health status impairment [25, 26]. To evaluate asthma control status during the previous 4 weeks, patients were asked to complete an ACT, an easy five-question test that evaluates their asthma symptoms [27, 28]. Each question is scored from 1 to 5, giving a total score in the range of 5 – 25, with low scores corresponding to a high level of symptoms and therefore poor asthma control. All adverse events during the study period were recorded.