UK Cystic Fibrosis Registry 2014 Annual Data Report

Transcription

1 UK Cystic Fibrosis Registry 2014 Annual Data Report Published August 2015

2

3 The content of this report may not be used or reproduced in publications without permission of the Cystic Fibrosis Trust. Contents Foreword 6 Executive summary 7 Introduction 8 Section 1: UK-wide analysis Summary of the UK Cystic Fibrosis Registry Age distribution by gender Median height percentiles among children and young persons (<20 years) Median weight percentiles among children and young persons (<20 years) Median BMI percentiles among children and young people (<20 years) Median BMI values among adults over the age of Education and employment in adults over 16 years of age 17 Diagnosis of cystic fibrosis Age at diagnosis and screening statistics among children under Age at diagnosis and screening statistics among adults aged 16 and over in Lung health Median FEV 1 (% predicted) Mean FEV 1 (% predicted) among patients aged 6 years and older by year in 2008 and Median FEV 1 (% predicted) vs BMI among patients aged 16 years and older 23 Lung infections Lung infections in Lung infections over time 26 Complications Prevalence of complications Incidence of complications CF-related diabetes Transplants 29 cysticfibrosis.org.uk 3

4 1.19 Ivacaftor use and outcomes Intravenous (IV) antibiotic use and outcomes 30 Nebulised drug treatments Inhaled antibiotic use among patients with chronic Pseudomonas aeruginosa DNase Hypertonic saline Long-term azithromycin use Physiotherapy Other therapy Feeding Age distribution of death in Genotypes 35 Section 2: UK-wide centre analysis 37 A guide to charts 38 Section 2a Paediatric centre analysis Median FEV 1 % predicted among patients aged 6 years and older by paediatric centre/clinic Median BMI percentile among patients aged 2 to 15 years by paediatric centre/clinic Proportion of patients with chronic P. aeruginosa by paediatric centre/clinic Proportion of patients receiving DNase treatment by paediatric centre/clinic 42 Section 2b Adult centre analysis Median age (years) by adult service Median FEV 1 % predicted by adult service Median BMI among patients aged 16 years and older by adult service Proportion of patients with chronic P. aeruginosa by adult service Proportion of patients receiving DNase treatment by adult service 47 Appendix 48 Appendix 1: Centre level data tables 48 Paediatric centres/clinics providing data in 2014 ordered by clinic ID 48 Adult centres/clinics providing data in 2014 ordered by clinic ID 50 Paediatric centres/clinics providing data in 2014 ordered alphabetically 52 Adult centres/clinics providing data in 2014 ordered alphabetically 54 Appendix 2: Glossary 56 Appendix 3: Composition of UK CF Registry Steering Committee 59 4 UK Cystic Fibrosis Registry 2014 Annual Data Report

5 UK Cystic Fibrosis Registry 2014 Annual Data Report An at-a-glance version of this report can be found at cysticfibrosis.org.uk/registryreports Report prepared by Siobhán Carr Rebecca Cosgriff Vian Rajabzadeh-Heshejin Consultant Respiratory Paediatrician Registry Lead Data Analyst With assistance from The UK CF Registry Steering Committee Chloe Ainsley Senior Graphic Designer Noreen Caine Registry Consultant Elaine Gunn Registry Data Manager Stephanie MacNeill Medical Statistician Acknowledgements First and foremost, the UK Cystic Fibrosis Registry team would like to thank people with cystic fibrosis and their families for their support, as well as anyone who has generously donated to the Cystic Fibrosis Trust. We would also like to express our gratitude to the UK centres and clinics, for their continued dedication to obtaining consent and submitting data to the Registry. The Cystic Fibrosis Trust and the Registry Steering Committee would like to extend a special thank you to Professor Diana Bilton, who has been instrumental in setting up and developing the UK CF Registry as Chair of the Registry Steering Committee from Contact information For more information about this report, or the UK Cystic Fibrosis Registry, please contact us by: registry@cysticfibrosis.org.uk cysticfibrosis.org.uk 5

6 Foreword I am delighted to introduce the UK Cystic Fibrosis Registry 2014 Annual Data Report. We are living through a time of extraordinary hope for people with cystic fibrosis (CF) and 2014 is the first year that the UK CF Registry has been able to publish information about the effect of ivacaftor, a transformational new treatment licensed for those with the G551D mutation. This therapy is the first of a potential pipeline of personalised treatment that tackles the root cause of CF, rather than its symptoms. As more treatments become available to an increasing number of people with CF, so data from the UK CF Registry will be instrumental in informing decisions by the NHS on whether and when to fund these expensive medications. This year, the Registry includes the data from 10,583 people, representing over 99% of people with CF in the UK. This shows an increase in the UK CF population of over 1,000 people since 2010; with an increase in the proportion of adults with the condition from 55.5% in 2010 to 59.3% in It is tremendous news that more people with CF are living to adulthood. Yet this brings with it new challenges. Providing care and support for people who are living longer, and experiencing additional complications of CF such as CF-related diabetes (shown to be present in almost a third of adults with CF in 2014), is a problem that will take the greatest minds, together with abundant and reliable healthcare data, to solve. The report also shows continued successes across the UK in reducing the rate of pseudomonas infections, although no real change in the incidence of nontuberculosis mycobacterium (NTM) (1.2% this year down from 1.3% in 2013). As the population of people with CF evolves, so too does its Registry. Early in 2015 the UK CF Registry surveyed the community s views on data sharing, protection, and reporting. We were told loud and clear that people with CF and their families want all of the information we can possibly give them, in as much detail as possible. I hope we have taken the first, modest step in meeting this request with this report. Previously we have published a summary report for people with cystic fibrosis, and a detailed report for the scientific community. This year we publish a detailed report, and an at-a-glance version, both intended to be accessible to all audiences, giving people with cystic fibrosis access to as much information as they desire. Developing the way that we report results from the UK CF Registry back to the wider CF community is a journey that we need everyone s help to complete. Any feedback on this report, positive or not, is very welcome and can be sent to us using the information in the contact us section of this report (page 5). The UK CF Registry survey report is available in detailed and at-a-glance form at Another important development on the horizon for the UK CF Registry is an update to the software that supports it. Due to launch in early 2016, the new Registry system will provide healthcare teams with more advanced tools to help them enter data, as well as keep track of what it shows them, to constantly work towards improving care for people with cystic fibrosis. The new platform will, in due course, also enable people with cystic fibrosis to enter and access their own data, something else people with CF have told us they want. Finally, I want to take this opportunity to thank all those who help to make the Registry such an extraordinary asset to the CF community from the multidisciplinary clinical teams in CF centres across the UK to the thousands of supporters whose fundraising efforts make it all possible. Most of all, I want to thank all those with cystic fibrosis and their guardians who give their consent for their data to be collected and used in this way. The Registry is a tremendous example of how our community works together for the common good, and we are committed to protecting and developing it to deliver maximum impact on the lives of people with cystic fibrosis. Ed Owen Chief Executive 6 UK Cystic Fibrosis Registry 2014 Annual Data Report

7 Executive summary The UK CF Registry holds more vital information now than ever before; not only do we have greater numbers of people with cystic fibrosis, 10,583 in 2014, but the quality of data is still improving. In 2014, 89% of people registered onto the database have complete data. To date 97.7% of people have a genotype value recorded, this is at a time when it is increasingly important for people with cystic fibrosis and their care teams to be aware of their genotypes, because of the new personalised therapies. With these large numbers comes a greater confidence in the results we are able to communicate to the cystic fibrosis community. These include the fact that people with cystic fibrosis are now diagnosed earlier something that is key to early intervention and better health. In 2014, after several years of plateau, the median age of diagnosis across the whole population has dropped to two months, which means we are finally seeing the effects of the newborn screening heel prick programme. 91.6% of the under-five age group are now diagnosed by newborn screening. As expected with any screening programme, it will not pick up 100% of babies born with cystic fibrosis, and both adult and paediatric clinicians still need to be alert for people presenting with cystic fibrosis on clinical grounds. We report the median predicted survival as 40.1 years in You will note this figure has fluctuated over the last few years. This variation in predicted survival is because there are small numbers of deaths relative to the whole cystic fibrosis population. The proportion of adults (>16 years) with cystic fibrosis is continuing to increase at 59.3%, with 70.1% of these adults reporting being either in work or education. This report suggests lung function (as shown by FEV 1 ), appears to be better across most age ranges than our comparison base year of The decrease in the prevalence of chronic Pseudomonas aeruginosa, also shown last year, has been maintained, with a peak of 57.7% in adults aged However, the prevalence of Staphylococcus aureus remains about the same at around the 20% mark once adulthood is reached. The prevalence of other complications such as ABPA (10.8%) remains fairly static. CF-related diabetes continues to be well screened for and there is a slight suggestion that treatment for this complication has been increasing over the last few years, with 32.3% of adults currently recorded as on treatment. Data on transplantation is shown over the last five years: showing a steady rise in the number evaluated for transplant (247), the number accepted on to transplant lists (146) and the number receiving transplants, with 59 people recorded as having bilateral lung transplants in There have been impressive increases in the use of preventative inhaled medication such as DNase (54.5%) and hypertonic saline (26.1%), with peak use for DNase being in the year age group. The consensus goal of 90% of people with chronic Pseudomonas being on a suitable suppressive inhaled antibiotic is nearly achieved this year, with 88.6% recorded on one of these therapies compared to 76.1% in The swap from nebulised antibiotics to dry powdered ones is also apparent and will be interesting to watch over time. The effect of these increases on requirement for rescue medication such as IV antibiotics is currently being explored by research groups. Finally, centre level data is presented in the second half of the report. As ever, care needs to be taken when interpreting these charts; there is no adjustment for factors that can influence an individual centre s results, such as age of the overall population (in an adult clinic), or genotype distribution. We hope that you find the contents of this report interesting and useful. We look forward to hearing your views about the report. Siobhán B Carr Acting Chair of the UK CF Registry Steering Committee cysticfibrosis.org.uk 7

8 Introduction This report is aimed at anyone who is interested in the health, care, and outcomes of people with cystic fibrosis (CF) in the UK. This includes people with CF, their families and clinical teams, healthcare managers, commissioners, and policy makers. An at-a-glance version of this report can be found at Cystic fibrosis Cystic fibrosis is an inherited disease caused by a faulty gene. The gene and the protein it makes, known as CFTR, controls the movement of salt and water in and out of cells. When the gene is faulty, the lungs can become clogged with mucus over time. This damages the lungs. Around 85% of people with cystic fibrosis also have difficulty digesting food. UK Cystic Fibrosis Registry The UK CF Registry has been sponsored and hosted by the Cystic Fibrosis Trust since It is a database of consenting people with CF in the UK. The Registry collects demographic, treatment, and health outcomes data. You can find a full list of the data items we collect at The purpose of the UK CF Registry is to improve the health of people with cystic fibrosis. This is done in a number of ways: Helping people with CF and their families understand cystic fibrosis, and make informed decisions. Giving clinical teams the evidence they need to improve the quality of care.! Monitoring the safety and effectiveness of new treatments for cystic fibrosis. Providing data for research to find out the best ways of treating, and beating cystic fibrosis. Helping commissioners provide funding to NHS CF centres that is proportionate. 8 UK Cystic Fibrosis Registry 2014 Annual Data Report

9 Governance The Registry Steering Committee (RSC) (Appendix 3) is responsible for making sure that the UK CF Registry is compliant with legislation like the Data Protection Act 1998, and its Research Ethics Study Protocol. The RSC also assesses applications for data, and makes recommendations about the future development of the Registry. Data are only recorded on the Registry if explicit written consent is given by the patient or, for a child, the patient s carer. When data are provided to third parties, such as the NHS or university researchers, they are either anonymised (all identifiable data removed completely) or pseudonymised (all identifiable data replaced with a unique identification number). Pseudonymisation is used so that data can be traced back to what is in the live database for the purposes of updating the data or answering queries. Anonymisation and pseudonymisation of the data means that the Registry data used for research, and the results that come from it, cannot identify the people whose data are stored on the UK CF Registry. Data collection Data are entered onto the UK CF Registry by NHS employees at cystic fibrosis centres in the UK, using a secure web portal. Where can I find more information? You can find out more about cystic fibrosis, and the UK CF Registry, at cysticfibrosis.org.uk 9

10 Section 1: UK-wide analysis Words in this report that appear in the glossary are highlighted the first time they appear and explained in appendix 2 on page 56. This section provides an overview of the cystic fibrosis population, health and care in the United Kingdom, including cystic fibrosis centres in England, Northern Ireland, Scotland, and Wales. 1.1 Summary of the UK Cystic Fibrosis Registry CF patients registered 1 Excluding diagnoses that year CF patients with complete data 2 ; n(%) (85%) 8679 (89%) 8794 (87%) (88%) (89%) Age in years; median All newly diagnosed patients (newborn screening and other) Number of patients born each year identified by newborn screening 4 Age at diagnosis in months; median 3 Adults aged 16 yrs and over; % Males; % Genotyped; % Median predicted survival in years (95% Confidence interval) (36.8, 46.7) 41.5 (35.7, 46.0) 43.5 (37.8, 49.9) 36.6 (34.4, 41.6) 40.1 (34.6, 46.7) Total deaths reported (%) (1.1%) 118 (1.2%) 106 (1.1%) Age at death in years; median (95% CI) 3 (25, 29) 146 (1.4%) 29 (27, 31) 137 (1.5%) 28 (25.5, 32) Notes: 1 The number of patients who were diagnosed with CF and had not died before 1 January in the given year. 2 A patient has complete data if their team has filled in an annual review for them for that year. Patients newly diagnosed in 2014 may not have their first annual review in the same year. If newly diagnosed patients are excluded, 91% of records are complete. 3 Calculated from patients with complete data in the given year. 4 Calculated from all patients registered on the database. Some diagnosis data are added after the data entry closure each year, so the figures from previous years have been updated for this report 5 Calculated from all patients registered on the database. Complete data: Patients with at least the minimum data entered at their annual review for analysis to be carried out. 10 UK Cystic Fibrosis Registry 2014 Annual Data Report

11 1.2 Age distribution by gender n=9432 The following chart shows the mix of ages and genders in the cystic fibrosis population in the UK Proportion (%) Overall Females Males Age (years) cysticfibrosis.org.uk 11

12 1.3 Median height percentiles of children and young people (<20 years) n=4461 The following chart and table show the height percentiles of people with CF, aged 19 and under, in relation to the UK growth data for the general population. If a person with CF is on the 40 th percentile, only 40% of the population at the same age are their height or shorter; 60% are taller. percentile Median height Age (years) Overall Females Males Overall Female Male Age N Median IQR N Median IQR N Median IQR Overall UK Cystic Fibrosis Registry 2014 Annual Data Report

13 1.4 Median weight percentiles among children and young people (<20 years) n=4461 The following chart and table show the weight of people with CF, aged 19 and under, in relation to UK growth data. If a person with CF is at the 40 th percentile, only 40% of the population at the same age are their weight or lower; 60% weigh more. 65 Median weight percentile Age (years) Overall Females Males Overall Female Male Age N Median IQR N Median IQR N Median IQR Overall cysticfibrosis.org.uk 13

14 1.5 Median Body Mass Index (BMI) percentiles in children and young people (<20 years) n=4461 The following chart and table show the BMI percentiles of people with CF, aged 19 and under, in relation to the target BMI percentile for a person of the same age without CF (the 50 th percentile, or the BMI percentile that half of the UK population of that age has achieved). If a person with CF is at the 40 th percentile, it means that only 40% of people of the same age have the same BMI or lower; 60% have a higher BMI. Median BMI percentile Target Age (years) Overall Females Males 14 UK Cystic Fibrosis Registry 2014 Annual Data Report

15 Overall Female Male Age N Median IQR N Median IQR N Median IQR Overall cysticfibrosis.org.uk 15

16 1.6 Median Body Mass Index (BMI) values among adults (20 years and over) n=4472 The following chart and table show the BMI of people with CF aged 20 and over in relation to the target BMI for a healthy adult; 22 for women and 23 for men Median BMI Target male 23 Target female Age (years) Overall Females Males Age N Overall Median (IQR) N Female Median (IQR) N Male Median (IQR) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Overall Stallings et al, J Am Diet Assoc. 2008;108: UK Cystic Fibrosis Registry 2014 Annual Data Report

17 1.7 Education and employment in adults 16 years and over n=5592 The following table shows how people with cystic fibrosis reported their education and employment status in Please note that the groups are not mutually exclusive; someone may be a student as well as part-time working, for example. Patient reported status Number of patients (%) (n=5592) Full-time employment 1634 (29.2) Part-time employment 703 (12.6) Student 976 (17.5) Homemaker 258 (4.6) Disabled 272 (4.9) Unemployed 821 (14.7) Retired 85 (1.5) Unknown entered 930 (16.6) No data recorded 39 (0.7) Of the 4623 adults aged 16 years and older for whom an employment status questionnaire was completed, 3243 (70.1%) reported being in work or study. cysticfibrosis.org.uk 17

18 Diagnosis of cystic fibrosis 1.8 Age at diagnosis and screening in children under 16 n=4105 Newborn screening for CF has been done routinely in the whole of the UK since July It is part of the heel prick blood spot testing done at five to seven days of age. The blood sample is tested for a number of conditions, including cystic fibrosis. This means that more babies born after 2007 receive an early diagnosis than those born before. Age at diagnosis All patients; n (%) Patients aged 10 years in 2014; n (%) Pre-natal <5 0 (0) 0 (0) Birth-3months 2822 (73.5) 135 (60.3) 219 (91.6) 4-6 months 205 (5.4) 17 (7.6) 5 (2.1) 7-12 months 139 (3.7) 11 (4.9) <5 1 yr 203 (5.4) 22 (9.8) <5 2 yrs 139 (3.7) 11 (4.9) <5 3 yrs 76 (2.0) 10 (4.5) <5 4 yrs 58 (1.5) 8 (3.6) <5 5 yrs 29 (0.8) <5-6 yrs 26 (0.7) <5-7 yrs 20 (0.5) <5-8 yrs 21 (0.6) <5-9 yrs 11 (0.3) yrs 7 (0.2) yrs < yrs < yrs < yrs < yrs <5 - - Overall Patients aged 5 years in 2014; n (%) The median (range) age at diagnosis for patients aged under 16 in 2014 is 27 days (0-3 months). Diagnosis in the first three months of life is more common in children aged five years in 2014 (born after the UK-wide newborn screening programme was in place) than in children aged 10 years in 2014 (born before the UK-wide newborn screening programme was in place). For the 50 children with complete data born in 2014, 41 (82%) were identified by newborn screening. A total of 130 patients born in 2014 were identified by newborn screening (including those without complete data). As there is a delay between newborn screening tests being performed and the results entering the Registry, these results are updated retrospectively each year to take updated data into account. Therefore the number of patients identified in 2013 is higher in this report (177) than was recorded in the 2013 report (127). It is likely that the 2014 figure of 130 will be updated in the next annual report in UK Cystic Fibrosis Registry 2014 Annual Data Report

19 1.9 Age at diagnosis and screening in adults aged 16 and over in 2014 n=5592, 5255 with a diagnosis date The table below shows the age of people aged 16 and over in 2014 when they were diagnosed. These people were born before newborn screening was done routinely across the UK. There were some regions with newborn screening prior to Age at diagnosis n (%) Pre-natal 1 (0) Birth-3 months 2225 (40.2) 4-6 months 508 (9.2) 7-12 months 354 (6.4) 1 yr 460 (8.3) 2 yrs 279 (5.0) 3 yrs 219 (4.0) 4 yrs 173 (3.1) 5 yrs 84 (1.5) 6 yrs 78 (1.4) 7 yrs 53 (1.0) 8 yrs 61 (1.1) 9 yrs 47 (0.9) 10 yrs 41 (0.7) 11 yrs 41 (0.7) 12 yrs 40 (0.7) 13 yrs 45 (0.8) 14 yrs 36 (0.7) 15 yrs 45 (0.8) yrs 161 (2.9) yrs 108 (2.0) yrs 103 (1.9) yrs 111 (2.0) yrs 87 (1.6) yrs 61 (1.1) yrs 34 (0.6) yrs 43 (0.8) 61 yrs+ 33 (0.6) cysticfibrosis.org.uk 19

20 Lung health For people with cystic fibrosis mucus in the lungs leads to repeat or chronic infections and inflammation, which can cause permanent damage. In CF the condition of the lungs is often measured using FEV 1 ; the forced expiratory volume of air in the first second of an exhaled breath. In this report, FEV 1 % predicted is based on the FEV 1 we would expect for a person without cystic fibrosis of the same age, gender, height, and ethnicity. A person with CF who has FEV 1 % predicted of 100 can breathe out the same amount of air in the first second of an exhaled breath as we would expect from a comparable person without cystic fibrosis. A person with FEV 1 % predicted of 50 breathes out half the volume of air as a comparable person without cystic fibrosis. For people with CF, an FEV 1 % predicted of 85 or higher is the target, as this indicates normal or near-normal lung health. Most people can continue to lead a relatively normal life, including going to school or work, with 50% of their predicted FEV 1. Once FEV 1 is lower than 50% of the predicted value, it becomes more difficult to lead a normal life. If FEV 1 declines to 30% or less, a patient may be considered for lung transplant. An aim of CF care is to prevent FEV 1 % predicted from falling as much as possible, for as long as possible. This is often a team effort between people with CF, their family, and their medical team, which can include doctors, nurses, physiotherapists, dieticians, and psychologists. The FEV 1 % predicted values shown in this report are calculated using an equation called Global Lung Initiative, or GLI. 20 UK Cystic Fibrosis Registry 2014 Annual Data Report

21 1.10 Median FEV 1 % predicted (GLI equations) among patients aged 6 years and older n=7356 The chart and table in this section show information about those patients whose FEV 1 data were complete. People with CF who have had lung transplants are excluded, as their new non-cf lungs would have lung health similar to a person without CF. Median FEV Target Age (years) Overall Females Males Target Age (yrs) Overall Female Male N Median IQR N Median IQR N Median IQR Overall cysticfibrosis.org.uk 21

22 1.11 Median FEV 1 % predicted over time (GLI equations) among patients aged 6 years and older (excluding patients post lung transplant) n=7356 in 2014, n=6082 in 2008 As we learn more about cystic fibrosis and how to treat it, we hope to improve the outcomes of people with the condition. The chart below shows how FEV 1 % predicted in 2014 compares to Registry data from is shown as the comparator year, as this is the earliest year that we can be confident that the coverage of the Registry gives an accurate reflection of the CF population. People with CF who have had lung transplants are excluded, as their new non-cf lungs would have lung health similar to a person without cystic fibrosis Target 70 Median FEV Age (years) An analysis was conducted in order to determine whether there were statistically significant differences in FEV 1 (% predicted) in 2014 compared to 2008 by age category. The results show that there was a small, but statistically significant difference in the age bands where the p value is less than Age (years) p-value UK Cystic Fibrosis Registry 2014 Annual Data Report

23 1.12 Median FEV 1 % predicted and BMI in patients 16 and older (excluding patients post-lung transplant) n=7356 The goal BMI for adults is 22 for women, and 23 for men. The chart below shows the relationship between BMI and FEV 1 % predicted. A healthy BMI can protect people with CF against lung infection, and help to preserve lung health. People with CF who have had lung transplants are excluded, as their new non-cf lungs would have lung health similar to a person without cystic fibrosis. Median FEV1 1 % %precicted predicted Target female 22 Target male BMI Females Males Each point represents the median FEV 1 % predicted of patients for each given BMI value. Due to the wide range of BMIs in this population all BMI 30 are grouped into one. cysticfibrosis.org.uk 23

24 Lung infections Lung infections can permanently reduce lung function in people with cystic fibrosis. Some lung infections can become chronic, meaning that they can t ever be removed completely using medicines. The definition for chronic on the Registry is three or more growths in a year, and is only reported for Pseudomonas aeruginosa and Staphylococcus aureus. Other bacteria are reported if they grow at all in the year Lung infections in 2014 n= Proportion of patients (%) Age (years) Chronic Staphylococcus aureus; n=1460 (15.5%) Chronic Pseudomonas aeruginosa; n=2963 (31.4%) Intermittent Pseudomonas aeruginosa; n=1659 (17.6%) Burkholderia cepacia complex; n=329 (3.5%) MRSA; n=278 (2.9%) Haemophilus Influenza; n=1310 (13.9%) 24 UK Cystic Fibrosis Registry 2014 Annual Data Report

25 N patients in age bands Chronic S. aureus; n (%) Chronic P. aeruginosa; n (%) Interrmittent P. aeruginosa; n (%) Intermittent S.aureus; n(%) Age (years) Overall Children (<16 years) (2.8) 26 (2.7) 179 (18.7) 152 (15.9) 55 (5.3) 32 (3.1) 218 (21.0) 184 (17.7) 94 (10.6) 64 (7.1) 217 (24.2) 196 (22.0) B. cepacia; n (%) 2 (0.2) 6 (0.6) 21 (2.3) MRSA; n (%) 13 (1.4) H. influenza; n (%) 276 (28.7) 25 (2.4) 320 (30.7) 24 (2.7) 211 (23.3) 125 (13.7) 183 (20.0) 198 (21.6) 193 (21.1) 20 (2.2) 39 (4.2) 110 (11.9) 183 (18.3) 307 (30.6) 212 (21.1) 191 (19.0) 47 (4.6) 24 (2.4) 105 (10.3) 252 (25.5) 448 (45.1) 204 (20.5) 180 (18.2) 46 (4.6) 37 (3.7) 83 (8.3) 227 (24.7) 515 (56.4) 117 (12.8) 161 (17.5) 50 (5.4) 32 (3.4) 66 (7.1) 147 (20.4) 414 (57.7) 79 (11.0) 107 (14.8) 39 (5.4) 30 (4.1) 40 (5.5) 106 (18.3) 339 (58.5) 76 (13.1) 83 (14.4) 31 (5.3) 17 (2.9) 31 (5.3) 61 (17.2) 195 (54.5) 48 (13.4) 57 (16.1) 24 (6.7) 13 (3.6) 25 (6.9) 70 (19.2) 177 (48.4) 39 (10.7) 43 (11.8) 22 (5.9) 54 (20.7) 123 (47.1) 36 (13.8) 30 (11.5) 12 (5.6) 59 (18.4) 140 (43.5) 36 (11.2) 48 (15.0) 6 (1.6) 5 (1.9) 13 (4.0) 19 (5.1) 9 (3.4) 15 (4.6) Adults ( 16 years) 301 (7.9) 1159 (21.0) 305 (8.0) 2658 (48.2) 812 (21.3) 847 (15.4) 725 (19.1) 900 (16.3) 9 (2.8) 49 (1.3) 280 (5.0) 101 (2.6) 177 (3.2) 917 (23.9) 393 (7.0) cysticfibrosis.org.uk 25

26 1.14 Lung infections over time 2008 n=6082 and 2014 n=9432 Proportion of patients (%) Age (years) Chronic Pseudomonas aeruginosa (2008) Chronic Pseudomonas aeruginosa (2014) Chronic Staphylococcus aureus (2008) Chronic Staphylococcus aureus (2014) Chronic P. aeruginosa; p-value Age (years) An analysis was conducted in order to determine whether there was a statistical difference between the proportion of people with chronic pseudomonas aeruginosa in 2014 compared to The results show that there is a statistically significant difference, after the age of UK Cystic Fibrosis Registry 2014 Annual Data Report

27 Complications 1.15 Prevalence of complications Overall (n=9432) <16 years (n=3840) 16 years (n=5592) N (%) N (%) N (%) Respiratory Related Nasal polyps requiring 214 (2.3) 41 (1.1) 173 (3.1) surgery; n (%) Sinus disease; n (%) 828 (8.8) 36 (0.9) 792 (14.2) Asthma; n (%) 1368 (14.5) 516 (13.4) 852 (15.2) ABPA; n (%) 1017(10.8) 298 (7.8) 719 (12.9) Haemoptysis; n (%) 775 (8.2) 41 (1.1) 734 (13.1) Pneumothorax requiring chest 67 (0.7) 3 (0.1) 64 (1.1) tube; n (%) Nontuberculous mycobacteria 433 (4.6) 208 (5.4) 225 (4.0) or atypical mycobacteria; n (%) Pancreas & Hepatobiliary Disease Liver enzymes; n (%) 1071 (11.4) 251 (6.5) 820 (14.7) Liver disease; n (%) 1322 (14.0) 342 (8.9) 980 (17.5) Cirrhosis with no portal 126 ( (0.7) 99 (1.8) hypertension; n (%) Cirrhosis with portal 163 (1.7) 20 (0.5) 143 (2.6) hypertension; n (%) Gall bladder disease requiring 36 (0.4) 0 (0.0) 36 (0.6) surgery; n (%) Pancreatitis; n (%) 68 (0.7) 4 (0.1) 64 (1.1) GI bleed req hosp variceal; n (%) 9 (0.1) 2 (0.1) 7 (0.1) Upper Gastrointestinal GORD; n (%) 1494 (15.8) 348 (9.1) 1146 (20.5) Peptic ulcer; n (%) 6 (0.1) 0 (0.0) 6 (0.1) GI bleed req hosp non variceal; 9 (0.1) 2 (0.1) 7 (0.1) n (%) Lower Gastrointestinal Intestinal obstruction; n (%) 556 (5.9) 123 (3.2) 433 (7.7) Fibrosing colonopathy/ colonic 3 (0.0) 0 (0.0) 0 (0.0) structure; n (%) Rectal prolapse; n (%) 31 (0.3) 24 (0.6) 7 (0.1) Renal Kidney stones; n (%) 85 (0.9) 5 (0.1) 80 (1.4) Renal failure; n (%) 50 (0.5) 3 (0.1) 47 (0.8) Muscolo-Skeletal Arthritis; n (%) 163 (1.7) 11 (0.3) 152 (2.7) Arthropathy; n (%) 532 (5.6) 19 (0.5) 513 (9.2) Bone fracture; n (%) 46 (0.5) 12 (0.3) 34 (0.6) Osteopenia; n (%) 1225 (13.0) 30 (0.8) 1195 (21.4) cysticfibrosis.org.uk 27

28 Osteoporosis; n (%) 519 (5.5) 2 (0.5) 517 (9.2) Other Cancer confirmed by histology; 33 (0.3) 2 (0.1) 31 (0.6) n (%) Port inserted or replaced; n (%) 552 (6.0) 202 (5.3) 350 (6.3) Absence of vas deferens (males 666 (7.1) 1 (0.3) 665 (12.0) only); n (%) Depression; n (%) 415 (4.4) 3 (0.1) 412 (7.4) Hearing loss; n (%) 213 (2.3) 28 (0.7) 185 (3.3) Hypertension; n (%) 236 (2.5) 2 (0.1) 234 (4.2) 1.16 Incidence of complications Overall (n=9052) <16 years (n=3839) 16 (n=5213) Overall (n=9432) <16 years (n=3840) 16 (n=5592) Non-tuberculosis 124 (1.3) 71 (1.8) 53 (1.0) 113 (1.2) 52 (1.4) 61 (1.1) mycobacteria or atypical mycobacteria; n (%) ABPA; n (%) 157 (1.7) 58 (1.5) 99 (1.9) 143 (1.5) 67 (1.7) 76 (1.4) Cirrhosis - no portal 30 (0.3) 12 (0.3) 18 (0.3) 37 (0.39) 6 (0.16) 31 (0.55) hypertension; n (%) Cirrhosis - with portal 26 (0.3) 6 (0.2) 20 (0.4) 22 (0.23) 6 (0.16) 16 (0.29) hypertension; n (%) Cancer confirmed by histology; n (%) 13 (0.1) 1 (0.03) 12 (0.2) 12 (0.13) 0 (0) 12 (0.21) 1.17 CF-related diabetes Cystic fibrosis-related diabetes (CFRD) is common in adults and adolescents with cystic fibrosis. This is because, for many people with CF, the pancreas does not work properly. This can mean that not enough insulin is produced, causing CFRD. CFRD is different from type 1 and type 2 diabetes, but has features of both. All 10 years (n=6970) years (n=1624) 16 years (n=5346) Treatment for CF-related 1924 (27.6) 195 (12.0) 1729 (32.3) diabetes; n(%) Screening for CF-related diabetes Yes 3939 (56.5) 1236 (76.1) 2703 (50.6) No 1051 (15.1) 189 (11.6) 862 (16.1) Known CF-related 1851 (26.6) 156 (9.6) 1695 (31. 7) diabetes Unknown 128 (1.8) 43 (2.7) 85 (1.6) 28 UK Cystic Fibrosis Registry 2014 Annual Data Report

29 1.18 Transplants Lung transplantation has been available to people with cystic fibrosis for almost 30 years. Today the most common operation carried out is called a double lung transplant, or a Bilateral Sequential Lung transplant. Survival is constantly improving, with approximately 85% of patients surviving for at least one year following the operation, and many returning to full time work or education. The following table shows transplant activity over time. Number of patients that year with annual review data evaluated for transplants Number accepted on the transplant list Number receiving transplants (<16) Types of transplants received: Bilateral lung Heart and lung Liver Other Number receiving transplants ( 16) 26 48* 52** 54* 67** Types of transplants received: Bilateral lung Heart and lung Liver Other * One patient received two transplants ** Two patients had two transplants 1.19 Ivacaftor Ivacaftor is a drug that began being prescribed as a treatment for cystic fibrosis in patients aged 6 years and over with at least one copy of the genotype G551D, in June The table shows ivacaftor use and outcomes from June 2012 December Number of patients on ivacaftor in the UK 402 Median (IQR) Sweat chloride before ivacaftor 104 (95-114) Sweat chloride 6-8 weeks after ivacaftor 50 (36-64) FEV 1 % before ivacaftor 61.1 ( ) FEV 1 % 6-8 weeks after ivacaftor 71.6 ( ) Number of patients stopped ivacaftor 10 People with CF have a higher amount of chloride in their sweat than a person without cystic fibrosis. This measurement is called sweat chloride and is measured in mmol/litre. cysticfibrosis.org.uk 29

30 1.20 Intravenous (IV) antibiotic use and outcomes n=(9432) When someone with cystic fibrosis becomes unwell with an infection, they might be prescribed intravenous (IV) antibiotics, which are given to the patient through their veins. This treatment can take a number of days and might take place as a hospital inpatient, or at home. Age N Patients N (%) Home Total Median days (IQR) Patients N (%) Median days (IQR) Patients N (%) Median days (IQR) (0.5) 10 (8-14) 231 (24.0) 14 (8-19) 233 (24.2) 14 (11-23) (1.1) 12 (9-25) 302 (29.0) 14 (8-21) 313 (30.0) 14 (14-29) (2.0) 20 (11-32) 308 (34.0) 14 (7-28) 348 (38.4) 27 (14-42) (2.6) 21 (12-32) 446 (48.1) 15 (10-38) 497 (53.6) 28 (14-53) (3.1) 21 (13-32) 460 (45.1) 17 (10-40) 543 (53.2) 28 (14-56) (3.7) 22 (13-42) 469 (46.8) 19 (10-41) 596 (59.5) 30 (14-56) (3.8) 24 (14-43) 454 (48.7) 19 (10-41) 567 (60.8) 30 (14-63) (3.9) 21(14-42) 292 (40.1) 17 (8-40) 407 (55.9) 30 (14-56) (4.0) 26 (14-43) 234 (39.7) 15 (9-34) 328 (55.7) 28 (14-56) (3.8) 27 (14-42) 130 (36.0) 16 (9-31) 183 (50.7) 28 (15-55) (3.1) 25 (14-38) 106 (28.5) 14 (8-30) 165 (44.4) 28 (14-50) (2.9) 17 (12-42) 87 (33.0) 19 (9-36) 112 (42.4) 28 (15-48) (22.8) 21 (14-36) 108 (33.3) 14 (9-32) 138 (42.6) 24 (14-49) Overall (26.8) 21 (13-39) 3627 (38.5) 15 (9-35) 4430 (47.0) 28 (14-50) Nebulised drug treatments Nebulised drugs are medications that are breathed in as a mist. They are changed into a mist by a pot holding liquid medication, called a nebuliser. Nebulised medications are used because: The medications go straight to where they need to work (in the lung) without having to go round the body. This can reduce side-effects. Some medication is only available as a nebulised medication, for example DNase. Large doses of medication can be given compared with some types of inhaler. It can be difficult to use some inhalers correctly. Using a nebuliser can mean that more of the medication gets into the lung. 30 UK Cystic Fibrosis Registry 2014 Annual Data Report

31 1.21 Inhaled antibiotic use among patients with chronic Pseudomonas aeruginosa Patients with chronic P. aeruginosa Overall <16 years 16 years Overall <16 years 16 years Tobramycin solution; n (%) 412 (19.6) 48 (16.1) 364 (20.2) 841 (28.4) 96 (31.5) 745 (28.0) Other aminoglycoside; n (%) 43 (2.0) 5 (0.2) 38 (2.1) 139 (4.7) 22 (7.2) 117 (4.4) Colistin; n (%) 914 (43.6) 174 (58.2) 740 (41.1) (51.1) 945 (35.6) (37.2) Promixin; n (%) 490 (23.4) 73 (24.4) 417 ( (31.0) 134 (43.9) 785 (18.2) Aztreonam; n (%) 395 (13.3) 10 (3.3) 385 (14.5) Colistimethate; n (%) 433 (14.6) 21 (6.9) 412 (15.5) Tobramycin Inhalation Powder; n (%) 802 (27.1) 24 (7.9) 778 (29.3) At least one of the above*; n (%) * In 2014, this includes Aztreonam (76.1) 257 (86.0) 1340 (74.5) 2625 (88.6) 288 (94.4) 2337 (87.9) The consensus view in the UK is that 90% of people chronically infected with P. aeruginosa should be prescribed at least one of the above inhaled antibiotics DNase DNase; n (%) Age Total patients Patients on Dnase Total patients Patients on Dnase p-value (2008 vs 2014) (7.6) (11.8) (20.1) (39.8) < (34.2) (61.6) < (46.4) (69.9) < (49.5) (68.7) < (44.0) (63.1) < (47.6) (65.3) < (43.4) (61.4) < (41.5) (60.3) < (35.0) (51.5) (35.7) (49.8) <0.001 Overall (37.2) (54.5) cysticfibrosis.org.uk 31

32 1.23 Hypertonic saline This treatment helps to thin mucus so that it is easier to cough out of the body. Age Hypertonic saline; n(%) Number of patients Patients on hypertonic saline Number of patients Patients on hypertonic saline p-value (2008 vs 2014) (0.5) (6.6) < (2.4) (16.6) < (3.5) (25.8) < (4.1) (36.7) < (4.3) (32.2) < (6.9) (28.4) < (9.9) (28.9) < (8.8) (34.5) < (11.2) (74.1) < (6.8) (26.6) < (8.0) (25.0) <0.001 Overall (5.4) (26.1) 1.24 Long-term azithromycin use in patients with and without chronic pseudomonas aeruginosa Azithromycin is an antiobiotic with anti-inflammatory properties used to treat certain infections, including P. aeruginosa Overall (n=1958) 0-3 years (n=15) 4-15 years (n=363) 16 years (n=1580) Overall (n=3705) 0-3 years (n=39) 4-15 years (n=594) 16 years (n=3072) Patients with chronic P. aeruginosa 1246 (63.6) 2 (13.3) 105 (28.9) 1139 (72.1) 1945 (52.5) 5 (12.8) 101 (17.0) 1839 (59.9) Patients without chronic P. aeruginosa 712 (36.4) 13 (86.7) 258 (71.1) 441 (27.9) 1760 (47.5) 34 (87.2) 493 (83.0) 1233 (40.1) 32 UK Cystic Fibrosis Registry 2014 Annual Data Report

33 1.25 Physiotherapy Physiotherapy helps people with cystic fibrosis clear sticky mucus from their lungs. Active cycle of breathing techniques; n (%) Autogenic drainage (including assited autogenic drainage); n (%) Overall (n=9432) <16 years (n=3840) 16 years (n=5592) 3033 (32.5) 1720 (45.4) 1313 (23.7) 1437 (15.4) 248 (6.54) 1189 (21.5) Any form of PEP; n (%) 5135 (55.1) 2568 (67.8) 2567 (46.4) VEST; n (%) 174 (1.9) 88 (2.3) 86 (1.6) Exercise; n (%) 3229 (34.6) 1479 (39.0) 1750 (31.6) Note that these techniques are not mutually exclusive and represent primary and secondary forms of physiotherapy Other therapy Overall (n=9432) <16 years (n=3840) 16 years (n=5592) NIV; n (%) 283 (3.0) 39 (1.0) 244 (4.36) Long-term oxygen; n (%) 653 (6.9) 94 (2.4) 559 (10.0) Among those who have long-term oxygen: Continuously 157 (1.7) 9 (0.2) 148 (2.7) Nocturnal or with exertion 152 (1.6) 18 (0.5) 134 (2.4) Pro re nata (PRN) 79 (0.8) 13 (0.3) 66 (1.2) With exacerbation 265 (2.8) 54 (1.4) 211 (3.8) 1.27 Feeding Supplementary feeding, often using a nasogastric (via the nose) or gastrostomy (via the abdomen) tube directly to the stomach, is considered when a person with CF has poor weight gain, or progressive weight loss, despite efforts to increase oral intake. Overall (n=9432) <16 years (n=3840) 16 years (5592) Any supplmental feeding; n (%) 3214 (34.1) 857 (22.3) 2136 (38.2) Nasogastric tube 114 (1.2) 12 (0.3) 102 (1.3) Gastrostomy tube/button 572 (6.1) 221 (5.8) 351 (6.3) Jejunal 6 (0.1) 0 6 TPN cysticfibrosis.org.uk 33

34 1.28 Age distribution of deaths in 2014 The table below shows the ages of the 137 people with cystic fibrosis who died in Age at death Number of cystic fibrosis patients Total UK Cystic Fibrosis Registry 2014 Annual Data Report

35 1.29 Genotypes Genotypes are part of the genetic makeup of a cell, organism, or individual that usually controls a particular characteristic (known as a phenotype). For people with cystic fibrosis, their genotype reveals which mutations of the CF gene causes their cystic fibrosis. Everyone living with cystic fibrosis has two mutations of the gene for CFTR; one on each allele. One is inherited from their mother, and one from their father. If both mutations (or genotypes) are the same, the person is said to be homozygous. Someone who has two different variants is heterozygous (97.7%) patients have been genotyped with a recorded value on at least one allele. DF508 Mutations; n (%) Homozygous DF (50.6%) Heterozygous DF (39.8%) No DF508 or both unidentified 886 (9.6%) Mutations Nucleotide Protein Legacy name N (%) c.1521_1523delctt p.phe508del ^F508 8, other other Other not identified not identified Not Identified c.1652g>a p.gly551asp G551D c.350g>a p.arg117his R117H c.1624g>t p.gly542x G542X c.489+1g>t no protein name 621+1G->T c.3909c>g p.asn1303lys N1303K c g>a no protein name G->A c g>a no protein name G->A c.1519_1521delatc p.ile507del ^I c.3528delc p.lys1177serfsx delC c.1679g>c p.arg560thr R560T c.1657c>t p.arg553x R553X c c>t no protein name kbC->T c.254g>a p.gly85glu G85E c.1477c>t p.gln493x Q493X c.3454g>c p.asp1152his D1152H c.178g>t p.glu60x E60X c.3846g>a p.trp1282x W1282X c.2052dela p.lys684asnfsx delA c g>a no protein name G->A c.1040g>c p.arg347pro R347P c.1646g>a p.ser549asn S549N c.1558g>t p.val520phe V520F c.3484c>t p.arg1162x R1162X c.1364c>a p.ala455glu A455E c.1000c>t p.arg334trp R334W c.1040g>a p.arg347his R347H cysticfibrosis.org.uk 35