title: The Impact of Common Inhaler Errors on Drug Delivery: Investigating Critical Errors with a Dry Powder Inhaler.
abstract: BACKGROUND
  Researchers, using checklists, have identified that 30%-90% of patients make errors in inhaler use. It is not certain whether these errors affect the delivery of medication. We have developed an electronic monitor (INCA™) that records audio each time an inhaler is used, providing objective information on inhaler technique. The aim of this study was to assess the effect that correctly identified inhaler errors, with the INCA device, have on drug delivery.
  
  
  METHODS
  This was a prospective study of healthy volunteers using a salbutamol Diskus™. The inclusion criteria allowed for the recruitment of healthy participants who were nonfrequent users of Salbutamol. Each participant was assigned to one control "phase" first and two/three subsequent error "phases." Each phase consisted of six doses of the drug taken 6 hours apart, and the participants' blood was drawn before and 25 minutes after doses one and six. This allowed us to sample their trough and peak serum salbutamol levels.
  
  
  RESULTS
  Fourteen healthy volunteers were studied. The inhaler technique errors simulated in this study included exhaling into the device after drug priming but before inhalation, low inspiratory flow, multiple inhalations, low breath hold, missed doses, and wrong inhaler position. Only the exhalation error, low inspiratory flow, and missed doses led to a significant reduction in serum salbutamol levels. After six doses of the exhalation error, there was a 62% reduction in peak salbutamol levels. Low inspiratory flow led to a 52% reduction in peak salbutamol levels and a 78% reduction in trough levels. Missed doses led to a 37% reduction in trough salbutamol levels.
  
  
  CONCLUSIONS
  These findings confirm that technique errors affect drug delivery. Furthermore, we were able to identify that the most critical technique errors with the Diskus inhaler are exhalation into the device before inhalation, poor inspiratory flow, and missing doses.
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Imran
authors.initials: I
authors.lastname: Sulaiman
authors.affiliation: 2 Special Chemistry Division, Department of Pathology, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Jansen
authors.initials: J
authors.lastname: Seheult
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Nirmal
authors.initials: N
authors.lastname: Sadasivuni
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Elaine
authors.initials: E
authors.lastname: MacHale
authors.affiliation: 3 Trinity Centre for Bioengineering, Trinity College, The University of Dublin , Dublin, Ireland .
authors.forename: Isabelle
authors.initials: I
authors.lastname: Killane
authors.affiliation: 2 Special Chemistry Division, Department of Pathology, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Spiros
authors.initials: S
authors.lastname: Giannoutsos
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Breda
authors.initials: B
authors.lastname: Cushen
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Matshediso Constantina
authors.initials: MC
authors.lastname: Mokoka
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Aoife Sartini
authors.initials: AS
authors.lastname: Bhreathnach
authors.affiliation: 4 Royal College of Surgeons in Ireland Population Health Sciences , Dublin, Ireland .
authors.forename: Fiona
authors.initials: F
authors.lastname: Boland
authors.affiliation: 3 Trinity Centre for Bioengineering, Trinity College, The University of Dublin , Dublin, Ireland .|5 School of Engineering, Trinity College, The University of Dublin , Dublin, Ireland .|6 School of Medicine, Trinity College, The University of Dublin , Dublin, Ireland .
authors.forename: Richard B
authors.initials: RB
authors.lastname: Reilly
authors.affiliation: 1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .|7 Department of Respiratory Medicine, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D004867:Equipment Design; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012646:Self Administration / Q000592:standards*; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D000420:Albuterol
keywords: INCA; adherence; drug delivery; inhalers; salbutamol; technique error