Respiratory syncytial virus prophylaxis and the "special population".

Bronchiolitis is the most frequent airway infection in the first 2 years of life, and the respiratory syncytial virus (RSV) is the most frequently responsible virus. In selected high-risk groups, RSV may cause severe respiratory disease leading to hospitalization, need for mechanical ventilation, and even death. These high-risk groups include children with congenital heart disease, infants with neuromuscular impairment, cystic fibrosis, Down Syndrome, immunodeficiency syndromes and others specific conditions. In these high-risk populations defined in literature as "special population", a 3- to 10-fold increase in the rate of RSV hospitalization has been observed, justifying RSV specific prophylaxis with palivizumab, a monoclonal antibody that binds a viral glycoprotein epitope and blocks the link between RSV and target cell. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomized clinical trials are not feasible. The purpose of this paper is to give an update from the literature of various conditions at higher risk to develop severe RSV infection, and to offer an overview of the efficacy of palivizumab in preventing RSV infection in these specific populations.

Retrocardiac Pneumomediastinum: Description of an Unusual Case and Review of Literature.

Retrocardiac pneumomediastinum (RP) is the consequence of air trapping in the inferior and posterior mediastinum. It is characterized by the presence of a right or left para-sagittal infrahilar oval or pyramidal air collection on a chest X-ray. It is usually detected in neonates because of alveolar rupture after invasive ventilation or invasive manoeuvres applied on airways or the digestive tract. A healthy child came to the emergency department (ED) for acute respiratory failure due to viral bronchiolitis when he was 2 months old. Because of his clinical condition, he underwent helmet continuous positive airway pressure (HCPAP). When the condition allowed, he was discharged and sent home. He was re-admitted into the hospital for asthmatic bronchitis 3 months later. A frontal chest X-ray taken during the second hospitalization showed an oval-shaped retrocardiac air lucency not previously detected. Differential diagnosis including digestive and lung malformations was made. Finally, the diagnosis of RP was made. We report an unusual case of retrocardiac pneumomediastinum in a 5-month-old male infant after the application of continuous positive pressure via a helmet. RP presentation after the administration of non-invasive ventilatory support beyond the neonatal age is unusual. Although surgical drainage is curative, conservative treatment can be considered in hemodynamically stable patients.

Severe Pediatric Asthma Therapy: Mepolizumab.

There is a growing need for advanced treatment in children with persistent and severe asthma symptoms. As a matter of fact, between 2 and 5% of asthmatic children experience repeated hospitalizations and poor quality of life despite optimized treatment with inhaled glucocorticoid plus a second controller. In this scenario, mepolizumab, a humanized monoclonal antibody, has proven to be effective in controlling eosinophil proliferation by targeting interleukin-5 (IL-5), a key mediator of eosinophil activation pathways. Mepolizumab is approved since 2015 for adults at a monthly dose of 100 mg subcutaneously and it has been approved for patients ≥ 6 years of age in 2019. Especially in children aged 6 to 11 years, mepolizumab showed a greater bioavailability, with comparable pharmacodynamics parameters as in the adult population. The recommended dose of 40 mg every 4 weeks for children aged 6 through 11 years, and 100 mg for patients ≥ 12 years provides appropriate concentration and proved similar therapeutic effects as in the adult study group. A marked reduction in eosinophil counts clinically reflects a significant improvement in asthma control as demonstrated by validated questionnaires, reduction of exacerbation rates, and the number of hospitalizations. Finally, mepolizumab provides a safety and tolerability profile similar to that observed in adults with adverse events mostly of mild or moderate severity. The most common adverse events were headache and injection-site reaction. In conclusion, mepolizumab can be considered a safe and targeted step-up therapy for severe asthma with an eosinophilic phenotype in children and adolescents.

E-cigarette or Vaping product use Associated Lung Injury (EVALI) in a 15 year old female patient - case report.

BACKGROUND: E-cigarettes are devices which allow to aerosolize liquids containing nicotine or other substances. Ever since they were released on the market in 2006, the number of users have been constantly increasing, especially among adolescents, ranging from 7,6% to 9,3% in the age group 18-24 years old from 2014 to 2019. Hand in hand with the spread of E-cigarettes many have been the efforts to understand their impact on health. EVALI (E-cigarette or Vaping product use Associated Lung Injury) is an emerging condition with a heterogeneous presentation with several reported cases worldwide. We mean to report a case of EVALI in a 15-year-old female Caucasian patient, who's currently attending her clinic follow-up at Bambino Gesù Pediatric Hospital in Rome. CASE PRESENTATION: The patient was admitted to the Emergency Room due to acute respiratory failure in November 2020. At admittance, she was severely dyspneic (HR 120 bpm, SatO2 75%). As she was hospitalized amid the COVID-19 pandemics, she underwent a nasopharyngeal swab for SARS-CoV2, which turned out negative, and a chest CT scan. Chest CT scan showed a central ground grass pattern with peripheral sparing. At the anamnestic recall, it was disclosed she was an e-cigarette smoker and occasional marijuana user. The microbiological work-up proved only positive for Rhinovirus. Her clinical and radiological case was discussed with our radiologist who suspected EVALI. She was assisted through HFNC, antibiotical therapy and corticosteroids with a dramatic recovery within the first 48 h. CONCLUSIONS: EVALI started being recognized a specifically nosological entity in summer 2019, with increasing cases being reported. No diagnostic criteria have been agreed upon yet, but its usual presentation includes respiratory, gastrointestinal and systemic symptoms of different degree and the diagnosis can be hypothesised in case the patient has an evocative clinical and radiological presentation and has been an E-cigarette smoker in previous 90 days. Due to the novelty of the condition and its heterogeneous presentation it is of interest to report the cases in which EVALI is identified to raise awareness about this emerging new-age disease.

Hypoventilation and sleep hypercapnia in a case of congenital variant-like Rett syndrome.

BACKGROUND: Breathing disturbances are often a primary clinical concern especially during wakefulness of the classic form of Rett syndrome, but data for atypical forms are lacking. CASE PRESENTATION: We report the case of a 20-month-old female affected by Rett syndrome with congenital variant-like onset, characterized by severe hypotonia and neurodevelopment impairment. She presented hypoventilation, persistent periodic breathing, and sustained desaturation during sleep, without obstructive or mixed events. Pulse oximetry and capnography during wakefulness were strictly normal. To the best of our knowledge, this is the first case of a patient affected by a congenital variant of Rett syndrome presenting sleep hypercapnia. 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. CONCLUSIONS: Thus, we suggest screening patients with congenital-like Rett syndrome through transcutaneous bedtime carbon dioxide and oxygen monitoring. Moreover, assisted control mode was a breakthrough to achieve adequate ventilation in our case.

Telemedicine in children with medical complexity on home ventilation during the COVID-19 pandemic.

Children with medical complexity (CMC) are patients with one or more complex chronic conditions dependent on medical technologies. In our unit (Pediatric Pulmonology and Respiratory Intermediate Care Unit, Department of Pediatrics, "Bambino Gesù" Children's Hospital and Research Institute), we regularly follow-up CMC patients, particularly children on long-term, invasive (IMV) or noninvasive (NIV), ventilation. Children suffering from chronic diseases and with medical complexity have lost the possibility to go to the hospital during the COVID-19 pandemic. The aim of this article is to describe our experience with telemedicine (teleconsultation [TC] and telemonitoring of ventilator [TM]) in CMC on ventilation. We presented 21 children on long-term ventilation (NIV or IMV) whose planned hospital admission was postponed due to lockdown. A total of 12 healthcare problems were detected during scheduled TCs. Only one problem was not solved by our remote intervention. Specifically, TM has allowed us to change the ventilator parameters and to monitor patients on ventilation remotely. In conclusion, the use of telemedicine in CMC ventilated patients resulted in a feasible tool to avoid in-person visits during the pandemic.

Effects of the COVID-19 pandemic and lockdown on symptom control in preschool children with recurrent wheezing.

INTRODUCTION: Preschool wheezers are at high risk of recurrent attacks triggered by respiratory viruses, sometimes exacerbated by exposure to allergens and pollution. Because of the COVID-19 infection, the lockdown was introduced, but the effects on preschool wheezers are unknown. We hypothesized that there would be an improvement in outcomes during the lockdown, and these would be lost when the lockdown was eased. MATERIALS AND METHODS: Patients underwent medical visits before and after the COVID-19 lockdown. We recorded the childhood Asthma Control Test (cACT) and a clinical questionnaire. Data on symptoms, the need for medications and the use of healthcare resources were recorded. We compared these data with retrospective reports from the preceding year and prospectively acquired questionnaires after lockdown. RESULTS: We studied 85 preschool wheezers, mean age 4.9 years. During the lockdown, cACT score was significantly higher (median 25 vs. 23); families reported a dramatic drop in wheezing episodes (51 vs. none), significant reductions in the day and nighttime symptoms, including episodes of shortness of breath (p < .0001); the use of salbutamol and oral corticosteroids (OCS) dropped significantly (p < .0001) and 79 (95%) patients needed no OCS bursts during the lockdown. Finally, patients had significantly fewer extra medical examinations, as well as fewer Emergency Room visits (p < .0001). All were improved compared with the same time period from the previous year, but outcomes worsened significantly again after lockdown (cACT median: 22). CONCLUSIONS: During the national lockdown, children with persistent preschool wheeze showed a significant clinical improvement with reduction of respiratory symptoms, medication use for exacerbations, and use of healthcare resources. This trend reversed when lockdown restrictions were eased.

Transition to Adult Care in Children on Long-Term Ventilation.

The number of children on long-term ventilation (LTV) has exponentially increased over the past few decades. Improvements in management of ventilation coupled with improvements in standards of medical care are increasingly allowing young people on LTV to survive into adulthood. The process of transition from the pediatric to the adult healthcare system is challenging and requires special attention. This review aims to provide an overview on transition to adult care for children on LTV. Firstly, examining effective models of transition in other childhood onset chronic conditions as a template, whilst highlighting the unique aspects of transition in LTV patients and secondly, summarizing the main relevant findings in the literature on the topic and emphasizing the importance of a multidisciplinary approach to this process.

Ventilators and Ventilatory Modalities.

Non-invasive ventilation is increasingly used in children for acute and chronic respiratory failure. Ventilators available for clinical use have different levels of complexity, and clinicians need to know in detail their characteristics, setting variables, and performances. A wide range of ventilators are currently used in non-invasive ventilation including bi-level ventilators, intermediate ventilators, and critical care ventilators. Simple or advanced continuous positive airway pressure devices are also available. Differences between ventilators may have implications on the development of asynchronies and air leaks and may be associated with discomfort and poor patient tolerance. Although pressure-targeted (controlled) mode is preferable in children because of barotrauma concerns, volume-targeted (controlled) ventilators are also available. Pressure support ventilation represents the most used non-invasive ventilation mode, as it is more physiological. The newest ventilators allow the clinicians to use the hybrid modes that combine the advantages of volume- and pressure-targeted (controlled) ventilation while limiting their drawbacks. The use of in-built software may help clinicians to optimize the ventilator setting as well as to objectively monitor patient adherence to the treatment. The present review aims to help the clinician with the choice of the ventilator and its ventilation modalities to ensure a successful non-invasive ventilation program.

Characteristics and outcomes in children on long-term mechanical ventilation: the experience of a pediatric tertiary center in Rome.

BACKGROUND: Children with chronic respiratory failure and/or sleep disordered breathing due to a broad range of diseases may require long-term ventilation to be managed at home. Advances in the use of long-term non-invasive ventilation has progressively leaded to a reduction of the need for invasive mechanical ventilation through tracheostomy. In this study, we sought to characterize a cohort of children using long-term NIV and IMV and to perform an analysis of those children who showed significant changes in ventilatory support management. METHODS: We performed a retrospective cohort study of pediatric (within 18 years old) patients using long-term, NIV and IMV, hospitalized in our center between January 1, 2000 and December 31, 2017. A total of 432 children were included in the study. Long Term Ventilation (LTV) was defined as IMV or NIV, performed on a daily basis, at least 6 h/day, for a period of at least 3 months. RESULTS: 315 (72.9%) received non-invasive ventilation (NIV); 117 (27.1%) received invasive mechanical ventilation (IMV). Children suffered mainly from neuromuscular (30.6%), upper airway (24.8%) and central nervous system diseases (22.7%). Children on IMV were significantly younger when they start LTV [NIV: 6.4 (1.2-12.8) years vs IMV 2.1 (0.8-7.8) years] (p < 0.001)]. IMV was likely associated with younger age at starting ventilatory support (aOR 0.9428; p = 0.0220), and being a child with home health care (aOR 11.4; p < 0.0001). Overtime 39 children improved (9%), 11 children on NIV (3.5%) received tracheostomy; 62 children died (14.3%); and 74 children (17.1%) were lost to follow-up (17.8% on NIV, 15.4% on IMV). CONCLUSIONS: Children on LTV suffered mainly from neuromuscular, upper airways, and central nervous system diseases. Children invasively ventilated usually started support younger and were more severely ills.

Built-in software in children on long-term ventilation in real life practice.

Information gathered with built-in software (BIS) on new ventilators allow clinicians to access long-term noninvasive ventilation (LTNIV) data. Nevertheless, few evidence are available in literature that highlight potential strengths and disadvantages of using BIS in pediatrics. We aim to evaluate the use of BIS in a cohort of 90 children on LTNIV in our unit, focusing mainly on adherence, air leaks, and residual sleep events. We found that caregivers' perception of ventilator use is independent from objective adherence (P = .137). Furthermore, we failed to find any predictors of adherence. As regards air leaks, we found that pre-scholars' (0-6 years old) total air leaks are lower than teenagers' (more than 12 years old) (P < .05). Multiple regressive analysis showed that age at the beginning of therapy is a predictor of total air leaks: prescholars are associated with lower values (P < .05), while scholars (6-12 years old) are associated with higher values (P < .05). Finally, we explored the validity of BIS automatic scoring of sleep events (AHIBIS ) as compared with the manual scoring of polygraphy (AHIPG ). AHIBIS is within a range of 3.98 from AHIPG in 95% of cases, with a 64% of sensitivity and a 67% of specificity in identifying a pathological state. The disagreement between the two methods seems to increase for high AHI values. In conclusion, data gathered by BIS are a useful support tool for the clinician in assessing the course of LTNIV. However, clinicians must be aware of the several limitations of built-in software, especially in pediatrics.

Transition to adult care in young people with neuromuscular disease on non-invasive ventilation.

BACKGROUND: Long-term mechanical ventilation (LTV) with non-invasive ventilation (NIV) prolongs survival in patients with Neuromuscular Diseases (NMDs). Transition from paediatric to adult healthcare system is an undervalued and challenging issue for children with chronic conditions on mechanical ventilation. METHODS: this retrospective study aims to compare issues of young adults in age to transition to adult care (≥ 15 years old) affected by NMDs on NIV in two different Paediatric Respiratory Units in two different countries: Bambino Gesù Children's Hospital, Research Institute, (Rome, Italy) (BGCH) and the Paediatric Respiratory Unit of the Royal Brompton Hospital (London, UK) (RBHT). RESULTS: The median (min-max) age at starting ventilation was significantly different in the two groups (16 years old vs 12, p = 0.0006). We found significant difference in terms of median age at the time of observation (18 (15-22) vs 17 (15-19) years, p = 0.0294) and of type of referral (all the patients from the BGCH group were referred to paediatric services (n = 15, 100%), median age 18 (15-22); only 6 patients, in the RBHT group, with a median age 15.50 (15-17) years, were entirely referred to paediatric service). We found different sleep-disordered breathing assessments 6 full Polysomnographies, 7 Cardio-Respiratory Polygraphies and 2 oximetry with capnography (SpO2-tcCO2) studies in the BCGH group, while all patients of RBHT group were assessed with an SpO2-tcCO2 study. All patients from both groups underwent multidisciplinary assessment. CONCLUSIONS: In conclusion, patients with NMDs on NIV in age to transition to adult require complex multidisciplinary management: significant efforts are needed to achieve the proper transition to adult care.

Asthma: Differential Diagnosis and Comorbidities.

Childhood asthma remains a multifactorial disease with heterogeneous clinical phenotype and complex genetic inheritance. The primary aim of asthma management is to achieve control of symptoms, in order to reduce the risk of future exacerbations and progressive loss of lung function, which results especially challenging in patients with difficult asthma. When asthma does not respond to maintenance treatment, firstly, the correct diagnosis needs to be confirmed and other diagnosis, such as cystic fibrosis, primary ciliary dyskinesia, immunodeficiency conditions or airway and vascular malformations need to be excluded. If control remains poor after diagnostic confirmation, detailed assessments of the reasons for asthma being difficult-to-control are needed. Moreover, all possible risk factors or comorbidities (gastroesophageal reflux, rhinosinusitis, dysfunctional breathing and/or vocal cord dysfunction, obstructive sleep apnea and obesity) should be investigated. At the same time, the possible reasons for poor symptom control need to be find in all modifiable factors which need to be carefully assessed. Non-adherence to medication or inadequate inhalation technique, persistent environmental exposures and psychosocial factors are, currently, recognized as the more common modifiable factors. Based on these premises, investigation and management of asthma require specialist multidisciplinary expertise and a systematic approach to characterizing patients' asthma phenotypes and delivering individualized care. Moreover, since early wheezers are at higher risk of developing asthma, we speculate that precocious interventions aimed at early diagnosis and prevention of modifiable factors might affect the age at onset of wheezing, reduce the prevalence of persistent later asthma and determine long term benefits for lung health.

Predictive value of circulating insulin-like growth factor I levels in ischemic stroke outcome.

CONTEXT: Cerebrovascular disease is highly prevalent in the general population, frequently leading to permanent invalidity and reduced quality of life. IGF-I is recognized as an important neuroprotective factor against cerebral hypoxic insult. OBJECTIVE: The objective of the study was to evaluate pituitary function, in particular GH-IGF-I axis, in adult patients receiving rehabilitation after an ischemic stroke. SUBJECTS AND METHODS: We studied 42 patients (12 females; age range, 50-88 yr) during rehabilitation after stroke, evaluating the relationship between the GH-IGF-I axis and the severity (National Institutes of Health stroke scale) and outcome [Rancho Los Amigos Scale of Cognitive Functioning (LCFS); Functional Independence Measure (FIM); modified Ranking Scale] from stroke. RESULTS: GH deficiency was demonstrated in five patients (11.9%). Peak GH after GHRH + arginine test and IGF-I levels did not correlate with severity of stroke. IGF-I was positively correlated with LCFS (r = 0.305, P < 0.05) and the difference between FIM on admission and at discharge from rehabilitation (DeltaFIM; r = 0.361, P < 0.02). Outcome indexes (LCFS, FIM at discharge, DeltaFIM) and occurrence of favorable outcome (modified Ranking Scale 0-1) were significantly (P < 0.05) higher in patients with IGF-I levels 161.8 mug/dl or greater (50th percentile of the patient distribution). LH-FSH deficiency (three cases), ACTH deficiency (one case), and hyperprolactinemia (two cases) were detected. One patient had primary hypogonadism, and six males had low testosterone with normal LH and FSH levels. By multivariate analysis, IGF-I level was the main significant predictor of DeltaFIM and LCFS. CONCLUSIONS: Ischemic stroke may be associated with pituitary dysfunction, particularly GH and gonadotropin deficiencies. The higher IGF-I levels observed in patients with better outcome suggest a possible neuroprotective role of IGF-I. Circulating IGF-I may predict functional performance during rehabilitation and ischemic stroke outcome.

Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P<.05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity<1) was detected in 2 of 6 patients with gigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (P<.05) higher in patients with gigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a longer period.

Opposite behavior of plasma levels surfactant protein type B and receptor for advanced glycation end products in pulmonary sarcoidosis.

BACKGROUND: No biological marker is currently available for evaluating pulmonary involvement and/or for monitoring the clinical course of sarcoidosis. The present pilot study focused on possible relationships between circulating plasma levels of surfactant protein type B (SP-B) and plasma receptor for advanced glycation end products (RAGE) and lung function abnormalities in patients with pulmonary sarcoidosis, since both SP-B and RAGE have been previously suggested as lung injury markers. The plasmatic levels of these two proteins were also investigated with respect to functional capacity, as assessed by a cardiopulmonary exercise test (CPET). METHODS: Thirty pulmonary sarcoidosis outpatients and fifteen volunteers (Control Group) underwent lung function tests and CPET. Resting SP-B and RAGE plasma levels were also determined. Patients were then categorized according to the severity of their pulmonary involvement, as assessed in terms of lung diffusion for carbon monoxide (DLCO) values. RESULTS: Group B showed SP-B levels higher and RAGE levels lower than Group A and Control Group (p < 0.01). Group A showed lower RAGE levels than Control Group (p < 0.01), whereas SP-B levels did not differ between these two groups. A significant univariate relationship was found between both SP-B and RAGE and several lung function data, particularly with DLCO (SP-B Vs DLCO: r: -0.437, p = 0.016; RAGE Vs DLCO: r: -0.451, p = 0.012). CONCLUSIONS: Circulating plasma levels of SP-B and RAGE showed an opposite behavior in patients with pulmonary sarcoidosis. SP-B values are directly related to alveolar unit damage, supporting a possible role of SP-B as a marker of disease severity in these patients. Differently, RAGE decreases in severe sarcoidosis, suggesting more complex underlying mechanisms.

NT-proatrial natriuretic peptide as a possible biomarker of cardiopulmonary involvement in sarcoidosis.

BACKGROUND: Lung diffusion for carbon monoxide (DLCO) has been shown to associate with the risk of pulmonary arterial hypertension development and, most likely, with right ventricular (RV) myocardial dysfunction in sarcoidosis patients. Besides its known role as a marker of left ventricular dysfunction, experimental evidence suggests a role of NT-proAtrial Natriuretic Peptide (NT-proANP) also in modulating pulmonary circulation. We therefore investigated possible relationships between NT-proANP, lung diffusion impairment and RV dysfunction. METHODS: Thirty-two pulmonary sarcoidosis outpatients and eighteen volunteers underwent full clinical assessment, including full lung function tests and Doppler echocardiography integrated with tissue Doppler imaging (TDI) study. Resting circulating NT-proBNP and NT-proANP plasma levels were also determined. RESULTS: NT-proANP and RV-myocardial performance index (RV-MPI) were significantly higher in those patients with the greatest DLCO impairment, whereas no differences were found for NT-proBNP values. At multivariable analysis, only DLCO (ß: -0.496; standard error: 3.38; p=0.000) and RV-MPI (ß: 0.373; standard error: 6.56; p=0.031) remained significantly associated with NT-proANP levels. CONCLUSIONS: Our finding may support a key role of NT-proANP in the complex mechanisms underlying modulation of lung function. An early increase in pulmonary vascular resistance may stimulate NT-proANP increase, thus explaining its association with signs of early RV myocardial dysfunction. This hypothesis warrants further confirmation.