title: 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.
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: redasthma@yahoo.co.jp.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Akamatsu
authors.affiliation: Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan. Electronic address: tmjkshi@general-hosp.pref.shizuoka.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: doc00009@yahoo.co.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: yassy19781119@yahoo.co.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: dai@hama-med.ac.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: fujisawa@hama-med.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujisawa
authors.affiliation: Department of Respiratory Medicine, Shizuoka City Shimizu Hospital, Japan. Electronic address: ttom@shimizuhospital.com.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: inui@hama-med.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: suda@hama-med.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: chidak11@hama-med.ac.jp.
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D000068759:Formoterol Fumarate; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000473:pathology; D012720:Severity of Illness Index; D013147:Spirometry; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D009569:Nitric Oxide; D019819:Budesonide; D000420:Albuterol; D000068759:Formoterol Fumarate
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