title: A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA).
abstract: BACKGROUND
  Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control.
  
  
  METHODS
  30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation.
  
  
  RESULTS
  There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance.
  
  
  CONCLUSIONS
  These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function.
  
  
  BACKGROUND
  NCT01171365. Protocol available at http://www.clinicaltrials.gov.
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: David
authors: D
authors: Hodgson
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: John
authors: J
authors: Anderson
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: Catherine
authors: C
authors: Reynolds
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: Garry
authors: G
authors: Meakin
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: Helen
authors: H
authors: Bailey
authors: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors: Ian
authors: I
authors: Pavord
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: Dominick
authors: D
authors: Shaw
authors: Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
authors: Tim
authors: T
authors: Harrison
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D011282:Pregnenediones / Q000008:administration & dosage / Q000627:therapeutic use*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011657:Pulmonary Eosinophilia / Q000175:diagnosis / Q000188:drug therapy*; D011788:Quality of Life; D013147:Spirometry; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011282:Pregnenediones; D009569:Nitric Oxide; C120481:ciclesonide; D011241:Prednisone
keywords: Asthma; Inhaler devices; Pulmonary eosinophilia