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Background: Seasonal allergic rhinoconjunctivitis (SAR) is a worldwide health problem, especially in Westernized countries. Previous studies of the “Panallergens in Pediatrics” (PAN-PED) cohort found that molecular spreading (ie, the progressive increase in serum specific IgE antibody levels) of the IgE response to the grass pollen, Phleum pratense, molecules is directly associated with polysensitization to pollen in general.The research question is aimed at verifying whether this association can also be detected for non-pollen allergens, specifically Dermatophagoides pteronyssinnus (D.pt), to better understand the relationship between a perennial allergen (D.pt) and a seasonal allergen (Phleum pratense).To this end, our first objective was to analyze the biobank of the PAN-PED cohort serum by measuring the IgE levels to D.pt and its major recombinant molecules (Der p1, Der p2, Der p23); subsequently we investigated their correlation towards Phleum pratense IgE response, studying also the relationship between the molecular spreading of these 2 different allergens. Methods: Among 1120 patients positive to Phleum pratense, 638 were also sensitized to D.pt. Patients underwent skin prick tests (SPT) for inhalant extracts, and their serum was tested for total IgE (tIgE), and sIgE to pollen and perennial allergens. Considering the molecular allergen detection through the component resolved diagnosis (CRD), out of 638 patients, 146 were further investigated by performing IgE tests of the 3 major D.pt. molecules: Der p1, Der p2, and Der p23. Results: We found that a broader molecular response to Phleum pratense molecules, assessed by CRD, was associated with higher tIgE levels, polysensitization to pollens, and higher IgE levels to pollens, but also to lower IgE levels to D.pt and lower degree of sensitization to rDer p1, r Der p2, and rDer p23. In a multivariate linear model, the number of Phleum pratense molecules recognized by IgE was still inversely associated with the IgE level to D.pt extract. Conclusions: The main finding of this study was the detection of an inverse association, never described in the literature, between the molecular spreading of the IgE response to Phleum pratense and the IgE response to D.pt. This led us to speculate on the etiopathogenetic hypothesis according to which, among the majority of pollen allergic patients, a strong and molecularly diversified IgE response may be limited to pollen allergens and may be preventing or contrasting the development of an equally strong and diversified IgE sensitization to D.pt molecules. The biological mechanisms underlying this phenomenon deserve to be investigated.

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.

Non-cystic fibrosis bronchiectasis is an emergent disease characterized by endobronchial suppuration, dilated airways with neutrophilic inflammation and chronic wet cough due to recurrent lower airway infections. A regular clinical follow-up and adequate management of exacerbations are essential to reduce symptoms and the worsening of lung injury. We report a retrospective study comprising 15 children and adolescents with NCFB followed in our hospital center of pediatric pulmonology. We retrospectively analyzed the main comorbidities associated with the presence of NCFB, the radiological aspect associated with the different etiologies and the therapeutic approach used. We also emphasized the importance of an effective preventive strategy to reduce and prevent pulmonary exacerbations.

Chronic cough is defined as a daily cough that persists longer than 4 weeks. Protracted bacterial bronchitis (PBB) is a common cause of chronic wet cough in preschool children with no symptoms or signs of other specific causes, and resolution usually follows a 2-week course of an appropriate oral antibiotic. The diagnosis is mainly clinical; generally, no instrumental examinations are necessary. The most common bacteria found in the bronchoalveolar lavage (BAL) of subjects with PBB include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Nowadays, there is no certain evidence of the role of viruses in PBB pathogenesis even though different types of viruses have been detected in BAL from children with PBB. Airway malacia is commonly found in children with PBB; conversely, there is no correlation with any type of immunodeficiency. Amoxicillin-clavulanate acid is the most commonly used antibiotic, as first-line, prolonged therapy (longer than 2 weeks) is sometimes required to cough resolution. When the wet cough does not improve despite prolonged antibiotic treatment, an underlying disease should be considered. Moreover, there are several hypotheses of a link between PBB and bronchiectasis, as recent evidences show that recurrent PBB (>3 episodes/years) and the presence of H. influenzae infection in the lower airways seem to be significant risk factors to develop bronchiectasis. This underlines the importance of a close follow-up among children with PBB and the need to consider chest computerized tomography (CT) in patients with risk factors for bronchiectasis. In this brief review, we summarize the main clinical and pathogenetic findings of PBB, a disease that may be related to a relevant morbidity and decreased quality of life during the pediatric age.

The prevalence of food allergy is increasing over the last decades. The role of vitamin D in the prevention of food allergy has been largely investigated. Its role on the physiology of calcium and bone is known, but calcitriol (active form of the vitamin D) also influences the epithelial cells, T cells, B cells, macrophages, and dendritic cells. Almost all cells of the adaptive immune system express the vitamin D receptor, making them also capable of being vitamin responsive. Specifically considering the potential role of vitamins in food allergy, vitamin D has been shown to affect several mechanisms that promote immunologic tolerance, including the T regulatory cell function and the induction of tolerogenic dendritic cells. The target of our review is to evaluate the role of vitamin D in the prevention of food allergy in children. There are contradictory data on the relationship among the vitamin D deficiency and the developing of food allergy. Some studies associate lower exposure to sunlight to food allergy; on the other hand, further research has found that higher vitamin D levels could increase the likelihood of allergic sensitization and food allergy. Therefore, there is an urgent need for well-planned randomized controlled trials on vitamin D supplementation, with particular regard to the prevention of food allergy. The role of vitamin D beyond bone and calcium metabolism is not fully understood.

Abstract Bronchiectasis in pediatric age is a heterogeneous disease associated with significant morbidity. The most common medical conditions leading to bronchial damage are previous pneumonia and recurrent lower airway infections followed by underlying diseases such as immune-deficiencies, congenital airway defects, recurrent aspirations and mucociliary clearance disorders. The most frequent symptom is chronic wet cough. The introduction of high-resolution computed tomography (HRCT) has improved the time of diagnosis allowing earlier treatment. However, the term “bronchiectasis” in pediatric age should be used with caution, since some lesions highlighted with HRCT may improve or regress. The use of chest magnetic resonance imaging (MRI) as a radiation-free technique for the assessment and follow-up of lung abnormalities in non-Cystic Fibrosis chronic lung disease is promising. Non-Cystic Fibrosis Bronchiectasis management needs a multi-disciplinary team. Antibiotics and airway clearance techniques (ACT) represent the pillars of treatment even though guidelines in children are lacking. The Azithromycin thanks to its antinflammatory and direct antimicrobial effect could be a new strategy to prevent exacerbations.

Asthma is a global problem affecting millions of people all over the world. Monitoring of asthma both in children and in adulthood is an indispensable tool for the optimal disease management and for the maintenance of clinical stability. To date, several resources are available to assess the asthma control, first is the monitoring of symptoms, both through periodic follow-up visits and through specific quality of life measures addressed to the patient in first person or to parents. Clinical monitoring is not always sufficient to predict the risk of future exacerbations, which is why further instrumental examinations are available including lung function tests, the assessment of bronchial hyper-reactivity and bronchial inflammation. All these tools may help in quantifying the future risk for each patient and therefore they potentially may change the natural history of asthmatic disease. The monitoring of asthma in children as in adults is certainly linked by many aspects, however the asthmatic child is a future asthmatic adult and it is precisely during childhood and adolescence that we should implement all the efforts and strategies to prevent the progression of the disease and the subsequent impairment of lung function. For these reasons, asthma monitoring plays a crucial role and must be particularly close and careful. In this paper, we evaluate several tools currently available for asthma monitoring, focusing on current recommendations emerging from various guidelines and especially on the differences between the monitoring in pediatric age and adulthood.

Asthma exacerbations are associated with significant childhood morbidity and mortality. Recurrent asthma attacks contribute to progressive loss of lung function and can sometimes be fatal or near-fatal, even in mild asthma. Exacerbation prevention becomes a primary target in the management of all asthmatic patients. Our work reviews current advances on exacerbation predictive factors, focusing on the role of non-invasive biomarkers and genetics in order to identify subjects at higher risk of asthma attacks. Easy-to-perform tests are necessary in children; therefore, interest has increased on samples like exhaled breath condensate, urine and saliva. The variability of biomarker levels suggests the use of seriate measurements and composite markers. Genetic predisposition to childhood asthma onset has been largely investigated. Recent studies highlighted the influence of single nucleotide polymorphisms even on exacerbation susceptibility, through involvement of both intrinsic mechanisms and gene-environment interaction. The role of molecular and genetic aspects in exacerbation prediction supports an individual-shaped approach, in which follow-up planning and therapy optimization take into account not only the severity degree, but also the risk of recurrent exacerbations. Further efforts should be made to improve and validate the application of biomarkers and genomics in clinical settings.

The term osteopetrosis describes a group of rare hereditary diseases of the skeleton, characterized by an increase in bone density, caused by a defect in the development or function of osteoclasts. It comprises a clinically and genetically heterogeneous conditions ranging from infantile onset life-threatening forms to mildest adult onset forms. “Malignant” osteopetrosis is characterized by bone fragility, short stature, compressive neuropathies, hypocalcaemia, pancytopaenia. The deficiency of carbonic anhydrase II causes a moderate form, presenting classically as a triad of osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification. This condition leads to specific craniofacial dysmorphisms associated with upper airway obstruction that may result in obstructive sleep apnea. Herein we report a case of osteopetrosis with RTA associated with severe OSAS successfully treated with continuous positive airway pressure (CPAP).

The inflammatory myofibroblastic tumor (IMT) is a rare lesion of unclear etiology and variable clinical course, consisting of a proliferation of fibroblasts and myofibroblasts, mixed with inflammatory cells. Synonyms of IMT are inflammatory pseudotumor and plasma cell granuloma reflecting the alleged inflammatory nature attributed to this lesion, even though this heterogeneity in the disease denomination is probably involved in a dispersion of the literature data. Among primary pulmonary neoplasms, it represents the most frequent endobronchial tumor of childhood and beyond the lung it has been described mainly in the bladder, mediastinum and mesentery. Despite having a tendency for local recurrence, the risk of distant metastasis is low. Clinical presentation depends on localization therefore lung peripheral lesions are often asymptomatic resulting in a delayed diagnosis. Radiological findings can suggest the diagnosis that must be confirmed by histopathology assessment. The tumor has been characterized by the application of immunohistochemical techniques, molecular biology and cytogenetics, which are very precious for the diagnosis. The therapeutic approach consists in the complete surgical excision of the lesion that normally ensures excellent survival. Due to the potential risk of recurrence, close clinical trial is indicated. To date only 24 cases of pulmonary IMT have been described, although the prevalence is probably higher. We present a case report of a 3-year-old girl with pulmonary IMT and a brief review of known literature cases in order to highlight the most common clinical presentations, the most useful diagnostic tools and therapeutic approach.

Over the past few decades, an increase in the prevalence of asthma and food allergy has been observed in the pediatric population. In infants, food sensitization, particularly to egg, has increased the risk of developing allergic asthma. This is even more likely if sensitization to food allergens occurs early within the first few years of life. It is indeed known that both diseases may be present simultaneously in the pediatric population, but coexistence may negatively influence the severity of both conditions by increasing the risk of life-threatening asthmatic episodes as well as food-related anaphylaxis. Therefore, an accurate clinical and phenotype characterization of this high-risk group of children with both asthma and food allergy and a more aggressive management might lead to reducing related morbidity and mortality. The aim of this review is to provide an updated overview on the close link between food allergy and asthma and their negative mutual influence.

Background and Objectives: Cow’s milk protein allergy (CMA) is the most common allergy in children. The natural history of CMA is generally favorable and the majority of children reach tolerance during childhood, even if studies show variable results. Atopic dermatitis (AD) is a complex disease from an immunological point of view. It is characterized by an impaired skin barrier function and is often the first clinical manifestation of the so-called “atopic march”. The aim of our study is to evaluate, in a cohort of children with CMA, if the presence of AD in the first months of life can influence the atopic status of patients, the tolerance acquisition to cow’s milk, the level of specific IgE (sIgE), and the sensitization towards food and/or inhalant allergens. Materials and Methods: We enrolled 100 children with a diagnosis of CMA referred to our Pediatric Allergology Unit, aged 1−24 months at the time of the first visit. Results: 71 children had AD and 29 did not. The mean follow-up was 5.28 years. The CMA manifestations were mainly cutaneous, especially in children with AD (91.6% vs. 51.7%; P < 0.001). Patients with AD showed higher rates of polysensitization to foods and higher levels of both total IgE and sIgE for milk, casein, wheat, peanuts, and cat dander at different ages when compared to patients without AD. We analyzed the presence of IgE sensitization for the main foods and inhalants at various ages in the two groups of patients: a statistically significant difference emerged in the two groups of patients for milk, yolk and egg white, hazelnut, peanuts, soybean, grass pollen and cat dander. Meanwhile, we did not find significant differences in terms of tolerance acquisition toward cow’s milk, which was nonetheless reached around 5 years of age in 61% of patients. The level of cow’s milk sIgE at the age of 5 years was significantly higher in the group of patients who did not acquire tolerance (38.38 vs. 5.22 kU/L; P < 0.0001). Conclusions: An early barrier deficiency appears to promote the development of allergic sensitization, but does not seem to influence the acquisition of tolerance.

Gluten-related disorders are very common in pediatric patients. Wheat allergy is triggered by an immunoglobulin E (IgE)-dependent mechanism; its prevalence varies according to the age and region, and in Europe has been estimated to be lower than 1%. Many studies investigated the potential role of several external factors that can influence the risk to developing wheat allergy, but results are still inconclusive. It can be responsible for several clinical manifestations depending on the route of allergen exposure: food-dependent exercise-induced anaphylaxis (FDEIA), occupational rhinitis or asthma (also known as baker’s asthma), and contact urticaria. The prognosis of IgE-mediated wheat allergy in children is generally favorable, with the majority of children becoming tolerant by school age. Patients who experienced an anaphylactic reaction prior to 3 years of age and patients with higher level of wheat- or ω-5 gliadin-specific IgE antibodies seem to be at higher risk of persistent wheat allergy. The current management of patients is dietary avoidance. Nowadays, oral immunotherapy has been proposed for wheat allergy with promising results, even if further studies are necessary to establish the best protocol in order to promote tolerance in wheat-allergic children.