Search Results (108)

Background/Objectives: RELiZORB immobilized lipase cartridge (ILC) is a single-use digestive enzyme cartridge that connects in-line with enteral feeding circuits to hydrolyze triglycerides in enteral formulas. It is cleared by the FDA for pediatric and adult use. Limited data have been published regarding the effect of ILC use on growth in children younger than 5 years of age. Methods: We performed a retrospective evaluation of real-world data extracted from a third-party reimbursement program database. All patients in the program database who initiated ILC use with enteral formula when 1 to 4 years of age between 2019 and 2023 were included. Baseline and follow-up weight, height/length, and body mass index (BMI) data were collected for up to 12 months. Results: A total of 186 patients from 90 clinics in the United States were included. A subset (143 patients) with baseline and follow-up growth measurements was included in the efficacy analysis population; 76% were diagnosed with cystic fibrosis. Mean weight and BMI z-scores improved significantly (0.63 [p < 0.001] and 0.53 [p = 0.006], respectively) from baseline to 12 months after initiation of ILC use. Significant improvement in the mean weight z-score was observed after 3 months. Among people with cystic fibrosis (pwCF) who initiated ILC use when 2 to 4 years of age, those with a BMI ≥ 50th percentile increased from 22% at baseline to 43% after 12 months (p = 0.021). Improvement in weight-for-length was also observed in 1-year-old pwCF. Conclusions: Real-world evidence showed that initiation of ILC use was associated with significant improvements in mean weight and BMI z-scores among young children. Full article

Background: Stenotrophomonas maltophilia is an intrinsically multidrug-resistant, biofilm- forming, non-fermenter increasingly implicated in hospital-acquired infections. Evidence from non-cystic fibrosis populations, especially in the Middle East, remains sparse. Methods: We conducted a retrospective observational cohort study at a tertiary academic center (Al-Khobar, Saudi Arabia) spanning 1 May 2001–30 April 2023. Hospitalized adults (≥18 years) with culture-confirmed, clinically diagnosed S. maltophilia infection and ≥72 h of antibiotic therapy were included. The primary outcome was all-cause mortality (14-day, 30-day, 1-year). Secondary outcomes were clinical response, microbiological eradication, and infection recurrence. Predictors of 30-day mortality were assessed using multivariable logistic regression; 14-day mortality was analyzed by Kaplan–Meier/log-rank according to susceptibility-guided versus alternative therapy. Results: Of 539 patients with positive cultures, 436 met the inclusion criteria. Mean age was 60.5 ± 19.3 years; 62.2% were male. Most infections were hospital-acquired (92.9%); pneumonia composed 64.7% and bloodstream infection 15.4%. Polymicrobial growth occurred in 55.5% (predominantly Gram-negative co-isolation). Susceptibility was 95.1% to trimethoprim–sulfamethoxazole, 76.4% to levofloxacin, and 43.6% to ceftazidime. Mortality at 14 days, 30 days, and 1 year was 22.8%, 37.9%, and 57.2%, respectively. On multivariable modelling, intensive care unit (ICU) admission, leukocytosis, neutrophilia, anemia, and thrombocytopenia independently predicted 30-day mortality. Susceptibility-guided therapy was associated with improved 14-day survival (log-rank p = 0.033). Conclusions: In this large, long-running non-cystic fibrosis cohort, host acuity and early alignment of treatment to susceptibility data were dominant drivers of outcome. High polymicrobial burden and limited reliably active agents underscore the need for meticulous stewardship, robust infection prevention, and cautious interpretation of S. maltophilia antimicrobial susceptibility testing. Full article

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators have been reported to improve lung function and reduce CF exacerbations. We aimed to investigate the efficacy of CFTR-modulators in CF-associated liver disease (CFLD) during long-term treatment. Longitudinal data were collected from genetically confirmed adult CF patients receiving CFTR-modulators. CFLD was diagnosed using conventional criteria combined with liver stiffness measurement (LSM). A total of 57 patients [56.1% male; median age at baseline (T0), 26 years (interquartile range [IQR], 23–35)] were included. Patients received lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor for a median of 43 months (range, 15–123) until last assessment (T2). The prevalence of CFLD decreased from 15 (26.3%) at T0 to 8 (14.0%) at T2 (p = 0.016), and no new cases of CFLD were observed. Median LSM decreased from 6.2 (IQR 4.9–8.0) to 5.0 kPa (IQR 4.1–6.2) in the overall cohort (p < 0.001) and from 10.2 (IQR 6.8–13) to 6.2 kPa (IQR 5.0–12.4) in the CFLD subgroup (p = 0.025). Mild, transient fluctuations in liver enzymes occurred in 26.3% of patients. In conclusion, adults with CF receiving long-term CFTR modulators, showed improvement of liver disease assessed by ultrasonography and transient elastography. At the last assessment, half of the patients no longer met the criteria for CFLD. Full article

Cystic fibrosis (CF) is a multisystemic, chronic disease that requires a large multidisciplinary team for effective treatment. Over the past 20 years, the landscape of cystic fibrosis care has evolved from an almost exclusively pediatric disease to both a pediatric and adult condition. The median age of cystic fibrosis patients is rising, and the number of adults with CF is also increasing. With new developments in cystic fibrosis care, patients’ health and needs have changed, and therefore the care model of the cystic fibrosis team has also changed. The introduction of highly effective CFTR modulator therapy, the COVID-19 pandemic, and the partnership of people with CF (PwCF) and their families have catalyzed the transformation of the CF care model, which includes the growth and evolution of the CF care team given the changes in the demographics of CF patients and the incorporation of telehealth and remote patient monitoring, shared decision-making, and coproduction of care. This narrative review, focusing on the United States (US) experience, explores the transformation of CF care, highlighting demographic changes, medical breakthroughs, and systemic adaptations. Full article

Background: Cystic fibrosis-related diabetes (CFRD) is a frequent comorbidity in individuals with cystic fibrosis (CF). While insulin secretion defects are the primary mechanism in CFRD pathophysiology, insulin resistance may contribute as an additional risk factor. Early detection of insulin resistance may help identify patients at higher risk for earlier CFRD development. Objective: The aim of this study was to evaluate the ability of the Matsuda Index to identify insulin resistance in pediatric CF patients and to compare it with HOMA-IR as complementary indicators of glucose metabolism. Methods: In this cross-sectional study, fifty children with CF aged 6–16 years were included. The study involved measuring anthropometric data, fasting insulin, fasting glucose levels, glycated hemoglobin (HbA1c), and C-peptide. An assessment of glucose and insulin levels was performed on the patients through an oral glucose tolerance test (OGTT) at 0, 60, and 120 min. The Matsuda Index was computed, wherein a threshold of ≤4.5 signifies the presence of insulin resistance. Statistical analyses were conducted to compare insulin resistance and sensitivity across groups, using t-tests, correlation, and ANOVA. Results: Among the 50 observed patients, the average Matsuda index score was 17.08 with a standard deviation of 11.16. Eleven individuals (22%) exhibited insulin resistance with a Matsuda Index ≤ 4.5. These patients showed significantly higher insulin levels at 60 and 120 min during the OGTT, with statistically significant p-values of 0.008 and 0.002, respectively. Conclusions: The Matsuda Index may serve as a useful adjunctive tool to help identify insulin resistance in pediatric CF patients, particularly during puberty. Early detection of insulin resistance through the Matsuda Index may facilitate risk stratification and enable timely interventions that could potentially delay the onset or progression of CFRD. However, it should be noted that the ≤4.5 cut-off value was derived from adult studies, and its validity in pediatric CF populations has not been established, which represents a limitation of our finding. Full article

In patients with cystic fibrosis (CF), infertility is a common issue in men, while women often experience subfertility. The introduction of CF transmembrane conductance regulator (CFTR) modulators has improved disease progression and enhanced quality of life, consequently leading to an increase in unplanned pregnancies. This article describes six cases of pregnancies in five patients diagnosed with severe CF who were treated with the combined therapy of elexacaftor/tezacaftor/ivacaftor (ETI). All women were under regular clinical and instrumental monitoring at the Regional CF Center for Adults at the University of Naples Federico II. The reported pregnancies were spontaneous, and all patients were followed throughout their pregnancies. Two pregnancies were carried to term by the same patient. All five patients with a severe CF phenotype were able to experience pregnancy without stopping their ETI treatment without any complications. In two cases, the patients chose to continue ETI therapy while breastfeeding, and there were no adverse events reported. A cesarean delivery was preferred in all cases to prevent potential respiratory distress. These five patients represent some of the few cases in Italy where pregnancy was achieved without interrupting treatment with ETI. However, the lack of more reliable data necessitates that doctors and patients carefully evaluate the risks and benefits of continuing or discontinuing treatment with CFTR modulators. In conclusion, the increasing number of pregnancies and the desire for children expressed by women with CF highlight the need for more data on the long-term effects of CFTR modulators. Full article

Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article

Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive and invasive. Non-invasive biomarkers like the Fibrosis-4 (FIB-4) index have shown promise in diagnosing liver fibrosis in various chronic liver diseases. This study explores the potential of the FIB-4 index to predict CFLD in an adult CF population and assesses its correlation with transient elastography (TE) as a potential diagnostic tool. The aim of this study is to evaluate the diagnostic performance of the FIB-4 index for CFLD in adults with CF and investigate its relationship with TE-based liver stiffness measurements (LSM). Methods: The study was conducted in a regional cystic fibrosis unit, including 261 adult CF patients. FIB-4 scores were calculated using an online tool (mdcalc.com) based on patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. In parallel, 29 patients underwent liver stiffness measurement using TE (Fibroscan^®). Statistical analyses included non-parametric tests for group comparisons and Pearson’s correlation to assess the relationship between FIB-4 scores and TE results. Results: The mean FIB-4 score in patients diagnosed with CFLD was higher (0.99 ± 0.83) compared to those without CFLD (0.64 ± 0.38), although the difference was not statistically significant (p > 0.05). TE results for CFLD patients (5.9 kPa) also did not show a significant difference compared to non-CFLD patients (4.2 ± 1.6 kPa, p > 0.05). However, a positive correlation (r = 0.401, p = 0.031) was found between FIB-4 scores and TE-based LSM, suggesting a potential complementary diagnostic role. Conclusions: The FIB-4 index, while not sufficient as a standalone diagnostic tool for CFLD in adults with CF, demonstrates potential when used in conjunction with other diagnostic methods like TE. This study introduces a novel approach for integrating non-invasive diagnostic markers in CF care, offering a pathway for future clinical practice. The combination of FIB-4 and TE could serve as an accessible, cost-effective alternative to invasive diagnostic techniques, improving early diagnosis and management of CFLD in the CF population. Additionally, future research should explore the integration of these tools with emerging biomarkers and clinical features to refine diagnostic algorithms for CFLD, potentially reducing reliance on liver biopsies and improving patient outcomes. Full article

Background: “CFTR modulators” (also named “caftor”) have been developed and introduced into clinical practice to improve the functionality of defective CFTR protein. Therapeutic drug monitoring (TDM) is not currently used for CFTR modulators in routine clinical practice and there is still much to learn about the pharmacokinetic/pharmacodynamic (PK/PD) and the safety profiles of these drugs in a real-world setting. Moreover, therapeutic ranges are not yet available for both pediatric and adult cystic fibrosis (CF) patients. Methods: A new and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for contemporary quantification of ivacaftor (IVA), tezacaftor (TEZ) and elexacaftor (ELX) in plasma samples has been developed and validated. The clinical performance of our method has been tested on samples collected during the routine clinical practice from n = 25 pediatric patients (aged between 7 and 17 years) affected by cystic fibrosis. This LC-MS/MS method has been validated according to ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines for the validation of bioanalytical methods. Results: Our method fulfilled ICH guidelines in terms of accuracy, precision, selectivity, specificity and carry-over. Intra- and inter-day accuracy and precision were ≤15%. The 9-day autosampler stability was 90–100% for TEZ and ELX; meanwhile, it fell to 76% for IVA. An injection volume of 1 µL and a wider quantification range (0.1–20 µg/mL) represent a novelty of our method in terms of sensitivity and fields of application. Finally, the evaluation of PK exposure parameters for IVA revealed strong agreement with previously published reports and with results from the summary of product characteristics (SmPCs). Conclusions: This method could be adopted to contemporarily measure ELX/TEZ/IVA plasma levels for both PK studies and monitor therapy compliance, especially in case of poor or partial responses to treatment, or to evaluate drug–drug interactions when multiple concomitant medications are required. Considering also the high cost burden of these medications to the health system, a TDM-based approach could facilitate more cost-effective patient management. Full article

Highly effective modulator therapy (HEMT) has been available for adults and young adults aged 12 years and over with cystic fibrosis for approximately 5 years, with real-world evidence (RWE) emerging that confirms the significant impacts of these novel medications in older patient groups. As licensing has been extended to younger children (2 years and above in some jurisdictions), we summarize the clinical experience of these medications in pre-school and school-aged children and compare how changes in the objective markers of the disease can be elucidated in younger children. We also discuss the different incidences and severity of side effect profiles, the efforts to mediate these in younger children, and the particular challenges in introducing novel medications into pediatrics. We speculate on the use of HEMT in younger infants and its potential use in prenatal care. Full article

Objectives: To describe the results of nutritional and morphofunctional assessment in a cohort of adults with cystic fibrosis; to evaluate differences in nutritional status between patients with and without exocrine and/or endocrine pancreatic involvement. Methods: Cross-sectional study: A cohort of adults with cystic fibrosis evaluated in a multidisciplinary unit was analyzed. Pancreatic status was examined, and malnutrition was diagnosed according to GLIM criteria. Morphofunctional assessment consisted of nutritional ultrasound, bioelectrical impedance, handgrip dynamometry, and anthropometry. Qualitative variables are expressed as n (%), quantitative variables as median (IQR). For group comparisons, Fisher’s exact test was used for qualitative variables and the non-parametric median comparison test for quantitative variables. Results: n = 101 participants were recruited, of whom 44 (43.6%) were women. Median age was 33 (25–40.5) years. A total of 64 participants (63.4%) had exocrine pancreatic insufficiency (EPI), 44 (43.6%) had endocrine pancreatic insufficiency, and 28 (27.7%) had cystic fibrosis-related diabetes (CFRD). Median BMI was 23.4 (20.1–24.89) kg/m². A total of 48 patients (47.5%) were malnourished. Males with EPI had a higher prevalence of undernourishment than those without (56.4% vs. 16.7%, p = 0.005), but not women. CFRD patients displayed no differences in morphofunctional assessment. Conclusions: Almost half the sample was undernourished using GLIM criteria. Males with exocrine pancreatic insufficiency had worse nutritional status. Endocrine pancreatic involvement did not affect nutritional status. Full article

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is showing remarkable beneficial effects in people with Cystic Fibrosis (pwCF) harboring the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Although this therapy is generally well tolerated in pwCF, some adverse events (AEs) have been recently described both in controlled studies and in post-marketing observations. Methods: We followed 414 pwCF carrying F508del CFTR that initiated ETI treatment, recording AEs for a period of 5 years. Results: A total of 142 AEs were reported. The most frequent AEs in the whole cohort were liver marker elevation, skin rush, epigastric pain, headache, and depression. Considering pediatric subjects, psychiatric and gastrointestinal disorders were the most frequent AEs. Only one patient reported a severe AE, leading to treatment discontinuation. In case of AEs, different decisions on ETI treatment were made, including temporary interruption and temporary or permanent dosage modification. Conclusions: Throughout the long-term observational period, almost 21% of pwCF experienced at least one AE. Psychiatric disorders, in particular attention deficit, were the most prevalent issue in our pediatric cohort, whereas adult patients mainly reported depression, anxiety and sleep disorders. This study therefore strengthen the recommendation of screening for changes in mental health during ETI treatment. AEs led to the permanent reduction of ETI dosage in 32% of cases, raising the issue of safety in relation to dosage reduction, efficacy, and minimum ETI levels. Eventually, this study highlights the need for a longitudinal monitoring of ETI safety since a significant number of AEs occurred after one year of treatment. Full article

Background: Elevated immunoglobulin G (IgG) levels are associated with worse lung function and disease severity in people with cystic fibrosis (PwCF). This study evaluated whether elevated IgG levels—defined as values above the 97.5th percentile (Z-score ≥ 1.96 standard deviations above the mean)—can predict progression to severe lung disease. Methods: A retrospective cohort study of children and adults with CF at a single-center clinic was performed. Patients with elevated baseline IgG Z-scores were compared to those with normal or low IgG levels. Progression to severe lung disease was defined as % predicted FEV₁ < 40%, referral for lung transplantation, or death. Kaplan–Meier survival curves and Cox models were used to analyze clinical outcomes. A sensitivity analysis was conducted for patients aged 18 years or older. Results: Of 97 patients, 31 (31.9%) had elevated IgG levels. Progression to severe lung disease occurred in 14 (14.4%) patients, 12 (85.7%) of whom had elevated IgG. These patients were significantly older and had a higher prevalence of Pseudomonas aeruginosa colonization. Among adults, those with elevated IgG had lower baseline % predicted FEV1 and greater annual lung function decline. Elevated IgG was independently associated with progression to severe lung disease (adjusted hazard ratio [aHR]: 9.8; 95% CI: 1.9–48.6), even after adjusting for Pseudomonas colonization and annual % predicted FEV1 decline. Conclusions: Elevated IgG was associated with progression to severe lung disease in PwCF and correlated with older age, Pseudomonas colonization, and—in adults—lower baseline lung function and faster decline. These findings highlight elevated serum IgG as a meaningful prognostic biomarker for identifying high-risk PwCF who may benefit from closer monitoring and earlier intervention. Full article

Poor sleep quality and excessive daytime sleepiness are commonly reported by individuals with cystic fibrosis. The potential impact of comorbid sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA), has not been extensively studied in the CF population. At present, there are no specific recommendations available to help clinicians identify patients with CF who are at increased risk of sleep disorders. Home sleep apnea testing using a validated peripheral arterial tonometry (PAT) device may offer an accurate diagnosis of OSA in a more convenient and low-cost method than in-lab polysomnography. In this single-center study of 19 adults with CF, we found an increased prevalence of OSA among individuals with CF compared to general population estimates. Although associations with an FEV < 70% predicted and a modified Mallampati score ≥ 3 were observed, these odds ratios did not reach statistical significance, likely reflecting limited power in this small pilot sample. There was no association found between the self-reported presence of nocturnal cough or snoring and OSA. We also found no association between OSA and abnormal scores on commonly used, validated sleep questionnaires, suggesting that CF-specific scales may be needed for effective screening in the CF clinic. Full article

Background and Objectives: Chronic respiratory diseases, such as COPD, cystic fibrosis, and post-COVID-19, are frequently accompanied by psychological distress and physical impairment. As a non-pharmacological intervention, progressive muscle relaxation (PMR) may benefit these patients psychologically and physiologically. This systematic review aimed to evaluate the effects of PMR on anxiety, depression, fatigue, sleep quality, dyspnea, and pulmonary function in patients with COPD, CF, and COVID-19. Materials and Methods: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, Web of Science, MEDLINE, Cochrane, SpringerLink, and ClinicalTrials.gov. Eligible studies assessed PMR in adult patients with COPD, CF, or COVID-19. Psychological and physical outcomes were extracted, and methodological quality and risk of bias were evaluated using standardized tools. Results: A total of 32 studies were included in the analysis. PMR was consistently associated with reductions in anxiety, depression, fatigue, and sleep-related distress, particularly in patients with COPD and COVID-19. Some also reported improvements in dyspnea and mild pulmonary function tests, but these were more variable. Only one study evaluated PMR in patients with cystic fibrosis, providing the first clinical data for this group. Interventions were predominantly short-term, with significant variation in design, duration, and methodology, and the risk of bias was often moderate or high. Conclusions: PMR is a helpful strategy in treating chronic respiratory diseases, particularly for reducing psychological distress and improving sleep. However, the evidence is limited by methodological variations and lack of long-term follow-up. Rigorous research is needed to support clinical application, particularly in cystic fibrosis. Full article