Canadian Cystic Fibrosis Patient Data Registry Report

Transcription

1 Canadian Cystic Fibrosis Patient Data Registry Report Breathing life into the future

2 What is cystic fibrosis? Cystic fibrosis (CF) is the most common, fatal, genetic disease affecting Canadian children and young adults. CF is a multisystem disease that affects mainly the lungs, and the digestive system. In the lungs, where the effects of the disease are most devastating, CF causes increasingly severe respiratory problems. In the digestive tract, CF makes it extremely difficult to digest food and absorb adequate vitamins and nutrients. As improved therapies have helped to address the malnutrition issues in CF, virtually all CF deaths are due to lung disease. What is the Canadian Cystic Fibrosis Foundation? The Canadian Cystic Fibrosis Foundation (CCFF) is a Canada-wide health charity established in 1960, with volunteers in more than 50 chapters across Canada. The mission of the CCFF is to help people with cystic fibrosis (CF). To this end, the Foundation: funds research towards the goal of a cure or effective control for CF; supports high quality CF care; promotes public awareness of CF; and raises and allocates funds for these purposes. 2

3 Table of Contents Message... 4 Canadian CF Clinics... 5 The Canadian CF Patient Data Registry (CPDR)... 6 CPDR Benefits People with CF... 7 Summary... 8 Summary Data... 9 Demographic Data Genotype Respiratory Nutrition Transplantation Microbiology CF-Related Diabetes (CFRD) Hospitalization and Home IV Survival Commonly Asked Questions

4 Message It is with great pleasure that I present the 2008 Canadian Cystic Fibrosis Patient Data Registry (CPDR) report. We continue to capture clinical data on the majority of individuals with CF in Canada, making the registry an important national resource. Since the 2007 report was published, we have continued to capture back-data on individuals with CF. Therefore, the graphs which summarize data over time may show some discrepancies between this report and the 2007 report as more back-data were available at the time that this report was generated. I would like to thank the Canadian Cystic Fibrosis Foundation, specifically Cathleen Morrison, Aida Fernandes, and Ian McIntosh, for their ongoing support and commitment to the registry. Further acknowledgement goes to John Rudson for database design and maintenance, and to the members of the CPDR Working group. Also, I would like to thank all the staff in CF clinics across Canada for their efforts in providing data for the registry and all the individuals with CF in Canada who agree to have their data collected within the CPDR. Sincerely, Dr. Anne Stephenson, MD, PhD Chair, Canadian CF Patient Data Registry Dr. Anne Stephenson and family CPDR Working Group Dr. Anne Stephenson (St. Michael s Hospital, Toronto) Dr. Yves Berthiaume (Hôtel-Dieu de Montréal) Dr. Mark Chilvers (B.C. Children s Hospital, Vancouver) Dr. Mary Corey (The Hospital for Sick Children, Toronto) Dr. Annie Dupuis (The Hospital for Sick Children, Toronto) Dr. Peter Durie (The Hospital for Sick Children, Toronto) Dr. Larry Lands (Montreal Children's Hospital) Dr. Mark Montgomery (Alberta Children's Hospital, Calgary) Dr. Hebe Quinton (Dartmouth Hitchcock Medical Center, Lebanon, NH) Dr. Elizabeth Tullis (St. Michael s Hospital, Toronto) 4

5 Canadian CF Clinics British Columbia Victoria General Hospital Royal Jubilee Hospital, Victoria B.C. Children's Hospital, Vancouver St. Paul's Hospital, Vancouver Alberta Alberta Children's Hospital, Calgary Foothills Hospital, Calgary University of Alberta Hospitals, Edmonton Saskatchewan Royal University Hospital, Saskatoon Regina General Hospital Manitoba Winnipeg Children's Hospital Health Sciences Centre, Winnipeg Ontario Hôpital régional de Sudbury Regional Hospital Windsor Regional Hospital London Health Sciences Centre/Children's Hospital of Western Ontario Grand River Hospital, Kitchener Chedoke-McMaster Hospital, Hamilton The Hospital for Sick Children, Toronto St. Michael's Hospital, Toronto Hotel-Dieu Hospital, Kingston Children's Hospital of Eastern Ontario, Ottawa Ottawa General Hospital Québec Centre hospitalier régional de l'outaouais, Hull Montreal Children's Hospital Montreal Chest Institute Hôpital Ste-Justine, Montréal Hôtel-Dieu de Montréal Centre Universitaire de Santé de l'estrie, Sherbrooke Centre hospitalier de l'université Laval, Ste-Foy Hôpital Laval, Ste-Foy Hôpital de Chicoutimi Centre hospitalier régional de Rimouski Centre hospitalier de Rouyn-Noranda Nova Scotia IWK Health Centre, Halifax QEII Health Sciences Centre, Halifax New Brunswick Saint John Regional Hospital Newfoundland Janeway Children's Health Centre, St. John's Health Sciences Centre, St. John's 5

6 The Canadian CF Patient Data Registry (CPDR) The CPDR has been in existence since the early 1970s. Initially, the registry was produced in conjunction with the US CF Foundation. The first formal joint US-Canadian CF report was published in 1977 detailing information on national CF birth and death rates, survival curves and age of diagnosis. In the late 1970s and early 1980s, clinical data such as lung function, nutrition markers (e.g. height and weight), and microbiology were added to the registry. In 1984, the Canadian CF Foundation negotiated with the US to bring the CPDR back to Canada and all previous data were returned. Since then, annual reports have been generated separately from the Canadian and the US databases. The goal of the CPDR is to monitor important clinical trends in the Canadian CF population. It has played an invaluable role in helping the CCFF make progress toward improving the quality and length of life of people with CF. Since the majority of CF medications (when prescribed through a designated CF clinic) are reimbursed by special provincial CF drug programs, and since the majority of CF patients attend one of 40 accredited CF clinics (pediatric and adult) within Canada, it is felt that the Canadian registry is very complete (i.e. it includes data on virtually all Canadians with CF) giving a comprehensive picture of the CF population in this country. The CPDR is one of the most complete longitudinal national CF data registries in the world. 6

7 CPDR Benefits People with CF The CPDR is used both by CF clinicians and researchers to better understand disease patterns and to improve care of individuals with CF. Each year, the data in the CPDR are analyzed and an annual statistical report is generated summarizing demographic and clinical data on all individuals with CF followed in the country. Since 2003, new privacy and confidentiality legislation has required that consent from all individuals with CF be obtained to have their data included in the registry. Progress on this enormous task has been slow but it is now complete. To date, only seven Canadians with CF have declined to participate in the CPDR. Therefore, the CPDR continues to capture information on essentially all Canadians with CF. This is an exciting time for the CPDR. Recently the CCFF received a government grant to upgrade the system to allow CF clinics to enter data securely online. CF clinicians now have immediate access to their patients data, thereby enhancing their understanding of their own clinic population. Furthermore, clinicians will be able to identify problem areas, such as poor nutritional outcomes in certain individual patients. Using this information, CF clinicians can examine more effectively dynamic health care issues, including nutritional status, infection control issues, pulmonary treatment, and more. The data collected within the CPDR can be used for quality improvement efforts. Clinics will be able to compare the pulmonary and nutritional outcomes of the individuals followed at their clinic to the national median value. Quality improvement initiatives can be developed and clinical outcomes can be tracked over time using the CPDR in order to show improvements. These efforts will ultimately translate into improved outcomes for all individuals with CF. In the past, the CPDR has not only played an important role in directing clinical care but also in clinical research. Investigators can use this information to formulate research questions and to guide the direction of future research. Epidemiologic research examines trends and improvements in a given population over time. Since CF patient data registries study large populations of individuals with CF over time, the CPDR is a powerful research tool. A case in point is the prescription of a high-fat CF diet. The majority of individuals with CF have pancreatic insufficiency leading to an inability to absorb fat from their diet. Consequently, in the past, many individuals with CF suffered from malnutrition. It used to be standard practice to prescribe low-fat diets for people with CF to avoid the discomfort associated with fat malabsorption. In the 1970s, Dr. Crozier, Director of the Toronto CF clinic at The Hospital for Sick Children, wondered if poor survival was directly related to malnutrition. He prescribed a high-fat diet and larger amounts of pancreatic enzymes in order to optimize weight gain. After this change in treatment, there was increased survival of Dr. Crozier s patients that was not seen in other CF clinics. This practice spread across Canada, and an improved survival rate was clearly seen in the CF data registry following this intervention. Consequently, the prescription of a high-fat diet with enzymes is now standard practice worldwide. In addition, the CPDR can be used as an educational tool. The summary statistics help to graphically show important clinical outcomes over time. Incorporating these summary statistics into presentations for the public, medical and allied health care professionals, and many other groups can increase knowledge about Canadians with CF. 7

8 The CPDR has played an important role in directing clinical care and research. Summary In conclusion, CF patient data registries, and the CPDR in particular, are incredible resources for CF clinicians, researchers, as well as individuals with CF and their families. The CPDR is viewed as a model by other countries interested in developing a patient registry and has helped the Canadian CF medical and research community remain at the forefront of CF care and research. With the continued cooperation and participation of clinical personnel and Canadians with CF, along with the generous support of the CCFF s many friends and donors, it will be possible to ensure that data remain available and worthy of study in the future. 8

9 Summary Data Table 1: Summary data from CPDR, 1983 to 2008 YEAR Patients with data in reporting year, n 2,108 2,562 2,969 3,247 3,222 3,343 Age, mean (yr) % over 18 yrs Age at diagnosis 1, mean (yr) median (mo) New diagnoses in year, n % with meconium ileus at birth Age at death 2, mean (yr) median (yr) Total death, n Crude mortality rate, % Median survival age, yr (5-yr window) males females Male, of total patients Race, % Caucasian Black Asiatic American Indian Other Unstated % with Height<CDC th %ile % with Weight<CDC th %ile % predicted 3 FEV 1, mean % with positive culture: first culture of the year: Pseudomonas aeruginosa Staphylococcus aureus Haemophilus species Burkholderia cepacia complex MRSA Stenotrophomonas maltophilia Aspergillus Calculated using all patients registered in the CPDR who have submissions for the specific year. 2 Calculated using only those patients who died in the reporting year. 3 Predicted values for children from Wang et al, Pediatr Pulmonol 1993;15:75-88, for adolescents and adults from Hankinson et al, Am J Respir Crit Care Med 1999:

10 Demographic Data Figure 1: Total Number of CF Patients and New Diagnoses in the CPDR, 1988 to 2008 In 2008, a total of 3,343 individuals with CF had clinical records submitted by 36 CF clinics. When an individual was seen at multiple clinics in one year, s/he was only counted once (i.e. unique individuals) for the purpose of generating this graph. The total number of individuals with CF each year represents those individuals who had data reported during the calendar year. The drop seen in 2003 is the result of several factors. First, at the time that the graph was generated, just over 90% of national data was available therefore some clinics had not yet submitted CPDR data. Secondly, the data collected between were entered at one time by most clinics and it is possible that some individuals were lost to follow up. Again in 2008 we see a slight decrease in the number of individuals followed in the CPDR. At the time this graph was generated we had 92% of national data which is likely contributing to this apparent decrease in counts. We anticipate that this number will increase moving forward as we capture more national data. As seen in Figure 1, the number of new CF diagnoses decreased between 2004 and 2006 but appears to have stabilized between In 2008, 91 individuals were newly diagnosed with CF. 10

11 Figure 2: Age Distribution of the CF Population, 2008 Figure 2 shows the age distribution of the Canadian CF population for The median age is 19 years with a range from birth to 75 years. Males account for 53.1% of individuals in the registry in 2008 while 46.9% are females. The proportion of individuals over the age of 18 years continues to increase. In 2008, 57.1% of individuals in the registry are over 18 years old (Figure 3). The proportion of individuals over the age of 18 years has been steadily increasing over time. 11

12 Figure 3: Proportion of individuals with CF over the age of 18 years Figure 4: Age at diagnosis, all patients

13 As seen in Figure 4, 50% of individuals are diagnosed by six months of age, and 73% by the age of two years. Adults continue to be diagnosed with CF, with 1.5% diagnosed after the age of 40 years. Since 2008, several Canadian provinces (Alberta, Ontario, Saskatchewan and British Columbia) have added CF to their newborn screening programs; and therefore, the distribution of this graph is expected to change over time. Since 2008, several Canadian provinces (Alberta, Ontario, Saskatchewan and British Columbia) have added CF to their newborn screening programs. 13

14 Genotype CF is caused by mutations in a single gene located on chromosome 7, termed the cystic fibrosis transmembrane regulator (CFTR) gene. The CFTR gene codes for a protein called the transmembrane conductance regulator (CFTR) which functions as a chloride channel and is involved in many cellular functions. To date, over 1600 different mutations in the CFTR gene have been identified. The most common mutation worldwide is a three basepair deletion resulting in the deletion of the phenylalanine residue at amino acid position 508, commonly referred to as F508. Table 2: Frequency of CF mutations (top five) Mutation n % Delta F G542X G551D 85 3 N1303K R117H Figure 5: Genotype (based on N=3,084) Of those individuals with 2008 data, 3,084 people had genetic information recorded within the registry. Of those individuals, 49.2% carry two F508 mutations and 88.3% carry at least one F508 mutation (Figure 5). 14

15 Respiratory Figure 6: Median percent predicted FEV 1 vs. age, 1990 and 2008 Median FEV 1 percent predicted has improved since Although this increase is seen across all ages from six to 30 years, it is larger in younger ages compared to older ages. Median FEV 1 in 2008 at 30 years of age is 78% predicted compared to 73% in 1990 (Figure 6). FEV 1 is the maximal amount of air you can forcefully exhale in one second. 15

16 Figure 7: Respiratory Severity of CF Children and Adults (FEV 1 percent predicted), 2008 Lung function is measured from age 6 years and onwards. For children ages 6-17, the majority of individuals with CF (47%) have an FEV 1 greater than 90% predicted; while for adults, the majority (43%) have lung function classified as moderate severity (Figure 7). Figure 8: Median FEV 1 percent predicted for CF patients 6 to 17 years of age by CF clinic,

17 In order for a CF clinic to be included in Figure 8, it had to report lung function data on 10 or more CF patients. Twenty pediatric CF clinics are included in the graph. The number of observations per clinic used to calculate the median FEV 1 ranges from 10 to 170. The national median FEV 1 is 89.5% predicted with a range from 59.8% to 99.1% (Figure 8). Figure 9 shows the median FEV 1 percent predicted by CF clinic for those 18 years of age and older. In order to be included in this graph, a CF clinic had to report lung function data on at least 10 CF patients. A total of 23 adult CF clinics are shown on the graph. The number of observations per clinic used to calculate the median FEV 1 ranges from 11 to 333. The national median FEV 1 is 63.1% predicted with a range from 48.6% to 76.4%. Figure 9: Median FEV 1 percent predicted for CF patients 18 years of age or more by CF clinic,

18 Nutrition In 2008, 87% of individuals with CF were taking supplemental pancreatic enzymes (pancreatic insufficient), whereas 13% were considered pancreatic sufficient (Figure 10). For those 40 years of age or older, 64.2% are pancreatic insufficient and 35.8% are pancreatic sufficient. This is likely a reflection of the fact that adults diagnosed with CF are more likely to have milder mutations that are associated with pancreatic sufficiency (Figure 11). Figure 10: Pancreatic sufficiency in CF Patients Figure 11: Pancreatic status by age group Figure 12: Median BMI Percentile for CF patients 2-17 years by CF clinic,

19 A total of 22 pediatric CF clinics are included in Figure 12. In order to be included in this graph, a CF clinic had to report data on at least 10 CF patients. In CF patients 2 to 17 years of age, the national median Body Mass Index percentile, as per the Center for Diseases Control (BMI CDC), is 46%. The median percentiles range from 29.9 to 69.4%. BMI percentile is not calculated for those under the age of two years. BMI percentile indicates the relative position of a child's BMI compared to typical values for other children of the same age. Weight Status Category Underweight Healthy weight Overweight Obese Percentile Range Less than the 5 th percentile 5 th percentile to less than the 85 th percentile 85 th to less than the 95 th percentile Equal to or greater than the 95 th percentile 19

20 Figure 13: Median BMI for CF patients 18 years of age and older by CF clinic, 2008 Figure 13 shows the median BMI by clinic for those CF patients 18 years of age and older. There are 20 CF clinics that are included in this graph. In order to be included in this graph, a CF clinic had to report data on at least 10 CF patients. The national median BMI is 21.9 kg/m 2. The median BMI ranges from 19.6 to 23.1 kg/m 2. BMI Categories: Underweight = <20.0 kg/m 2 Adequate weight = kg/m 2 Overweight = kg/m 2 Obesity = BMI of 30 kg/m 2 or greater Body mass index (BMI) is used to estimate a healthy body weight based on an adult's height. 20

21 Figure 14: BMI classification for CF patients, by sex, 2008 Figure 14 shows the breakdown of BMI categories (see previous page for categories) for adult males and females. A larger proportion of females are considered underweight compared to males (BMI < 20 kg/m2). Often young men who are muscular and fit can have a BMI in the overweight category (BMI kg/m2) simply due to high muscle mass. These individuals would not truly be considered overweight. Overall, 2.5% of the CF adult population has a BMI in the obese category. Of those 46 adults, 60.9% are pancreatic sufficient and 39.1% are pancreatic insufficient. Figure 15: Percentage with BMI < 22 for females and < 23 for males for CF patients 18 years of age and older by CF clinic, 2008 The national average percentage of CF patients with BMI < 22 kg/m 2 for females and < 23 kg/m 2 for males in patients 18 years of age and older is 58% with a range from 41% to 73%. In order to be included in Figure 13, a CF clinic had to report data on at least 10 CF patients. 21

22 Transplantation Figure 16: Number of patients transplanted per year, 1991 to 2008 The number of transplants carried out per year is increasing. Figure 16 shows the number of transplants carried out per year as reported in the CPDR (orange bars) and as reported by the transplant centres on their incentive grant applications (green bars). Although the numbers provided represent primarily lung transplants, individuals who received other combinations (e.g. lung-liver, liver, heart-lung, etc.) are also included in the total. There is likely some under-reporting of transplants within the registry and efforts are underway to ensure we capture this information more rigorously in future. Based on the transplant statistics reported in the transplant centres incentive grant application, the number of CF patients transplanted in 2008 was

23 Microbiology Figure 17: Prevalence of species of bacteria cultured in airways in CF patients (all ages), 2008 Overall, Pseudomonas aeruginosa and Staphylococcus aureus are the most common pulmonary pathogens in Canadians with CF (Figure 17). The prevalence of Aspergillus species, Stenotrophomonas maltophilia, and MRSA have increased between 2007 and 2008 P. aeruginosa and (Figure 18). The largest increase S. aureus are the most common was seen in Aspergillus species. pulmonary pathogens in The increased prevalence may be Canadians with CF. partly due to increase surveillance for these organisms. Conversely, the prevalence of Burkholderia cepacia complex has decreased over the years, to 4.9% in The prevalence of MRSA in 2008 was 3.2%. MRSA was not captured in the CPDR prior to

24 Figure 18: Prevalence of Microbiology, 2007 vs Figure 19: Age Specific Prevalence of Respiratory Infections in CF Patients, 2008 As expected, Staphyloccocus aureus is more common in the pediatric population whereas Pseudomonas aeruginosa is more common in the adult CF population. Stenotrophomonas maltophilia does not appear to be more common in one age category over another (Figure 19). Burkholderia cepacia complex is more commonly seen in older individuals with CF which represents the fact that new acquisition of B. cepacia complex in general has decreased substantially over the years making its prevalence in children low. However those individuals who previously acquired B. cepacia complex are aging making the prevalence of this organism higher in older individuals. 24

25 CF-Related Diabetes (CFRD) Figure 20: Percentage of patients with CFRD by age category, 2008 Overall, CFRD was reported in 11.5% of individuals with CF in In those individuals 35 years of age and older, the prevalence of CFRD is 23.6% in The prevalence of CFRD increases with age (Figure 20). Of those with CFRD, 52% are female and 48% are male. Hospitalization and Home IV Table 3: Number of Hospital days and Home IV courses, 2008 Total # Hospitalizations 1,450 Hospital days 20,663 Home IV courses 514 Home IV days 6,799 # clinic visits 11,466 In 2008, 1,450 hospitalizations were recorded in the CPDR. Multiple reasons for hospitalizations could be captured within the registry but the most common recorded reason for admission was a pulmonary exacerbation. Of those hospitalized, the frequency ranged from one to 10 times in the year. In 2008, 514 courses of home IV therapy were recorded in the CPDR. Of those who received home IV therapy, the frequency ranged from one to eight courses. 25

26 Survival Figure 21: Age at death, 2004 to 2008 Since there are relatively few deaths per year, the sum of all deaths from 2004 to 2008 were included in Figure 21. There were 51 deaths recorded in the registry for The median age at death for 2008 was 30 years of age, which is an increase of 5 years compared to The most common cause of death recorded in the CPDR was pulmonary-related (77%). Figure 22: Median age of survival for a moving 5-year window by sex 26

27 Figure 23: Canadian male CF survival by birth cohort 1973 to 2008 Figure 24: Canadian female CF survival by birth cohort 1973 to

28 The median age of survival for Canadians with CF is currently estimated to be 46.6 years of age, which is quite remarkable (Figure 22). Figure 23 and Figure 24 show the survival of males and females by birth cohort. Some key points to highlight from these graphs are: 1. At any given age, the survival is higher for those born more recently suggesting that, over time, there have been advances in CF care that are keeping people healthier. 2. The slope of each line is different. As the birth cohorts become more recent, the slope of the line is more gradual. This means that the survival for someone born in 1973 is not the same for someone born in The point at which the line crosses the 50% survival mark is the median age of survival. This can only be calculated for those males and females born between since this is the only line that cross the 50% survival on the y-axis. The majority of persons with CF in Canada may now expect to live into their 40s, and even beyond. Since our last report in 2007, we have continued our efforts to ensure we are capturing deaths accurately within the registry. These efforts have yielded some death dates that were previously not recorded in the registry. Because of this, we anticipated that the median survival age would not continue its upward trend but instead, that it would show some adjustment in this most recent analysis. As expected, the median survival age in 2008 has decreased slightly from 47.7 years to 46.6 years. We will continue to work with all the Canadian CF clinics as well as transplant centres to ensure accurate capture of CPDR data including information on deaths and transplants. As mentioned in last year s report, the significant increase in survival over the past six years almost seems too good to be true and begs the question, Why has survival in CF increased so dramatically in Canada? An increasing number of individuals with CF are diagnosed in adulthood which often represents milder disease with better survival. One may wonder whether adding individuals with mild disease to the CPDR analysis is driving up the median survival age in Canada rather than true improvements in survival for those with classic CF. In order to answer this question, we conducted a sensitivity analysis whereby we excluded all individuals diagnosed with CF after the age of 20 years and repeated the survival analysis. The median survival age remained significantly higher than it was in When we excluded adult diagnoses, the median survival age went from 46.6 years to 44.8 years, only a 1.8 year difference. This suggests that adult diagnosis is contributing to the improved survival but the 28

29 improved survival cannot be explained by this factor alone. One can hypothesize that lifesaving therapy with lung transplantation is another significant contributor to improved Canadian survival. Finally, we may be seeing the impact of aggressive nutritional support, instituted in Canada in the 1970s and 1980s. Individuals born at that time had the benefit of nutritional supplementation and essentially normal nutrition throughout their entire lives. Now in their thirties, and at a time when they may have been at higher risk for death from progressive lung disease, the lung function of these individuals has been maintained longer than had been seen previously, perhaps due to early nutritional support. It is not possible to know for certain the reason for the improvement seen in survival for Canadians with CF and in truth, there are likely multiple factors. Certainly it is a statistic that would not be possible without the hard work and dedication of CF families, CCFF chapter volunteers, partners, donors, researchers and CF clinic teams, and everyone can be very proud of this accomplishment. Commonly Asked Questions Why is the median age at death so different than the median age of survival? Median age at death is calculated simply by taking all those individuals who died in a given year, placing them in ascending order, and determining which age is the middle number. If the total number of deaths is an even number, then you take the average of the two middle numbers to calculate the median. The median age at death is calculated using only those individuals who have died. In other words, of those who died, ½ died before the median age of death and ½ died later than the median age of death. This calculation doesn t tell you anything about the individuals who have survived! You need to know the ages of those still living to get information on median survival. Is median age of survival the same as life expectancy? No! The life expectancy is the expected average length of life based on current age-specific mortality rates. Life expectancy at birth in Canada for example is 77.3 years. This means that a baby born now will, on average, be expected to live 77.3 years. Median age of survival is the estimated duration of time until 50% of a given population dies. Half of the population are still alive and half have died. The age at which this occurs is the median survival age. 29

30 Charitable registration: RR0001 Breathing life into the future Cette publication est aussi disponible en français. 30