title: Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations.
abstract: BACKGROUND
  Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.
  
  
  METHODS
  This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months. Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2-12. Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score.
  
  
  RESULTS
  Overall, 2,331 and 1,799 patients were included in the 0-2- and 0-12-month responder analyses, respectively, and 2,360 patients in the 2-12-month exacerbation rate analysis. At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders. The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters. Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14-7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83-5.31). Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.
  
  
  CONCLUSIONS
  Early FEV1 and SGRQ treatment responses relate to their changes at 12 months. FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients. This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required.
authors.affiliation: Pulmonary and Rehabilitation Research Group, University Hospital Aintree, Liverpool, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Department of Pulmonary Medicine and Tuberculosis, Gronigen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health Sciences Center, School of Medicine, University of Texas, San Antonio, TX, USA; South Texas Veterans Health Care System, San Antonio, TX, USA.
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Anzueto
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado, Denver, CO, USA.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.affiliation: Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Eriksson
authors.affiliation: StatMind AB, Lund, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Peterson
authors.affiliation: George Institute for Global Health, Concord Clincal School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Jenkins
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012720:Severity of Illness Index; D000067251:Symptom Flare Up; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D019819:Budesonide; D000068759:Formoterol Fumarate
keywords: anti-inflammatories; bronchodilator effect; chronic obstructive pulmonary disease; predictors; risk assessment; risk factors