title: Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations. We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients.
  
  
  METHODS
  We performed a retrospective analysis of data from a study (ClinicalTrials.gov registration: NCT00419744) comparing budesonide/formoterol 320/9 μg with formoterol 9 μg (both twice daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 μg was provided. First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk. Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and ≥10 inhalations/day.
  
  
  RESULTS
  Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted). First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use. Mean reliever use over 1 week was predictive of long-term exacerbation risk. Patients with mean use of 2-5, 6-9, and ≥10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day. Budesonide/formoterol was associated with lower short- and long-term exacerbation risk than formoterol in all reliever-use groups.
  
  
  CONCLUSIONS
  SABA reliever use is a predictor of short- and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol.
authors: Department of Thoracic Medicine, Concord Hospital, University of Sydney and The George Institute for Global Health, Hospital Rd, Concord, Sydney, NSW, 2139, Australia. christine.jenkins@sydney.edu.au.
authors: Christine R
authors: CR
authors: Jenkins
authors: Department of Pulmonary Medicine and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands. d.s.postma@umcg.nl.
authors: Dirkje S
authors: DS
authors: Postma
authors: Pulmonary Section, Department of Medicine, University of Texas Health Science Center, and South Texas Veterans Health Care System, San Antonio, TX, USA. anzueto@uthscsa.edu.
authors: Antonio R
authors: AR
authors: Anzueto
authors: Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado Denver School of Medicine, 1400 Jackson Street, K729, Denver, CO, 80206, USA. makeb@njhealth.org.
authors: Barry J
authors: BJ
authors: Make
authors: StatMind, Medicon Village AB, Scheelevägen 2, 22363, Lund, Sweden. stefan.peterson@statmind.se.
authors: Stefan
authors: S
authors: Peterson
authors: Department of Respiratory Medicine and Allergology, University Hospital, Lund, 221 87, Sweden. goran.eriksson@med.lu.se.
authors: Göran
authors: G
authors: Eriksson
authors: Clinical Sciences Department, Institute of Ageing and Chronic Disease, University Hospital Aintree, Lower Lane, Liverpool, L9 7AL, UK. pmacal@liverpool.ac.uk.
authors: Peter M
authors: PM
authors: Calverley
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D000420:Albuterol