This review presents current updates of pancreatic enzyme replacement therapy in children with cystic fibrosis based on literature published in the last decade and some special considerations regarding pancreatic enzyme replacement therapy in the era of new therapies, such as cystic fibrosis transmembrane conductance regulator modulator therapies. Few articles evaluate the efficacy of pancreatic enzyme replacement therapy in the pediatric population, and most studies also included children and adults with cystic fibrosis. Approximately 85% of cystic fibrosis patients have exocrine pancreatic insufficiency and need pancreatic enzyme replacement therapy. Fecal elastase is the most commonly used diagnostic test for exocrine pancreatic insufficiency, although this value can fluctuate over time. While it is used as a diagnostic test, it cannot be used for monitoring the effectiveness of pancreatic enzyme replacement therapy and for adjusting doses. Pancreatic enzyme replacement therapy, the actual treatment for exocrine pancreatic insufficiency, is essential in children with cystic fibrosis to prevent malabsorption and malnutrition and needs to be urgently initiated. This therapy presents many considerations for physicians, patients, and their families, including types and timing of administration, dose monitoring, and therapy failures. Based on clinical trials, pancreatic enzyme replacement therapy is considered effective and well-tolerated in children with cystic fibrosis. An important key point in cystic fibrosis treatment is the recent hypothesis that cystic fibrosis transmembrane conductance regulator modulators could improve pancreatic function, further studies being essential. Pancreatic enzyme replacement therapy is addressed a complication of the disease (exocrine pancreatic insufficiency), while modulators target the defective cystic fibrosis transmembrane conductance regulator protein. Exocrine pancreatic insufficiency in cystic fibrosis remains an active area of research in this era of cystic fibrosis transmembrane conductance regulator modulator therapies. This new therapy could represent an example of personalized medicine in cystic fibrosis patients, with each class of modulators being addressed to patients with specific genetic mutations.

Background: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. Methods: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. Results: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. Conclusions: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.

Background. Patients with cystic fibrosis (CF) frequently require modulatory therapies such as Lumacaftor/Ivacaftor (LI) and Elexacaftor/Tezacaftor/Ivacaftor (ETI) to manage their condition. Given the potential hepatic complications associated with CF, it is critical to understand the impact of these therapies on liver function and fibrosis indices. This study aimed to evaluate the changes in liver function markers and fibrosis indices in CF patients undergoing LI and ETI therapies, with a specific focus on the influence of underlying hepatic disease. Methods. In this retrospective analysis, liver function markers and fibrosis indices were assessed in CF patients receiving ETI (n=24), LI (n=4), or a combination of both (LI/ETI, n=8). Key liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, platelet count, and fibrosis indices (APRI and FIB-4), were measured at baseline and at various time points up to 12 months. Results. In patients receiving LI therapy, ALT and AST levels demonstrated a slight but non-significant decrease over six months, accompanied by significant fluctuations in total bilirubin levels. Among those receiving ETI therapy, ALT and AST levels initially increased but stabilized over time, while total bilirubin levels significantly increased from baseline to 12 months. No significant differences were observed in liver function markers between patients with and without hepatic disease under ETI therapy. Trends in fibrosis indices (APRI and FIB-4) were modest and largely non-significant across both therapies. Conclusions. ETI therapy appears to be safe for CF patients, including those with pre-existing hepatic disease, with no significant deterioration in liver function over a 12-month period. However, the observed fluctuations in bilirubin levels underscore the necessity for ongoing monitoring. Further research is warranted to investigate the long-term hepatic effects of LI and ETI therapies.

Background. Hepatic disease represents a significant complication in children with cystic fibrosis (CF), yet its relationship with specific genetic factors, including CFTR (Cystic fibrosis transmembrane conductance regulator) mutations and SERPINA1 alleles, is not well understood. This study aims to clarify these associations within a Romanian pediatric CF population. Methods. In this cross-sectional, prospective study, we examined 71 children with CF, comparing those with hepatic disease (n=25) to those without (n=46). We collected comprehensive clinical, biochemical, and genetic data, focusing on CFTR genotypes and SERPINA1 alleles. Key outcomes included the prevalence of hepatic disease in relation to specific genotypes, fibrosis markers, and liver function tests. Results. The DF508/DF508 genotype was the most prevalent, occurring in 49% of the cohort. No significant associations were found between hepatic disease and specific CFTR genotypes or SERPINA1 alleles. However, children with hepatic disease exhibited significantly higher fibrosis scores (APRI and FIB-4), suggesting more advanced liver involvement. Additionally, a slight delay in CF diagnosis was observed in those with hepatic disease, though this difference did not reach statistical significance. Conclusion. This pioneering study in Romania underscores the complexity of hepatic disease in CF. While specific CFTR genotypes and SERPINA1 alleles were not significantly associated with hepatic complications, the findings emphasize the importance of early diagnosis and monitoring using fibrosis markers to identify children at risk for liver involvement.

Background: Acute bronchiolitis is among the most common causes of lower respiratory tract infection in infancy and remains a clinically heterogeneous syndrome. Current international guidelines recommend supportive management and generally discourage routine bronchodilator administration; however, physiological responsiveness may exist in a subset of patients. Tidal breathing analysis (TBA) provides a non-invasive, bedside method for objectively assessing respiratory mechanics and may objectively quantify physiological changes following bronchodilator administration. Case Presentation: We report a 23-month-old boy presenting with severe RSV bronchiolitis-like wheezing illness complicated by acute respiratory failure. Bronchodilator responsiveness was evaluated using predefined TBA parameters before and after inhaled bronchodilator administration. Following treatment, time to peak tidal expiratory flow (tPTEF) increased from 0.17 to 0.33 s (+94%), while the tPTEF/TE ratio increased from 0.12 to 0.27 (+125%). Expiratory time (TE) and total respiratory cycle duration (Ttot) decreased by 12.6% and 5.1%, respectively, whereas tidal volume (VT) and minute ventilation (MV) increased by 12.1% and 18.3%. Peak expiratory flow remained unchanged (0.14 L/s before and after bronchodilator administration). Discussion: To our knowledge, this is among the first reports using bedside TBA to characterize acute bronchodilator responsiveness in severe bronchiolitis-like illness. The improvement in expiratory timing indices, accompanied by shorter expiratory time without changes in peak expiratory flow, is consistent with improved expiratory flow dynamics following bronchodilator administration. These findings support the hypothesis that a bronchodilator-responsive physiological phenotype may exist. Previous studies have demonstrated an association between severe bronchiolitis during infancy and subsequent recurrent wheezing or asthma; however, whether acute bronchodilator responsiveness, measured objectively by TBA, represents a testable hypothesis for future longitudinal studies. Conclusions: This case illustrates the feasibility of bedside TBA for identifying physiological bronchodilator responsiveness in severe bronchiolitis-like illness. Prospective longitudinal studies are warranted to determine whether TBA-defined responsiveness represents an early physiological marker requiring prospective validation and whether such physiological stratification may support individualized follow-up strategies.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in characteristic features of CF, including chronic airway infection and inflammation, airways damage, and progressive lung disease [1]. CF patients experience alterations in their microbiome, which contribute to the development of chronic bacterial lung infections, leading to excessive lung inflammation and impair airway epithelial barrier function [2-3]. Staphylococcus aureus (SA) is considered one of the main causes of the recurrent acute pulmonary infections and progressive lung function decline in patients with CF [4]. Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in CF patients and is typically associated with complications. Despite antibiotic treatment, these infections often become chronic. MRSA is linked to an increased frequency of annual pulmonary exacerbations and a higher rate of hospitalization. We present the case of a 17-year-old female patient, diagnosed with CF since the age of 12, who presented to the emergency room due to dyspnea and worsening chronic respiratory failure, accompanied by a productive cough and greenish sputum. Sputum culture revealed multidrug-resistant SA. Initially, the patient’s clinical course was unfavorable, resulting in the development of a right pneumothorax after a coughing episode. However, with appropriate surgical treatment and antibiotic therapy guided by antimicrobial susceptibility testing (AST), the patient’s condition subsequently improved. When MRSA is detected, it should be promptly eradicated [5]. However, despite the introduction of new antibiotics, there is a lack of consensus regarding the optimal choice of antibiotics, dosing, and duration of treatment. Pneumothorax is a potentially life-threatening complication that can arise in both MRSA lung infections and CF patients. As a result, managing MRSA infections in CF patients continues to pose significant challenges.