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BackgroundHigh-flow nasal cannula (HFNC) therapy is increasingly used for lower respiratory tract infections (LRTIs) in infants and young children, but recommendations vary, and standardised practice is lacking.ObjectiveTo systematically review national or international guidelines on HFNC use in children aged 1–23 months with LRTIs, focusing on initiation, administration, monitoring, discontinuation and feeding.MethodsWe searched MEDLINE, EMBASE, CINAHL, Web of Science and professional society websites (2014–2025) for guidelines on HFNC use in this age group. Four reviewers independently screened, extracted data and assessed quality with the AGREE II tool. Interguideline concordance was calculated for all guidelines and separately for those addressing bronchiolitis and for evidence-based versus consensus-based guidelines. Recommendations were synthesised narratively.ResultsFifteen guidelines were included, including nine bronchiolitis guidelines. All addressed HFNC initiation, with low oxygen saturation (73%) and respiratory distress (47%) as common indications. Initial flow recommendations varied; 2 L/kg/min was most frequent (57%), and all bronchiolitis guidelines reporting it advised weight-based settings. Only two guidelines included weaning or discontinuation protocols, and seven addressed failure criteria. Monitoring typically included pulse oximetry and clinical observation; pulse oximetry was endorsed by all bronchiolitis guidelines that reported it (8/9). Enteral feeding was supported by all reporting guidelines (6/15). Guideline quality was moderate to high, though applicability and updating were frequent gaps.ConclusionsHFNC guideline recommendations for young children with LRTIs remain inconsistent, particularly regarding weaning, failure criteria and procedural details. Regular updates and greater standardisation are needed to improve care and optimise resource use.PROSPERO registration numberCRD42024622544.

Long-term noninvasive ventilation modalities for the pediatric population have undergone a continuous evolution. Hybrid noninvasive ventilation modalities have been recently introduced in clinical practice. Combining the advantages of conventiol ventilation, hybrid modes use algorithms that automatically adjust the ventilator’s settings to achieve a predefined ventilation target. Most of the recommendations on the use and settings of hybrid noninvasive ventilation modalities in children are derived from adult experience. Therefore, there is a lack of evidence on its implementation in pediatric chronic respiratory diseases. This scoping review aims to map the existing information regarding the use of hybrid ventilation modalities in the pediatric population and identify knowledge or research gaps. We performed a literature search using MEDLINE and PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Alyses extension for Scoping Reviews. We included 13 studies (10 studies on average volume-assured pressure-support ventilation, 2 studies on intelligent volume-assured pressure-support ventilation, and 1 study on adaptive servoventilation). The use of new noninvasive ventilation modes in the pediatric population has been applied for the treatment of neuromuscular and hypoventilation syndromes as an altertive therapeutic option in the case of the failure of conventiol noninvasive ventilation. Their widespread use has been hampered by the limited evidence available. Longitudil studies on a larger number of patients are needed to confirm their effectiveness and evaluate their long-term clinical and functiol outcomes.

Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are frequently encountered in obese children. Whether OSAS and intermittent hypoxia are associated with liver injury in pediatric NAFLD is unknown. To assess the relationship of OSAS with liver injury in pediatric NAFLD. Sixty-five consecutive children with biopsy-proven NAFLD (age, mean ± SD, 11.7 ± 2.1 yr; 58% boys; body mass index z score, 1.93 ± 0.61) underwent a clinical-biochemical assessment and a standard polysomnography. Insulin sensitivity, circulating proinflammatory cytokines, markers of hepatocyte apoptosis (cytokeratin-18 fragments), and hepatic fibrogenesis (hyaluronic acid) were measured. Liver inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3, and CD163, surface markers of leukocytes, T cells, and activated macrophage/Kupffer cells, respectively. OSAS was defined by an apnea/hypopnea index (AHI) greater than or equal to 1 event/h, and severe OSAS was defined by an AHI greater than or equal to 5 events/h. Fifty-five percent of children with NAFLD had nonalcoholic steatohepatitis (NASH), and 34% had significant (stage F ≥ 2) fibrosis. OSAS affected 60% of children with NAFLD; the presence and severity of OSAS were associated with the presence of NASH (odds ratio, 4.89; 95% confidence interval, 3.08-5.98; P = 0.0001), significant fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23-7.42; P = 0.0001), and NAFLD activity score (β, 0.347; P = 0.029), independently of body mass index, abdominal adiposity, metabolic syndrome, and insulin resistance. This relationship held also in nonobese children with NAFLD. The duration of hemoglobin desaturation (Sa(O2) < 90%) correlated with increased intrahepatic leukocytes and activated macrophages/Kupffer cells and with circulating markers of hepatocyte apoptosis and fibrogenesis. In pediatric NAFLD, OSAS is associated with biochemical, immunohistochemical, and histological features of NASH and fibrosis. The impact of hypoxemia correction on liver disease severity warrants evaluation in future trials.

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.

Acute viral bronchiolitis is the most common cause of hospitalization in children under 12 months of age. The variable clinical presentation and the potential for sudden deterioration of the clinical conditions require a close monitoring by healthcare professionals. In Italy, first access care for children is provided by primary care physicians (PCPs) who often must face to a heterogeneous disease presentation that, in some cases, make the management of patient with bronchiolitis challenging. Consequently, Italian studies report poor adherence to national and international guidelines processed to guide the clinicians in decision making in acute viral bronchiolitis. This paper aims to identify the potential factors contributing to the lack of adherence to the suggested guidelines derived by clear and evidence-based recommendations among primary care physicians operating in an outpatient setting, with a specific focus on the context of Italy. Particularly, we focus on the prescription of medications such as β2-agonists, systemic steroids, and antibiotics which are commonly prescribed by PCPs to address conditions that can mimic bronchiolitis.

The gold standard for the diagnosis of sleep apnoea (SA) is polysomnography, consisting of overnight in-lab tests, which are expensive for both patients and healthcare systems. Airflow and pulse/oximetry signals contain most of the necessary information for detecting SA and widely simplify the data acquisition process, hence holding the promise to increase the availability of SA diagnosis and reduce waitlists. Deep learning has recently shown some interesting steps forward in analysing these signals in paediatric patients. Here we introduce a novel platform, REST, that is able to simultaneously detect the presence of apnoea, desaturation, and artefacts in input signals. To achieve this goal, we developed a novel 1D deep neural network architecture that leverages prior knowledge of the information distribution across signals, allowing for the concurrent detection and interpretation of target events. The platform was trained, validated, and tested on data from 86 paediatric patients. We show that our approach outperforms other three approaches from the literature, reaching 92.50% (1.10%), 98.30% (0.43%), and 97.59% (0.28%) balanced classification accuracies for apnoea, desaturation, and artefact, respectively (mean and standard deviation, in brackets). Notably, the REST platform also gives a confidence score as output, highlighting to the doctor the samples that need to be reviewed and further boosting the performances of the other samples. Lastly, based on gradient-weighted class activation mapping (grad-CAM) heatmaps, our platform allows the explanation of the decision process, pointing out the regions of the input signals in which events occur, increasing the reliability of the whole process for a human user.

Background During the pandemic, the pneumology team at Bambino Gesù Children’s Hospital highlighted that telemedicine was a valuable tool for remotely managing the medical needs of children with medical complexity (CMC). Following the telemedicine experience during the emergency phase, a telemedicine service was established, and new tools were tested to optimize televisits and the overall eHealth approach for patients. In this context, the TytoHome™ device was tested for performing objective examinations remotely. This pilot study, conducted at our hospital, explored the management of CMC patients on long-term mechanical ventilation via the telemedicine platform and the TytoHome™ device. Methods This study involved the treatment of 10 pediatric patients over one year using this approach. The patients were already receiving care at our hospital and were undergoing long-term mechanical ventilation (LTV) at home—4 on invasive mechanical ventilation (IMV) and 6 on non-invasive ventilation (NIV). A database was developed to collect patient data, including personal details, vital parameters, objective examinations, audio quality, and patient satisfaction. A descriptive analysis was subsequently performed using the data collected during the earlier stages of the study. Results The utility of the TytoCare device for medically complex children was evaluated. The families were “satisfied” with the remote follow-up visits, and healthcare personnel rated the audio quality of the visits as “good.” Conclusions In conclusion, the remote management of these patients using the Tyto device offered several advantages. In our experience, Tyto proved to be a useful tool for the remote medical management of complex patients.

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by an impaired ventilatory response to hypercapnia and hypoxia, particularly during sleep, and frequently associated with autonomic dysfunction. It is caused by pathogenic variants in the PHOX2B gene. Although CCHS is typically diagnosed in the neonatal period, milder forms may present later in infancy or childhood, often triggered by respiratory infections. Case presentation: We report the case of 16-month-old male diagnosed with CCHS following an episode of hypoxemic–hypercapnic respiratory failure during respiratory syncytial virus (RSV) infection. His medical history included neonatal respiratory distress requiring oxygen therapy and recurrent wheezing. At 15 months, he developed acute respiratory distress with severe hypercapnia (PaCO2 70 mmHg), requiring admission to the Pediatric Intensive Care Unit and invasive mechanical ventilation. Persistent sleep-related hypercapnia and hypoxemia prompted evaluation for central hypoventilation, confirmed by means of transcutaneous capnography and nocturnal pulse oximetry. Genetic testing revealed a de novo nonsense mutation in exon 1 of PHOX2B (p.Tyr14Ter). Brain magnetic resonance imaging showed diffuse white matter changes suggestive of gliosis. Further investigations identified early-onset systemic hypertension, requiring antihypertensive therapy. The patient was discharged on nocturnal non-invasive ventilation and enrolled in a neurodevelopmental rehabilitation program. Conclusions: This case highlights the phenotypic variability of CCHS and the importance of considering this diagnosis in children presenting with unexplained hypercapnia and sleep-related hypoxemia. It underscores the need for comprehensive autonomic evaluation, including blood pressure monitoring. The p.Tyr14Ter variant may allow partial protein function, potentially accounting for the relatively mild phenotype.

This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3–7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non–COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non–COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non–COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in Faecalibacterium , Fusobacterium , and Neisseria and reduced in Bifidobacterium , Blautia , Ruminococcus , Collinsella , Coprococcus , Eggerthella , and Akkermansia , compared with CTRLs ( p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non–COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort ( p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella , Clostridium , Dialister , Ruminococcus , and Streptococcus and a decrease of Bifidobacterium , Blautia , Granulicatella , and Prevotella , compared with CTRLs. Stratifying for disease severity, the GM associated to “moderate” COVID-19 was characterized by lower α-diversity compared with “mild” and “asymptomatic” and by a GM profile deprived in Neisseria , Lachnospira , Streptococcus , and Prevotella and enriched in Dialister , Acidaminococcus , Oscillospora , Ruminococcus , Clostridium , Alistipes , and Bacteroides. The ML models identified Staphylococcus , Anaerostipes , Faecalibacterium , Dorea , Dialister , Streptococcus , Roseburia , Haemophilus , Granulicatella , Gemmiger , Lachnospira , Corynebacterium , Prevotella , Bilophila , Phascolarctobacterium , Oscillospira , and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)–based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients’ GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2–infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19–related GM.

Background Preschool wheezing and mild asthma are among the most frequent chronic respiratory conditions in children. These conditions can significantly affect quality of life, be associated with wheeze exacerbations, and predispose to persistent airway disease. Early recognition and tailored management are crucial to prevent long-term morbidity. Objective This Expert Opinion paper aims to translate the 2025 Global Initiative for Asthma (GINA) Strategy Report into the Italian clinical context, providing guidance for early recognition, risk stratification, and personalized management of pediatric patients with wheezing and mild asthma. Content The paper discusses the heterogeneity of preschool wheezing phenotypes and the emerging concept of “pre-asthma”, highlighting the prognostic role of biomarkers such as blood eosinophils, fractional exhaled nitric oxide (FeNO), and early aeroallergen sensitization in predicting disease persistence. It also addresses the impact of early-life wheezing on lung function trajectories, challenges in defining mild asthma, and the rationale for stepwise treatment strategies according to age. Particular emphasis is placed on practical aspects of care, such as the use of low dose of inhaled corticosteroids (ICS), suboptimal adherence to therapy, inhaler misuse, the benefits of dose counters to avoid pseudo-adherence, and the importance of caregiver education and shared decision-making in inhaler selection. Summary Applying GINA 2025 principles through individualized, biomarker-informed, and education-based strategies can improve outcomes in children with early or mild asthma, bridging the gap between evidence-based recommendations and usual pediatric care in Italy.