UK Cystic Fibrosis Registry Annual Data Report

Transcription

1 UK Cystic Fibrosis Registry 2015 Annual Data Report Published August 2016

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3 UK Cystic Fibrosis Registry 2015 Annual Data Report An at-a-glance version of this report can be found at Report prepared by Siobhán Carr Consultant Respiratory Paediatrician Royal Brompton Rebecca Cosgriff UK CF Registry Lead Cystic Fibrosis Trust Vian Rajabzadeh-Heshejin Data Analyst Imperial College London With assistance from The UK CF Registry Steering Committee Chloe Ainsley Senior Graphic Designer Cystic Fibrosis Trust Elaine Gunn UK CF Registry Data Manager Cystic Fibrosis Trust Annie Jeffery UK CF Registry Coordinator Cystic Fibrosis Trust 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 cystic fibrosis centres and clinics, for their continued dedication to obtaining consent and submitting data to the Registry. Contact information For more information about this report, or the UK Cystic Fibrosis Registry, please contact The content of this report may not be used or reproduced in publications without permission of the Cystic Fibrosis Trust. cysticfibrosis.org.uk 3

4 Contents Acknowledgements 3 Contact information 3 Foreword 6 Executive summary 7 Introduction 8 Cystic fibrosis 8 UK Cystic Fibrosis Registry 8 Governance 9 Data collection 9 Section 1: UK-wide analysis Summary of the UK Cystic Fibrosis Registry 10 UK Cystic fibrosis population Age distribution by gender Median height percentiles among children and young people (<20 years) Median weight percentiles among children and young people (<20 years) Median Body Mass Index (BMI) percentiles among children and young people (<20 years) Median Body Mass Index (BMI) values among adults (20 years and over) Education and employment in adults over 16 years of age Pregnancy 16 Diagnosis of cystic fibrosis Age at diagnosis and screening statistics among children under 16 in Age at diagnosis and screening statistics among adults aged 16 and over in Lung health Median FEV 1 % predicted (GLI equations) among people aged 6 years and older Mean FEV 1 % predicted over time (GLI equations) among people aged 6 years and older Median FEV 1 % predicted and BMI among people aged 16 years and older Median best FEV 1 % predicted in people aged 6 years and older 22 Lung infections Lung infections in Lung infections over time 25 Complications Prevalence of complications Incidence of complications 27 4 UK Cystic Fibrosis Registry 2015 Annual Data Report

5 1.19 Nontuberculous mycobacteria (NTM) or atypical mycobacteria CF-related diabetes 27 Therapies Transplant Ivacaftor use and outcomes Intravenous (IV) antibiotic use and outcomes Inhaled antibiotic use among patients with chronic Pseudomonas aeruginosa Mannitol DNase Hypertonic saline Long-term azithromycin use Physiotherapy Other therapy Feeding Survival Age distribution of deaths in Genotypes Genotypes a Most common genotypes by devolved nation 37 Section 2 and 3: Centre-level analysis 38 A guide to charts 39 Section 2 Paediatric centre analysis Median FEV 1 % predicted among patients aged 6 years and older by paediatric centre/clinic (without a history of lung transplant) (GLI equations) Median BMI percentile among patients aged 2 to 15 years by paediatric centre/clinic Proportion of patients with chronic Psuedomonas aeruginosa by paediatric centre/clinic Proportion of patients receiving DNase treatment by paediatric centre/clinic Proportion of patients receiving hypertonic treatment by paediatric centre/clinic DNase and Hypertonic Saline use by by paediatric centre/clinic 46 Section 3 Adult centre analysis Median age (years) by adult service Median FEV 1 % predicted by adult service (without a history of lung transplant) (GLI equations) 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 Proportion of patients receiving hypertonic treatment by adult service DNase and Hypertonic Saline use by adult service 53 Appendices 54 Appendix 1: Centre level data tables 54 Paediatric centres/clinics providing data in 2015 ordered by clinic ID 54 Adult centres/clinics providing data in 2015 ordered by clinic ID 56 Paediatric centres/clinics providing data in 2015 ordered alphabetically by city 58 Adult centres/clinics providing data in 2015 ordered alphabetically by city 60 Appendix 2: Glossary 62 Appendix 3: UK CF Registry Steering Committee structure 65 cysticfibrosis.org.uk 5

6 Foreword I am very pleased to introduce to you the UK Cystic Fibrosis Registry 2015 Annual Data Report. The CF Registry plays an integral part in our wider fight for a life unlimited by cystic fibrosis (CF), by boosting worldclass research, driving quality improvement in clinical care and directly empowering those living with the condition. Yet it has the potential to provide even greater impact and we are investing significant resources to enhance its capability. The first phase of this was to move to a new software platform, completed in February this year. This will enable the Registry to collect clinical trial data from CF teams and quality of life data direct from those with cystic fibrosis who choose to provide it. We are also developing a portal that will, in time, allow those with cystic fibrosis to access their own clinical data online. Keep an eye on our website, social media, and CF Life magazine for updates on all these developments. It is heartening to see from this year s report the impact of the Trust s Genotype Matters campaign, launched in 2015.Today, more than 98% of people with cystic fibrosis on the UK CF Registry have a genotype recorded for both cystic fibrosis mutations. The completeness of these data are vital, to ensure people can gain access to the best medicines for them, and to further important research into new therapies. Our work continues to bring the completeness of these data as close to 100% as possible. Find out more at genotypematters.org. As the lives and life choices of people with cystic fibrosis change, so the CF Registry needs to reflect it. For the first time this year, for example, the report includes information about pregnancies, 90 women with cystic fibrosis reported as having a live birth or still pregnant in For those wanting more information about fertility and family planning in cystic fibrosis, please download our new fertility booklet from cysticfibrosis.org.uk/fertility or contact our helpline by calling or ing helpline@cysticfibrosis.org.uk. This report demonstrates the positive impact of national newborn screening for cystic fibrosis with more than 9 out of 10 five-year-olds with cystic fibrosis in 2015 having being diagnosed at birth. It also shows that 71% of people with cystic fibrosis over 16 are in work or study, with almost a third in full-time employment. The Registry is an extraordinary asset to the UK CF community, and I would like to thank everyone who helps make it possible. From the multidisciplinary teams in CF centres throughout the UK to the thousands of generous supporters who raise money or donate and enable us to maintain the Registry we couldn t do it without you. Above all, thank you to everyone living with cystic fibrosis and their friends and family who consent to their data being collected for this world-class resource; we will keep working to develop the potential of the Registry so that we can deliver maximum impact for everyone affected by cystic fibrosis. Ed Owen Chief Executive 6 UK Cystic Fibrosis Registry 2015 Annual Data Report

7 Executive summary The UK Registry annual report is designed to show a snap-shot of the health of people with cystic fibrosis (CF) in 2015, using data recorded at a person s annual review. This year we continue to show comparisons against previous years, demonstrating increasing numbers of people with CF, improvements in health outcomes and increased use of new therapies. This year also sees the first publication of centre-level funnel plots, as well as the box and whisker plots included in previous reports. These plots are designed to make it easier to understand the data shown for individual centres, and how they compare to the national medians. A guide and example plot is provided on page 39 of this report to explain how they should be read and interpreted sees another rise in the CF population, with 10,810 now registered, allowing analysis of data from annual reviews of 9,587 people. Looking back to 2011, there has been an increase of over 1,000 people with CF in the UK, with nearly 60% of the UK CF population now aged 16 and over. With the growing importance of personalised medicines aimed at different genetic mutations, we are pleased to see such high levels of people with genotypes recorded (98%), and for the first time the top six genotypes represented across all four devolved nations are reported. The completeness and quality of the data enables us to confidently evaluate changes in CF over time. The reduction in the rate of chronic Pseudomonas aeruginosa continues and is particularly noteworthy in the age group, where the prevalence of this infection has reduced by 15.2% to 29.9% since Nontuberculous mycobacterium (NTM) figures for the last two years appear stable with a prevalence of 5.6% in Comparisons with data from 2008 also show great strides in maintaining lung health, measured as FEV 1 % predicted, shown in figure 1.11 as having a statistically significant improvement between these two years. There is an increase in overall treatment for CF-related diabetes (28%) since the 2011 data report (18.3%), which appears to reflect a rise in adolescents receiving treatment, up to 10% of the year old population. This report follows through on our previous commitment to move to new, more accurate median predicted survival figures using groups of three years worth of data (section 1.32). The group has a 47-year median predicted survival. A preliminary breakdown suggests there may also be a gender difference in survival, and an overall improvement over time. The summary table continues to show the single year calculation, as previously used in the reports. Transplant activity has fallen, with 42 lung transplants being carried out in 2015 compared to 59 in This is in the context of a European Cystic Fibrosis Society Patient Registry Report using 2013 data that showed 3% of people in the UK living with a transplant, compared to 5.3% across Europe. There are many other interesting examples of change in this report. We hope that you find the contents interesting and useful. We always look forward to hearing your views and welcome feedback. Dr Siobhán B Carr 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 known as CFTR. The gene and the protein it makes control the movement of salt and water in and out of cells. When the gene is faulty, it can cause thicker mucus that blocks airways. This affects the lungs, which over time makes it hard to breathe. Around 85% 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 registry. 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 to their patients disease severity. 8 UK Cystic Fibrosis Registry 2015 Annual Data Report

9 Governance The Registry Steering Committee (RSC) is responsible for making sure that the UK CF Registry is compliant with legislation like the Data Protection Act 1998, and its Research Ethics Committee approved study protocol. It also makes recommendations about the future development of the Registry. A subcommittee of the RSC, known as the Registry Research Committee, assesses applications for data and guides the Registry research strategy. Please see appendix 3 for members of each committee. Data are only recorded on the UK CF Registry if explicit written consent is given by the person with cystic fibrosis or, for a child, their parent or guardian. 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. This 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 CF 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 i A glossary of terms highlighted in teal in this report can be found on page 62. cysticfibrosis.org.uk 9

10 Section 1: UK-wide analysis This section provides an overview of the cystic fibrosis (CF) population, health outcomes, and care in the United Kingdom, including CF 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; n(%) (89%) (87%) (88%) (89%) (89%) Age in years; median All newly diagnosed patients (newborn screening and other) Number of patients born 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) (35.7, 46.0) 43.5 (37.8, 49.9) 36.6 (34.4, 41.6) 40.1 (34.6, 46.7) 45.1 (39.9, 49.1) Total deaths reported (%) (1.2%) 106 (1.1%) Age at death in years; median (95% CI) 3 (25, 29) 146 (1.4%) 29 (27, 31) 132 (1.2%) 28 (25.5, 32) 125 (1.2%) 28 (27, 33) 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 2015 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 (see footnote 2, above) 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. This is the last year that survival will be shown as an annual figure. Please see section Complete data: Patients with at least the minimum data entered at their annual review. 10 UK Cystic Fibrosis Registry 2015 Annual Data Report

11 1.2 Age distribution by gender n=9587 The following chart shows the mix of ages and genders in the cystic fibrosis population in the UK Proportion (%) Age (years) Overall Females Males cysticfibrosis.org.uk 11

12 1.3 Median height percentiles of children and young people (<20 years) n=4483 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 40th percentile, only 40% of people the same age are their height or shorter; 60% are taller. n=4483) Median height percentile Age (years) Overall Females Males Overall Female Male Age N Median IQR N Median IQR N Median IQR Overall UK Cystic Fibrosis Registry 2015 Annual Data Report

13 1.4 Median weight percentiles of children and young people (<20 years) n=4483 The following chart and table show the weight 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 40th percentile, only 40% of people 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=4483 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 healthy person of the same age (the 50th percentile, or the BMI percentile that half of the UK population people of that age has achieved). If a person with CF is on the 40th percentile, it means that only 40% of the population at the same age are their BMI or lower; so 60% have a higher BMI. Median BMI percentile Age (years) Overall Females Males Overall Female Male Age N Median IQR N Median IQR N Median IQR Overall UK Cystic Fibrosis Registry 2015 Annual Data Report

15 1.6 Median Body Mass Index (BMI) values among adults (20 years and over) n=4743 The following chart and table show the BMI of people with CF aged 20 and over in relation to the target BMI for adults; 22 for women and 23 for men Median BMI Target male 23 Target female Age (years) Overall Females Males Overall Female Male Age N Median IQR N Median IQR N Median IQR Overall Stallings et al, J Am Diet Assoc. 2008;108: cysticfibrosis.org.uk 15

16 1.7 Education and employment in adults (16 years and over) n=4930 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 working part-time, for example Number of patients n (%) (n=4933) Number of patients n (%) (n=5062) Number of patients n (%) (n=5213) Number of patients n (%) (n=5592) Number of patients n (%) (n=5742) Number of people who completed questionnaire Full-time 1436 (29.1) 1425 (28.2) 1502 (28.8) 1634 (29.2) 1811 (31.5) employment Part-time 706 (14.3) 653 (12.9) 664 (12.7) 703 (12.6) 768 (13.4) employment Student 933 (18.9) 917 (18.1) 922 (17.7) 976 (17.5) 927 (16.1) Homemaker 216 (4.4) 231 (4.6) 232 (4.5) 258 (4.6) 264 (4.6) Unemployed 793 (16.1) 684 (13.5) 685 (13.1) 821 (14.7) 761 (13.3) Disabled 255 (5.2) 273 (5.4) 298 (5.7) 272 (4.9) 365 (6.4) Retired 78 (1.6) 75 (1.5) 78 (1.5) 85 (1.5) 108 (1.9) Unknown 548 (11.1) 862 (17.0) 914 (17.5) 930 (16.6) 850 (14.8) entered No data 76 (1.5) 38 (0.8) 21 (0.4) 39 (0.7) 27 (0.5) recorded Number of people in work or study 3111 (70.6) 3020 (71.0) 3098 (71.3) 3243 (70.1) 3489 (70.8) 1.8 Pregnancy At the time of their 2015 annual review, 64 women with cystic fibrosis had a live birth. 26 women were still pregnant UK Cystic Fibrosis Registry 2015 Annual Data Report

17 Diagnosis of cystic fibrosis 1.9 Age at diagnosis and screening in children under 16 in 2015 n=3780 with a diagnosis date Newborn screening for CF has been done routinely in the whole of the UK since mid It is part of the heel prick blood spot testing done at 5-7 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 <16; n (%) Patients aged 10 years in 2015; n (%) Pre-natal <5 0 (0) 0 (0) Birth-3 months 2921 (77.3) 144 (63.4) 255 (92.7) 4-6 months 174 (4.6) 16 (7.0) < months 130 (3.4) 14 (6.2) <5 1 yr 187 (4.9) 15 (6.6) 5 (1.8) 2 yrs 127 (3.4) 14 (6.2) <5 3 yrs 70 (1.9) 6 (2.6) <5 4 yrs 48 (1.3) 5 (2.2) <5 5 yrs 28 (0.7) <5 <5 6 yrs 24 (0.6) <5-7 yrs 13 (0.3) <5-8 yrs 19 (0.5) 0 (0) - 9 yrs 14 (0.4) <5-10 yrs 9 (0.2) <5-11 yrs < yrs < yrs < yrs < yrs Overall Patients aged 5 years in 2015; n (%) The median (range) age at diagnosis for patients aged under 16 in 2015 is 26 days (15-92 days). Diagnosis in the first three months of life is more common in children aged 5 years in 2015 (born after the UK-wide newborn screening programme was implemented) than in children aged 10 years in 2015 (born before the UK-wide newborn screening programme was put in place nationally). There is a delay between newborn screening tests being performed and the results entering the Registry, these statistics are updated retrospectively each year to take updated data into account. Therefore the number of patients identified in 2014 is higher in this report than was recorded in the report published in It is likely that the 2015 figure will be updated in the next annual report. cysticfibrosis.org.uk 17

18 1.10 Age at diagnosis and screening in adults aged 16 and over in 2015 n=5684 with a diagnosis date The table below shows the age that people aged 16 and over in 2015 were when they were diagnosed. People aged 16 or over in 2015 were born before newborn screening was done routinely in the UK. Age at diagnosis n (%) Pre-natal 0 (0) Birth-3 months 2297 (40.4) 4-6 months 525 (9.2) 7-12 months 349 (6.1) 1 yr 482 (8.5) 2 yrs 293 (5.2) 3 yrs 222 (3.9) 4 yrs 176 (3.1) 5 yrs 86 (1.5) 6 yrs 83 (1.5) 7 yrs 58 (1.0) 8 yrs 67 (1.2) 9 yrs 48 (0.8) 10 yrs 38 (0.7) 11 yrs 40 (0.7) 12 yrs 41 (0.7) 13 yrs 47 (0.8) 14 yrs 33 (0.6) 15 yrs 44 (0.8) yrs 160 (2.8) yrs 109 (1.9) yrs 105 (1.8) yrs 115 (2.0) yrs 83(1.5) yrs 62 (1.1) yrs 32 (0.6) yrs 89 (1.6) 61 yrs+ 0 (0) Overall 5684 In people aged 16 or over were newly diagnosed with CF. 755 (13.3%) of adults with CF were diagnosed after the age of UK Cystic Fibrosis Registry 2015 Annual Data Report

19 Lung health For people with cystic fibrosis mucus in the lungs is linked to repeat or chronic infections, which can cause permanent damage, making it harder to breathe. 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, an 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, maintaining 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 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 a team effort between people with CF, their family, and their medical team, which can include doctors, nurses, physiotherapists, dietitians, and psychologists. The FEV 1 % predicted values shown in this report are calculated using an equation called Global Lung Function Initiative, or GLI. cysticfibrosis.org.uk 19

20 1.11 Median FEV 1 % predicted (GLI equations) among people aged 6 years and over n=7625 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 cystic fibrosis Target Median Median FEV1 FEV Overall Females Males 0 Age (years) Age (yrs) Overall Female Male N Median IQR N Median IQR N Median IQR Overall UK Cystic Fibrosis Registry 2015 Annual Data Report

21 1.12 Median FEV 1 % predicted over time (GLI equations) among people aged 6 and over (excluding patients post lung transplant) n=7625 in 2015, n=4388 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 in 2015 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 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 2015 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 cysticfibrosis.org.uk 21

22 1.13 Median FEV 1 % predicted and BMI in people aged 16 and over (excluding patients post-lung transplant) n=7625 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 appears to protect people with CF against lung infection, and help to preserve lung health. This chart excludes people who have had a lung transplant. Median FEV1 1 % predicted Target female 22 Target male 23 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 Median best FEV 1 % predicted in people aged 6 and over n=5970 The following table shows the highest FEV 1 % predicted value recorded during the year for that patient. Other lung health calculations use the value that was taken during the person s annual review, which may not represent their best value during the year. People who are recorded as having had a lung transplant are excluded. Overall Female Male N Median IQR N Median IQR N Median IQR Overall UK Cystic Fibrosis Registry 2015 Annual Data Report

23 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 Lung infections in 2015 n=9587 Chronic infection with Pseudomonas aeruginosa or Staphylococcus aureus is defined as three or more positive samples in the last year. In 2015 only 6.1% of children (aged under 16) had chronic Pseudomonas. 46% of adults aged 16 and over were recorded as having chronic Pseudomonas. There is a steady increase with age in those with chronic Pseudomonas, peaking at 59% in those aged years. 60 Proportion of patients (%) Age (years) Chronic Staphylococcus aureus Chronic Pseudomonas aeruginosa Intermittent Pseudomonas aeruginosa Intermittent Staphylococcus aureus B.cepacia MRSA H. influenza cysticfibrosis.org.uk 23

24 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) (3.2) 20 (2.2) 189 (20.8) 129 (14.3) 60 (5.6) 25 (2.3) 208 (19.4) 238 (22.1) 100 (10.8) 58 (6.3) 216 (23.4) 217 (23.5) B. cepacia; n (%) 3 (0.3) 9 (0.8) 17 (1.8) MRSA; n (%) 11 (1.2) H. influenza; n (%) 260 (28.2) 20 (1.82) 325 (29.6) 27 (2.9) 191 (20.2) 100 (11.5) 131 (15.1) 178 (20.5) 206 (23.8) 18 (2.1) 37 (4.2) 97 (11.0) 170 (17.3) 295 (29.9) 204 (20.7) 166 (17.0) 46 (4.6) 34 (3.4) 87 (8.7) 234 (23.8) 409 (41.6) 180 (18.3) 209 (21.3) 48 (4.8) 26 (2.6) 89 (9.9) 212 (22.7) 486 (52.1) 125 (13.4) 169 (18.1) 57 (6.0) 29 (3.0) 71 (7.4) 158 (21.5) 403 (55.0) 96 (13.1) 107 (14.6) 36 (4.8) 19 (2.5) 49 (6.5) 106 (17.2) 367 (59.2) 72 (11.6) 93 (15.1) 35 (5.5) 15 (2.4) 44 (6.9) 80 (19.9) 224 (55.9) 41 (10.2) 43 (10.7) 25 (6.1) 14 (3.4) 22 (5.4) 61 (16.7) 181 (49.7) 38 (10.4) 51 (13.9) 21 (5.7) 54 (19.8) 125 (45.3) 39 (14.1) 35 (12.8) 14 (5.1) 58 (16.8) 135 (39.0) 57 (16.5) 60 (17.4) 13 (3.7) 2 (0.5) 1 (0.4) 12 (3.4) 21 (5.7) 21 (7.7) 17 (4.8) Adults ( 16 years) 289 (7.7) 1133 (20.1) 234 (6.2) 2625 (46.5) 791 (21.0) 852 (15.1) 790 (20.9) 933 (16.6) 47 (1.2) 295 (5.1) 95 (2.5) 152 (2.7) 873 (22.7) 421 (7.3) 24 UK Cystic Fibrosis Registry 2015 Annual Data Report

25 1.16 Lung infections over time 2008 n=6082 and 2015 n= Proportion of patients (%) Age (years) Chronic Pseudomonas aeruginosa (2008) Chronic Pseudomonas aeruginosa (2015) Chronic Staphylococcus aureus (2008) Chronic Staphylococcus aureus (2015) Age (years) % Chronic S. aureus; Chronic S. aureus; Chronic P aeruginosa; 2015 Chronic P. aeruginosa; An analysis was conducted in order to determine whether there was a statistical difference between the proportion of people with chronic pseudomonas aeruginosa in 2015 compared to The results show that there is a statistically significant difference in the age bands where the p value is less than Chronic P. aeruginosa; p-value Chronic S. aureus; p-value Age (years) cysticfibrosis.org.uk 25

26 Complications 1.17 Prevalence of complications Overall (n=9587) <16 years (n=3845) 16 years (n=5742) N (%) N (%) N (%) Respiratory Related Nasal polyps requiring 221 (2.3) 44 (1.1) 177 (3.1) surgery; n (%) Sinus disease; n (%) 939 (9.8) 53 (1.4) 886 (15.4) Asthma; n (%) 1382 (14.4) 497 (12.9) 885 (15.4) ABPA; n (%) 1043 (10.9) 243 (6.3) 800 (13.9) Haemoptysis; n (%) 762 (7.9) 38 (1.0) 724 (12.6) Pneumothorax requiring chest 59 (0.6) <5 58 (1.0) tube; n (%) Nontuberculous mycobacteria 536 (5.6) 113 (2.9) 423 (7.4) or atypical mycobacteria; n (%) Pancreas & Hepatobiliary Disease Raised Liver enzymes; n (%) 1116 (11.6) 264 (6.9) 852 (14.8) Liver disease; n (%) 1371 (14.3) 340 (8.8) 1031 (18.0) Cirrhosis with no portal 116 (1.2) 26 (0.7) 90 (1.6) hypertension; n (%) Cirrhosis with portal 164 (1.7) 26 (0.7) 138 (2.4) hypertension; n (%) Gall bladder disease requiring 40 (0.4) <5 39 (0.7) surgery; n (%) Pancreatitis; n (%) 70 (0.7) <5 66 (1.1) GI bleed req hosp variceal; n (%) 5 (0.1) 0 (0.0) 5 (0.1) Upper Gastrointestinal GERD; n (%) 1583 (16.5) 341 (8.9) 1242 (21.6) Peptic ulcer; n (%) 5 (0.1) 0 (0.0) 5 (0.1) GI bleed req hosp non variceal; 11 (0.1) <5 9 (0.2) n (%) Lower Gastrointestinal Intestinal obstruction; n (%) 539 (5.6) 116 (3.0) 423 (7.4) Fibrosing colonopathy / colonic <5 0 (0.0) 0 (0.0) structure; n (%) Rectal prolapse; n (%) 31 (0.3) 23 (0.6) 8 (0.1) Renal Kidney stones; n (%) 96 (1.0) 12 (0.3) 84 (1.5) Renal failure; n (%) 57 (0.6) <5 55 (1.0) Muscolo-Skeletal Arthritis; n (%) 158 (1.6) 7 (0.2) 151 (2.6) Arthropathy; n (%) 517 (5.4) 18 (0.5) 499 (8.7) Bone fracture; n (%) 46 (0.5) 14 (0.4) 32 (0.6) Osteopenia; n (%) 1297 (13.5) 36 (0.9) 1261 (22.0) 26 UK Cystic Fibrosis Registry 2015 Annual Data Report

27 Osteoporosis; n (%) 511 (5.3) <5 507 (8.8) Other Cancer confirmed by histology; 34 (0.4) <5 32 (0.6) n (%) Port inserted or replaced; n (%) 559 (5.8) 180 (4.7) 379 (6.6) Depression; n (%) 452 (4.7) <5 448 (7.8) Hearing loss; n (%) 244 (2.5) 28 (0.7) 216 (3.8) Hypertension; n (%) 260 (2.7) <5 259 (4.5) Meconium ileus; n(%) 1458 (15.2) 643 (16.7) 815 (14.2) 1.18 Incidence of complications Overall (n=9432) <16 years (n=3840) 16 (n=5592) Overall (n=9587) <16 years (n=3845) 16 (n=5742) ABPA; n (%) 143 (1.5) 67 (1.7) 76 (1.4) 99 (1.0) 38 (0.4) 61 (0.6) Cirrhosis - no portal 37 (0.4) 6 (0.2) 31 (0.6) 33 (0.3) 14 (0.1) 19 (0.2) hypertension; n (%) Cirrhosis - with portal 22 (0.2) 6 (0.2) 16 (0.3) 20 (0.2) 8 (0.1) 12 (0.1) hypertension; n (%) Cancer confirmed by histology; n (%) 12 (0.1) 0 (0) 12 (0.2) 9 (0.1) 0 (0) 9 (0.1) 1.19 Nontuberculous mycobacteria (NTM) or atypical mycobacteria 2014 n= n=9587 NTM Prevalence (%) 583 (6.2%) 536 (5.6%) On NTM treatment in the given year (%) of total NTM prevelance 294 (50.4%) 300 (56.0%) NTM Incidence (%) 82 (0.9%) 63 (0.7%) M.abscessus complex incidence (%) 62 (0.7%) 47 (0.5%) 1.20 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 diabetes; n (%) 1982 (28.0) 134 (10.0) 1848 (32.2) Screening for CF-related diabetes Yes 3759 (53.1) 982 (73.1) 2777 (48.4) No 1192 (16.8) 205 (15.3) 987 (17.2) Known CF-related 1987 (28.0) 109 (8.1) 1878 (32.7) diabetes Unknown 99 (1.4) 30 (2.2) 69 (1.2) cysticfibrosis.org.uk 27

28 Therapies 1.21 Transplants Lung transplantation has been available to people with cystic fibrosis for almost 30 years. Today the most common operation carried out is a double lung transplant, called a Bilateral Sequential Lung Transplant. The following table gives information about 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) <5 <5 <5 5 <5 Types of transplants received: Bilateral lung <5 <5 <5 <5 <5 Heart and lung Liver 0 <5 <5 <5 <5 Other <5 Number receiving transplants ( 16) 48* 52** 54* 67** 46 Types of transplants received: Bilateral lung Heart and lung <5 < Liver <5 6 <5 5 <5 Other <5 <5 <5 5 <5 * One patient received two transplants ** Two patients had two transplants 1.22 Ivacaftor Ivacaftor began being prescribed as a treatment for CF in patients aged 6 years and over with at least one copy of the genotype G551D in June In July 2015 NHS England commissioned ivacaftor for the treatment of CF in patients aged 6 years and over with at least one copy of gating mutation G187R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G139D. The table shows information about ivacaftor use and outcomes from June 2012 December Number of patients on ivacaftor in the UK 439 Median (IQR) Sweat chloride before ivacaftor 105 ( ) Sweat chloride 6-8 weeks after ivacaftor 49 (37-64) FEV 1 % before ivacaftor 55.4 ( ) FEV 1 % 6-8 weeks after ivacaftor 64.1 ( ) Number of patients stopped ivacaftor 7 People with CF tend to 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. 28 UK Cystic Fibrosis Registry 2015 Annual Data Report

29 1.23 Intravenous (IV) antibiotic use and outcomes n=9587 When someone with CF becomes unwell with an infection, they might be prescribed intravenous (IV) antibiotics. IV antibiotics 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) (5.1) 8 (6-13) 257 (27.9) 14 (8-20) 258 (28.0) 14 (10-21) (10.4) 12 (7-21) 295 (26.9) 14 (9-19) 306 (27.9) 14 (14-28) (18.7) 14 (10-28) 335 (35.4) 14 (8-28) 363 (38.4) 22 (14-43) (23.1) 21 (10-24) 374 (42.5) 18 (11-35) 416 (47.3) 28 (14-49) (27.9) 19 (12-35) 437 (43.7) 15 (8-40) 513 (51.4) 28 (14-56) (33.2) 21 ( ) 448 (44.8) 16 (10-38) 547 (54.7) 28 (14-56) (38.2) 21 (14-39) 444 (46.5) 17 (10-40) 561 (58.8) 28 (14-58) (37.9) 22 (14-39) 313 (41.8) 18 (10-42) 430 (57.4) 28 (14-56) (36.1) 26 (14-47) 245 (38.6) 17 (9-37) 330 (52.1) 31 (15-56) (36.1) 24 (14-40) 147 (36.1) 16 (10-31) 208 (51.1) 28 (14-51) (28.4) 26 (14-42) 119 (32.2) 15 (8-36) 163 (44.1) 28 (14-55) (26.7) 23 (14-37) 87 (31.4) 18 (11-41) 111 (40.1) 35 (14-60) (21.0) 15 (11-42) 113 (32.1) 18 (10-34) 138 (39.2) 28 (14-47) Overall (25.3) 19 (12-37) 3614 (37.7) 15 (9-33) 4344 (45.3) 28 (14-49) 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. cysticfibrosis.org.uk 29

30 1.24 Inhaled antibiotic use among people with chronic Pseudomonas aeruginosa Patients with chronic P. aeruginosa Tobramycin solution; n (%) Other aminoglycoside; n (%) Overall <16 years 16 years Overall <16 years 16 years (19.6) 48 (16.1) 364 (20.2) 653 (22.8) 86 (36.8) 567 (21.6) 43 (2.0) 5 (0.2) 38 (2.1) 95 (3.3) 15 (6.4) 80 (3.1) Colistin; n (%) 914 (43.6) 174 (58.2) 740 (41.1) 840 (29.4) 108 (46.2) 732 (28.0) Promixin; n (%) 490 (23.4) 73 (24.4) 417 ( (31.3) 111 (47.4) 785 (29.9) Aztreonam; n (%) (17.0) 8 (3.4) 477 (18.2) Colistimethate (DPI); (18.8) 22 (9.4) 515 (19.6) n (%) Tobramycin Inhalation (31.1) 25 (10.7) 863 (32.9) Powder; n (%) At least one of the above*; n (%) 1597 (76.1) 257 (86.0) 1340 (74.5) 2547 (89.1) 226 (96.6) 2321 (88.4) *In 2015, this includes Aztreonam, Colistimethate and Tobramycin Inhalation Powder. 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. Muco-active therapies 1.25 Mannitol 2015 Age Total patients Patients on Mannitol < < < < (2.4) (5.7) (8.6) (6.5) (6.6) (6.1) (4.6) Overall (3.4) 30 UK Cystic Fibrosis Registry 2015 Annual Data Report

31 1.26 DNase DNase; n (%) Age Total patients Patients on DNase Total patients Patients on DNase (7.6) (13.1) (20.1) (43.5) (34.2) (70.3) (46.4) (74.3) (49.5) (73.4) (44.0) (65.4) (47.6) (63.8) (43.4) (62.8) (41.5) (59.3) (35.0) (55.3) (35.7) (51.7) Overall (37.2) (57.3) 1.27 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 (0.5) (6.0) (2.4) (18.0) (3.5) (29.8) (4.1) (40.8) (4.3) (35.4) (6.9) (29.0) (9.9) (29.0) (8.8) (32.8) (11.2) (31.1) (6.8) (30.0) (8.0) (24.8) Overall (5.4) (27.4) cysticfibrosis.org.uk 31

32 1.28 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 Pseudomonas aeruginosa. Patients with chronic P. aeruginosa Patients without chronic P. aeruginosa Overall (n=1958) 1246 (63.6) 0-3 years (n=15) 4-15 years (n=363) <5 105 (28.9) 712 (36.4) 13 (86.7) 258 (71.1) 16 years (n=1580) 1139 (72.1) Overall (n=3719) 1874 (50.4) 441 (27.9) 1845 (49.6) 0-3 years (n=26) 4-15 years (n=590) 16 years (n=3103) <5 94 (15.9) 1776 (57.2) 22 (84.6) 496 (84.1) 1327 (42.8) 1.29 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=9587) <16 years (n=3845) 16 years (n=5742) 2708 (28.7) 1534 (40.3) 1174 (20.8) 1431 (15.1) 196 (5.2) 1235 (21.9) Any form of PEP; n (%) 5282 (55.9) 2706 (71.1) 2576 (45.6) VEST; n (%) 174 (1.8) 92 (2.4) 82 (1.5) Exercise; n (%) 3552 (37.1) 1541 (40.1) 2011 (35.0) Note that these techniques are not mutually exclusive and represent primary and secondary forms of physiotherapy. 32 UK Cystic Fibrosis Registry 2015 Annual Data Report

33 1.30 Other therapy Non Invasive Ventillation (NIV); n (%) Long-term oxygen; n (%) Among those who have long-term oxygen: Overall (n=9587) <16 years (n=3845) 16 years (n=5742) 303 (3.2) 45 (1.2) 258 (4.5) 604 (6.3) 93 (2.4) 511 (8.9) Continuously 162 (1.7) 5 (0.1) 157 (2.7) Nocturnal or with exertion 163 (1.7) 24 (0.6) 139 (2.4) As required (PRN) 51 (0.5) <5 47 (0.8) With exacerbation 228 (2.4) 60 (1.6) 168 (2.9) 1.31 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=9587) <16 years (n=3845) 16 years (5742) Any supplmental feeding; n (%) 3126 (32.6) 1120 (29.1) 2006 (34.9) Nasogastric tube 109 (1.1) 15 (0.4) 94 (1.6) Gastrostomy tube/button 557 (5.8) 220 (5.7) 337 (5.9) Jejunal 7 (0.1) <5 <5 Total Parenteral Nutrition (TPN) <5 <5 <5 cysticfibrosis.org.uk 33

34 1.32 Survival Median predicted survival is a calculation based on people with CF recorded in the Registry as alive in the given year. A mathematical formula 7, which takes into account the age of those people in 2015, predicts how long we expect half of them to live. For 2015, this means that half of people registered as alive on the database are predicted to live to at least 45.1 years of age. Half of people alive today are currently predicted to die before they reach that age. Using one year of data can show big variations in median predicted survival age each year, which can be due to chance alone and does not necessarily reflect a decline or improvement in real-world outcomes. Grouping several years together gives a better estimate of survival. An analysis of median predicted survival grouped together in three year windows is shown below. median age outcome group upper/lower Cl Year Overall Males Females Male and Female Median age Lower 95% CI Upper 95% CI Median age Lower 95% CI Upper 95% CI Median age Lower 95% CI Upper 95% CI p-values comparing survival A standardized approach to estimating survival statistics for population-based cystic fibrosis registry cohorts Sykes, Jenna et al. Journal of Clinical Epidemiology. 2016, Volume 70, UK Cystic Fibrosis Registry 2015 Annual Data Report