Pharmacogenetics of anti-inflammatory treatment in children with asthma: rationale and design of the PACMAN cohort.
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.
Koster
Ellen S
ES
Utrecht University, Faculty of Science, Division of Pharmacoepidemiology and Pharmacotherapy, 3508 TB Utrecht, The Netherlands.
Raaijmakers
Jan Am
JA
Koppelman
Gerard H
GH
Postma
Dirkje S
DS
van der Ent
Cornelis K
CK
Koenderman
Leo
L
Bracke
Madelon
M
Maitland-van der Zee
Anke Hilse
AH
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
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D020024:Leukotriene Antagonists