UK Cystic Fibrosis Registry

Transcription

1 UK Cystic Fibrosis Registry Annual Data Report 2017 Scotland

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3 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland Report prepared by Andrew Lee Statistician Cystic Fibrosis Trust Susan Charman Senior Statistician Cystic Fibrosis Trust Rebecca Cosgriff Director of Data & Quality Improvement Cystic Fibrosis Trust With assistance from The UK Cystic Fibrosis Registry Steering Committee Chloe Ainsley Lead Graphic Designer Cystic Fibrosis Trust Elaine Gunn Registry Data Manager Cystic Fibrosis Trust Kieran Earlam Registry Administrator 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 us: 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 Report prepared by 3 Acknowledgements 3 Contact information 3 Introduction 6 Cystic fibrosis 6 UK Cystic Fibrosis Registry 6 Governance 7 Data collection 7 Where can I find more information? 7 Section 1: Scotland-wide analysis Summary of the UK Cystic Fibrosis Registry Age distribution by gender Height percentiles of children and young people (<20 years) Weight percentiles of children and young people (<20 years) Body Mass Index (BMI) percentiles in children and young people (<20 years) Body Mass Index (BMI) in adults (>20 years) Education and employment in adults (>16 years) Pregnancy 14 Diagnosis of cystic fibrosis Age at diagnosis and screening in children under 16 in Age at diagnosis and screening in adults aged 16 and over in Mode of presentation 17 Lung health FEV 1 % predicted (GLI equations) in patients aged six years and older who have not had 19 a lung transplant 1.13 Best FEV 1 % predicted (GLI equations) in patients aged six years and older who 20 have not had a lung transplant 1.14 FEV 1 % predicted (GLI equations) and BMI in people 20 years and older who have 21 not had a lung transplant Lung infections Lung infections in Lung infections in Nontuberculous mycobacteria (NTM) or atypical mycobacteria Lung infections over time 25 Complications Prevalence of complications 27 4 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

5 1.20 Incidence of complications CF-related diabetes 28 Antibiotics Intravenous (IV) antibiotics Inhaled antibiotic use among patients with chronic Pseudomonas aeruginosa Long-term azithromycin use Prophylactic flucloxacillin use 31 Muco-active therapies Mannitol DNase Hypertonic saline Burden of treatment 33 Other Therapies CFTR modifiers Oxygen and non-invasive ventilation Physiotherapy Feeding Transplants 35 Genotypes Genotypes in the UK population 36 Section 2: Centre-level analysis 38 A guide to the charts 39 Box plots 39 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 15 years by paediatric centre/clinic Data completeness 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 42 Section 2b: Adult centre analysis Median age (years) by adult service Median FEV 1 % predicted by adult service (without a history of lung transplant) Median BMI among patients aged 16 years and older by adult service Proportion of patients with chronic P. aeruginosa by adult service Inhaled antibiotic use for patients with chronic P. aeruginosa Data completeness by adult service Proportion of patients receiving DNase treatment by adult service Proportion of patients receiving hypertonic saline treatment by adult service 46 Appendices 47 Appendix 1: Centre-level data tables 48 Paediatric centres/clinics providing data in Adult centres/clinics providing data in Glossary 52 Appendix 2: UK Cystic Fibrosis Registry Steering Committee Structure 54 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 the UK. This includes people with CF, their families and clinical teams, healthcare managers, commissioners, and policy makers. You can find a glossary of scientific and clinical terms on page 53. Cystic fibrosis Cystic fibrosis is an inherited disease caused by a faulty gene known as CFTR. The gene and the protein it makes help control the movement of salt and water in and out of cells. When the gene is faulty, it can cause thicker mucus. One of the main areas affected is the lungs; over time this thick mucus blocks and damages airways, leading to infections and making it hard to breathe. People with CF may develop other problems, such as liver disease or CF-related diabetes (CFRD). Around 85% of people with CF also have difficulty digesting food effectively. 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 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 provide funding to NHS CF centres that is proportionate to their patients disease severity. 6 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

7 Governance The Registry Steering Committee (RSC) is responsible for making sure that the UK CF Registry is compliant with data protection legislation, and its Research Ethics Committee-approved Study Protocol. It also makes recommendations about the future development of the Registry. A sub-committee of the RSC, the Registry Research Committee, assesses applications for data and guides the Registry research strategy. Please see Appendix 1: UK CF Registry Committee Structure. Data are only recorded on the UK CF Registry if explicit written consent is given by the person with CF 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 by the Registry team 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. If requests from pharmaceutical companies are granted, for research or submissions to regulators or the NHS, the data are analysed and aggregated by Registry statisticians and only summary data are provided. 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? i You can find out more about CF, and the UK CF Registry, at cysticfibrosis.org.uk 7

8 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 2017 UK Scotland CF patients registered 1 10, Excluding diagnoses that year 10, CF patients with an annual review; n(%) 2 9,887 (96%) 858 (93%) Age in years; median All newly diagnosed patients (newborn screening and other) Number of patients born identified by newborn screening Age at diagnosis in months; median Adults aged 16 years and over; % Males; % Genotyped; % 3 (both mutations identified) Total deaths reported (%) (1.3%) 19 (2.1%) Age at death in years; median (95% CI) 5 31 (29, 35) 32 (27, 35) Notes: 1 Number of patients diagnosed with CF, seen in the past two years, and alive at 1 January in the given year. This number reduced in 2016 as a result of a data cleaning exercise. We followed up on patients who were registered but did not have data submitted in If they were no longer being cared for within the NHS (eg they had moved abroad), they were marked as inactive and excluded from this number. 2 As patients newly diagnosed in a given year may not have their first annual review in the same year, the proportion with an annual review is calculated from the total registered excluding those diagnosed in the given year. 3 Calculated from patients with an annual review in the given year (see footnote 2 above). 4 Calculated from all patients registered on the database. Some diagnosis data are added after the data entry closure each year, so figures from previous years have been updated for this report. 5 Calculated from all registered patients who died in the given year. Annual review: A Registry Annual Review form contains a combination of data relating to a person with CF s once yearly annual review appointment at their CF centre, and their clinical care and health over the past 12 months. 8 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

9 1.2 Age distribution by gender N=858 The following chart shows the mix of ages and genders in the CF population in Scotland Overall Females Males Proportion (%) Age (years) Age All; n (%) Females; n (%) Males; n (%) (7.0) 28 (7.1) 32 (6.9) (9.9) 36 (9.2) 49 (10.5) (11.3) 49 (12.5) 48 (10.3) (9.1) 35 (8.9) 43 (9.2) (7.7) 34 (8.7) 32 (6.9) (11.7) 48 (12.2) 52 (11.2) (10.3) 41 (10.4) 47 (10.1) (7.6) 31 (7.9) 34 (7.3) (7.5) 27 (6.9) 37 (8.0) (5.2) 16 (4.1) 29 (6.2) (3.1) 12 (3.1) 15 (3.2) (2.3) 8 (2.0) 12 (2.6) (2.6) 9 (2.3) 13 (2.8) (2.7) 10 (2.5) 13 (2.8) (0.6) <5 < (1.5) 7 (1.8) 6 (1.3) < (37.3) 148 (37.7) 172 (37.0) (62.7) 245 (62.3) 293 (63.0) < (40.6) 166 (42.2) 182 (39.1) (59.4) 227 (57.8) 283 (60.9) Overall cysticfibrosis.org.uk 9

10 1.3 Height percentiles of children and young people (<20 years) 6 N=386 The following chart and table show the height percentiles of people with CF, aged 19 and under, in relation to 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. Median height percentile Age (years) Overall Females Males Overall Female Male Age n Median IQR n Median IQR n Median IQR < Overall 378* *Number with non-missing data 6 Based on UK-WHO growth charts, 1990 (updated 1996) 10 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

11 1.4 Weight percentiles of children and young people (<20 years) 6 N=386 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. Median weight percentile Overall Females Males Age (years) Overall Female Male Age n Median IQR n Median IQR n Median IQR < Overall 379* *Number with non-missing data 6 Based on UK-WHO growth charts, 1990 (updated 1996) cysticfibrosis.org.uk 11

12 1.5 Body Mass Index (BMI) percentiles in children and young people (<20 years) 6 N=386 The following chart and table show the BMI 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, it means that only 40% of the population at the same age are their BMI or lower; so 60% have a higher BMI Overall Females Males Median BMI percentile Age (years) Overall Female Male Age n Median IQR n Median IQR n Median IQR < Overall 378* *Number with non-missing data 6 Based on UK-WHO growth charts, 1990 (updated 1996) 12 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

13 1.6 Body Mass Index (BMI) in adults (20 years and over) N=472 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 Overall Females Males Median BMI Target (male): 23 Target (female): Age (years) Overall Female Male Age n Median IQR n Median IQR n Median IQR <5 - - < Overall *Number with non-missing data 7 Stallings et al, J Am Diet Assoc. 2008;108: cysticfibrosis.org.uk 13

14 1.7 Education and employment in adults (16 years and over) N=538 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 patients n (%) Number who completed questionnaire; n (%) 525 (97.6) Full-time employment; n (%) 189 (35.1) Part-time employment; n (%) 95 (17.7) Student; n (%) 78 (14.5) Homemaker; n (%) 16 (3.0) Unemployed; n (%) 101 (18.8) Disabled; n (%) 20 (3.7) Retired; n (%) 15 (2.8) Unknown entered; n (%) 11 (2.0) No data recorded; n (%) -* No. in work or study; n (%) 362 (69.0) 1.8 Pregnancy 8 women with cystic fibrosis had babies in men with cystic fibrosis became fathers in 2017 * No data recorded is no longer available to select. 14 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

15 Diagnosis of cystic fibrosis 1.9 Age at diagnosis and screening in children under 16 in 2017 N=320 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; n (%) Prenatal 0 (0) 0 (0) 0 (0) Birth-3 months 281 (88.9) 17 (100.0) 21 (91.3) 4-6 months 9 (2.8) - < months 8 (2.5) yr < yrs 8 (2.5) - <5 3 yrs < yrs < yrs yrs yrs yrs yrs yrs < yrs < yrs yrs yrs yrs Overall 316* Patients aged 5 years; n (%) The median (range) age at diagnosis for patients aged under 16 in 2017 is 46 days (0-192 months). Diagnosis in the first three months of life is more common in children aged five years in 2017 (born after the UK-wide newborn screening programme was in place) than in children aged 10 years in 2017 (born during the final year of the introduction of universal newborn screening in the UK). A total of 7 patients born in 2017 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 statistics are updated retrospectively each year to take updated data into account. Therefore the number of patients identified in 2017 is higher (6) in this report than was recorded in the previous. It is likely that the 2017 figure will be updated in the next annual report in *Number with non-missing data cysticfibrosis.org.uk 15

16 1.10 Age at diagnosis and screening in adults aged 16 and over in 2017 N=538 The table below shows the age at diagnosis for people aged 16 and over in People aged 16 or over in 2017 were born when newborn screening was carried out done in a few areas of the UK, before it became universal in mid Age at diagnosis n (%) Birth-3 months 186 (34.7) 4-6 months 50 (9.3) 7-12 months 33 (6.2) 1 year 40 (7.5) 2 years 35 (6.5) 3 years 25 (4.7) 4 years 17 (3.2) 5 years 10 (1.9) 6 years 7 (1.3) 7 years 7 (1.3) 8 years 8 (1.5) 9 years 6 (1.1) 10 years <5 11 years 6 (1.1) 12 years 6 (1.1) 13 years 4 (0.7) 14 years <5 15 years 7 (1.3) years 14 (2.6) years 9 (1.7) years 10 (1.9) years 16 (3.0) years 11 (2.1) years 8 (1.5) years < years < years < years < years <5 60+ years <5 Overall 536* Overall, 85 (14.5%) adults with CF in the Registry in 2017 were diagnosed at age 16 or over. In 2017, 5 people aged 16 or over were newly diagnosed with cystic fibrosis *Number with non-missing data 16 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

17 1.11 Mode of presentation The following table shows the number of patients diagnosed through each mode of presentation. Patients may present with multiple symptoms. The Venn diagram below shows the three most common modes of presentation excluding newborn screening (NBS), and the combinations of them. All patients Age <16 at diagnosis* Age 16 at diagnosis* Total patients Number diagnosed by NBS Total non-nbs Mode of presentation (excluding NBS) All patients (n=614) Age <16 at diagnosis* (n=526) Persistent or acute respiratory infection 230 (37.6) 182 (34.6) 48 (55.8) Failure to thrive/malnutrition 167 (27.3) 167 (31.7) 0 (0) Abnormal stools/fatty stool (steatorrhea)/ malabsorption 132 (21.6) 127 (24.1) 5 (5.8) Meconium ileus 102 (16.7) 102 (19.4) 0 (0) Family history 86 (14.1) 74 (14.1) 12 (14.0) Genotype 29 (4.7) 21 (4.0) 8 (9.3) Unknown 45 (7.4) 33 (6.3) 10 (11.6) Rectal prolapse 18 (2.9) 18 (3.4) 0 (0) Nasal polyps 5 (0.8) <5 <5 Electrolyte imbalance 24 (3.9) 5 <5 Prenatal <5 <5 <5 Bronchiectasis 7 (1.1) <5 5 Liver disease <5 <5 <5 Fertility <5 <5 <5 Pancreatitis <5 <5 <5 Oedema <5 <5 <5 Age 16 at diagnosis* (n=86) Top three non-nbs presentation routes Patients (%) Abnormal stools/fatty stool (steatorrhea)/malabsorption Failure to thrive/malnutrition Persistent or acute respiratory infection 59 (9.6%) 40 (6.5%) 41 (6.7%) 25 (4.1%) 43 (7.0%) 26 (4.2%) 136 (22.1%) Other: 242 (39.6%) *Age stratified figures are presented only for those with non-missing diagnosis date. This means that the number of people in <16 and 16 age groups will not necessarily add up to the All patients number, which is shown for all patients, even if the diagnosis date is missing. cysticfibrosis.org.uk 17

18 Lung health For people with CF, mucus in the lungs is linked to repeat or chronic infections. This 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 a forced exhaled breath. In this report, an FEV 1 % predicted is based on the FEV 1 we would expect for a person without CF 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. Each individual with CF will have their own FEV 1 target, based on their own lung function results and trends. 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, dietitians, and psychologists. The FEV 1 % predicted values shown in this report are calculated using an equation called Global Lungs Initiative, or GLI 8 8 Quanjer PH et al. Eur respir J Dec; 40(6): UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

19 1.12 FEV 1 % predicted (GLI equations) in patients aged six years and older who have not had a lung transplant N=761 People with CF who have had lung transplants are excluded, as their new non-cf lungs may have lung health similar to a person without cystic fibrosis. For the best FEV 1 calculation, where best FEV 1 % was missing or less than the FEV 1 % at annual review, the annual review FEV 1 % was used. Median FEV 1 % predicted Overall Best Overall Females Males Age (years) Overall Female Male Age (yrs) n Median IQR n Median IQR n Median IQR <5 - - <5 - - < < < Overall 693* *Number with non-missing data cysticfibrosis.org.uk 19

20 1.13 Best FEV 1 % predicted (GLI equations) in patients aged six years and older who have not had a lung transplant N=761 Overall Female Male Age (yrs) n Median IQR n Median IQR n Median IQR <5 - - <5 - - < < < Overall 704* * Where Best FEV 1 % was missing or less than the FEV 1 % at annual review, annual review FEV 1 % was used instead. *Number with non-missing data 20 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

21 1.14 FEV 1 % predicted (GLI equations) and BMI in people aged 20 years and over who have not had a transplant N=417* 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. This chart excludes people who have had a lung transplant Females Males Median FEV% predicted Target female 22 Target male BMI *Due to missing data, medians are calculated from a population of 417. 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 with a value of 30 of more, these are grouped into one. cysticfibrosis.org.uk 21

22 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. All other infections are reported if they have occurred at least once as a positive growth in the 12 months prior to the patient s annual review data set Lung infections in 2017 N= Proportion of patients (%) Age (years) Chronic Staphylococcus aureas Chronic Pseudomonas aeruginosa Burkholderia cepacia complex Haemophilus influenzae Aspergillus Intermittent Staphylococcus aureas Intermittent Pseudomonas aeruginosa Methicillin-resistant Staphylococcus aureus Non tuberculosis mycobacterium 22 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

23 1.16 Lung infections in 2017 <16 years N=320; 16 years N=538 Infections in this table reflect bugs grown in the 12 months prior to the 2017 annual review. The UK CF Registry definition of chronic is three or more isolates in the last 12 months. Paediatric age range (years) Overall Paediatric (<16 years) Number in age range Number who had culture taken Chronic S. aureus n (%) <5 13 (15.3) 19 (19.8) 17 (21.8) 51 (16.0) Intermittent S. aureus n (%) 15 (25.4) 17 (20.0) 19 (19.8) 15 (19.2) 66 (20.8) Chronic P. aeruginosa n (%) <5 <5 <5 8 (10.3) 14 (4.4) Intermittent P. aeruginosa n (%) 7 (11.9) 10 (11.8) 12 (12.5) 8 (10.3) 37 (11.6) B. cepacia complex n (%) <5 <5 <5 <5 6 (1.9) B. cenocepacia n (%) <5 <5 <5 <5 <5 B. multivorans n (%) <5 <5 <5 <5 <5 B. cepacia (other) n (%) <5 <5 <5 <5 <5 MRSA n (%) <5 <5 <5 <5 <5 H. influenza n (%) 21 (35.6) 44 (51.8) 28 (29.2) 16 (20.5) 109 (34.3) NTM n (%) <5 <5 <5 <5 6 (1.9) Aspergillus n (%) <5 <5 9 (9.4) 6 (7.7) 18 (5.7) cysticfibrosis.org.uk 23

24 Adult Age Range (Years) Number in age range Overall Adults ( 16 years) Number who had culture taken Chronic S. aureus n (%) 25 (41.0) 44 (45.4) 27 (35.5) 23 (39.0) 21 (38.9) 21 (50.0) 189 (39.5) Intermittent S. aureus n (%) 9 (14.8) 15 (15.5) 12 (15.8) 6 (10.2) 7 (13.0) 6 (14.3) 60 (12.6) Chronic P. aeruginosa n (%) 14 (23.0) 39 (40.2) 38 (50.0) 29 (49.2) 24 (44.4) 19 (45.2) 209 (43.7) Intermittent P. aeruginosa n (%) <5 10 (10.3) 10 (13.2) <5 5 (9.3) <5 37 (7.7) B. cepacia complex n (%) <5 9 (9.3) 7 (9.2) 5 (8.5) 6 (11.1) <5 44 (9.2) B. cenocepacia n (%) <5 <5 <5 <5 <5 <5 11 (2.3) B. multivorans n (%) <5 <5 <5 <5 <5 <5 25 (5.2) B. cepacia (other) n (%) <5 <5 <5 <5 <5 <5 5 (1.0) MRSA n (%) <5 <5 <5 <5 <5 <5 10 (2.1) H. influenza n (%) 6 (9.8) 13 (13.4) 9 (11.8) 10 (16.9) 6 (11.1) 6 (14.3) 61 (12.8) NTM n (%) 7 (11.5) 13 (13.4) <5 <5 <5 <5 32 (6.7) Aspergillus n (%) 8 (13.1) 7 (7.2) 5 (6.6) 6 (10.2) <5 <5 43 (9.0) Adult Age Range (Years) Overall Adults ( 16 years) Number in age range Number who had culture taken < Chronic S. aureus n (%) 7 (30.4) <5 8 (42.1) 6 (33.3) <5 <5 189 (39.5) Intermittent S. aureus n (%) <5 <5 <5 <5 <5 <5 60 (12.6) Chronic P. aeruginosa n (%) 13 (56.5) 7 (50.0) 8 (42.1) 10 (55.6) <5 6 (54.5) 209 (43.7) Intermittent P. aeruginosa n (%) <5 <5 <5 <5 <5 <5 37 (7.7) B. cepacia complex n (%) 5 (21.7) <5 <5 <5 <5 <5 44 (9.2) B. cenocepacia n (%) <5 <5 <5 <5 <5 <5 11 (2.3) B. multivorans n (%) <5 <5 <5 <5 <5 <5 25 (5.2) B. cepacia (other) n (%) <5 <5 <5 <5 <5 <5 5 (1.0) MRSA n (%) <5 <5 <5 <5 <5 <5 10 (2.1) H. influenza n (%) <5 <5 <5 <5 <5 <5 61 (12.8) NTM n (%) <5 <5 <5 <5 <5 <5 32 (6.7) Aspergillus n (%) <5 <5 <5 <5 <5 <5 43 (9.0) 24 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

25 1.17 Nontuberculous mycobacteria (NTM) or atypical mycobacteria Non-tuberculous mycobacterium is slow to grow and takes time to treat. It may be present for several years before eradication, or may never be cleared. In the table below, prevalence represents all people reported in that year as having a positive culture. Incidence represents all positive cultures in individuals that have not reported having any in the previous two years of data (n=795) 2016 (n=829) 2017 (n=858) NTM Prevalence (%) 37 (4.7%) 44 (5.3%) 38 (4.4%) On NTM treatment in the given year (% of NTM prevalence in given year) 12 (32%) 16 (36%) 11 (29%) NTM Incidence M. abscessus prevalence M. abscessus incidence* Lung infections over time N=429 in 2008, N=809 in 2013, N=858 in Proportion of patients (%) Age group (years) Chronic Staphylococcus aureus (2008) Chronic Staphylococcus aureus (2013) Chronic Staphylococcus aureus (2017) Chronic Pseudomonas aeruginosa (2008) Chronic Pseudomonas aeruginosa (2013) Chronic Pseudomonas aeruginosa (2017) *M. abscessus incidence cannot be evaluated prior to 2016 as enhanced NTM reporting was not available before cysticfibrosis.org.uk 25

26 Chronic Staphylococcus aureus 2008 (%) 2013 (%) 2017 (%) p-value * * * <16 years N/A 16 years N/A <18 years N/A 18 years N/A Chronic Pseudomonas aeruginosa 2008 (%) 2013 (%) 2017 (%) p-value * <16 years N/A 16 years N/A <18 years N/A 18 years N/A *Sample size too low for hypothesis test 26 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

27 Complications 1.19 Prevalence of complications The number shown is for a complication that has been present in the preceding 12 months * Overall (n=795) <16 years (n=298) 16 years (n=497 Overall (n=858) <16 years (n=320) 16 years (N=538) Respiratory related Nasal polyps requiring surgery - <5 9 (1.7) - <5 16 (3.0) Sinus disease - <5 164 (31.5) - <5 122 (22.7) Asthma 79 (9.5) 14 (4.5) 64 (12.5) 63 (7.3) 9 (2.8) 54 (10.0) Allergic bronchopulmonary aspergillosis (ABPA) - <5 33 (6.3) 37 (4.3) 7 (2.2) 30 (5.6) Any haemoptysis 23 (2.8) 0 23 (4.4) - <5 25 (4.6) Massive haemoptysis Pneumothorax requiring chest tube Pancreas & hepatobiliary disease Raised liver enzymes - <5 25 (4.8) 41 (4.8) 14 (4.4) 27 (5.0) Liver disease 104 (12.5) 23 ( (15.6) 68 (7.9) 18 (5.6) 50 (9.3) Cirrhosis with no portal hypertension - <5 12 (2.3) - <5 13 (2.4) Cirrhosis with portal hypertension 19 (2.3) 6 (1.9) 13 (2.5) - <5 13 (2.4) Gall bladder disease requiring surgery <5 <5 <5 - <5 <5 Pancreatitis - <5 7 (1.3) - <5 10 (1.9) Upper gastrointestinal Gastroeosophageal reflux disease (GERD) - <5 99 (19.0) - <5 113 (21.0) Peptic ulcer GI bleed (varices as source) GI bleed (non varices as source) - 0 <5 - <5 <5 Lower gastrointestinal Intestinal obstruction <5 0 Distal intestinal obstruction syndrome <5 94 (17.5) Fibrosing colonopathy/colonic stricture - <5 88 (16.9) Rectal prolapse <5 <5 Renal Kidney stones - <5 <5-0 <5 Renal failure 13 (1.6) 0 13 (2.5) 13 (1.5) 0 13 (2.4) Musculo-skeletal Arthritis - <5 <5 5 (0.6) 0 5 (0.9) Arthropathy 33 (4.0) 0 44 (6.3) 32 (3.7) 0 32 (5.9) Bone fracture <5 Osteopenia 107 (12.9) (20.6) 107 (12.5) (19.9) Osteoporosis 42 (5.1) 0 42 (8.1) 40 (4.7) 0 40 (7.4) Other Cancer confirmed by histology <5 <5 Port inserted or replaced - <5 <5 18 (2.1) 6 (1.9) 12 (2.2) Depression 21 (2.5) 0 21 (4.0) 19 (2.2) 0 19 (3.5) Hearing loss - <5 9 (1.7) - <5 7 (1.3) Hypertension 17 (2.1) 0 17 (3.3) 17 (2.0) 0 17 (3.2) Please note that in 2017 the data entry pathway for complications changed, which has resulted in a drop in prevalence for several complications. Results in 2017 should be interpreted with caution until 2018, when we will confirm whether this is a true decrease. cysticfibrosis.org.uk 27

28 1.20 Incidence of complications The table below describes new cases of a complication that have not been reported for an individual in at least the previous two years. Newly identified in 2016 Newly identified in 2017 Overall (n=829) <16 years (n=309) 16 years (n=520) Overall (n=858) <16 years (n=320) Allergic bronchopulmonary aspergillosis 11 (1.3) (ABPA); n (%) < (1.2) <5 5 Cirrhosis - no portal hypertension; n (%) 13 (1.6) <5 5 9 (1.0) <5 5 Cirrhosis - with portal hypertension; n (%) 7 (0.8) <5 <5 6 (0.7) <5 5 Cancer confirmed by histology; n (%) <5 <5 <5 <5 < years (n=538) 1.21 CF-related diabetes N=667 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, or it may not work properly, causing CFRD. CFRD is different from type 1 and type 2 diabetes, but has features of both. All 10 years (n=667) years (n=129) 16 years (n=538) On CFRD treatment; n (%) 150 (22.5) 7 (5.4) 143 (26.6) CFRD screening; n (%) Yes 354 (53.1) 115 (89.1) 239 (44.4) No 133 (19.9) 6 (4.7) 127 (23.6) Existing CFRD diagnosis 152 (22.8) 7 (5.4) 145 (27.0) Unknown 9 (1.3) < UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

29 Antibiotics 1.22 Intravenous (IV) antibiotics N=858 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 Home Hospital Total Patients n (%) Median days (IQR) Patients n (%) Median days (IQR) Patients n (%) Median days (IQR) <5-11 (18.3) 13 (13-13) 11 (18.3) 14 (7-18) (5.9) 25 (12-34) 18 (21.2) 14 (12-34) 20 (23.5) 15 (14-40) (9.3) 40 (28-47) 28 (28.9) 15 (28-47) 30 (30.9) 35 (14-68) (10.3) 26 (23-45) 23 (29.5) 17 (23-45) 27 (34.6) 26 (14-42) (19.7) 18 (14-37) 19 (28.8) 16 (14-37) 24 (36.4) 26 (14-49) (33.0) 14 (10-28) 42 (42.0) 14 (10-28) 52 (52.0) 25 (14-44) (29.5) 14 (14-35) 29 (33.0) 14 (14-35) 38 (43.2) 26 (14-42) (27.7) 27 (10-42) 18 (27.7) 15 (10-42) 24 (36.9) 33 (25-51) (18.8) 25 (14-39) 16 (25.0) 19 (14-39) 22 (34.4) 29 (14-42) (33.3) 16 (13-49) 7 (15.6) 25 (13-49) 16 (35.6) 37 (14-52) (33.3) 17 (14-28) 8 (29.6) 13 (14-28) 14 (51.9) 14 (13-36) <5 - <5 16 (10-31) 5 (25.0) 14 (13-44) <5 - <5 41 (49-68) 5 (22.7) 61 (55-63) (21.7) 14 (12-14) 9 (39.1) 14 (12-14) 11 (47.8) 14 (14-14) (0.0) - <5 - < <5 9 (4-32) 6 (46.2) 10 (4-32) 6 (46.2) 14 (14-39) < (7.2) 28 (22-41) 80 (25.0) 14 (22-41) 88 (27.5) 23 (14-43) (26.4) 18 (13-39) 161 (29.9) 14 (13-39) 218 (40.5) 27 (14-44) < (8.3) 27 (18-40) 89 (25.6) 14 (18-40) 100 (28.7) 23 (14-42) (26.7) 17 (13-40) 152 (29.8) 14 (13-40) 206 (40.4) 27 (14-45) Overall (19.2) 21 (13-40) 241 (28.1) 14 (13-40) 306 (35.7) 26 (14-44) cysticfibrosis.org.uk 29

30 1.23 Inhaled antibiotic use among people with chronic Pseudomonas aeruginosa Overall <16 years 16 years Overall <16 years 16 years Overall <16 years 16 years Patients with chronic P. aeruginosa Tobramycin solution; n (%) 6 (9.0) <5 <5 48 (19.9) < (15.2) <5 5 Other aminoglycoside; n (%) <5 0 <5 Colistin; n (%) 21 (31.3) 15 (53.6) 6 (15.4) 92 (38.2) 13 (76.5) 79 (35.3) 55 (24.7) 6 (42.9) 49 (23.4) Promixin; n (%) <5 0 <5 41 (17.0) < (15.7) 5 (35.7) 30 (14.4) Aztreonam; n (%) <5 0 < (7.6) (8.1) Colistimethate (DPI); n (%) (24.2) <5 5 Tobramycin Inhalation Powder; n (%) (28.7) 0 64 (30.6) At least one of the above; n (%) 28 (41.8) 17 (60.7) 11 (28.2) 151 (62.7) 15 (88.2) 136 (60.7) 183 (82.1) 12 (85.7) 171 (81.8) 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 Long-term azithromycin use Azithromycin is an antibiotic with some anti-inflammatory properties. It is recommended for long-term use as a prophylactic antibiotic in people with chronic Pseudomonas aeruginosa infection. Patients with chronic P. aeruginosa; n (%) 2008 Overall (n=429) 29 (46.0) 34 (54.0) 0-3 years (n=91) <5 < years (n=236) 12 (35.3) 22 (64.7) 16 years n=(102) 17 (60.7) 11 (39.3) 2013 Overall (n=809) 185 (49.9) 186 (50.1) 0-3 years (n=70) <5 < years (n=244) 8 (17.0) 39 (83.0) 16 years (n=495) 176 (54.7) 146 (45.3) 2017 Overall (n=858) 190 (43.0) 252 (57.0) 0-3 years (n=60) 0 (0) < years (n=260) 11 (13.3) 72 (86.7) 16 years (n=538) 179 (50.1) 178 (49.9) Patients without chronic P. aeruginosa; n (%) *In 2013, this includes Aztreonam. In 2017 it includes Aztreonam, Colistimethate and Tobramycin Inhalation Powder. 30 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

31 1.25 Flucloxacillin Flucloxacillin is an antibiotic, that is used prophylactically to prevent infection with bacteria. Age Total patients Patients on Flucloxacilin; n (%) (55.2) (34.1) (33.7) (33.8) (31.3) (29.0) (20.7) (12.5) (11.9) < < < < < <16 years (37.9) 16 years (17.4) <18 years (35.9) 18 years (17.6) Overall (25.1) cysticfibrosis.org.uk 31

32 Muco-active therapies 1.26 Mannitol Age Total patients Patients on Mannitol; n (%) < < < < < < < <16 years years (2.0) <18 years years (2.1) Overall (1.2) 1.27 DNase Age Total Patients on Total Patients on Total Patients on patients DNase; n (%) patients DNase; n (%) patients DNase; n (%) <5 70 <5 58 < (11.5) (10.9) (22.0) (22.7) (26.8) (45.7) (35.9) (44.3) (49.4) (37.5) (41.4) (51.6) < (43.3) (61.0) < (38.7) (50.0) < (37.3) (46.9) < (24.5) (42.4) < (26.9) (33.3) <5 19 < (48.0) < (31.8) 17 7 (41.2) < (30.0) 19 8 (42.1) <5 0 7 < (31.8) < <5 60+ <5 0 7 <5 13 <5 <16 years (18.3) (20.1) (32.0) 16 years (22.5) (36.2) (47.3) <18 years (20.3) (23.7) (33.2) 18 years (15.2) (35.0) (47.3) Overall (19.3) (29.9) (41.5) 32 UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

33 1.28 Hypertonic saline This treatment helps to thin mucus so that it is easier to cough out of the body. Age Patients on Patients on Total patients Total patients hypertonic Total patients hypertonic saline; n (%) saline; n (%) Patients on hypertonic saline; n (%) < (10.3) (5.9) (14.6) < (12.2) (23.9) < (19.7) (32.5) (26.3) (29.7) (25.8) (24.0) (12.0) (17.1) < (10.4) (25.0) (10.2) (18.6) (11.9) <5 25 < <5 17 < < <5 19 < <5 <5 7 <5 22 < < <5 0 7 <5 13 <5 <16 years 327 < (9.2) (21.0) 16 years 102 < (16.4) (19.5) <18 years 350 < (12.7) (22.0) 18 years 79 < (14.3) (18.8) Overall 429 < (13.6) (20.1) 1.29 Burden of treatment The Venn diagram shows how many people with CF are on one or more inhaled therapies and the combinations they take. A total of 451 (54.9%) people in Scotland are on no inhaled therapies. No inhaled therapy: 451 (54.9%) Inhaled antibiotics DNase Hypertonic saline or mannitol 96 (11.7%) 39 (4.7%) 96 (11.7%) 61 (7.4%) 145 (17.6%) 30 (3.6%) 41 (5.0%) cysticfibrosis.org.uk 33

34 Other Therapies 1.30 CFTR modifiers Ivacaftor Ivacaftor was first approved for use on the NHS in England in January Soon after, it was made available in Wales, Scotland and Northern Ireland. Since this time, ivacaftor s license has expanded across age ranges and mutation types. At the time of writing, ivacaftor is approved for use on the NHS across the UK for people aged two and older with a least one copy of nine specific CFTR mutations, known as gating mutations. Ivacaftor is additionally approved for use on the NHS in Wales for people aged 18 and over with the R117H mutation. Number of patients on ivacaftor in Scotland 70 Sweat chloride before ivacaftor 99 (95-104) Sweat chloride 6-8 weeks after ivacaftor 49 (40-67) FEV 1 % before ivacaftor 62.5 ( ) FEV 1 % 6-8 weeks after ivacaftor 72.5 ( ) Number of patients stopped ivacaftor ever 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. Ivacaftor/Lumacaftor Ivacaftor/Lumacaftor is licensed for use in patients aged 12 and over with two copies of the F508del mutation. In 2017 it was available to specific people with CF in the UK through a named patient access scheme. In Scotland, seven people received this drug in Oxygen and non-invasive ventilation Overall (n=858) <16 years (n=320) 16 years (n=538) <18 years (n=348) Non-invasive ventilation (NIV); n (%) 9 (1.0) <5 5 < years (n=510) Long-term oxygen; n (%) 44 (5.1) 5 (1.6) 39 (7.2) 6 (1.7) 38 (7.5) Among those who have long-term oxygen: Continuously 10 (22.7) <5 5 < 5 5 Nocturnal or with exertion 12 (27.3) 0 (0.0) 12 (30.8) 0 (0.0) 12 (31.6) As required (PRN) 7 (15.9) 0 (0.0) 7 (17.9) <5 5 With exacerbation 15 (34.1) <5 5 < UK Cystic Fibrosis Registry 2017 Annual Data Report - Scotland

35 1.32 Physiotherapy Physiotherapy helps people with CF clear sticky mucus from their lungs. Overall (n=858) <16 years (n=320) 16 years (n=538) <18 years (n=348) 18 years (n=510) Active cycle of breathing techniques; n (%) 137 (16.0) 23 (7.2) 114 (21.2) 29 (8.3) 108 (21.2) Autogenic drainage (including assisted autogenic drainage); n (%) 380 (44.3) 73 (22.8) 307 (57.1) 86 (24.7) 294 (57.6) Postural drainage; n (%) 7 (0.8) 5 <5 5 <5 Any form of positive expiratory pressure (PEP); n (%) 421 (49.1) 268 (83.8) 153 (28.4) 284 (81.6) 137 (26.9) VEST; n (%) <5 <5 <5 <5 <5 Exercise; n (%) 457 (53.3) 141 (44.1) 316 (58.7) 155 (44.5) 302 (59.2) Other; n (%) 188 (21.9) 138 (43.1) 50 (9.3) 143 (41.1) 45 (8.8) 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 intake. Overall (n=858) <16 years (n=320) 16 years (n=538) <18 years (n=348) 18 years (n=510) Any supplemental feeding; n (%) 191 (22.3) 67 (20.9) 124 (23.0) 70 (20.1) 121 (23.7) Nasogastric tube; n (%) 15 (1.7) 5 (1.6) 10 (1.9) 5 (1.4) 10 (2.0) Gastrostomy tube/button; n (%) 26 (3.0) 13 (4.1) 13 (2.4) 13 (3.7) 13 (2.5) Jejunal; n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Total parenteral nutrition (TPN); n (%) <5 0 (0.0) <5 0 (0.0) < 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 Bilateral Sequential Lung Transplant. The following table gives information about transplant activity over time Number evaluated Number accepted Number receiving transplants <5 6 <5 6 <5 Bilateral lung <5 6 <5 <5 <5 Heart and lung Liver Other <5 <5 cysticfibrosis.org.uk 35