UK Cystic Fibrosis Registry

Transcription

1 UK Cystic Fibrosis Registry 2016 Annual Data Report Scotland

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3 UK Cystic Fibrosis Registry 2016 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 Hospital Susan Charman Registry Senior Statistician Cystic Fibrosis Trust Roisin Connon Registry Data Analyst Cystic Fibrosis Trust Rebecca Cosgriff UK Cystic Fibrosis Registry Lead Cystic Fibrosis Trust Andrew Lee Registry Statistician Cystic Fibrosis Trust With assistance from The UK CF Registry Steering Committee Chloe Ainsley Senior Graphic Designer Cystic Fibrosis Trust Elaine Gunn UK Cystic Fibrosis Registry Data Manager 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 Introduction 6 Cystic fibrosis 6 UK Cystic Fibrosis Registry 7 Governance 7 Data collection 7 Section 1: Scotland-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 (>20 years) Education and employment in adults (>16 years) Pregnancy 14 Diagnosis of cystic fibrosis Age at diagnosis and screening statistics among children (<16 years) Age at diagnosis and screening statistics among adults ( 16 in 2016) 16 Lung health Median FEV 1 % predicted, GLI equations among patients aged 6 years and over Median FEV 1 % predicted vs BMI among patients aged 20 years and older Median best FEV 1 % predicted (GLI equations) among patients aged 6 years and older 19 Lung infections Lung infections in Non-tuberculous mycobacteria (NTM) or atypical mycobacteria Lung infections over time 22 Complications Prevalence of complications Incidence of complications Cystic fibrosis-related diabetes 24 4 UK Cystic Fibrosis Registry 2016 Annual Data Report

5 Antibiotics Intravenous (IV) antibiotiocs Inhaled antibiotic use among patients with chronic Pseudomonas aeruginosa Long-term use of azithromycin among patients with and without chronic Pseudomonas aeruginosa 26 Muco-active therapies Mannitol DNase Hypertonic saline 27 Other therapies CFTR modifiers Oxygen and non-invasive ventilation Physiotherapy Feeding Transplants 29 Genotypes Genotypes 30 2 and 3: Centre-level analysis 38 Section 2: Centre-level analysis 31 A guide to charts 32 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 Proportion of patients receiving hypertonic saline by paediatric centre/clinic 35 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 Proportion of patients receiving hypertonic saline treatment by adult service 38 Appendices 39 Glossary 39 Appendix 1: Centre-level data tables 42 Paediatric centres/clinics providing data in 2016 ordered by clinic ID 42 Adult centres/clinics providing data in 2016 ordered by clinic ID 42 Paediatric centres/clinics providing data in 2016 ordered alphabetically 44 Adult centres/clinics providing data in 2016 ordered alphabetically 44 Appendix 2: Composition of UKCystic Fibrosis Registry Steering Committee cysticfibrosis.org.uk 5

6 Introduction This report is aimed at anyone who is interested in the health, care, and outcomes of people with cystic fibrosis (CF) in Scotland. This includes people with CF, their families and clinical teams, healthcare managers, commissioners, and policymakers. 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 a build-up of thick mucus that blocks airways. Over time, this makes it harder to breathe and increases the risk of lung infections. Around 85% of people with CF also have difficulty digesting food due to the build-up of mucus in the pancreas and digestive system. 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 via 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 CF, 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 in England provide funding to NHS CF centres that is proportionate to their patients disease severity. 6 UK Cystic Fibrosis Registry 2016 Annual Data Report

7 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 Study Protocol. The RSC also makes recommendations about the future development of the Registry. A sub-committee of the RSC, known as the Registry Research Committee, assesses applications for data and guides the Registry research strategy. Please see appendix 2 on page 46 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 cystic fibrosis centres in the UK, using a secure web portal. Where can I find more information? You can find out more about the UK CF Registry at i Words in this report that appear in the glossary are highlighted the first time they appear and explained on page 39. cysticfibrosis.org.uk 7

8 Section 1: Scotland-wide analysis This section provides an overview of the cystic fibrosis population, health and care in Scotland. 1.1 Summary of the UK Cystic Fibrosis Registry 2016 UK Scotland CF patients registered Excluding 2016 diagnoses CF patients with complete data 2, n (%) 9695 (95%) 829 (92%) Age in years, median All newly diagnosed patients (newborn screening and other) Newly diagnosed patients identified through newborn screening 4 Age at diagnosis in months; median³ 2 2 Adults aged 16 years and over, % Males, % Genotyped, % Total deaths reported (1.5%) 17 (1.9%) Age at death in years, median 5 (95%CI) 31 (29, 33) 31 (28, 39) Notes: 1 This is calculated as the number of patients on the database 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 that year. Patients newly diagnosed in 2016 may not have their first annual review in the same year. If newly diagnosed patients are excluded, 92% of records are complete. 3 Calculated from patients with complete data in that given year. 4 Calculated from all patients registered. 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 patients who died in the given year. Complete data: patients with at least the minimum data entered at their annual review for analysis to be carried out. 8 UK Cystic Fibrosis Registry 2016 Annual Data Report

9 1.2 Age distribution by gender n=829 This chart shows the mix of ages and genders in the cystic fibrosis population in Scotland. Proportion (%) Age (years) Overall Female Male Age All; n (%) Female; n (%) Male; n (%) (6.6) 29 (7.5) 26 (5.9) (11.5) 41 (10.6) 54 (12.2) (10.6) 42 (10.9) 46 (10.4) (8.6) 39 (10.1) 32 (7.2) (8.6) 30 (7.8) 41 (9.3) (11.9) 51 (13.2) 48 (10.9) (10.1) 39 (10.1) 45 (10.2) (8.2) 33 (8.5) 35 (7.9) (6.8) 25 (6.5) 31 (7.0) (5.2) 15 (3.9) 28 (6.3) (3.6) 12 (3.1) 18 (4.1) (3.1) 11 (2.8) 15 (3.4) (3.9) 14 (3.6) 18 (4.1) (1.3) 6 (1.6) 5 (1.1) Overall Total cysticfibrosis.org.uk 9

10 1.3 Median height percentiles among children and young persons (<20 years) 6 n=357 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 the population at the same age are their height or shorter, 60% are taller. Median height percentile Age (years) Overall Females Males Where there are fewer than 5 people in an age group the plotted value on the graph is the midpoint of the two values at either side. Overall Female Male Age N Median IQR* N Median IQR* N Median IQR* (years) <5 N/A N/A Overall Based on UK-WHO growth charts 1990 (updated 1996) *Interquartile range 10 UK Cystic Fibrosis Registry 2016 Annual Data Report

11 1.4 Median weight percentiles of children and young persons (<20 years) 6 n=357 The following chart and table show the weight 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 at the 40th percentile, only 40% of the population at the same age are their weight or lower, 60% weigh more. 70 percentile Median weight Age (years) Overall Females Males Where there are fewer than 5 people in an age group the plotted value on the graph is the midpoint of the two values at either side Age (years) Overall Female Male N Median IQR* N Median IQR* N Median IQR* <5 N/A N/A Overall Based on UK-WHO growth charts 1990 (updated 1996) *Interquartile range cysticfibrosis.org.uk 11

12 1.5 Median Body Mass Index (BMI) percentiles among children and young people (<20 years) 6 n=357 The following chart and table show the body mass index (BMI) percentiles of people with CF, aged 19 years and younger, in relation to the target BMI percentile for a person of the same age without CF (the 50th percentile, or the BMI percentile that half of the UK population of that age achieved). If a person with CF is at the 40th 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 Age (years) Overall Females Males Where there are less than 5 people in an age group the plotted value on the graph is the midpoint of the two values at either side. Overall Female Male Age N Median IQR N Median IQR N Median IQR <5 N/A N/A Overall Based on UK-WHO growth charts 1990 (updated 1996) 12 UK Cystic Fibrosis Registry 2016 Annual Data Report

13 1.6 Median Body Mass Index (BMI) values among adults (20 years and over) n=449 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 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 13

14 1.7 Education and employment in adults aged 16 years and over n=520 The following table shows how people with CF 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 people n (%) Number of people who completed questionnaire 506 Full-time employment 177 (35.0) Part-time employment 92 (18.2) Student 72 (14.2) Homemaker 19 (3.8) Unemployed 100 (19.8) Disabled 18 (3.6) Retired 13 (2.6) Unknown entered 15 (3.0) Number of people in work or study 341 (67.4) 1.8 Pregnancy 7 women with cystic fibrosis had babies in men with cystic fibrosis became fathers in UK Cystic Fibrosis Registry 2016 Annual Data Report

15 Diagnosis of cystic fibrosis 1.9 Age at diagnosis in children under 16 n= 309* 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 between five and 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 2016; n (%) Pre-natal 0 (0.0) 0 (0.0) 0 (0.0) Birth-3months 270 (88.2) 26 (89.7) 25 (89.3) 4-6 months 9 (2.9) <5 < months 6 (2.0) <5 <5 1 years <5 <5 <5 2 years 9 (2.9) <5 <5 3 years <5 <5 <5 4 years <5 <5 <5 5 years <5 <5 <5 6 years <5 <5-7 years <5 <5-8 years <5 <5-9 years <5 <5-10 years <5 <5-11 years < years < years < years < years <5 - - Overall Patients aged 5 years in 2016; n (%) *n=306 had exact diagnosis dates The median (range) age at diagnosis for patients under 16 in 2016 is 20 days (0-140 months) cysticfibrosis.org.uk 15

16 1.10 Age at diagnosis in adults aged 16 years and over in 2016 n=520 The table below shows the age at diagnosis of people aged 16 and over in 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 0 (0.0) Birth-3 months 186 (35.8) 4-6 months 51 (9.8) 7-12 months 33 (6.3) 1 years 39 (7.5) 2 years 34 (6.5) 3 years 24 (4.6) 4 years 17 (3.3) 5 years 9 (1.7) 6 years 8 (1.5) 7 years 6 (1.2) 8 years 8 (1.5) 9 years 5 (1.0) 10 years <5 11 years 6 (1.2) 12 years 6 (1.2) 13 years <5 14 years <5 15 years 7 (1.3) years 16 (3.1) years 7 (1.3) years 18 (3.5) years 11 (2.1) years 6 (1.2) years 5 (1.0) years < years 7 (1.3) 61 years+ <5 Overall UK Cystic Fibrosis Registry 2016 Annual Data Report

17 Lung health For people with CF, mucus in the lungs is linked to repeated or chronic infections, which can cause permanent damage, making it harder to breathe. 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 a year. In people with 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 Function Initiative, or GLI. cysticfibrosis.org.uk 17

18 1.11 Median FEV 1 (% predicted, GLI equations) among patients aged 6 years and older n=692 The chart and table in this section show the 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 Median FEV 1 % predicted Age (years) Overall Females Males Age (years) Overall Female Male N Median IQR N Median IQR N Median IQR Overall UK Cystic Fibrosis Registry 2016 Annual Data Report

19 1.12 Median FEV 1 % predicted and BMI among patients aged 20 years and older n=445 The goal BMI for adults is 22 for women and 23 for men. The chart 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 FEV 1 % 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 we grouped all patients with BMI 30 together Median best FEV 1 % predicted (GLI equations) among patients aged 6 years and older n=657 Age (years) Overall Female Male N Median IQR N Median IQR N Median IQR Overall cysticfibrosis.org.uk 19

20 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 2016 <16 years n=309, 16 years n= Proportion of patients (%) Age ( years ) Chronic Staphylococcus aureus (%) Chronic Pseudomonas aeruginosa (%) B. cepacia complex (%) H. influenza (%) Intermittent Staphylococcus aureus (%) Intermittent Pseudomonas aeruginosa (%) Meticillin-resistant Staphylococcus aureus (MRSA) (%) NTM (%) Chronic infection with S. aureus or P. aeruginosa were identified from annual review. Data on B. cepacia, MRSA and H.influenzae were collected from culture results at annual review. 20 UK Cystic Fibrosis Registry 2016 Annual Data Report

21 Paediatric Age Range (Years) Overall Paediatric (<16 years) Number in age range Chronic S.aureus, n (%) 5 (9.1%) 9 (9.5%) 16 (18.2%) 7 (9.9%) 37 (12%) Intermittent S.aureus, n (%) 6 (10.9%) 15 (15.8%) 21 (23.9%) 27 (38%) 69 (22.3%) Chronic P. aeruginosa, n (%) 0 (0%) 6 (6.3%) <5 5 (7%) - (3.9%) Intermittent P. aeruginosa, n (%) 10 (18.2%) 13 (13.7%) 12 (13.6%) 8 (11.3%) 43 (13.9%) B. cepacia complex, n (%) 0 (0%) 0 (0%) <5 <5 - (1.3%) MRSA, n (%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) H. influenza, n (%) 25 (45.5%) 36 (37.9%) 21 (23.9%) 16 (22.5%) 98 (31.7%) NTM, n (%) 0 (0%) <5 5 (5.7%) 8 (11.3%) - (4.5%) Adult Age Range (Years) Overall Number in age range Chronic S.aureus, n (%) Intermittent S.aureus, n (%) Chronic P. aeruginosa, n (%) Intermittent P. aeruginosa, n (%) B. cepacia complex, n (%) Adults ( 16 years) (33.8%) 16 (22.5%) 16 (22.5%) 5 (7%) 7 (9.9%) 41 (41.4%) 7 (7.1%) 35 (35.4%) 7 (7.1%) 6 (6.1%) 32 (38.1%) 6 (7.1%) 46 (54.8%) 6 (7.1%) <5 26 (38.2%) <5 29 (42.6%) 20 (35.7%) 6 (10.7%) 30 (53.6%) <5 <5 9 (13.2%) 18 (41.9%) 7 (23.3%) 8 (30.8%) 13 (30.2%) 189 (36.3%) <5 <5 <5 <5 50 (9.6%) 14 (32.6%) 8 (18.6%) 12 (40%) 9 (34.6%) 19 (44.2%) 210 (40.4%) <5 0 (0%) <5 37 (7.1%) <5 <5 <5 <5 <5 40 (7.7%) MRSA, n (%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) H. influenza, n (%) NTM, n (%) 6 (8.5%) 6 (8.5%) 10 (10.1%) 12 (12.1%) 6 (7.1%) 6 (8.8%) 6 (10.7%) 7 (16.3%) <5 <5 5 (11.6%) 50 (9.6%) <5 <5 <5 0 (0%) <5 <5 <5 30 (5.8%) 1.15 Nontuberculous mycobacteria (NTM) or atypical mycobacteria* 2014 (n=782) 2015 (n=795) 2016 (n=829) NTM prevalence (%) 34 (4.3%) 37(4.7%) 44 (5.3%) On NTM treatment in the given year (% of 8 (24) 12(32) 16(36) NTM prevalence in given year) NTM incidence M.abscessus prevalence** * Non tuberculous mycobacterium is slow to grow and slow to treat and may be present for several years before eradication, or may never be cleared.in the table 1.15, prevalence represents all people reported in that years as having a positive culture. Incidence represents all positive cultures in individual who have not reported any in the previous 2 years. ** M.abscessus incidence in 2016 was 11. Prior years cannot be evaluated as enhanced NTM reporting was not available prior to cysticfibrosis.org.uk 21

22 1.16 Lung infections over time patients(%) Proportion of Age (years) Chronic Pseudomonas aeruginosa (2008) Chronic Pseudomonas aeruginosa (2016) Chronic Staphylococcus aureus (2008) Chronic Staphylococcus aureus (2016) Age (years) % Chronic S. aureus; 2016 Chronic P. aeruginosa; 2016 Chronic S. aureus; 2008 Chronic P. aeruginosa; UK Cystic Fibrosis Registry 2016 Annual Data Report

23 Complications 1.17 Prevalence of complications Respiratory Related Overall (n=795) <16 years (n=298) 16 years (n=497) N (%) N (%) N (%) Nasal polyps requiring surgery - <5 9 (1.7) Sinus disease - <5 164 (31.5) Asthma 79 (9.5) 14 (4.5) 65 (12.5) Allergic bronchopulmonary aspergillosis (ABPA) - <5 33 (6.3) Haemoptysis 23 (2.8) 0 (0.0) 23 (4.4) Pneumothorax requiring chest tube 0 (0.0) 0 (0.0) 0 (0.0) Pancreas & Hepatobiliary Disease Elevated Liver enzymes - <5 25 (4.8) Liver disease 104 (12.5) 23 (7.4) 81 (15.6) Cirrhosis with no portal hypertension - <5 12 (2.3) Cirrhosis with portal hypertension 19 (2.3) 6 (1.9) 13 (2.5) Gallbladder disease requiring surgery <5 <5 <5 Pancreatitis - <5 7 (1.3) Upper Gastrointestinal (GI) Gastroesophageal reflux disease (GERD) 100 (12.1) <5 99 (19.0) Peptic ulcer 0 (0.0) 0 (0.0) 0 (0.0) GI bleed req hospital variceal 0 (0.0) 0 (0.0) 0 (0.0) GI bleed req hospital non variceal <5 0 (0.0) <5 Lower GI Intestinal obstruction 0 (0.0) 0 (0.0) 0 (0.0) Fibrosing colonopathy/colonic structure - <5 88 (16.9) Rectal prolapse 0 (0.0) 0 (0.0) 0 (0.0) Meconium ileus <5 <5 0 (0.0) Renal Kidney stones <5 <5 <5 Renal failure 13 (1.6) 0 (0.0) 13 (2.5) Musculoskeletal Arthritis <5 <5 <5 Arthropathy 33 (4.0) 0 (0.0) 33 (6.3) Bone fracture 0 (0.0) 0 (0.0) 0 (0.0) Osteopenia 107 (12.9) 0 (0.0) 107 (20.6) Osteoporosis 42 (5.1) 0 (0.0) 42 (8.1) Other Cancer confirmed by histology 0 (0.0) 0 (0.0) 0 (0.0) Port inserted or replaced 7 (0.8) <5 <5 Depression 21 (2.5) 0 (0.0) 21 (4.0) Hearing loss - <5 9 (1.7) Hypertension 17 (2.1) 0 (0.0) 17 (3.3) cysticfibrosis.org.uk 23

24 1.18 Incidence of complications Newly identified in 2015 Newly identified in 2016 Overall (n=795) <16 years (n=298) 16 years (n=497) Overall (n=829) <16 years (n=309) 16 years (n520) ABPA; n (%) 7 (0.9) <5 <5 11 (1.3) <5 8 (1.5) Cirrhosis with no portal <5 0 <5 13 (1.6) <5 11 (2.1) hypertension; n (%) Cirrhosis with portal 14 (1.8) <5 10 (2.0) 7 (0.8) <5 <5 hypertension; n (%) Cancer confirmed by histology; n (%) <5 0 <5 <5 <5 < 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. Treatment for CF-related diabetes; n(%) All 10 years (n=640) years (n=120) 16 years (n=520) 155 (24.2) 11 (9.2) 144 (27.7) Screening for CF-related diabetes Yes 357 (55.8) 101 (84.2) 256 (49.2) No 117 (18.3) 13 (10.8) 104 (20.0) Known CF-related 131 (20.5) 5 (4.2) 126 (24.2) diabetes Unknown 13 (2.0) <5 12 (2.3) 24 UK Cystic Fibrosis Registry 2016 Annual Data Report

25 Antibiotics 1.20 Intravenous (IV) antibiotic use When someone with CF 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 in hospital or at home. Age Number in age band Home Hospital Total N (%) Median N (%) Median N (%) days (IQR) days (IQR) Median days (IQR) <5 10 (18.2) 13 (7-20) 10 (18.2) 14 (12-20) (8.4) 25 (13-48) 20 (21.1) 21 (14-33) 23 (24.2) 27 (14-52) (12.5) 14 (9-48) 30 (34.1) 19 (14-43) 32 (36.4) 37 (14-54) (16.9) 33 (16-42) 21 (29.6) 39 (14-70) 25 (35.2) 43 (26-70) (19.7) 14 (12-49) 22 (31.0) 14 (6-28) 27 (38.0) 27 (14-50) (35.4) 28 (14-39) 37 (37.4) 14 (7-28) 50 (50.5) 26 (14-42) (31.0) 14 (13-36) 30 (35.7) 14 (7-23) 41 (48.8) 14 (14-53) (35.3) 24 (14-53) 22 (32.4) 15 (13-29) 35 (51.5) 28 (14-51) (21.4) 17 (14-35) 15 (26.8) 19 (11-35) 21 (37.5) 26 (15-42) (23.3) 35 (29-56) 10 (23.3) 13 (8-14) 13 (30.2) 42 (29-55) (33.3) 13 (8-20) 6 (20.0) 13 (6-14) 12 (40.0) 14 (12-28) (23.1) 38 (14-41) <5 8 (30.8) 38 (14-43) (18.6) 16 (9-29) 13 (30.2) 13 (3-14) 15 (34.9) 14 (12-28) Overall (21.4) 20 (13-41) 239 (28.8) 14 (10-32) 312 (37.6) 27 (14-50) 1.21 Inhaled antibiotic use among patients with chronic Pseudomonas aeruginosa Overall <16 years 16 years Overall <16 years 16 years Patients with chronic pseudomonas Tobramycin solution, n(%) 33 (15.9) 5 (35.7) 28 (14.5) <5 35 (16.7) Other aminoglycoside, n(%) <5 0 <5 <5 0 <5 Colistin, n(%) 64 (30.9) 8 (57.1) 56 (29.0) 76 (34.2) 9 (75.0) 67 (31.9) Promixin, n(%) 37 (17.9) <5 34 (17.6) <5 31 (14.8) Aztreonam, n(%)* <5 0 <5 10 (4.5) 0 10 (4.8) Colistimethate(DPI), n(%)* <5 33 (17.1) <5 44 (21.0) Tobramycin Inhalation Powder, n(%)* <5 58 (30.1) 68 (30.6) 0 68 (32.4) At least one of the above, n(%)* 163 (78.7) 12 (85.7) 151 (78.2) 173 (77.9) 11 (91.7) 162 (77.1) *Not reported for 2008 The consensus view in the UK is that 90% of patients chronically infected with Pseudomonas aeruginosa should be prescribed at least one of the above nebulised antibiotics. cysticfibrosis.org.uk 25

26 1.22 Long-term use of azithromycin among patients with and without chronic Pseudomonas aeruginosa Azithromycin is an antibiotic with anti-inflammatory properties used to treat certain infections, including P.aeruginosa Patients with chronic P. aeruginosa; n (%) Patients without chronic P. aeruginosa; n (%) Overall (n=63*) 0-3 years (n<5) 4-15 years (n=34) 16 years (n=28) Overall 0-3 years (n=59) 4-15 years (n=239) 16 years (n=497) 29 (46.0) 0 (0) 12 (35.3) 17 (60.7) 187 (43.4) 0 (0) 10 (11.2) 177 (51.8) 34 (54.0) <5 22 (64.7) 11 (39.3) 244 (56.6) 0 (0) 79 (88.8) 165 (48.2) *number on azithromycin in the given year 26 UK Cystic Fibrosis Registry 2016 Annual Data Report

27 Muco-active therapies 1.23 Mannitol 1.24 DNase Age 2016 Total Patients Patients on Mannitol < < < < <5 Overall (1.3) Age DNase; n (%) Total patients Patients on DNase; n (%) Total patients Patients on DNase; n (%) < (10.9) (11.5) (20.0) (22.7) (45.5) (35.9) (50.7) (37.5) (56.3) < (53.5) < (46.4) < (41.2) < (30.4) < (32.6) (35.7) (26.3) Overall (19.4) (38.4) 1.25 Hypertonic saline This treatment helps to thin mucus so that it is easier to cough up and expel from the body. Hypertonic saline; n (%) Age Number of patients Patients on hypertonic saline; n (%) Number of patients Patients on hypertonic saline; n (%) < (8.4) < (22.7) < (38.0) (23.9) (27.3) (21.4) < (25.0) (8.9) (11.6) (10.1) Overall 429 < (19.1) cysticfibrosis.org.uk 27

28 Other therapies 1.26 CFTR modifiers 1.26a Ivacaftor Ivacaftor is a drug that has been prescribed as a treatment for cystic fibrosis in patients aged six years and over with at least one copy of the genotype G551D since June Number of patients on Ivacaftor in Scotland 66 Sweat chloride before Ivacaftor 106 (96, 106) Sweat chloride 6-8 weeks after Ivacaftor 53 (44, 67) FEV 1 % before Ivacaftor 61.4 (49.9, 72.8) FEV 1 % 6-8 weeks after Ivacaftor 68.9 (53.7, 81.4) Number of patients stopped Ivacaftor ever <5 People with CF tend to have more chloride in their sweat than people without cystic fibrosis. This measurement is called sweat chloride and is measured in mmol/litre. 1.26b Ivacaftor/Lumacaftor Ivacaftor/Lumacaftor is licensed for use in patients aged 12 and over with two copies of the F508del mutation. In 2016 it was available to specific people with CF in the UK through a named patient access scheme. In Scotland one person received this drug in Oxygen and non-invasive ventilation Overall (n=829) <16 years (n=309) 16 years (n=520) Non-invasive ventilation (NIV), n (%) <5 5 (1.0) Long-term oxygen, n (%) 39 (4.7) 7 (2.3) 32 (6.2) Among those who have long-term oxygen: Continuous <5 5 (1.0) Nocturnal or with exertion <5 11 (2.1) As required (PRN) <5 0 <5 With exacerbation 17 (2.1) 5 (1.6) 12 (2.3) 28 UK Cystic Fibrosis Registry 2016 Annual Data Report

29 1.28 Physiotherapy Physiotherapy helps people with CF clear sticky mucus from their lungs. Active cycle of breathing techniques, n (%) Autogenic drainage (including assisted autogenic drainage), n (%) Overall (n=829) <16 years (n=309) 16 years (n=520) 160 (19.3) 36 (11.7) 124 (23.8) 340 (41.0) 93 (30.1) 247 (47.5) Any form of PEP, n (%) 400 (48.3) 251 (81.2) 149 (28.7) VEST, n (%) <5 <5 <5 Exercise, n (%) 362 (43.7) 84 (27.2) 278 (53.5) Note that these techniques are not mutually exclusive and represent primary and secondary forms of physiotherapy 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 food intake. Overall (n=829) <16 years (n=309) 16 years (n=520) Any supplemental feeding, n (%) 176 (21.2) 52 (16.8) 124 (23.8) Nasogastric tube, n (%) <5 9 (1.7) Gastronomy tube/button, n (%) 33 (4.0) 14 (4.5) 19 (3.7) Jejunal Total parenteral nutrition (TPN) Transplants Lung transplantation has been available to people with CF for almost 30 years. Today, the most common operation carried out is a double lung transplant, or a Bilateral Sequential Lung transplant. Post-transplant survival rates are 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 evaluated Number accepted Number receiving transplants <5 5 <5 5 <5 6 Type of transplant received: Bilateral lung <5 5 <5 5 <5 <5 Heart and lung Liver Other <5 cysticfibrosis.org.uk 29

30 Genotypes Genotypes are part of the genetic makeup of a cell, organism, or individual that usually controls a particular characteristic (known as phenotype). For people with CF, their genotype reveals which mutations of the CF gene cause their cystic fibrosis. Everyone living with CF 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. 824 (99.4%) patients have been genotyped with a recorded value. DF508 Mutations; n (%) Homozygous DF (43.6) Heterozygous DF (47.0) No DF508 or both unidentified 78 (9.5) 1.31 Genotypes Mutations Nucleotide Protein Legacy name N % c.1521_1523delctt p. Phe508del F508del c.1652g->a p. Gly551Asp G551D c.350g->a p. Arg117His R117H c.1624g->t p. Gly542X G542X c.200c->t p. Pro67Leu P67L c.1679g->c p. Arg560Thr R560T c g->a G->A c.1477c->t p. Gln493X Q493X c.489+1g->t 621+1G->T c.3909c->g p. Asn1303Lys N1303K c.3454g->c p. Asp1152His D1152H c g->a G->A c.3528delc p. Lys1177SerfsX delC c.178g->t p. Glu60X E60X c.1558g->t p. Val520Phe V520F c.948delt p. Phe316LeufsX delT c c->t kbC->T c [5 (AJ :g.152T[5]) 5T c.1705t->g p. Tyr569Asp Y569D c.1364c->a p. Ala455Glu A455E <5 0.5 c g->a G->A <5 0.5 c.1519_1521delatc p. Ile507del I507del <5 0.5 c.3196c->t p. Arg1066Cys R1066C <5 0.4 c a->g A->G <5 0.2 c.3484c->t p. Arg1162X R1162X <5 0.2 c.2988g->a 3120G->A <5 0.2 c.254g->a p. Gly85Glu G85E <5 0.2 c.2012delt p. Leu671X 2143delT <5 0.2 c.223c->t p. Arg75X R75X <5 0.2 c _2657+3insa insA <5 0.2 c g->a G->A <5 0.2 c.2052dela p. Lys684AsnfsX delA <5 0.2 c.3846g->a p. Trp1282X W1282X <5 0.2 c.1657c->t p. Arg553X R553X <5 0.1 c.1466c->a p. Ser489X S489X <5 0.1 c.2583delt p. Phe861LeufsX3 2711delT <5 0.1 c.579+3a->g 711+3A->G <5 0.1 c g->a G->A <5 0.1 c.3705t->g p. Ser1235Arg S1235R <5 0.1 c.274g->a p. Glu92Lys E92K <5 0.1 c.3884_3885inst p. Ser1297PhefsX5 4016insT <5 0.1 c.579+1g->t 711+1G->T <5 0.1 c.3276c->a p. Tyr1092X Y1092X(C->A) <5 0.1 c.1329_1330insagat p. Ile444ArgfsX3 1461ins4 <5 0.1 c.273+1g->a 405+1G->A <5 0.1 c g->a G->A <5 0.1 Other selected UK Cystic Fibrosis Registry 2016 Annual Data Report

31 Section 2: Centre-Level Analysis Cystic fibrosis care in Scotland is led by eight regional centres, two stand-alone clinics and three networked clinics. The breakdown of centres and clinics delivering paediatric and adult care is shown below: Paediatric Adult Total Regional centres Stand-alone clinics Section 2 shows analysis of data for individual CF centres. This allows people with CF, their families, and healthcare providers to compare centres with one another, and the national average. This level of transparency helps to improve standards of care by giving people with CF and healthcare providers alike the chance to make informed choices about what questions to ask their team, and which types of treatment may be best for each individual. It is important to remember that lots of different factors can affect the outcomes of people with CF in centres, not all of which are within the centre s control. This might include the economic profile of the area, the age at which the person with CF was diagnosed and referred to the centre, certain patient characteristics such as their gender, as well as facilities, care pathways, and the medical team providing care. If a person with CF or a member of their family has questions about the results for their CF centre or clinic, they should discuss this with their CF team. Full tables of data are shown in Appendix 1 on page 42. Key Paediatric centre Adult centre cysticfibrosis.org.uk 31

32 A guide to the charts Box plots This whisker shows the highest value. This line shows the upper quartile. The width of the box shows the interquartile range. This line shows the median. This line shows the lower quartile. This whisker shows the lowest value. The box shows the middle half of the data for that centre, going from the first quartile to the third quartile. The longer the box, the more varied the data for that centre. The horizontal line within the box shows the median result for that centre. The whiskers above and below the box shows the highest and lowest values for that centre, excluding any outliers. The position of the box between the whiskers shows any skew in the data. If a box is towards the top of the whisker, more of the people for this centre were recorded at the high end of the scale. 32 UK Cystic Fibrosis Registry 2016 Annual Data Report

33 Section 2a Paediatric centre analysis This section shows results for the six paediatric centres with their network clinics, and one stand-alone clinic. 2.1 Median FEV 1 % predicted among patients aged 6 and older by paediatric centre/clinic (without a history of lung transplant) (GLI equations) FEV1 % predicted * * 75* 90 94* * * UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The median FEV 1 % predicted of patients attending paediatric centres/clinics in Scotland is 90% predicted (IQR: 80-98). * Centre/clinic with a dataset submission of fewer than 20 patients. 2.2 Median Body Mass Index (BMI) percentile among patients aged 2-15 years by paediatric centre/clinic Percentile * * * UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The median BMI percentile of patients attending paediatric centres/clinics in Scotland is 53 (IQR: 31-76). * Centre/clinic with a dataset submission of fewer than 20 patients. cysticfibrosis.org.uk 33

34 2.3 Proportion of patients with chronic P. aeruginosa by paediatric centre/clinic Proportion (%) * * UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The proportion of patients attending paediatric centres/clinics in Scotland with chronic P. aeruginosa is 4%. * Centre/clinic with a dataset submission of less than 20 patients. 34 UK Cystic Fibrosis Registry 2016 Annual Data Report

35 2.4 Proportion of patients receiving DNase treatment by paediatric centre/clinic Proportion (%) * * UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The proportion of patients attending paediatric centres/clinics in Scotland receiving DNase treatment is 33%. * Centre/clinic with a dataset submission of less than 20 patients. 2.5 Proportion of patients receiving hypertonic saline treatment by paediatric centre/clinic Proportion (%) * * UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The proportion of patients attending paediatric centres/clinics in Scotland receiving hypertonic saline treatment is 19.5%. cysticfibrosis.org.uk 35

36 Section 2b: Adult Centres Analysis This section shows results for the three adult centres with any network clinics. 2.6 Median age (years) by adult service Age (years) UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The median age of patients attending adult services in Scotland is 28 years (IQR: 22-37). 2.7 Median FEV 1 % predicted by adult service (without a history of lung transplant) (GLI equations) FEV1 % Predicted UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The median FEV1 % predicted of patients attending adult services in Scotland is 65% (IQR: 45 82). 36 UK Cystic Fibrosis Registry 2016 Annual Data Report

37 2.8 Median BMI among patients aged 16 years and older by adult service BMI Key Services in the UK UK SC Centre/Clinic ID Services in Scotland The median BMI of patients attending adult services in Scotland is 23 (IQR: 20 25). 2.9 Proportion of patients with chronic P. aeruginosa by adult service Proportion (%) UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The proportion of patients attending adult services in Scotland with chronic P. aeruginosa is 40%. cysticfibrosis.org.uk 37

38 2.10 Proportion of patients receiving DNase treatment by adult service Proportion (%) UK SC Centre/Clinic ID The proportion of patients attending adult services in Scotland receiving DNase treatment is 39%. Key Services in the UK S in Services in Scotland S in 2.11 Proportion of patients receiving hypertonic saline treatment by adult service Proportion (%) UK SC Centre/Clinic ID Key Services in the UK Services in Scotland The proportion of patients attending adult services in Scotland receiving hypertonic saline treatment is 23%. 38 UK Cystic Fibrosis Registry 2016 Annual Data Report

39 Glossary Words in this report that appear in this glossary are highlighted the first time they appear. Word/Phrase Meaning January December ABPA (Allergic Bronchopulmonary Aspergillosis) Arthritis Arthropathy Asthma B. cepacia complex BMI (Body Mass Index) CF CFTR (Cystic Fibrosis Transmembrane conductance Regulator) Chronic Cirrhosis CI (Confidence Interval) Enzymes FEV 1 (Forced Expiratory Volume in one second) FEV 1 % predicted Fibrosing colonopathy Gall bladder When a person develops a respiratory allergic reaction to Aspergillus fumigatus. A condition causing pain and inflammation in the joints. A condition causing pain in the joints. A respiratory condition causing reversible episodes of difficulty breathing, often associated with wheezing. Burkholderia cepacia complex is a group of bacteria, some of which threaten the health of people with cystic fibrosis. A measure designed to show whether a person is a healthy weight for their height. Cystic fibrosis. A protein at the cell surface that controls the salt and water balance across a cell. The gene that causes cystic fibrosis is the blueprint for the CFTR protein. Everyone has two copies of the gene for CFTR. To be born with cystic fibrosis, both CFTR genes must be affected by a CF-causing mutation. Persistent, or long-lasting. A chronic liver disease. A way of expressing how certain we are about our statistical estimates of a clinical measure (eg BMI). It gives a range of results that is likely to include the true value for the population. A narrow confidence interval indicates a more precise estimate. A wide confidence interval indicates more uncertainty about the true value of the clinical measure - often because a small group of patients has been studied. The confidence interval is usually stated as 95% CI, which means that the range of values has a 95 in 100 chance of including the true value. Biological molecules that help complex reactions, such as digestion of food, occur in the body. This is the amount of air that a person can blow out of the lungs in the first second of a forced exhaled breath. People with healthy lungs can blow out most of the air held in this time. The FEV 1 can be converted from absolute litres of air blown out into a predicted percentage (%). A healthy range for % predicted is calculated from a very large population sample, and is normally considered to be between % predicted. A condition causing narrowing of part of the colon. The small sac-shaped organ under the liver that stores bile after it is secreted by the liver, before it is released into the intestine. cysticfibrosis.org.uk 39