title: A simple rule to identify patients with chronic obstructive pulmonary disease who may need treatment reevaluation.
abstract: BACKGROUND
  A simple rule based on short-acting inhaled β2-agonist (SABA) use could identify patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbations and signal the need for maintenance therapy change, similar to asthma "Rules of Two(®)".
  
  
  METHODS
  Associations between SABA use, COPD exacerbations, and health care costs over 1 year were examined retrospectively using de-identified patient data from the Optum Research Database (ORD; N = 56,581) and the Impact National Benchmark Database (IMPACT™; N = 9423). Nebulized and metered-dose inhaler (MDI) SABA doses were normalized to 2.5 mg and 90 mcg albuterol equivalents, respectively.
  
  
  RESULTS
  The GOLD initiative establishes ≥2 exacerbations/year as indicative of increased risk in COPD. We identified a correlation (p < 0.0001) between 1.5 SABA doses/day and this frequency of exacerbations. In ORD, patients using ≥1.5 versus <1.5 SABA doses/day experienced significantly more exacerbations: 1.92 (95% confidence interval [CI], 1.89-1.96) versus 1.36 (95% CI, 1.34-1.38) per patient year (PPY). Above-threshold use was associated with higher average annual COPD-related costs (2010 $US): $21,868 (standard deviation [SD], $53,910) versus $11,686 (SD, $32,707) for nebulized SABA only, $9216 (SD, $30,710) versus $7334 (SD, $24,853) for MDI SABA only, and $15,806 (SD, $35,260) versus $11,233 (SD, $27,006) for both nebulized and MDI SABA. IMPACT™ validated these findings.
  
  
  CONCLUSIONS
  Patients with COPD using ≥1.5 SABA doses/day were at increased risk of exacerbations. Our results suggest a "Rule of 3-2": SABA use ≥3 times in 2 days should be considered a clinical marker for needing treatment reevaluation.
authors.affiliation: Pulmonary and Critical Care, Baylor College of Medicine, MEDVA Medical Center Bldg. 100 (111i), Houston, TX 77030, USA. Electronic address: amirs@bcm.edu.
authors.forename: Amir
authors.initials: A
authors.lastname: Sharafkhaneh
authors.affiliation: Health Economics and Outcomes Research, OptumInsight, 13625 Technology Drive, Eden Prairie, MN 55344, USA. Electronic address: Aylin.Altan@optum.com.
authors.forename: Aylin E
authors.initials: AE
authors.lastname: Altan
authors.affiliation: Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center, 110 Irving Street, Washington DC, 20010, USA. Electronic address: Gene.Colice@Medstar.net.
authors.forename: Gene L
authors.initials: GL
authors.lastname: Colice
authors.affiliation: Pulmonary and Critical Care, Baylor College of Medicine, One Baylor Plaza-BCM621, Houston, TX 77030, USA. Electronic address: hanania@bcm.tmc.edu.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.affiliation: Pulmonary Diseases and Critical Care Medicine, University of North Carolina School of Medicine, 4125 BioInformatics Building, 130 Mason Farm Road, CB 7020, Chapel Hill, NC 27599, USA. Electronic address: james_donohue@med.unc.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Donohue
authors.affiliation: Health Economics and Outcomes Research, OptumInsight, 13625 Technology Drive, Eden Prairie, MN 55344, USA. Electronic address: Jonathan.Kurlander@optum.com.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kurlander
authors.affiliation: Thorax Institute, Hospital Clinic-CIBERES, IDIBAPS, Universitat de Barcelona, Villarroel, 170 (Esc 2 - Planta 2), 08036 Barcelona, Spain. Electronic address: rororo@clinic.ub.es.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.affiliation: Mylan Specialty, L.P., 110 Allen Road, 4th Floor, Basking Ridge, NJ 07920, USA. Electronic address: Pablo.Altman@gmail.com.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Altman
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015897:Comorbidity; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D017048:Health Care Costs / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000191:economics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000420:Albuterol
keywords: COPD; Exacerbation; Maintenance therapy; SABA