Background Cystic fibrosis (CF) is a multi-system disease that causes chronic respiratory failure, malnutrition and poor growth as a result of a negative energy balance due to maldigestion and malabsorption. Achieving linear growth and height above the 50 th percentile is associated with improved lung function. In October 2022, the use of Elexacaftor/Tezacaftor/Ivacaftor (ETI) was approved for children with CF from the age of 6 years. Analyses on the effect of ETI on height velocity (HV) are not usually available from trial and real life data and our work aims to study growth pattern by HV. A secondary aim was to check for any differences according to the CFTR variants severity. Methods We conducted a single-center prospective study at the CF Unit of the Bambino Gesù Children’s Hospital, including children aged 6-11 years who were eligible for ETI. The whole population of 24 people with CF (pwCF) underwent evaluation of height, weight, body mass index (BMI), bone mineral density (BMD), body composition analysis with bioelectrical impedance analysis (BIA), and muscle weakness using the one-minute sit-to-stand test (1STST) before starting the new drug. Height, weight, height velocity (HV), BMI standard deviation scores (SDS) were calculated for both 6 months before and 6 months after the start of ETI treatment. Results The mean age of the population was 8.7 years (SD 1.87), with a balanced gender distribution (F/M 12/12) and majority naïve to previous CFTR modulators. We found a significant difference in the growth rate achieved when comparing the calculated mean HV between T (-6 months) and T0 (4.2±2.0 cm/year; -1.96±2.4 SDS) with the HV between T0 and T (+6 months) (7.1±3.0 cm/year; +1.5±3.7 SDS) (p<0.0001). The group with F508del/minimal function mutations (F/MF) – 15 pwCF – had a higher average speed than those with homozygous F508del (F/F) – 5 pts – and those with F508del/residual function mutations (F/RF) – 4 pts – ( p< 0.0001). We found no significant differences in the three different genetic groups concerning BMD and initial lean mass. Conclusion The results highlight the benefit of ETI in the pediatric CF population, particularly by increasing the HV in children aged 6-11, especially those with the F/MF genotype. This study further emphasizes the impact of CFTR restoration on a fundamental aspect of the CF child’s well-being, growth.

Central apneas are a prevalent yet complex phenomenon, particularly among children. This retrospective study, conducted over a decade (from 2012 to 2022), analyzed central apneas in a cohort of 612 pediatric patients who underwent ventilation at the Sleep Medicine and Long-Term Ventilation Unit of the Bambino Gesù Children’s Hospital in Rome, Italy. Among this group, 67 patients met the inclusion criteria for central apneas. Central apneas often arise within the context of various underlying pathologies, including neurological disorders, genetic syndromes, and brain tumors. We categorized patients into three main groups including patients with “exclusively central apneas”, “predominantly central apneas”, and “predominantly obstructive apneas”. Ventilation modes were diverse, with pressure-controlled ventilation and pressure support being commonly used, reflecting the individualized nature of therapy. The choice of ventilation mode has been influenced by the underlying diagnosis and the severity of central apneas, with pressure support ventilation being the most frequently employed mode. Continuous Positive Airway Pressure was also employed in select cases. A statistically significant reduction (p<0.05) in mean cAHI was observed in patients with multimalformation syndromes, hypoxic-ischemic encephalopathy and Prader-Willi Syndrome. The reduction in mean cAHI was not statistically significant in the case of patients with brain tumors. While non-invasive ventilation was commonly used, invasive mechanical ventilation was selectively employed in more severe cases. The study highlights the need for personalized therapeutic strategies when managing central apneas in pediatric patients.

Breathing disturbances are often a major clinical concern during wakefulness of classic form of Rett syndrome, but data for atypical forms are lacking. We report the case of a 20-month-old female affected by the congenital variant of Rett syndrome, that is characterized by severe hypotonia and neurodevelopment impairment. She presented hypoventilation, persistent periodic breathing and sustained desaturation during sleep time, without obstructive nor central events; pulse oximetry and capnography during wakefulness were strictly normal. To the best of our knowledge, this is the first case of Rett syndrome presenting hypoventilation. Hypotonia may play a major role in the genesis of hypoventilation and hypoxemia in our patient. Non-invasive ventilation led to quality-of-life improvements. Thus, we suggest screening patients with congenital Rett variant through transcutaneous bedtime carbon dioxide and oxygen monitoring. Moreover, in our case, assisted control mode was a breakthrough to achieve adequate ventilation.

Background: Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF. Methods: A single-center study was conducted at CF Unit of Bambino Gesù Children’s Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic intravenous treatment for 14 days. MBW and spirometry were evaluated within 72 hours of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated. Results: Fifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI 2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average improvement of -6% in 37/57 patients. 26/57 are stable in LCI values. A significant elevation of +7.30% was found for FEV1%. 4/57 (7.02 %) had a significant deterioration in LCI values at the end of IV antibiotic treatment. A positive good correlation among LCI 2.5 and Scond (rho= +0.615, p=0.000) and LCI 2.5 and Sacin (rho=+0.649, p=0.000) and a negative strong correlation between FEV1% and LCI 2.5 were found in post treatment period. A better increase of LCI 2.5 in < 18 years (-10.27% vs -4.57%) than adult was noticed. Conclusions: LCI may have a role in the routine clinical care of CF patients as a good tool to assess response to intravenous antibiotic therapy.

Pediatric palliative care (PPC) is an active and total approach to the care of children with life-limiting conditions and to their families. PPC programs provide ongoing care for children with medical complexity (CMC), many of whom will reach adulthood. The aim of the study is to describe a population of CMC afferent in 4 months to the Intermediate Care Unit of a tertiary referral hospital for southern and central Italy. We enrolled all CMC patients admitted at our unit in 4 randomized months. We registered pathologies and different categories of childhood diseases, devices and needs, hospitalization and home care plan. Among 195 admitted to our unit, 87 CMC were included. Median age was 9 (0.1 – 35.7) years. The main pathologies recorded were neuromuscular, neurological, respiratory, metabolic, malformative, genetic syndromes and outcomes of prematurity. Comorbidity made by respiratory, digestive, neurological, cardiac and urological involvement was present in a high percentage of cases. Among our patients, only 24 hadn’t any devices. The average length of hospitalization was 7.0 (1.0 – 270.0) days with 2 (1.0 – 7.0) admissions per year for patient. Home care activation was not required for only 24 of 87 patients. Children eligible for CPP are increasing and their survival results in a rise in comorbidities and special needs demanding multi-level interventions. Respiratory symptoms are the most recurrent observed demonstrating the need for an expert in CPP to have respiratory skills. Sharing data and knowledge of CMC needs may help to improve care coordination and interventions.

Tracheoesophageal fistula (TEF) with esophageal atresia (EA) is a common congenital anomaly that is associated with significant respiratory morbidity throughout life. The objective of this document is to provide a framework for the diagnosis and management of the respiratory complications that are associated with the condition. As there are no randomized controlled studies on the subject, a group of experts used a modification of the Rand Appropriateness Method to describe the various aspects of the condition in terms of their relative importance, and to rate the available diagnostic methods and therapeutic interventions on the basis of their appropriateness and necessity. Specific recommendations were formulated and reported as Level A, B, C based on whether they were based on “strong”, “moderate” or “weak” agreement. The tracheomalacia that exists in the site of the fistula was considered the main abnormality that predisposes to all other respiratory complications due to airway collapse and impaired clearance of secretions. Aspiration due to impaired airway protection reflexes is the main underlying contributing mechanism. Flexible bronchoscopy is the main diagnostic modality, aided by imaging modalities, especially CT scans of the chest. Non-invasive positive airway pressure support, surgical techniques such as tracheopexy and rarely tracheostomy are required for the management of severe tracheomalacia. Regular long-term follow-up by a multidisciplinary team was considered imperative. Specific templates outlining the elements of the clinical respiratory evaluation according to the patients’ age were also developed.