BACKGROUND: Men with cystic fibrosis (CF) have sexual health concerns such as delayed puberty, infertility, and hypogonadism. The causes and prevalence of hypogonadism have not been well studied. The purpose of this study was to determine the prevalence of a low testosterone concentration in men with CF.
METHODS: This retrospective study was approved by the Emory University Institutional Review Board (IRB). Data were extracted from the electronic medical records of adult men with CF receiving care at the Emory Cystic Fibrosis Center. A total of 129 men with CF were followed at our center from 2016 to 2023. Of these individuals, 76 men with CF (58.9%) had at least one serum total testosterone measurement. Seven individuals were excluded from this study since they were currently receiving testosterone therapy, leaving a final sample size of 69 individuals for the analysis. Demographic data, serum testosterone concentrations, and other factors associated with low testosterone concentrations were collected. Low testosterone was defined as a value below 300 ng/dL. Regression analyses were used to determine factors associated with low testosterone levels.
RESULTS: The mean (± SD) age of the 69 eligible participants was 33.34 ± 10.98 years. The mean testosterone concentration was 421 ± 158.5 ng/dL with 27.54 percent of men with a testosterone value below 300 ng/dL. The mean hemoglobin level was 14.23 ± 2.18 g/dL. Testosterone levels were positively related to hemoglobin levels. Time of day of measurement and age were not associated with testosterone levels.
CONCLUSIONS: Roughly a quarter of men with CF demonstrated low testosterone in our sample. Low hemoglobin was associated with low testosterone levels in men with CF. Neither time of day nor age influenced testosterone concentrations in this sample.

BACKGROUND: The pathophysiological mechanisms underlying the natural history of glucose intolerance and its fluctuations in subjects with cystic fibrosis (CF) are still unclear.
OBJECTIVE: To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in CF subjects.
METHODS: Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 CF subjects, aged 10-25 years, who underwent two OGTT tests over at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) versus OGIS.
RESULTS: OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (p<0.02, R2Nagelkerke=0.55), whereas age, gender, z-BMI, CF genotypes, and baseline PCadj were not.
CONCLUSIONS: In CF subjects, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.

BACKGROUND: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.
METHODS: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at 24 weeks.
RESULTS: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV1 points with LAU-7b and 1.95 ppFEV1 with placebo, a 0.77 ppFEV1 (40 s) difference, p=0.345, and a 0.95 ppFEV1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV1, in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile.
CONCLUSIONS: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.

BACKGROUND: 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 predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1.
METHODS: 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.
RESULTS: 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 chronic Pseudomonas 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.
CONCLUSIONS: 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.

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.