title: Phenotypic predictors of response to oral glucocorticosteroids in severe asthma.
abstract: BACKGROUND
  Systemic glucocorticosteroids are side-effect prone but often necessary for the treatment of severe asthma (SA). Our goal was to assess the usefulness of medical history, physiological variables and biomarkers as predictors of response to oral steroids.
  
  
  METHODS
  After 4 weeks of treatment optimization, 84 patients with SA and 62 with mild-to-moderate asthma (MA) underwent a 2 week double-blind placebo-controlled oral prednisolone intervention (0.5 mg/kg BW daily) (NCT00555607).
  
  
  RESULTS
  Responders had a lower FEV1% (73.7 vs. 88.0), lower FEV1/FVC ratio (0.65 vs. 0.73), lower quality of life (SGRQ score 39.1 vs. 31.4), lower total sputum cell number (1.0 vs. 4.5×10(6)) and higher number of sputum eosinophils (16.8% vs. 6.3%) (p<0.05). For all asthmatics, the degree of improvement in FEV1 correlated with sputum eosinophils, level of asthma control, FeNO, quality of life, age of asthma onset and blood eosinophils. In SA, sputum eosinophils≥3% (OR 9.91), FEV1≤60% (OR 3.7), and SGRQ>42.2 (OR 3.25) were associated with a good response to oral prednisolone. The highest sensitivity and specificity to predict more than 12% increase in FEV1 in SA after oral prednisolone was found for sputum eosinophils≥3% and FeNO>45 ppb.
  
  
  CONCLUSIONS
  Sputum eosinophils and FeNO were the best predictors of favorable response to oral prednisolone in severe asthmatics. A guided approach to glucocorticosteroid treatment should be recommended as it favors better control of the disease and presumably a lower rate of adverse events. The study has been registered at the site: clinicaltrials.gov with number: NCT00555607.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden; Medical University of Lodz, Poland. Electronic address: maciek.kupczyk@ki.se.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kupczyk
authors.forename: Shushila
authors.initials: S
authors.lastname: Haque
authors.forename: Roelinde J M
authors.initials: RJ
authors.lastname: Middelveld
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D011788:Quality of Life; D012680:Sensitivity and Specificity; D013183:Sputum / Q000166:cytology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D009569:Nitric Oxide; D011239:Prednisolone
keywords: Oral glucocorticosteroids; Phenotypes of asthma; Severe asthma