Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents
| Autor: | Thomas Ruffles, Steve Turner, Jonathan Grigg, Romanie Hannah, Somnath Mukhopadhyay, Roberta Littleford, Kristina Pilvinyte, Brian Lipworth, Helen Smith, Petra Rauchhaus, Fiona Hogarth, Christina J Jones, Roger Tavendale, Colin N. A. Palmer |
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| Přispěvatelé: | Lee Kong Chian School of Medicine (LKCMedicine) |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Adolescent Genotype MEDLINE law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Quality of life Adrenal Cortex Hormones law Internal medicine Administration Inhalation Health care Humans Medicine Medicine [Science] Anti-Asthmatic Agents 030212 general & internal medicine Child Alleles Asthma business.industry Bronchoprotective Subsensitivity Quality-of-Life Guideline medicine.disease Clinical research England 030228 respiratory system Drug Therapy Combination business |
| Zdroj: | European Respiratory Journal. 58:2004107 |
| ISSN: | 1399-3003 0903-1936 |
| Popis: | IntroductionThe A allele of rs1042713 (Arg16 amino acid) in the β2-adrenoreceptor is associated with poor response to long-acting β2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second-line controller with LABA or a leukotriene receptor antagonist according to Arg16Gly genotype would result in improvements in Pediatric Asthma-Related Quality of Life Questionnaire (PAQLQ).MethodsWe performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12–18 years with asthma taking inhaled corticosteroids. 241 participants (mean±sd age 14.7±1.91 years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 4-week run-in participants were followed for 12 months. The primary outcome measure was change in PAQLQ. Asthma control, asthma exacerbation frequency and healthcare utilisation were secondary outcomes.ResultsGenotype-directed prescribing resulted in an improvement in PAQLQ compared to standard care (0.16, 95% CI 0.00–0.31; p=0.049), although this improvement was below the pre-determined clinical threshold of 0.25. The AA genotype was associated with a larger improvement in PAQLQ with personalised versus standard care (0.42, 95% CI 0.02–0.81; p=0.041).ConclusionThis is the first RCT demonstrating that genotype-driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care. Adolescents with the AA homozygous genotype benefited most. The potential role of such β2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration. |
| Databáze: | OpenAIRE |
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