The impact of suboptimal asthma control and adherence to medication on health-related outcomes for children with asthma Katherine Marie Harris Submitted in partial fulfilment of the requirements of the Degree of Doctor of Philosophy 2018 Supervisors: Professor Jonathan Grigg Professor James Thomas Centre for Genomics and Child Health Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary, University of London 1 Acknowledgements I would like to thank my supervisors, Professor Jonathan Grigg and Professor James Thomas, for their continued support, advice and guidance throughout the course of my PhD. Thank you to the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC), particularly Professor Jonathan Grigg, for giving me the opportunity to do this PhD, and to the CLAHRC for their support and encouragement over the last four years. A big thank you to all of the schools, teachers and students who participated in this research. I would not have been able to complete my PhD without the support of everyone who participated; and thank you to all the schools for their continued interest and support in this work. Thank you to all the members of the Grigg team in the Blizard Institute. You have made the last four years so enjoyable, and it has been a pleasure to work with such a great team. A final big thank you to all of my friends and family for being so supportive and believing in me from the beginning. Especially my mum, dad, sister and Mark for never doubting me. I would never have been able to complete this PhD without your continued encouragement. 2 Statement of Originality I, Katherine Marie Harris, confirm that the research included within this thesis is my own work or that where it has been carried out in collaboration with, or supported by others, that this is duly acknowledged below and my contribution indicated. Previously published material is also acknowledged below. I attest that I have exercised reasonable care to ensure that the work is original, and does not to the best of my knowledge break any UK law, infringe any third party’s copyright or other intellectual property right, or contain any confidential material. I accept that the college has the right to use plagiarism detection software to check the electronic version of the thesis. I confirm that this thesis has not been previously submitted for the award of a degree by this or any other university. The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author. Signature: Date: 5th July 2018 Details of publications: 1. Harris K., Mosler G., Williams S.A., Whitehouse A., Raine R., Grigg J. (2017). Asthma control in London secondary school children. Journal of Asthma, 1-18 2. Pike K., Harris K., Kneale D. (2016). Interventions for autumn exacerbations of asthma in children. The Cochrane Library 3. Harris K. M., Kneale D., Lasserson T. J., McDonald V. M., Grigg J., Thomas J. (2015). School-based self-management interventions for asthma in children and adolescents: A mixed methods systematic review. The Cochrane Library 3 4. Kneale D., Thomas J., Harris K. (2015). Developing and optimising the use of logic models in systematic reviews: Exploring practice and good practice in the use of programme theory in reviews. PloS one, 10(11), e0142187 Details of conference abstracts: 1. Harris K., Williams SA. School absenteeism in young people with asthma: A cross- sectional study. Asthma UK Centre for Applied Research Annual Scientific Meeting. 2014. 2. Harris K., Williams SA. Mosler G., Grigg J. Impact of asthma control and medication adherence in schools: A pilot study. HSRN Symposium. 2015. 3. Harris K., Mosler G., Williams SA., Grigg J. Suboptimal asthma control and asthma medication adherence in UK secondary school children. American Thoracic Society Annual Meeting. 2016. 4. Harris K., Ahenda L., Cameron-Mowat L., Casement T., Alder J., James J., Grigg J. Development of an asthma awareness film in London secondary schools. 2017. 5. Harris K., Mosler G., Grigg J. Nonadherence with asthma medication in teenagers. European Respiratory Society Annual Meeting. 2017. Details of collaborations: 1. The learning and outreach officer on the team assisted with the recruitment of schools for the study. 2. Dr Dylan Kneale, research officer at the Institute of Education, worked with me on the systematic review. Dr Kneale and I independently conducted the database searches, screened the identified papers, and independently extracted the data from the included studies for analysis. Dr Kneale ran the statistical analyses for the review and contributed to the write-up of the Cochrane review. 3. This PhD was funded by the NIHR CLAHRC North Thames. 4 Data sharing and audit: All of the data that has been used for the purposes of this thesis has been stored in accordance with the research protocol and ethical recommendations. All of the questionnaire data files have a timestamp, and are stored securely on a password protected document on a Queen Mary University of London (QMUL) computer. The focus group data has been transcribed externally (a copy of the confidentiality agreement can be found in the appendices) and all transcriptions and original voice recordings are stored on a QMUL computer behind password protected firewalls. This data can be accessed via a password for the purposes of audit. The systematic review data is stored on the EPPI-Reviewer server, and can be accessed by members of the review team via a password protected user name and password server. 5 Abstract Background: Asthma is the most common long-term condition in children in the United Kingdom (UK). Asthma-related hospitalisations and mortality are disproportionally higher in the UK, compared with other European countries, however the reasons for this disparity remain unclear. A putative explanation is that that prevalence of suboptimal asthma control in children in the UK is higher than in continental Europe. If this is indeed correct, then the drivers of suboptimal control, such as poor adherence to therapy resulting from poor understanding of the role of preventer medication (inhaled corticosteroids (ICS)) in UK children would be of significant clinical interest. Therefore, in this thesis, I sought to first identify the levels of asthma control and medication adherence in a non-random sample of London secondary school children. Then, I used focus groups to further highlight the barriers to good medication adherence, and generate insights into potential solutions. To achieve these aims, I developed and implemented an online questionnaire to be delivered in schools, which included the validated Asthma Control Test (ACT). Methods: This thesis is divided into three main sections. The first and second sections include original data from an observational research study, which collected data about asthma control, from 24 London secondary schools between December 2014 and March 2016. The aim of the first section was to assess current levels of asthma control and medication adherence among children with asthma in London secondary schools. Data were collected using an online questionnaire, which included the validated ACT to measure asthma control, as well as additional questions about knowledge, healthcare use, medication use, school attendance, lifestyle and emotion and behaviour, using the validated Me and My School (M&MS) questionnaire. The second section of this thesis includes data generated from six focus groups, conducted in four London secondary schools with 56 students. In order to generate data to inform future interventions, discussions focused on the barriers to medication adherence among teenagers, and how these barriers could be addressed. 6 The third section comprises a systematic review of school-based self-management interventions for children with asthma. The review uses a mixed-methods approach, and includes both quantitative and qualitative study data. A process evaluation is also included, to identify intervention elements that are associated with implementation success. Results: 766 children with asthma from 24 schools were surveyed. Almost half of the students (45.7%; n = 350) had poor asthma control by ACT score. Adherence with asthma medication was low, regardless of asthma control (56.2% self-reported forgetting to use their ICS “preventer” inhaler; 29% self-reported not using their SABA “reliever” inhaler when they needed it, at least some of the time). Health care involvement was relatively high, with at least one unplanned GP visit, due to asthma in the previous four weeks, reported by 28.1% of students; at least one unplanned hospital visit was self-reported by 15.7% of students; and at least one unplanned school nurse visit due to asthma was self-reported by 16% of students. At least one whole school absence was reported by 20.9% of students. Unplanned medical care and school absences were higher among children with poor asthma control, according to the ACT. Themes from focus groups suggested that social stigma, fear of embarrassment, forgetfulness, and incorrect attitudes towards medication were all contributory factors to poor medication adherence. Communications with healthcare professionals were also identified as key unmet needs of teenagers with asthma. The findings from the meta-analyses, included in the systematic review of school-based self- management interventions, showed that