Background: Although, in most children with asthma, good symptom control is achieved with a low to moderate dose of inhaled corticosteroids, a small group of patients still experiences frequent symptoms, and even severe exacerbations, impairment of lung function, and reduced quality of life. Some of these subjects with severe asthma require biologic drugs as add-on therapy. In the past decade, numerous monoclonal antibodies have been approved for children or adolescents with severe asthma, in addition to their increasing use in adult asthma. However, the available evidence on how to select the most appropriate biologic based on a single patient’s clinical, functional, and laboratory characteristics is still scant, and is insufficient to guide clinicians in the decision-making process of a personalized treatment. Materials and Methods: We report a case series of four patients with severe eosinophilic asthma treated with mepolizumab, an anti-interleukin-5 monoclonal antibody, and review the existing literature on this treatment in children and adolescents. Results: Our patients, all with blood eosinophilia and elevated fractional exhaled nitric oxide levels, developed poor symptom control despite prolonged treatment with high-dose inhaled corticosteroids plus a second controller, addressing the addition of a biologic drug. In all of them, a 12-month treatment with subcutaneous mepolizumab showed a reduction in the blood eosinophil count and in asthma exacerbations, as well as an improvement on the Asthma Control Test. The results of the literature search focused on the strengths and limitations of the pediatric use of mepolizumab and highlighted the areas worthy of further research. Conclusions: Mepolizumab has proven effective in improving symptom control in pediatric patients with severe asthma. Additional well-powered clinical trials will be helpful in developing evidence-based guidelines regarding biologic drugs in the pediatric population.

Background: Rett syndrome (RS) is a rare neurodevelopmental disorder primarily affecting females, characterized by severe neurological impairment and complex comorbidities, including epilepsy, scoliosis, and respiratory dysfunction. Respiratory complications, such as recurrent infections and sleep-disordered breathing (SDB), are increasingly recognized as significant contributors to morbidity. This study aimed to evaluate the prevalence, severity, and management of major comorbidities—including epilepsy, scoliosis, respiratory infections, and SDB—in a pediatric cohort with genetically confirmed RS. Methods: We conducted a retrospective review of medical records from 23 female patients under 18 years of age with MECP2 mutations, referred to our tertiary care center from 2021 to 2025. Data on epilepsy, scoliosis, respiratory infections, and nutritional status were collected. The presence of SDB was assessed through overnight home polygraphy (oPG) and transcutaneous carbon dioxide monitoring in selected cases. Results: Epilepsy affected 65% of patients, all with good seizure control. Scoliosis was present in 52%, with two patients requiring spinal surgery. At least one episode of lower respiratory tract infection (LRTI) was presented in 39% of our girls. LRTIs positively correlated with the number of hospitalization and antibiotic treatment. Among patients undergoing oPG, 67% presented obstructive sleep apnea, with its severity positively correlating with the frequency of lower respiratory infections. Severe nocturnal hypercapnia was documented in three patients, leading to non-invasive or invasive ventilation. Conclusions: Our findings highlight the high prevalence of sleep-related respiratory disorders and their association with respiratory infections in children with RS. Systematic respiratory assessment, including sleep studies, and early implementation of airway clearance techniques and ventilatory support are crucial to improving clinical outcomes in this vulnerable population.