Bronchiolitis guidelines: what about the Italian situation in a primary care setting?

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 ß2-agonists, systemic steroids, and antibiotics which are commonly prescribed by PCPs to address conditions that can mimic bronchiolitis.

Pediatric airway compression in aortic arch malformations: a multidisciplinary approach.

Background: Aortic arch malformations (AAMs) should be suspected in the presence of persistent respiratory symptoms despite medical treatment or feeding problems at the pediatric age. Aim: We report a descriptive cohort of patients with AAMs and the local management protocol applied. Methods: A total of 59 patients with AAM were retrospectively reviewed. Three groups were identified: double aortic arch (DAA), group 1; complete vascular ring (non-DAA), group 2; and anomalous origin of the innominate artery (IA), group 3. Results: Prenatal diagnosis was available for 62.7% of the patients. In all, 49.2% of children were symptomatic. There was a significantly different prevalence of respiratory symptoms within the three groups: 73.7% in group 1, 24.2% in group 2, and 100% in group 3 (p-value: <0.001). Surgery was considered in the presence of symptoms in patients with DAA and in those with reduction of the tracheal section area greater than 50%. A total of 52.5% of the patients underwent surgical repair (median age 6 months). The median follow-up interval was 21.9 months. Respiratory symptoms improved in most symptomatic patients. Conclusions: No specific protocols are available for the management of patients with AAMs. Conservative treatment seems to be reasonable for asymptomatic patients or those with airway stenosis less than 50%. A close follow-up is necessary to identify early patients who become symptomatic.

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 asthma guidelines in children and adolescents: A practical document for physicians.

Asthma is a common disease in childhood with a minority of affected children suffering from severe asthma. Patients with severe asthma require high dose inhaled glucocorticoids plus a second controller and/or systemic corticosteroids to be well-controlled or remain uncontrolled despite such treatment. Although only a small subset of children and adolescents falls in this category, the management of affected patients represents a major concern for pediatricians. Guidelines and recommendations have been designed to guide the management of this group of patients. Though the terms "recommendations" and "guidelines" are often used interchangeably, it should be noted that the first one should be used more narrowly to identify specific actions and the second one to broadly refer to the umbrella under which multiple recommendations for a specific condition are provided. Moreover, the availability of several and sometimes-conflicting documents on severe asthma management both in adult and pediatric age could generate confusion among health care professionals. The manuscript analyses seven papers addressing severe asthma, comparing any key aspects and differences. Finally, we tried to create a more practical document for physicians to simplify the interpretation of the several available documents on severe asthma management focusing the pediatric age.

Long term respiratory morbidity in patients with vascular rings: a review.

Abnormalities in position and/or branching of the aortic arch can lead to vascular rings that may cause narrowing of the tracheal lumen due to external compression, or constriction of the oesophagus, causing symptoms that vary in relation to the anatomical vascular pattern and the relationship between these structures. Respiratory morbidity related to external airways compression is a major concern in children affected by vascular rings. Clinical presentation depends on the severity of the tracheal lumen reduction and the presence of associated tracheomalacia. Recurrent respiratory infections, wheezing, atelectasis, and hyperinflation are mostly reported. As they are nonspecific and therefore difficult to recognize, attention should be given to all children with history of respiratory distress, extubation failure, noisy breathing, and recurrent respiratory infections. Early diagnosis and referral to specialized centres can prevent the long-term complications and improve the respiratory outcomes of these patients.

Long-Term Ventilation in Children with Medical Complexity: A Challenging Issue.

Children with medical complexity (CMCs) represent a subgroup of children who may have congenital or acquired multisystemic disease. CMCs are frequently predisposed to respiratory problems and often require long-term mechanical ventilation (LTMV). The indications for LTMV in CMCs are increasing, but gathering evidence about indications, titration, and monitoring is currently the most difficult challenge due to the absence of validated data. The aim of this review was to examine the clinical indications and ethical considerations for the initiation, continuation, or withdrawal of LTMV among CMCs. The decision to initiate long-term ventilation should always be based on clinical and ethical considerations and should be shared with the parents.

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.

Noncystic fibrosis bronchiectasis in children and adolescents: Follow-up over a decade.

BACKGROUND: Noncystic fibrosis bronchiectasis (NCFB) is still considered an "orphan disease" in pediatric age. OBJECTIVE: The study describes the clinical and functional features, the instrumental, and microbial findings of a large cohort of patients with NCFB, followed in a single tertiary level hospital. METHODS: Children and adolescents diagnosed with NCFB from January 1, 2010 to December 31, 2019 were included. Data from the diagnosis and during the years of follow-up were recorded retrospectively. RESULTS: One hundred and thirty-eight patients were enrolled. The most common cause of NCFB was postinfectious (33%), followed by primary ciliary dyskinesia (PCD) (30%), esophageal atresia (EA) (9.5%), and secondary immunodeficiency (9.5%). Chronic cough was the most frequent symptom. The median age of symptoms presentation was 3 years (interquartile age [IQR]: 12-84), with a precocious onset in PCD and EA groups. The median age of CT diagnosis was 9 years for all groups but PCD patients who were diagnosed at older age. Lingula, medium, upper, and lower lobes were more involved in PCD group, while diffuse distribution was observed in the postinfectious one. Microbial exams showed Pseudomonas aeruginosa colonization higher in PCD patients (22%). Despite microbial differences in airways colonization, no difference in respiratory exacerbation rate was recorded among groups. Lung function tests demonstrated the stability of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) over time, except for the secondary immunodeficiency group. CONCLUSIONS: The role of infections in developed countries should not be underestimated and a major effort to obtain an earlier identification of bronchiectasis should be taken. A prompt diagnosis of NFCB could help to reduce the frequency of exacerbations and improve the stability of lung function over time.

How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center.

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disorder whose clinical phenotype is closely related to genotype. Methods: A retrospective analysis has been conducted on 22 patients with CCHS, who were referred to the Pediatric Pulmonology and Respiratory Intermediate Care Unit of Bambino Gesù Children's Hospital (Italy) for a multidisciplinary follow-up program between 2000 and 2020. Results: Apnea and cyanosis were the most frequent symptoms at onset (91%). Overall, 59% of patients required tracheostomy and invasive mechanical ventilation (IMV) in the first months of life. Thirty-two percent of patients had Hirschsprung disease (HSCR) that was associated with longer polyalanine repetitions or non-polyalanine repeat expansion mutations (NPARMs). Polyalanine repeat expansion mutations (PARMs) were more frequent and two novel NPARMs (c.780dupT and C.225-256delCT) were described in 14% of patients. Focal epilepsy was first described in 14% of patients and neurocognitive and neuromotor impairment involved 27% and 23% of children, respectively. Symptoms due to autonomic nervous system dysfunction/dysregulation (ANSD)-including strabismus (27%), dysphagia (27%), abnormal heart rhythm (10%), breath-holding spells (9%), and recurrent seizures due to hypoglycemia (9%)-were associated with an increased number of polyalanine repetitions of exon 3 or NPARMs of PHOX2B gene. Overall, the number of patients with moderate to severe phenotype initially treated with non-invasive ventilation (NIV) increased over time, and the decannulation program was concluded with 3 patients who started with IMV. Conclusions: Our study confirms that more severe phenotypes of CCHS are related to the number of polyalanine repetitions or to NPARMs. Although invasive ventilation is often required by patients with severe genotype/phenotype, gradual acquisition of specific skills in the management of patients with CCHS and technological improvements in mechanical ventilation allowed us to improve our therapeutic approach in this population.

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.

Difficult and Severe Asthma in Children.

Asthma is the most frequent chronic inflammatory disease of the lower airways affecting children, and it can still be considered a challenge for pediatricians. Although most asthmatic patients are symptom-free with standard treatments, a small percentage of them suffer from uncontrolled persistent asthma. In these children, a multidisciplinary systematic assessment, including comorbidities, treatment-related issues, environmental exposures, and psychosocial factors is needed. The identification of modifiable factors is important to differentiate children with difficult asthma from those with true severe therapy-resistant asthma. Early intervention on modifiable factors for children with difficult asthma allows for better control of asthma without the need for invasive investigation and further escalation of treatment. Otherwise, addressing a correct diagnosis of true severe therapy-resistant asthma avoids diagnostic and therapeutic delays, allowing patients to benefit from using new and advanced biological therapies.

Care recommendations for the respiratory complications of esophageal atresia-tracheoesophageal fistula.

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, and 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. Noninvasive 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.

Recurrent Wheezing in Pre-school Age: Not Only Airway Reactivity!

Background: About a fifth of all mediastinal masses are primary cysts arising in the absence of other underlying pathology. Bronchogenic cysts, although rare, are the most frequent type responsible for lower airways compression as they often develop in the peripheral branches of the tracheobronchial tree. Case presentation: We report the case of a 6-months-old child admitted for acute respiratory distress and wheezing not responsive to asthma treatment. Digestive and airway endoscopy proved a mild and a marked reduction of the esophageal and tracheal lumen, respectively. The nocturnal polygraphy showed an underlying obstructive disorder and the chest CT scan confirmed the presence of a wide mediastinal cyst compressing the trachea. The mass, later identified as a bronchogenic cyst, was surgically removed with complete resolution of the patient's respiratory symptoms. Discussion: Our case shows that differential diagnosis of wheezing in pre-school aged children should encompass causes others than airway reactivity, thus prompting further evaluation and management.

Frequency and Identification of Risk Factors of Uveitis in Juvenile Idiopathic Arthritis: A Long-term Follow-up Study in a Cohort of Italian Children.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood. The JIA-associated uveitis represents the most common extra-articular manifestation. OBJECTIVES: The main aim of this study was to evaluate frequency and risk factors of uveitis in a pediatric population affected by JIA. METHODS: One hundred eight Italian children with JIA were followed during a follow-up period of 13 years. Association between uveitis, antinuclear antibodies (ANAs), and subtype of arthritis has been estimated, and Kaplan-Meier curves were generated to assess the probability of ocular complications during the follow-up period. RESULTS: Twenty-one patients developed uveitis, after 96.5 ± 50.4 months from the enrollment. According to JIA subtypes, the oligoarthritis subtype was characterized by the highest prevalence (39%) of uveitis. The greatest risk of uveitis has been detected in oligoarthritis patients associated to ANA positivity (risk ratio, 8.6; 95% confidence interval, 2.27-32.9; χ = 20.4), whereas the worst evolution was revealed in patients with oligoarthritis and high levels of ANAs, with a progression time of 36 months (log-rank χ = 16.39; p < 0.0001; risk ratio, 18; 95% confidence interval, 7.3-44.2). CONCLUSIONS: Patients with early-onset ANA-positive oligoarticular JIA have the highest risk of developing uveitis. A routine ophthalmological follow-up is required at regular intervals, even though the joint disease is clinically quiescent.

Options of immunotherapeutic treatments for children with asthma.

Introduction: Asthma is the most common chronic disease in children. Avoiding triggers, and pharmacologic treatment with short acting beta-agonist, inhaler corticosteroids and anti-leukotriene are often enough to obtain symptoms control. Nevertheless, there is a subset of children with severe asthma and poor symptom control despite maximal therapy. In these patients, anti-IgE and anti-IL5 monoclonal antibodies are suggested as the fifth step of Global Initiative for Asthma guidelines. Area covered: Immunotherapeutic treatments are now suggested for asthma management. This article will discuss the available evidence on allergen immunotherapy and biologic drugs in pediatric asthma treatment. Expert opinion: Previously published studies demonstrated a good efficacy and safety profile of Allergen Immunotherapy in patients with mild-moderate asthma and sensitization to one main allergen. New understanding of mechanisms underlying severe asthma inflammation has allowed the identifications of specific biomarkers guiding the clinician in the choice of patient specific drug. Among the suggested immunotherapeutic options, omalizumab (blocking IgE) remains the first choice for atopic 'early onset' asthma in patients aged over 6 years. Instead, mepolizumab (blocking the IL5 ligand) should be considered for 'eosinophilic' asthma. Other biologic drugs are under consideration but data on the pediatric population are still lacking.

Decannulation in children affected by congenital central hypoventilation syndrome: A proposal of an algorithm from two European centers.

RATIONALE: Long-life ventilatory assistance is necessary for survival in pediatric patients with congenital central hypoventilation syndrome (CCHS). Invasive mechanical ventilation (IMV) through tracheostomy is the most used method, especially in the first years of life when the central nervous system is maturing. Nevertheless, IMV via tracheostomy is not ideal because tracheostomy in children is associated with impaired speech and language development, also frequent infections of the lower airway tract occur. OBJECTIVE: Only few reports describe the transition from IMV to the noninvasive method, ending with decannulation in CCHS affected patients. We aim to provide our experience regarding decannulation program in CCHS affected children and to describe a proposal of an algorithm concerning transition from invasive to noninvasive ventilation (NIV) in CCHS patients. METHODS: The study has been conducted retrospectively. Four children from two European centers underwent tracheostomy removal and decannulation, upon request of patients and their families. RESULTS: All children were trained to carry out tracheostomy capping before decannulation and underwent endoscopic assessment of upper and lower airway. Subsequently they started training to NIV at mean age of 106.25 months (±40.7 SD). Decannulation occurred 12 months after and no patients needed the reintroduction of tracheal cannula in either short or long term follow up. CONCLUSIONS: our study shows that effective liberation from IMV, the transition to NIV and decannulation are possible in CCHS affected children and offers a proposal of an algorithm which can be applied in selected centers.