Cystic Fibrosis Register Research Articles

Study of the genetic and molecular epidemiology of cystic fibrosis based on the patient registry for planning targeted therapy in Russian Federation

Cystic fibrosis (CF) is a genetically inherited disorder characterized by a wide range of clinical manifestations and genetic variations. This study focuses on the genetic and molecular epidemiology of CF in the Russian population, utilizing data from the national CF registry. The birth prevalence of CF in Russia has been analyzed over a span of years, revealing variations in frequency. The study delves into the genetic landscape of CFTR gene variants in Russian patients, showcasing a diverse spectrum with a predominance of severe variants, some of which are rare and distinct from global populations. A total of 233 variants have been documented, exhibiting frequencies ranging from 0.01% to 51.5%, with 47 of these variants remaining uncharted within international genetic databases. As of 2021, CFTR modulator therapy has been introduced for patients under 19 years, heightening the importance of genetic diagnosis. In 2023, more than 1,850 patients under 19 received CFTR modulator therapy. Notably, the impact of complex alleles on disease progression and response to targeted therapies is gaining recognition. Comparisons with European registries highlight distinctive features of the Russian population, such as differences in age distribution among patients. Additionally, the study emphasizes the need to ascertain clinical significance and pathogenicity of newly identified genetic variants, along with exploring their suitability for targeted therapies. The integration of genetic insights into the management of CF offers potential for enhanced personalized therapeutic interventions. In conclusion, this thorough analysis provides a comprehensive understanding of the genetic nuances within the Russian CF population. By illuminating the intricate relationship between genetic variations and disease manifestation, the study underscores the essential role of genetics in shaping therapeutic strategies and improving patient outcomes. Further research and ongoing genetic exploration are crucial for optimizing the care of individuals with CF in the era of evolving therapeutic options.

One-Year Effect of Elexacaftor/Tezacaftor/Ivacaftor Therapy on HbA1c Levels and Insulin Requirement in Patients with Insulin-Dependent Cystic Fibrosis-Related Diabetes: A Retrospective Observational Study.

The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T3mo), 6 months (T6mo) and 12 months (T12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T3mo and T6mo, but not at T12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment.

Long-Term Outcomes of Allergic Bronchopulmonary Aspergillosis and Aspergillus Colonization in Children and Adolescents with Cystic Fibrosis.

Observational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8-17 years in 2009-2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term.

Socioeconomic burden of cystic fibrosis in Canada

BackgroundCost of illness studies are important tools to summarise the burden of disease for individuals, the healthcare system and society. The lack of standardised methods for reporting costs for cystic...

Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predictedforced expiratory volume in 1 s(ppFEV1) based on the data of theCF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronicPseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval[CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95%CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study

Background: Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates has not been quantified.Methods: We performed a longitudinal analysis of data from a cohort of 7099 adults with cystic fibrosis (between 18 and 49 years old) from the UK cystic fibrosis registry, containing annual review data between 1996 and 2020. A mixed-effects location-scale model is used to quantify mean FEV1 (forced expiratory volume in 1 s) trajectories and FEV1 within-individual variability as a function of sex, age at annual review, diagnosis after first year of life, homozygous F508 genotype and birth cohort.Results: Mean FEV1 decreased with age and lung function variability showed a near-quadratic trend by age. Males showed higher FEV1 mean and variability than females across the whole age range. Earlier diagnosis and homozygous F508 genotype were also associated with higher FEV1 mean and variability. Individuals who died during follow-up showed on average higher lung function variability than those who survived.Conclusions: Key variables known to be linked with mean lung function in cystic fibrosis are also associated with an individual’s lung function variability. This work opens new avenues to understand the role played by lung function variability in disease progression and its utility in predicting key outcomes such as mortality.

Direct healthcare costs in the first 2 years of life: A comparison of screened and clinically diagnosed children with cystic fibrosis – The Irish comparative outcomes study of CF (ICOS)

BackgroundIn July 2011, Cystic Fibrosis (CF) was added to the Newborn Bloodspot Screening Programme in Ireland. The Irish Comparative Outcomes Study (ICOS) is a historical cohort study established to compare outcomes between clinically-detected and screen-detected children with CF. Here we present the results of economic analysis comparing direct healthcare costs in the first 2 years of life of children born between mid-2008 and mid-2016, in the pre-CF transmembrane conductance regulator modulator era. MethodsHealthcare resource use information was obtained from Cystic Fibrosis Registry of Ireland (CFRI), medical records and parental questionnaire. Hospital admissions, emergency department visits, outpatient appointments, antibiotics and maintenance medications were included. Costs were estimated using the Health Service Executive Casemix, Irish Medicines Formulary and hospital pharmacy data, adjusted for inflation using Consumer Price Index data from the Central Statistics Office. A Negative Binomial regression was used, with time in the study as an offset. ResultsOverall participation was 93 %. After exclusion of those with meconium ileus, data from 139 patients, with follow-up to 2 years of age, were available. 72 (51.8 %) were from the clinically diagnosed cohort. In the final model (n=105), clinically diagnosed children had 2.62-fold higher costs per annum (p<0.0001), when adjusted for confounders, including homozygous ΔF508 or G511D mutation, socio-demographic factors and time between diagnosis and first CFRI interaction. ConclusionsThere are few studies evaluating economic aspects of newborn screening for CF using routine care data. These results imply that the benefits of newborn screening extend to direct healthcare costs borne by the State.

A Longitudinal Study of Adherence among Cystic Fibrosis Patients: Associations with Gratitude Over the Course of One Year.

Daily airway clearance therapy (ACT) is a critical aspect of treatment in cystic fibrosis (CF), but poor adherence is a prominent concern. Identifying factors that might enhance or diminish adherence is a priority for treatment centers. Gratitude, a generalized tendency to notice and appreciate positive facets of experience, is a psychosocial resource that has commanded growing research interest. This longitudinal study examined whether gratitude at baseline was associated with ongoing or persistent ACT adherence over the course of a year. Trait gratitude was evaluated at baseline using a validated measure, among adults receiving care at a regional CF treatment center. Self-reported adherence to ACT was assessed at baseline, 6months, and 12months using the Cystic Fibrosis Treatment Questionnaire. Average age of participants was 27.2years, 45.5% were women, and 19.7% had severe disease. In multivariable logistic regression models that accounted for disease severity (Forced Expiratory Volume1% predicted) and other clinical and demographic variables, individuals with higher baseline gratitude were significantly more likely to demonstrate persistent adherence over the course of the year. Gratitude remained predictive after additionally adjusting for other well-known psychosocial resource variables (social support and emotional well-being). This is among the first demonstrations that gratitude is associated with persistent self-reported adherence to treatment over time. Findings suggest that gratitude may be important psychosocial resource for adults with CF, as they contend with complex, highly burdensome treatment regimens. Further research is warranted to examine these relationships and their impact on downstream health outcomes.

P012 Advancing precision in cystic fibrosis registries: identification and classification of patients with unclear diagnosis in the Norwegian cystic fibrosis patient registry

P012 Advancing precision in cystic fibrosis registries: identification and classification of patients with unclear diagnosis in the Norwegian cystic fibrosis patient registry

P031 Determining the genotypic and phenotypic characteristics of patients in the Turkish National Cystic Fibrosis Registry System

P031 Determining the genotypic and phenotypic characteristics of patients in the Turkish National Cystic Fibrosis Registry System

P121 Updating the UK Cystic Fibrosis Registry’s genotype cleaning processes and minimising free-text to improve data quality

P121 Updating the UK Cystic Fibrosis Registry’s genotype cleaning processes and minimising free-text to improve data quality

EPS6.04 Getting ready for the storm: what cardiovascular disease metrics do national cystic fibrosis registries currently collect?

EPS6.04 Getting ready for the storm: what cardiovascular disease metrics do national cystic fibrosis registries currently collect?

EPS6.08 The new frontier of spirometry: the implications of using race-neutral reference equations in the Canadian Cystic Fibrosis Registry

EPS6.08 The new frontier of spirometry: the implications of using race-neutral reference equations in the Canadian Cystic Fibrosis Registry

P112 Real-time estimation of individual long- and short-term lung functions trends in persons with cystic fibrosis within the Swedish cystic fibrosis registry

P112 Real-time estimation of individual long- and short-term lung functions trends in persons with cystic fibrosis within the Swedish cystic fibrosis registry

P130 Developing a study protocol to assess the feasibility and acceptability of implementing patient reported outcome measures in the Cystic Fibrosis Registry of Ireland

P130 Developing a study protocol to assess the feasibility and acceptability of implementing patient reported outcome measures in the Cystic Fibrosis Registry of Ireland

UK Cystic Fibrosis Registry Website Enhancements: A User-Centred Approach to the Data Access Transparency

BackgroundAs a member of the HDR UK Alliance, Cystic Fibrosis Trust is committed to adopting and maintaining the transparency standards within the UK CF Registry (UKCFR). Our website is the primary source for providing information on UKCFR and data access processes. We aimed to review use and accessibility across all user groups to shape website enhancements. This project aimed to improve transparency by conducting user experience (UX) research, and based on user feedback, enhance our website. For this project, we reviewed all of the HDR UK Transparency Standards. For this poster, we will focus on Standards 3 (Clear Website Navigation and 4 (Consider Target Audience). IntroductionThe primary objective was to enhance Transparency Standards by understanding audience needs and customise website improvements based on their needs. We envisaged that the outcome would be an improved and streamlined data access process to support transparency and trust among both data applicants and the public. MethodsWe employed a multi-method approach which incorporates public involvement throughout the whole process. We conducted on-site polls to intercept website visitors and gather quick feedback during their visit. Additionally, we created and distributed targeted surveys to various groups, including public and CF professionals, to delve deeper into their website experiences. Results The website’s overall rating is high at 7.4/10. UX research respondents: public 57% public and 43% CF Professionals. The top reasons for visiting the website are accessing reports and statistics and finding out more about UK CF Registry. Ease of finding information has fairly even spread, indicating room for improvement.

Considerations for the use of inhaled antibiotics for Pseudomonas aeruginosa in people with cystic fibrosis receiving CFTR modulator therapy

The major cause of mortality in people with cystic fibrosis (pwCF) is progressive lung disease characterised by acute and chronic infections, the accumulation of mucus, airway inflammation, structural damage and...

Identifying people living with cystic fibrosis in the Danish National Patient Registry: A validation study

BackgroundThe Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR. MethodsUsing the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact. ResultsAn algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months). ConclusionsThe DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis – A cross sectional study

ObjectivesCystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. MethodsA cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. Results64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. ConclusionIn this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. Clinical significanceClinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries

BackgroundRelieving gastrointestinal symptoms is a research priority in cystic fibrosis. Emerging evidence highlights effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on gastrointestinal function, including pancreatic sufficiency. This study explores ivacaftor licensing and treatment on recorded pancreatic enzyme replacement therapy (PERT) prescription in the US and UK CF registries. MethodsRetrospective longitudinal registry study of recorded pancreatic PERT use between 2008 and 2017. Interrupted time series analysis in propensity-matched cohorts estimated annual change and step change according to ivacaftor eligibility before and after licensing year, 2012. Generalised estimating equations assessed adjusted risk of PERT use in individuals treated with ivacaftor after 2012 compared to untreated individuals. ResultsIn the US CF registry, the difference in annual change in prevalence of PERT use post-2012 between eligible cases and ineligible controls was -5.0 per 1000 people/year (95 %CI -7.6; -2.3, p = 0.001). The step change and annual change in prevalence of PERT use in eligible cases was not significantly different to controls in the UK CF registry. Relative to the relationship in 2013, ivacaftor treatment in the US CF registry was associated with a lower adjusted risk ratio of PERT use compared to untreated individuals by 2016 (0.97, 95 %CI 0.96; 0.99), which was not observed in the UK CF registry. ConclusionsLicensing of ivacaftor was followed by a lower prevalence of PERT use in the eligible US population compared to pre-licensing period, as well as lower risk of PERT use in those who received treatment. Inconsistencies in US and UK CF registries were observed.