title: Pharmacogenetics of anti-inflammatory treatment in children with asthma: rationale and design of the PACMAN cohort.
abstract: OBJECTIVE
  To investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes.
  
  
  METHODS
  The Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects (PACMAN) study was initiated in April 2009 as an observational retrospective pharmacy-based study, including at least 1000 children with asthma medication (aged 4-12 years). Data on respiratory symptoms and medication use behavior will be collected using a questionnaire; complete medication histories will be extracted from the pharmacy information system; additional health information will be requested from the general practitioner; quality of inhalation technique and lung function measurements will be performed and saliva samples for DNA extraction and genotyping will be collected. Two groups of patients will be defined based on questionnaire data and lung function measurements: responders and nonresponders to anti-inflammatory asthma treatment. These two groups will be compared with respect to genetic variation. Corrections will be made for potential confounding factors.
  
  
  RESULTS
  The main study end point is treatment response, including asthma control, medication use and exhaled nitric oxide as a measure of airway inflammation. Whilst our focus is on genetic factors, this study allows us to also investigate other treatment response determinants, such as inhalation technique and therapy adherence.
  
  
  CONCLUSIONS
  Results from the PACMAN study could eventually lead to a more individualized therapy approach. PACMAN will focus on pharmacogenetics of asthma medication in children, while knowledge will be gained of relevant interest to the treatment of the asthma population at large.
authors: Utrecht University, Faculty of Science, Division of Pharmacoepidemiology and Pharmacotherapy, 3508 TB Utrecht, The Netherlands.
authors: Ellen S
authors: ES
authors: Koster
authors: Jan Am
authors: JA
authors: Raaijmakers
authors: Gerard H
authors: GH
authors: Koppelman
authors: Dirkje S
authors: DS
authors: Postma
authors: Cornelis K
authors: CK
authors: van der Ent
authors: Leo
authors: L
authors: Koenderman
authors: Madelon
authors: M
authors: Bracke
authors: Anke Hilse
authors: AH
authors: Maitland-van der Zee
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D009426:Netherlands; D010597:Pharmacogenetics / Q000379:methods*; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D020024:Leukotriene Antagonists