Prescribing Asthma Controller Medication According to Gene Status to Improve Quality of Life in Young People With Asthma

Summary

One in every 11 children in the United Kingdom (UK) has asthma. Children with asthma cough, wheeze and have difficulty breathing. The symptoms which children experience can mean they miss school and makes it difficult for children to take part in playground games and sports. Some have to be admitted to hospital. In fact, in the UK a child is admitted to hospital every 18 minutes because of their asthma. Effective medicines are available, but a child's response to these medicines is currently unpredictable. This project focuses on an asthma controller medicine called salmeterol. According to reports, tens of thousands of children may be taking this medicine in the UK, but evidence suggests it might not work for around one in seven of them. The study team are investigating whether a new approach to treatment, where prescribing is personalised according to a child's genetic make-up, improves the child's quality of life and provides better control of their asthma. Treatment that is tailored in this way to a person's genetic features is often called 'personalised medicine'. At the moment, doctors commonly prescribe salmeterol to relieve asthma symptoms if children do not benefit enough from other medicines. But evidence suggests salmeterol may not work properly in children with a certain genetic makeup. The study team are investigating whether it helps to take children and young people's genetic makeup into account when deciding whether to give them salmeterol or an alternative medicine called montelukast. A simple and inexpensive saliva test can provide the information needed to guide decision making.

Timeline

Start

2016-02

Primary completion

2019-07

Completion

2019-07

Publications

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• Background Juniper EF, Guyatt GH, Ferrie PJ, Griffith LE. Measuring quality of life in asthma. Am Rev Respir Dis. 1993 Apr;147(4):832-8. doi: 10.1164/ajrccm/147.4.832.
• Background Juniper EF, Guyatt GH, Willan A, Griffith LE. Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol. 1994 Jan;47(1):81-7. doi: 10.1016/0895-4356(94)90036-1.
• Background Basu K, Palmer CN, Tavendale R, Lipworth BJ, Mukhopadhyay S. Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. J Allergy Clin Immunol. 2009 Dec;124(6):1188-94.e3. doi: 10.1016/j.jaci.2009.07.043.
• Background Palmer CN, Lipworth BJ, Lee S, Ismail T, Macgregor DF, Mukhopadhyay S. Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax. 2006 Nov;61(11):940-4. doi: 10.1136/thx.2006.059386. Epub 2006 Jun 13.
• Background Joos S, Miksch A, Szecsenyi J, Wieseler B, Grouven U, Kaiser T, Schneider A. Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax. 2008 May;63(5):453-62. doi: 10.1136/thx.2007.081596.
• Background Liggett SB. The pharmacogenetics of beta2-adrenergic receptors: relevance to asthma. J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S487-92. doi: 10.1016/s0091-6749(00)90048-4.
• Background Lipworth BJ, Basu K, Donald HP, Tavendale R, Macgregor DF, Ogston SA, Palmer CN, Mukhopadhyay S. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Clin Sci (Lond). 2013 Apr;124(8):521-8. doi: 10.1042/CS20120528.
• Background Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999 Oct;14(4):902-7. doi: 10.1034/j.1399-3003.1999.14d29.x.
• Background British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. Thorax. 2003 Feb;58 Suppl 1(Suppl 1):i1-94. doi: 10.1136/thorax.58.suppl_1.1i. No abstract available.
• Background Lemanske RF Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Covar RA, Guilbert TW, Larsen G, Morgan WJ, Moss MH, Spahn JD, Taussig LM; Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010 Mar 18;362(11):975-85. doi: 10.1056/NEJMoa1001278. Epub 2010 Mar 2.
• Background Juniper EF, Svensson K, Mork AC, Stahl E. Modification of the asthma quality of life questionnaire (standardised) for patients 12 years and older. Health Qual Life Outcomes. 2005 Sep 16;3:58. doi: 10.1186/1477-7525-3-58.
• Ruffles T, Jones CJ, Palmer C, Turner S, Grigg J, Tavendale R, Hogarth F, Rauchhaus P, Pilvinyte K, Hannah R, Smith H, Littleford R, Lipworth B, Mukhopadhyay S. Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents. Eur Respir J. 2021 Aug 19;58(2):2004107. doi: 10.1183/13993003.04107-2020. Print 2021 Aug.

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