Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: A systematic review

Autor: Zulfan Zazuli, Marielle W. Pijnenburg, Niloufar Farzan, Colin N. A. Palmer, Nadia M. B. Oliveri, Gerard H. Koppelman, Anke H. Maitland van der Zee, Elise M A Slob, Susanne J. H. Vijverberg
Přispěvatelé: Pediatrics, AII - Inflammatory diseases, Graduate School, APH - Personalized Medicine, Pulmonology, Paediatric Pulmonology
Rok vydání: 2018
Předmět:
0301 basic medicine
medicine.medical_specialty
bronchodilator
medicine.drug_class
Immunology
GENE POLYMORPHISMS
THERAPY
law.invention
03 medical and health sciences
FEV1/FVC ratio
SALMETEROL
0302 clinical medicine
Randomized controlled trial
law
Bronchodilator
Internal medicine
Administration
Inhalation
genetic polymorphism
Immunology and Allergy
Medicine
Humans
Anti-Asthmatic Agents
SEVERE EXACERBATIONS
BETA-AGONIST
BETA-2-ADRENERGIC RECEPTOR
Adrenergic beta-2 Receptor Agonists
Asthma
FORMOTEROL
Polymorphism
Genetic
business.industry
medicine.disease
Clinical trial
long-acting beta-agonist
BETA(2)-ADRENOCEPTOR
030104 developmental biology
030228 respiratory system
ADRB2
Pharmacogenetics
Pediatrics
Perinatology and Child Health
Observational study
Salmeterol
Receptors
Adrenergic
beta-2
business
CLINICAL-TRIALS
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Adenylyl Cyclases
Zdroj: Pediatric Allergy and Immunology, 29(7), 705-714. Blackwell Publishing
Pediatric allergy and immunology, 29(7), 705-714. Blackwell Munksgaard
ISSN: 0905-6157
Popis: BACKGROUND: Long-acting beta2-agonists (LABA) are recommended in asthma therapy; however, not all asthma patients respond well to LABA. We performed a systematic review on genetic variants associated with LABA response in patients with asthma. METHODS: Articles published until April 2017 were searched by two authors using PubMed and EMBASE. Pharmacogenetic studies in patients with asthma and LABA response as an outcome were included. RESULTS: In total, 33 studies were included in this systematic review; eight focused on children (n = 6051). Nineteen studies were clinical trials, while 14 were observational studies. Studies used different outcomes to define LABA response, for example, lung function measurements (FEV1 , PEF, MMEF, FVC), exacerbations, quality of life, and asthma symptoms. Most studies (n = 30) focused on the ADRB2 gene, encoding the beta2-adrenergic receptor. Thirty studies (n = 14 874) addressed ADRB2 rs1042713, 7 ADRB2 rs1042714 (n = 1629), and 3 ADRB2 rs1800888 (n = 1892). The association of ADRB2 rs1042713 and rs1800888 with LABA response heterogeneity was successfully replicated. Other variants were only studied in three studies but not replicated. One study focused on the ADCY9 gene. Five studies and a meta-analysis found an increased risk of exacerbations in pediatrics using LABA carrying one or two A alleles (OR 1.52 [1.17; 1.99]). These results were not confirmed in adults. CONCLUSIONS: ADRB2 rs1042713 variant is most consistently associated with response to LABA in children but not adults. To assess the clinical value of ADRB2 rs1042713 in children with asthma using LABA, a randomized clinical trial with well-defined outcomes is needed.
Databáze: OpenAIRE
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