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.

UNASSIGNED: Cystic fibrosis related diabetes (CFRD) is correlated with worsening of nutritional status and greater deterioration of lung function. The role of new technologies for the treatment of CFRD is little explored. The aim of the study was to evaluate the efficacy of Advanced Hybrid Closed Loop (AHCL) systems on glycemic control in CF patients.
UNASSIGNED: A single-center retrospective study on CFRD patients using AHCL systems was performed. Glycated hemoglobin (HbA1c) values and Continuous Glucose Monitoring (CGM) metrics were collected at T0 (AHCL placement), T1 (1-month), T2 (6-months) and T3 (1-year) to evaluate glycemic control.
UNASSIGNED: 10 patients were included in the study. Data showed a reduction of HbA1c value (7.31 ± 0.34 to 6.35 ± 1.00; p=0.03), glycemic variability (p=0.05) and insulin requirement (p=0.03). The study population reached American Diabetes Association (ADA) recommended glycemic targets at 1-year. An increase in the Time in Range (TIR) and a reduction in time in hyperglycemia were also observed, although not statistically significant.
UNASSIGNED: In patients with CFRD, the use of AHCL leads to an improvement in glycemic control in terms of HbA1c and glycemic variability. The increase in TIR and the reduction of time in hyperglycemia, although not statistically significant, are extremely encouraging from a clinical point of view. Further studies with a larger population and a longer follow-up are needed. The results of this study demonstrate the importance of proposing the use of AHCL even in CF patients, who could benefit from glycemic improvement also in terms of nutritional status and respiratory function.

BACKGROUND: In 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.
METHODS: Healthcare 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.
RESULTS: Overall 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.
CONCLUSIONS: There 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.

OBJECTIVE: Telehealth and home spirometry feasibility for children has been established, but their impact on cystic fibrosis (CF) disease progression remains unassessed. We aimed to evaluate the effects of telehealth and home spirometry on CF disease progression and care.
METHODS: Children with CF aged 5-17 years from all Swedish CF centers were provided with home spirometers. A minimum of two in-person visits were replaced with telemedicine visits and participants were instructed to conduct home spirometry before visits. Linear mixed-effects models were used to compare annual CF disease trajectories during the intervention period and prepandemic period (1 January 2019 to 28 February 2020). Participants and caregivers completed study questionnaires.
RESULTS: A total of 59 individuals completed the study over a mean (SD) period of 6.8 (1.4) months, made 3.1 (1.0) physical visits and 2.2 (0.6) telehealth visits per patient year during the study period. The mean difference (95% CI) between the intervention and prepandemic period progression rate for FEV1%, lung clearance index and BMI were -0.4 (-1.3 to 0.5, p = 0.39), 0.11 (-0.07 to 0.28, p = 0.25) and -0.02 (-0.13 to 0.08, p = 0.70), respectively. There were no major shifts in the incidence of airway pathogens, sputum cultures, or antibiotics use between the periods (p > 0.05). The intervention did not increase stress. Almost all participants and caregivers expressed a desire to continue with home spirometry and telemedicine.
CONCLUSIONS: Combining telehealth and physical visits with access to home spirometry demonstrated comparable effectiveness as exclusively in-person care with enhanced flexibility and personalization of CF care.

OBJECTIVE: To study the prevalence of cystic fibrosis related liver disease (CFLD) as defined by ultrasound (US) and describe difference in clinical and radiological features in those with CFLD and those without CFLD (nCFLD); with and without portal hypertension (PHT and nPHT).
METHODS: Children with CF (CwCF) from our clinic who had regular screening liver US from 3 years of age were included. Liver parenchyma findings were classified into normal, homogeneous, heterogeneous and nodular. For our study, we defined PHT as US evidence of splenomegaly and/or ascites, abnormal portal flow, varices, ligamentum teres recanalization if present. Demographic, clinical, nutritional and lung function between the two groups-CFLD/nCFLD; and subgroups- PHT and nPHT were compared. Gamma glutamyl transferase (GGT)/ platelet ratio (GPR) as a marker of fibrosis was measured.
RESULTS: From 227 CwCF,40 (17 %) were excluded (below the age of 3 years or alternative cause of liver disease). Of the remaining 187, 107 (57 %) had a normal US, 80 (43 %) had CFLD; 25 (13.4 %) had PHT. There was no significant difference in demographics, BMI-z score, lung function, presence of gastrostomy or pancreatic insufficiency in CFLD vs nCFLD and PHT vs nPHT. CF related diabetes mellitus (CFRD) was significantly associated with CFLD vs nCFLD (P = 0.0086). GGT was higher and platelet count was lower in PHT vs nPHT (P = 0.0256 and P = 0.0001). Nodularity was strongly associated with an elevated GPR (P = 0.016). There was a strong association between nodularity on US and PHT (P = 0.0006).
CONCLUSIONS: Nodularity is a clear marker for advanced liver disease with higher scores for a non-invasive marker for fibrosis. There was no difference in nutrition and FEV1 between advanced liver disease and absent/ milder liver disease.

Background: Modulator therapies improve weight and body mass index (BMI) in cystic fibrosis (CF) patients. We aimed to compare the nutritional risk index (NRI) in adult CF patients receiving modulator (MT) or only non-modulator (conventional) therapies (non-MT). Methods: A single-center prospective cohort study was conducted between June and December 2023. The NRI based on weight gain and albumin was calculated at beginning and end of a 12-week period in both groups. This design was pragmatic, since it was based on individual patient access to MT for 12 weeks. Results: In total, 107 patients were included [mean (SD) age: 23.85 (4.98) years, 54.7% male, 46.7% MT]. In the MT group, mean (SD) weight (kg) and albumin (g/dL) increased significantly [changes: +3.09 (2.74) and +0.17 (0.37); p < 0.001]. In the non-MT group, weight and albumin decreased significantly [changes: -0.99 (1.73) and -0.12 (0.30); p < 0.001]. Compared to the MT group, baseline mean (SD) NRI in the non-MT group was significantly higher [100.65 (11.80) vs. 104.10 (10.10); p = 0.044]. At the end of the 12 weeks, mean (SD) NRI in the MT group was higher than in the non-MT group [104.18 (10.40) vs. 102.58 (12.39); p = 0.145]. In the MT group, the NRI category improved in 22 (44%), and worsened in 3 (6%) patients (p < 0.001). In the non-MT group, the NRI category improved in 2 (3.5%), and worsened in 10 (17.5%) patients (p < 0.001). Conclusions: This is the first study reporting on a positive effect of MT on NRIs, based on weight gain and albumin. Personalized nutrition and routine follow-up of adults with CF based on NRI is recommended prior to MT initiation.

BACKGROUND: Non-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV1, functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening.
METHODS: Lung function (LCI, FEV1) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 - 8 years) and 75 age-matched healthy controls. Clinical information was collected throughout childhood.
RESULTS: LCI, ventilation and perfusion defects, and structural MRI scores were significantly higher in children with CF compared with controls, but FEV1 was not different between groups. Lung MRI outcomes correlated significantly with LCI (morphology score (r = 0.56, p < 0.001); ventilation defects (r = 0.43, p = 0.001); perfusion defects (r = 0.64, p < 0.001), but not with FEV1. Lung MRI outcomes were more sensitive to detect impairments in children with CF (abnormal ventilation and perfusion outcomes in 47 %, morphology score in 30 %) compared with lung function (abnormal LCI in 21 % and FEV1 in 4.8 %). Pulmonary exacerbations, respiratory hospitalizations, and increase in patient-reported cough was associated with higher LCI and higher structural and functional MRI outcomes.
CONCLUSIONS: The LCI and lung MRI outcomes non-invasively detect even mild early lung disease in young children with CF diagnosed following newborn screening. Pulmonary exacerbations and early respiratory symptoms were risk factors for structural and functional impairment in childhood.

BACKGROUND: Wearables hold potential to improve chronic disease self-management in conditions like cystic fibrosis (CF) through remote monitoring, early detection of illness and motivation. Little is known about the acceptability and sustainability of integrating wearables into routine care from the perspectives of people with CF (pwCF) and their treating clinicians.
METHODS: A cross-sectional qualitative study involving semi-structured interviews with adult pwCF and focus groups comprising members of a CF multidisciplinary team (MDT) were conducted at a specialist CF centre in Australia. A phenomenological orientation underpinned the study. Inductive thematic analysis was performed using the Framework method. The study adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist.
RESULTS: Nine pwCF and eight members of a CF MDT, representing six clinical disciplines, participated in the study. Eight themes were inductively generated from the data, of which four were identified from each group. PwCF valued wearables for providing real-time data to motivate healthy behaviours and support shared goal-setting with healthcare providers. Wearables did not influence adherence to CF-specific self-management practices and had some hardware limitations. Members of the CF MDT recognised potential benefits of remote monitoring and shared goal-setting, but advised caution regarding data accuracy, generating patient anxiety in certain personality traits, and lack of evidence supporting use in CF self-management.
CONCLUSIONS: Perspectives on integrating wearables into CF care were cautiously optimistic, with emerging risks related to patient anxiety and lack of evidence moderating acceptance.

Cystic fibrosis (CF) is a disease characterized by long-term and troublesome symptoms that affect the patient\'s life. This study aimed to assess and compare the health-related quality of life (HRQoL) of Polish CF patients and identify factors influencing it. The study group consisted of 79 patients (6 to 42 years old), who filled in an age-appropriate Cystic Fibrosis Questionnaire-Revised. Medical data were collected from each patient\'s medical records. The domains with the highest HRQoL median were eating problems (88.89), digestive symptoms (77.78) and physical functioning (75.00). The lowest-rated domain was social functioning (61.90). Age negatively correlated with eight domains, and most strongly with treatment burden (rho = -0.474). Physical functioning positively correlated with all spirometry parameters, and most strongly with FEV1% (rho = 0.588). Treatment burden, body image and respiratory symptoms were positively correlated with all spirometry parameters except PEF%. Present exacerbations reduced scores in almost all domains, and in the MANCOVA model they were a significant factor differentiating patients\' HRQoL. The univariate analysis of MANCOVA showed the significant effects of both health condition (F = 8.32, p = 0.005) and the COVID-19 pandemic (F = 5.89, p = 0.018) on social functioning domain, and of the place of residence on body image (F = 5.60, p = 0.21). A decreasing HRQoL with increasing age and during exacerbations indicates that it is important to focus on these aspects of patients\' lives and ensure they received the necessary support from their healthcare providers.

BACKGROUND: We are assisting to an increase in survival rates among individuals with cystic fibrosis (CF). Until now, renal involvement was a minority issue, but with the rise in life expectancy, we will likely see an increase in its prevalence. Our main objective was to assess renal function in CF and study risk factors associated with its deterioration.
METHODS: A cross-sectional, retrospective study was conducted, including adults with CF. Clinical, respiratory function, microbiological, blood and urine analysis, and major chronic treatments received were collected.
RESULTS: Eighty nine patients with a mean age of 35±12 years were analyzed. Mean serum creatinine levels were 0.8±0.2mg/dL. 10.6% had a glomerular filtration rate less than 90mL/min/1.73m2. No patient showed albuminuria. In multivariate model, only age was an independent risk factor for reduced glomerular filtration (OR: 0.344; 95%CI: 0.004-0.017; P=.002).
CONCLUSIONS: 11% of CF adults show decreased glomerular filtration, with age being the sole independent risk factor. Vigilance for this uncommon condition is crucial.