title: Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics.
abstract: BACKGROUND
  In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it.
  
  
  METHODS
  We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders".
  
  
  RESULTS
  On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/μL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04).
  
  
  CONCLUSIONS
  Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.
authors.affiliation: Medical University Sofia, Bulgaria. Electronic address: ted.popov@gmail.com.
authors.forename: T A
authors.initials: TA
authors.lastname: Popov
authors.forename: D
authors.initials: D
authors.lastname: Petrova
authors.forename: T Z
authors.initials: TZ
authors.lastname: Kralimarkova
authors.forename: Y
authors.initials: Y
authors.lastname: Ivanov
authors.forename: T
authors.initials: T
authors.lastname: Popova
authors.forename: M
authors.initials: M
authors.lastname: Peneva
authors.forename: T
authors.initials: T
authors.lastname: Odzhakova
authors.forename: Y
authors.initials: Y
authors.lastname: Ilieva
authors.forename: P
authors.initials: P
authors.lastname: Yakovliev
authors.forename: T
authors.initials: T
authors.lastname: Lazarova
authors.forename: O
authors.initials: O
authors.lastname: Georgiev
authors.forename: V
authors.initials: V
authors.lastname: Hodzhev
authors.forename: E
authors.initials: E
authors.lastname: Hodzheva
authors.forename: M T
authors.initials: MT
authors.lastname: Staevska
authors.forename: V D
authors.initials: VD
authors.lastname: Dimitrov
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D000068759:Formoterol Fumarate; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011788:Quality of Life; D013147:Spirometry; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D019819:Budesonide; D002097:C-Reactive Protein; D001507:Beclomethasone; D000420:Albuterol; D000068759:Formoterol Fumarate
keywords: Asthma; Beclomethasone dipropionate; Extra fine inhalation drug delivery; Formoterol; Small airways