Cystic Fibrosis Foundation Research Articles

Initial Antibiotic Selection Based on Microbiologic History in Pediatric Cystic Fibrosis-Related Pulmonary Exacerbations.

The Cystic Fibrosis (CF) Foundation guideline for the treatment of pulmonary exacerbations (PEx) does not address empiric antibiotic selection. The primary objective of this study is to characterize how patient-specific microbiological histories are utilized in initial antibiotic selection for CF-related PEx at a pediatric institution. The secondary outcome was to characterize why changes were made to empiric antibiotic regimens. This single-center, retrospective study evaluated individuals aged 1-21 years hospitalized for CF-related PEx at Children's Medical Center Dallas between August 1, 2016 and July 31, 2018. Among 285 screened hospital encounters, 156 encounters met inclusion criteria. Median age was 12.9 years with a median baseline forced expiratory volume (FEV1) of 84% predicted. Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia were the organisms most targeted by empiric antibiotics with median months since last growth of 1.5, 9.2, and 5.5, respectively. A difference was observed in median time since last growth for targeted organisms versus those not targeted by the initial antibiotics, but wide overlapping timeframes were noted. Organisms isolated on admission cultures were sensitive to the initial antibiotics regimen in 78.2% of encounters. While variable, patient-specific microbiologic history and time since last growth of historical organisms are taken into consideration when selecting initial antibiotics for the treatment of PEx in children with CF. Expanding initial antibiotic coverage to target microbiological growth histories beyond 1 year prior to a hospital admission did not appear to increase the likelihood of providing coverage for organism(s) isolated on the admission sputum culture in children hospitalized for CF-related PEx.

Clinical features associated with self-reported food insecurity in people with cystic fibrosis.

Food insecurity (FI) is more prevalent in people with cystic fibrosis (PwCF) than the reported national prevalence, but there are limited data on the relationship between FI and health outcomes in PwCF. The objective of this study was to analyze the relationship between FI in PwCF and pulmonary and nutritional status. We leveraged an electronic cross-sectional survey that ascertained FI status and gave participants the option to link their survey data to their records in the Cystic Fibrosis Foundation Patient Registry (CFFPR). Linear regression and negative binomial models were used to estimate the associations in mean differences between FI and percent predicted FEV1 (ppFEV1), nutritional indices, and hospitalizations. There were 1,856 respondents, 1,234 (66.5 %) of whom granted permission to link to the CFFPR. FI was present in 352 (28 %) of the respondents. FI was associated with lower ppFEV1 (-6.5; 95 % CI -9.9, -3.1); however, this was no longer statistically significant after adjusting for confounders. FI was independently associated with increased hospitalizations. Higher weight for age was significantly associated with FI in the adjusted model, but there were no significant associations between height for age or absolute weight and body mass index (BMI) in adults. FI in PwCF is associated with adverse health outcomes. These results support screening for FI during routine visits. Further studies are needed to investigate causal relationships between FI and adverse clinical outcomes.

"It's Like You're Feeding Your Child Twice": Barriers and Facilitators to Human Milk Feeding Children With Cystic Fibrosis.

Cystic Fibrosis Foundation guidelines recommend human milk (HM) as the ideal source of nutrition for children with CF (cwCF). Despite known pulmonary and nutritional benefits, fewer cwCF ever receive HM compared to the general population. Early nutrition choices are preference-sensitive, yet little is known about the factors that impede or sustain HM feeding among parents of cwCF. Explore perceptions and experiences of mothers of cwCF who initiated HM feeding. Mothers of cwCF aged ≤ 10 years completed audio-taped, semi-structured interviews describing their experiences with HM feeding. Interviews were transcribed and two researchers independently coded the transcripts and conducted content and thematic analysis using an inductive approach. Participants included 28 mothers who initiated HM feeding. Major themes included: (1) the impact of a CF diagnosis on HM feeding plans; (2) CF-specific challenges to HM feeding; (3) mixed perceptions of the CF care team's support for HM feeding and of the role of formula in CF nutritional care; and (4) the benefit of lactation consultants as part of the CF care team. Many parents prioritize HM for their cwCF given the well-established health benefits. However, CF-specific barriers to HM feeding are common and nutritional challenges necessitating fortification add additional barriers to sustained HM feeding efforts. While HM may improve long-term pulmonary outcomes, our findings demonstrate the need for personalized support for mothers desiring to HM feed to facilitate shared decision-making around options to optimize early nutritional status among cwCF.

A Global Perspective on Transition Models for Pediatric to Adult Cystic Fibrosis Care: What Has Been Made So Far?

Interest in the transition of care for cystic fibrosis (CF) patients has grown significantly over time, driven by advancements in treatment that have extended life expectancy. As more CF patients survive into adulthood, the need for structured transition strategies has become a priority for healthcare systems worldwide. Transition programs for CF differ globally, reflecting varying resources and healthcare systems. In North America, the US CF Foundation has fostered adult care since the 1990s, with accreditation standards mandating adult programs and structured transition guidelines, exemplified by the CF RISE program for gradual responsibility shifts. Canada integrates US-inspired models, emphasizing national advocacy and outcomes evaluation. In Europe, approaches varies widely; the UK leads with structured programs like the Liverpool model and robust registry support, while France and Germany adopt multidisciplinary methods. In Australia and New Zealand, youth-centered policies prioritize early planning and access via telemedicine. In Asia, where CF is rare, transitions are less formalized, with some progress in countries like Japan and Turkey, though resource gaps and limited data tracking remain significant challenges. Despite varied approaches across countries, common barriers like resource limitations and psychological readiness continue to challenge successful transitions. Highlighting the importance of centralized, well-coordinated transition programs, recent initiatives have focused on the implementation of national and international CF registries to enhance health outcomes and quality of life. This narrative review provides a global perspective on transition strategies developed across various healthcare systems for CF patients, identifying best practices, common challenges, and outcomes related to the continuity of care.

Predictors of frequency of CF care in the US Cystic Fibrosis Foundation Patient Registry.

Prolonged gaps in care of >12-months are frequent among people with cystic fibrosis (pwCF) and are associated with reduced lung function. Comprehensive analysis of patient-level predictors of visit frequency is needed to optimize protocols for stable pwCF and identify subgroups at high risk of gaps and poor outcomes, promoting equitable treatment for all pwCF. To determine sociodemographic and disease-related factors predictive of visit frequency in pwCF and to assess how these effects vary across the lifespan. We conducted an observational cohort study using data from 2004-2016 for pwCF aged 6-60 years in the US Cystic Fibrosis Foundation Patient Registry. We modeled the relationship between patient-level characteristics and between-visit interval (BVI) using multivariable longitudinal semiparametric regression. BVI was defined as the number of days from the index encounter to the previously recorded visit. The study included 28,588 pwCF with 859,568 encounters. Overall, 55% of visits occurred within 90 days of the prior visit, adhering to national guidelines. On average, adults without common CF-complications attended clinic approximately every 4 months, with a BVI ≥ 110 days from age 23-56. Males attended clinic less frequently than females (9.8% longer BVI; 95% CI 9.1%, 10.5%; p<0.001), as did non-white individuals (3.6% longer BVI than whites; 95% CI 2.2%, 5.0%; p<0.001), with the greatest differences seen in young adults. Those with public and private insurance largely adhered to current guidelines (maximum average BVI of 90 and 95 days, respectively). In contrast, uninsured individuals over age 25 had a mean BVI ≥ 30 days longer than the insured. Frequent visits in those with CF-complications likely reflects higher need, while less frequent visits in male, non-white, and uninsured individuals may reflect patient-preference or structural barriers to care. Risk factors for gaps in care should inform changes to CF care recommendations going forward.

Linaclotide Use for the Treatment of Constipation and Gastrointestinal Symptoms in People With Cystic Fibrosis.

Cystic Fibrosis (CF) is a multisystem autosomal recessive disease characterized by thick, sticky mucus which causes lung disease, pancreatic insufficiency, and many other manifestations. Constipation is a common complication in CF and few advances in treatment have been made until recent years. Linaclotide is a treatment approved for chronic idiopathic constipation and irritable bowel syndrome with constipation. This case series investigates the potential for use of this agent in adult people with CF (pwCF). A retrospective case series of 39 pwCF who are currently or previously prescribed linaclotide was completed at two adult Cystic Fibrosis Foundation (CFF) Accredited Care Centers. All patients 18 years and older were included with no exclusions. We reported results using descriptive statistics. A total of 39 patients were identified for inclusion. The daily starting dose of linaclotide did vary with 18%, 72%, and 10% started on 72 mcg, 145 mcg, and 290 mcg respectively. Most patients (n = 30, 77%) reported experiencing no side effects. Of the total patients, 15% (n = 6) reported the medicine was not effective and 10% (n = 4) had to stop therapy due to adverse reactions. More than half of patients started on therapy were able to reduce baseline treatments for constipation. While this case series shows compelling data that may indicate benefit and tolerability of linaclotide use in pw CF, more research is needed to fully evaluate safety and efficacy of linaclotide for treating constipation in pwCF.

Elexacaftor/tezacaftor/ivacaftor and mental health: A workshop report from the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health working group.

This report summarizes the 2023 inaugural annual meeting of the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health (PRIME) working group. This workshop focused on mental health and elexacaftor/tezacaftor/ivacaftor (ETI). We reviewed existing literature and identified key gaps and study design considerations in preclinical work, pharmacokinetics/pharmacodynamics, mood/anxiety, quality of life/self-perception, neuropsychological symptoms, sleep, and symptom management. Limited studies have identified behavioral changes with modulator exposure in rodent models of depression, anxiety, and cognition. Longitudinal human studies reporting mean changes generally show no change or improvement. However, case reports and single-center studies identify subgroups reporting new or worsening symptoms. Future studies should focus on understanding the role of CFTR in the nervous system, defining ETI impacts in preclinical models, and mechanistic investigations. Innovative methods with larger samples and comprehensive assessments are needed to determine the incidence of new/worsening symptoms throughout the lifespan and effective management strategies.

Process and Validity of Linking Cystic Fibrosis Patient Registry with National Medicaid Databases

BackgroundThe Cystic Fibrosis Foundation Patient Registry (CFFPR) provides valuable clinical and demographic data but includes limited information on health services and medications provided outside of CF Care Centers. Linking CFFPR to claims databases such as national Medicaid data could address these data gaps. MethodsLinkage algorithms based on state of residence, gender, and date of birth were utilized to match individuals with CF diagnostic codes in national Medicaid databases (2016) to individuals in the CFFPR (2015-2016). Subsets of individuals with partial social security numbers or residing in the state of North Carolina were utilized to validate the accuracy of linkages and perform exploratory analyses on care utilization and costs. ResultsOf the 32,152 individuals in CFFPR, 10,616 were uniquely linked to national Medicaid databases. The 372 linked individuals within the NC extract had 8.0±7.6 visits to outpatient providers, substantially higher than the 4.2±2.4 CF Care Center outpatient visits documented within CFFPR. Similarly, linked individuals had 2.1±1.7 oral antibiotic prescriptions within CMS pharmacy databases versus 0.5±1.9 oral antibiotic prescriptions in CFFPR. Total pharmacy costs for the linked individuals in NC were $16.4 million, with pancrealipase (19%), dornase alfa (24%), and CFTR modulators (29%) the largest expenditures. Total non-pharmacy costs were $7.5 million, with inpatient hospitalization representing 53% of costs. ConclusionLinkage of data from Medicaid and CFFPR can produce valid comprehensive data on low-income people with CF and provide opportunities to examine utilization/adherence or comparative effectiveness and safety of medications as well as conduct economic analyses in the low-income CF population.

The Real-World Effectiveness of Antifungals in People with Cystic Fibrosis and Aspergillus-Positive Cultures.

The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus positive cultures using the Cystic Fibrosis Foundation patient registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test if antifungal exposure was associated with forced expiratory volume in one second percent predicted (FEV1pp) and pulmonary exacerbation rate, while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). A total of 14,754 individuals with Aspergillus positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV1pp (adjusted estimate -0.96 percentage points, 95% CI -2.21,0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (IV) antibiotics (adjusted IRR=1.29, 95% CI 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA< antifungals were associated with 1.88 lower FEV1pp (95% CI -3.35, -0.41) and an increased rate of pulmonary exacerbations (adjusted IRR= 1.30, 95% CI 1.21,1.40). Whereas, in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV1pp. Antifungal therapy in PwCF and Aspergillus positive cultures was not associated with improvements in FEV>1pp. While antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections are warranted.

Comparison of Longitudinal Outcomes in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder than CF in childhood, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD; pathogenic variants in CCDC39 and CCDC40, causing inner dynein arm/microtubular defects (IDA/MTD), are associated with more severe disease. Objectives: To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency). Methods: Children with PCD enrolled in a prospective, multicenter, observational study were matched with patients with CF from the Cystic Fibrosis Foundation Patient Registry by birth cohort, age, sex, race/ethnicity, and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD vs. all other defects and CF-minimal vs. residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models. Results: Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean forced expiratory volume in 1 second percent predicted compared with CF (e.g., at age 10, -5.4% predicted lower; 95% confidence interval [CI], -7.7, -3.1). Compared with the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar body mass index; estimated mean forced expiratory volume in 1 second percent predicted was significantly lower by age 10 (mean difference, -10.6%; 95% CI, -14.7, -6.4), increasing at age 14 (mean difference, -15.7%; 95% CI, -20.3, -11.2). The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared with children with PCD (67% vs. 27%; P < 0.001); there was no difference in the prevalence of P. aeruginosa between children with PCD-IDA/MTD and PCD-other. Conclusions: In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.

Secular and modulator-specific drifts in the predictive performance of a rapid lung function decline algorithm: a cystic fibrosis patient registry study

PurposePredicting the onset of pulmonary exacerbation for people with cystic fibrosis (CF) is critical to identify those at high risk in advance and allows timely clinical intervention. The FEV1-indicated exacerbation signal (FIES) has been proposed by the CF Learning Network to identify pulmonary exacerbation events, but temporal predictive performance of this marker is unknown.MethodsTo assess the epidemiologic impact of secular trends in CF care and treatments on algorithms aimed at prediction of pulmonary exacerbation, we evaluated prediction model “drift” using a longitudinal retrospective cohort of 29,476 individuals from the U.S. CF Foundation Patient Registry (2011–2018). The FIES marker was defined for each clinical encounter using relative drops in lung function, measured as forced expiratory volume in 1 s of % predicted (FEV1pp). We formed predictive probabilities for each FIES event via a target function for a predictive algorithm of FEV1pp. Models were trained using 2 year data windows with prediction performance tested on subsequent years.ResultsYear-over-year FIES event discrimination remained consistent (area under the receiver-operator characteristic curve, AUC > 80%). Annual drift was < 1% with actual drop in AUC ~ 3% in 6 years. The model performed best in individuals with moderate-to-low baseline FEV1pp (AUC range: 84–85%). For relatively higher FEV1pp levels, discrimination was slightly lower with higher AUC variability.ConclusionWhile model fit improved by accounting for modulator therapy, prediction performance was similar. Most impactful model drifts occurred after 2012 coinciding with increased ivacaftor modulator use. Additional evaluation will be necessary given recent, broad uptake of highly effective modulators.

A Qualitative Exploration of Women With Cystic Fibrosis and Urinary Incontinence.

Women with cystic fibrosis (CF) historically experience a high prevalence of urinary incontinence (UI). However, this area is understudied, especially in the modern era of highly effective modulator therapy (HEMT). This study aimed to explore the UI experiences, knowledge, care-seeking behavior, and treatment preferences of women with CF. We recruited women aged ≥18 years through the CF Foundation's Community Voice national registry if they had a diagnosis of CF and reported UI. Participants underwent individual, semistructured interviews exploring their experiences, attitudes, and preferences toward UI that were audiorecorded and transcribed. Two coders performed thematic analysis using deductive and inductive coding approaches. Twenty-six participants completed interviews (average age, 45.1 years; range, 24-61 years). Key themes included the following: (1) most women with CF and UI report low bother from symptoms likely related to stress UI, and HEMT has greatly improved UI symptoms and decreased bother; (2) most women with CF and UI had previously discussed UI symptoms with family and/or peers but had not sought care due to stigma or low priority; (3) women with CF and UI had minimal knowledge about UI in general and how it relates to CF; (4) most desired broad screening for UI from their CF team and improved multidisciplinary care; and (5) highly effective UI treatment options with low-time commitment and easily accessible resources are desired. Women with CF and UI report low knowledge and care-seeking behavior related to this condition and desire improved care provision. Importantly, HEMT may improve UI symptoms among people with CF.

Long-term impact of ivacaftor on mortality rate and health outcomes in people with cystic fibrosis

BackgroundIvacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of...

Impact of age at ivacaftor initiation on pulmonary outcomes among people with cystic fibrosis

BackgroundIvacaftor (IVA) improves lung function and other extrapulmonary outcomes in people with cystic fibrosis (CF). However, the effect of initiating IVA at earlier versus later ages has not been studied.MethodsWe...

A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis.

Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1s (ppFEV1) was estimated over 5years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5years. Findings were generally consistent with those of shorter follow-up periods. IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).

Evaluation of the GenoType NTM-DR line probe assay for nontuberculous mycobacteria using whole genome sequences as reference standard

Pulmonary nontuberculous mycobacteria (NTM) disease is an emerging public health challenge that is especially problematic in people with cystic fibrosis (CF). Effective treatment depends on accurate species and subspecies identification and antimicrobial susceptibility status. We evaluated the GenoType NTM-DR VER 1.0 assay using biobanked NTM isolates with whole genome sequence (WGS) data and control isolates (total n=285). Species and subspecies detection sensitivity and specificity were 100 % for all species and subspecies except for two subspecies of M. intracellulare, that demonstrated a small degree of discrepant identification between M. intracellulare subspecies intracellulare and subspecies chimaera. All antimicrobial resistance markers were identified with 100 % sensitivity and specificity.We conclude that the GenoType NTM-DR assay offers a rapid and accurate option for identifying the most frequently encountered pathogenic NTM taxa and drug resistance markers.SUPPORT: Colorado CF Research Development Program and Colorado CF National Resource Centers funded by the Cystic Fibrosis Foundation, NJH Advanced Diagnostics Laboratories, Colorado Advanced Industries Accelerator Grant

Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.

Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on in vitro data in the USA for those carrying at least one of 177 rare CFTR (cystic fibrosis transmembrane conductance regulator) variants. PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV1) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively. A total of 1791 individuals aged ≥6 years with rare CFTR variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV1 % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators. Extension of the ETI label to rare CFTR variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.

Assessment of patients' baseline cystic fibrosis knowledge levels following translation and adaptation of the CF R.I.S.E translation program into Turkish.

Cystic fibrosis (CF) patients have a limited life expectancy, but significant medical advances now highlight the need for successful transition programs from pediatric to adult care. The goal of this project was to introduce the transition program CF R.I.S.E (Responsibility. Independence. Self-care. Education.) to a CF center with limited resources at Marmara University (MU). The program was adapted and translated into Turkish with the CF Foundation's permission. A team of experts collaborated to develop educational materials for patients and families. After translation and implementation of the CF S.O.B.E program, 11 Knowledge Assessment Questionnaire (KQA) tests were administered online to the patients aged between 16 and 25 years to assess the lack of patient knowledge. The CF R.I.S.E program was successfully implemented within 6 months. A pilot study showed positive feedback from randomly selected patients, indicating the program's effectiveness and understandability. The mean age of the patients was 19.4 ± 2.9 years, and 42 (52%) were female. The mean forced expiratory volume (FEV1pp) was 76.3 ± 23.2. Fourteen (17.3%) and 4 (4.9%) of the patients colonized with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA), respectively. Fifteen (18.5%) were on modulator therapy. Eleven Knowledge Assessment Questionnaires (KAQ) surveys were administered to 81 patients. The percentage of correct responses to the KAQs ranged from 47.9% to 68.3%. MU CF Center in Turkey implemented the CF S.O.B.E (Responsibility, Self-care, Independence, and Education in Turkish) program. The center aims to make the program a regular practice and expand collaboration with adult clinics. Future studies will assess its long-term impact and applicability in different health settings. The final goal is to disseminate the program's resources and promote structured transition practices across the country.

Evaluation of elexacaftor–tezacaftor–ivacaftor treatment in individuals with cystic fibrosis and CFTRN1303K in the USA: a prospective, multicentre, open-label, single-arm trial

CFTR modulators are approved for approximately 90% of people with cystic fibrosis in the USA and provide substantial clinical benefit. N1303K (Asn1303Lys), one of the most common class 2 CFTR defects, has not been approved for these therapies by any regulatory agency. Preclinical investigation by our laboratories showed N1303K CFTR activation with elexacaftor-tezacaftor-ivacaftor (ETI). In this trial, we evaluate whether ETI improves CFTR function, measured by sweat chloride and other clinical outcomes, in people with cystic fibrosis and CFTRN1303K. In this prospective, open-label, single-arm trial, participants aged 12 years or older with cystic fibrosis encoding at least one N1303K variant and at least one CFTRN1303K allele who were ineligible for modulator therapy by US Food and Drug Administration labelling were given ETI for 28 days followed by a 28-day washout period at two cystic fibrosis centres in the USA. Participants received two orally administered pills of 100 mg elexacaftor, 50 mg tezacaftor, and 75 mg ivacaftor once daily in the morning, and 150 mg ivacaftor once daily in the evening. The primary endpoint was mean change in sweat chloride from baseline up to day 28 compared with mixed-effects models. Secondary endpoints were changes in percentage of predicted FEV1 (ppFEV1), Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain, BMI, and weight after ETI therapy. Safety was assessed in all participants who received at least one dose of the study drug and primary and secondary analyses were performed in all participants who took the study drug per protocol. The trial was registered at ClinicalTrials.gov (NCT03506061) and remains open for reporting purposes. Between June 7, 2022, and Oct 20, 2023, 20 participants (ten male and ten female) were enrolled and received ETI treatment. One participant was lost to follow-up but was included in intention-to-treat analyses. At 28 days, the mean sweat chloride reduction was -1·1 mmol/L (95% CI -5·3 to 3·1; p=0·61) with only one participant showing a sweat chloride decrease greater than 15 mmol/L. There was a mean increase in ppFEV1 from baseline at day 28 of 9·5 percentage points (6·7-12·3; p<0·0001) with 15 (75%) participants showing at least a 5% increase in ppFEV1. Improvements were also identified in mean CFQ-R respiratory domain score (20·8 increase [95% CI 11·9-29·8]; p<0·0001), BMI (0·4 kg/m2 increase [0·2-0·7]; p=0·0017), and weight (1·0 kg increase [0·4-1·7]; p=0·0020) after 28 days of ETI treatment. 14 (70%) of 20 participants had adverse events (12 [60%] mild, one [5%] moderate), with one (5%) serious adverse event of hospitalisation attributed to pneumonia. No deaths were recorded in the study. Individuals with CFTRN1303K showed no change in sweat chloride after 28 days of treatment with ETI. However, there were improvements in secondary clinical endpoints, which suggest clinical efficacy. Our approach provides support for the use of in vitro model systems to inform clinical trials for rare CFTR variants. The Cystic Fibrosis Foundation and the US National Institutes of Health.

Lung transplant referral considerations for individuals with cystic fibrosis.

The cystic fibrosis (CF) Foundation issued guidelines to promote timely lung transplant referral for people with cystic fibrosis (pwCF) in 2019. Since then more has been published to help refine this complex decision. The goal of this review is to summarize the recent literature informing disease severity in CF, barriers to referral for pwCF and guide timely and appropriate lung transplant referrals. Existing guidelines utilize the degree of airflow limitation as the primary criteria to refer for lung transplant, yet this variable has some prognostic uncertainty. Novel prognostic tools may provide more reliable metrics for predicting who with CF is at greatest risk of dying from their lung disease and could be used as an indicator for when to refer. In addition, updated analyses of national registry data have highlighted the significance of hemoptysis, low body mass index, and extra-pulmonary organ failure, as important prognostic markers. PwCF with these complications have historically been under-referred for lung transplant despite data suggesting lung transplant can be safe for some in these populations. Early referral should be considered in the presence of these complications. This review builds on existing guidelines by incorporating novel data to better determine when lung transplant referral is most appropriate. Improved prognostic tools are still needed to decrease the chances of pwCF dying without consideration of lung transplant. It is still unclear how novel therapies for CF may change the need and timing for lung transplant referral.