Long-term effects of bronchopulmonary dysplasia on lung function: a pilot study in preschool children's cohort.

INTRODUCTION: Although the long term negative effects of bronchopulmonary dysplasia (BPD) are well known, follow-up studies of preterm infants with BPD into childhood are lacking. METHODS: Forty-two preschool children (age range 3-6 years) who were born before 32 weeks of gestational age and affected by BPD were enrolled. Pre-, peri-, and post-natal data were collected. During the follow up appointment complete physical examination and lung function (impulse oscillometry (IOS)) were recorded. The European Community Respiratory Health Survey (ECRHS) questionnaire was administered to all enrolled subjects. RESULTS: Thirty patients were included in the final analysis. The BPD group did not differ in comparison to the non-BPD group in terms of lung function (p > 0.05). By comparing all subjects enrolled, We detected extremely low-birth-weight (ELBW) infants with height-, weight-, and gender-related reference values and a significant trend of increasing resistance values (R5Hz, R5-20 Hz) and respiratory impedance (Z5Hz) (p < 0.05). No significant difference in bronchial reversibility test was observed among BPD non-BPD groups (p < 0.05). The frequency of gastroesophageal reflux disease was significantly higher in patients with BPD when compared to non-BPD group (p < 0.05). Significant differences in gestational age, oxygen supplementation (days), mechanical ventilation therapy (days), and sepsis between BPD and non-BPD groups were also observed (p < 0.05). There were no significant differences in the prevalence of family and personal history of atopy and/or allergic diseases, tobacco exposure, respiratory symptoms, respiratory syncytial virus bronchiolitis, exercise induced dyspnea, treatment with ß-2 bronchodilators and inhaled corticosteroids among the groups (p > 0.05). CONCLUSIONS: The respiratory function in preschool children born with ELBW is characterized by an increase in impedance and resistance of small airways. No statistically significant differences were found between ELBW children with BPD and without BPD. With regards to the smallest gestational age, the longer duration of O2 therapy during hospitalization, and sepsis significantly resulted in a worse respiratory function.

Antihistamines in children and adolescents: A practical update.

Histamine is a chemical mediator, released predominantly by tissue mast cells, circulating basophils, and neurons, which are activated in response to various immunological and non-immunological stimuli. Histamine has to bind to specific receptors to exert its physiological and pathophysiological functions. Endogenous histamine is the main mediator of the immediate allergic response, which moreover, performs other multiple functions, including regulation of gastric secretion, neurotransmission in the central nervous system, and immunomodulatory activity. The involvement of histamine in various disorders and the importance of receptors in the clinical features have relevant implications in clinical practice. Anti-H1 antihistamines contrast the histamine-dependent effects, mainly concerning nasal symptoms and cutaneous itching and wheal. Antihistamines are among the most prescribed drugs in pediatric care. This review updates the practical use of antihistamines in children and adolescents.

Hexavalent vaccines in preterm infants: an update by Italian Society of Pediatric Allergy and Immunology jointly with the Italian Society of Neonatology.

Hexavalent vaccines, protecting against six diseases (diphtheria, tetanus, pertussis [DTaP], poliovirus, hepatitis B virus [HBV], and Haemophilus influenzae type b [Hib], are routinely the standard of care in Europe. The use of combined vaccines allows the reduction of number of injections and side effects, the reduction of costs, and the increase in adherence of the family to the vaccination schedule both in terms of the number of doses and timing. The safety profile, efficacy and effectiveness of hexavalent vaccines have been extensively documented in infants and children born at term, and data are accumulating in preterm infants. Hexavalent vaccines are particularly important for preterm infants, who are at increased risk for severe forms of vaccine preventable diseases. However, immunization delay has been commonly reported in this age group. All the three hexavalent vaccines currently marketed in Italy can be used in preterm infants, and recent data confirm that hexavalent vaccines have a similar or lower incidence of adverse events in preterm compared to full-term infants; this is likely due to a weaker immune system response and reduced ability to induce an inflammatory response in preterm infants. Apnoea episodes are the adverse events that can occur in the most severe preterm infants and / or with history of respiratory distress. The risk of apnoea after vaccination seems to be related to a lower gestational age and a lower birth weight, supporting the hypothesis that it represents an unspecific response of the preterm infant to different procedures. High seroprotection rates have been reported in preterm infants vaccinated with hexavalent vaccine. However, a lower gestational age seems to be associated with lower antibody titres against some vaccine antigens (e.g. HBV, Hib, poliovirus serotype 1, and pertussis), regardless of the type of hexavalent vaccine used. Waiting for large effectiveness studies, hexavalent vaccines should be administered in preterm infants according to the same schedule recommended for infants born at term, considering their chronological age and providing an adequate monitoring for cardio-respiratory events in the 48-72 h after vaccination, especially for infants at risk of recurrence of apnoea.

Magnesium alginate in children with uncontrolled asthma.

Gastroesophageal reflux disease (GERD) may be frequently associated with asthma in children and may affect asthma control. Proton pump inhibitors (PPI) are commonly prescribed in asthmatic children, despite uncertain efficacy on respiratory symptoms and risk of relevant adverse effects.

Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules.

BACKGROUND: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities, and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood. METHODS: We examined 1120 children (age 4-18 years) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA. RESULTS: The analysis of IgE responses against eight P. pratense molecules showed 87 profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE, and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SARg, and complex profiles were associated with longer disease duration. CONCLUSIONS: In a large pediatric population, the complexity of IgE sensitization profiles against P. pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

ATOPIC DERMATITIS: EXPRESSION OF IMMUNOLOGICAL IMBALANCE.

Atopic dermatitis is a chronic relapsing-remitting inflammatory skin condition, characterized by a skin barrier dysfunction resulting in epidermal damage and altered permeability to allergens and microbes. Although pathogenesis of atopic dermatitis is complex and still not fully understood, it has been hypothesized that genetic predisposition, environmental factors, and skin barrier dysfunction are involved. Innate and adaptive immune system has also a pivotal role in the development, maintenance and flare-up of atopic dermatitis. The immune-pathogenesis of atopic dermatitis is determined by the impairment of different T helper cells, of their cytokine secretion profiles as well as of their specific receptor. In this review, we focus on the current knowledge of the etiopathogenetic pathways of atopic dermatitis in relationship to the critical role of the innate and adaptive immune system, providing a unifying view.

CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME AND ATOPIC DISEASES: IS THERE A RELATIONSHIP?

Nephrotic syndrome is a condition of massive proteinuria that leads to hypoalbuminaemia and oedema. In the pediatric age, the most common form of nephrotic syndrome is childhood idiopathic nephrotic syndrome (CINS). Although the etiological mechanisms underlying CINS are still unclear, the disease is considered to be immune-mediated. Several studies have previously reported a possible association between CINS and atopy, with the latter defined as abnormal immunoglobulin-E response on the background of a T-helper 2 (Th2)-driven immune system. In fact, both experimental and clinical studies have suggested that idiopathic nephrotic syndrome can be associated and/or triggered by a wide array of atopic diseases, though this remains a highly controversial topic. Exposure to inhalant-allergens (and/or introduction of food-allergens) has been previously correlated with the onset and/or the relapse of CINS in some children and a significant worse response to steroid therapy has been also described in reports of CINS associated to concomitant atopic diseases. In this review, we analyzed previous studies with the aim to clarify, basing on the existent literature, the association between atopy and idiopathic nephrotic syndrome. Additionally, we also speculated on the underlying immunological pathways that could potentially make some children prone to both CINS and atopic diseases.

Mannitol bronchial challenge test in asthmatic children.

Bronchial asthma is a chronic inflammatory disease characterized by bronchial obstruction, usually reversible spontaneously or after therapy, bronchial hyperreactivity and accelerated decrease of lung function that may possibly evolve into irreversible obstruction of the respiratory tract. Bronchial provocation tests can be used in order to assess the presence and degree of bronchial hyper reactivity. The recently introduced mannitol powder inhalation indirect test seems to have an interesting and promising role, especially in childhood, because of its high diagnostic specificity, easiness of execution and best standardization. In this study the authors focused on the significance and clinical use of mannitol bronchial challenge test in asthmatic children.

PROBIOTICS AND ALLERGIC RESPIRATORY DISEASES.

Probiotics are able to restore microbiome and the normal intestinal permeability, improve the immunological function of gut barrier and reduce the intestinal inflammatory response and the production of pro-inflammatory cytokine characteristics of local and systemic allergic inflammation. Clinical studies have demonstrated the efficacy of probiotics in the treatment of various clinical conditions such as atopic dermatitis and food allergies and in the primary prevention of atopy. Recent studies have shown that oral administration of certain probiotic exerts therapeutic effects in the treatment of allergic respiratory diseases such as asthma and rhinitis.

SAFETY AND EFFICACY OF SUBLINGUAL SPECIFIC IMMUNOTHERAPY TO HOUSE DUST MITE USING A DIFFERENT DOSAGE: A PILOT STUDY.

The aim of this randomized open study was to evaluate the safety and efficacy of different dosages (2000 UI vs 4000 UI) of sublingual immunotherapy (SLIT) in patients with allergic diseases such as asthma associated to rhinitis and rhinoconjunctivitis sensitized to house dust mites. We enrolled 61 patients with a history of allergic asthma, and a positive skin prick test for Dermatophagoides (D.) pteronyssinus/farinae. Patients were randomly assigned to receiving SLIT at dosage of 2000 UI (Group A) or 4000 UI (Group B) maintenance dose. We evaluated: subjective symptoms using a Visual Analogic Scale (VAS), the amount of prescribed symptomatic drugs, bronchial reactivity to methacoline and side effects using a specific questionnaire. A significant improvement in symptoms, assessed by VAS, was observed with both SLIT doses with no significant differences between groups. The provocation dose of methacoline inducing a 20% fall of FEV1 significantly increased after 12 months only in the 4000 UI dose group. In conclusion, both monomeric allergoid dosages of SLIT (2000 UI and 4000 UI) are a safe and efficacy option to reduce symptoms in patients with allergic asthma caused by house dust mites. Moreover, both dosages are efficacious even to protect against airway reactivity but it seems that monomeric allergoid of SLIT at higher dosage (4000 UI) is better than at the lower dosage (2000 UI).

VITAMIN D AND BRONCHIAL INFLAMMATION IN ASTHMATIC CHILDREN.

The role of the vitamin D in calcium homeostasis and bone metabolism is well known. In recent years it has been recognized that in addition to the traditional functions, vitamin D modulates a variety of processes such as host defense, inflammation and immunity. Epidemiological data indicate that low levels of vitamin D in serum are associated with impaired lung function and increased incidence of inflammatory diseases, infectious diseases and cancer. The authors studied the correlation among vitamin D levels, allergic inflammation, lung function and control of asthma and found a significant decrease of FeNO values (p= 0.0018) in children with vitamin D levels>30 ng/ml. These findings confirm that vitamin D plays a major role in bronchial inflammation.

ALLERGIC RHINITIS AND ADENOID HYPERTROPHY IN CHILDREN: IS ADENOIDECTOMY ALWAYS REALLY USEFUL?

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common in children and are often associated with each other. Recent studies have shown improvement of respiratory symptoms and reduction in the adenoid volume after anti-allergic medical therapy (intranasal corticosteroids, antihistamines). The aim of our retrospective study is to evaluate the effectiveness of adenoidectomy on respiratory symptoms in pediatric patients with AR. We recruited 404 pediatric patients with AR, and we divided them into 4 groups (1. intermittent-mild rhinitis; 2. intermittent-moderate/severe rhinitis; 3. persistent-mild rhinitis; 4. persistent-moderate/severe rhinitis), using ARIA classification. For each patient we evaluated: age at onset of AR; family history of allergy; the presence of other allergic diseases; serum total IgE values; skin prick test (SPT) results; presence of AH evaluated by rhino-laringeal fibroscopy; adenoidectomy and its efficacy on respiratory symptoms. Our data show an association between AR and AH: 90 of 404 (22%) children with AR had AH of a degree greater than 2nd. A significant percentage (80%) of children suffering from AR did not present satisfactory benefits from adenoidectomy. They reported persistence or recurrence of rhinitic symptoms after surgery or only partial benefits, especially of recurrent respiratory tract infections and nasal obstruction. The local allergic persistent inflammation on nasal mucosa and adenoid tissue is probably the cause of the unsatisfactory results of adenoidectomy, therefore surgery cannot be the first therapeutic step for these children. It is important to extinguish the local inflammation by medical anti-allergic therapy to obtain improvements of nasal symptoms and to prevent adenoid regrowth.

SUBLINGUAL IMMUNOTHERAPY IN CHILDREN: STATE OF ART.

Allergic immunotherapy (AIT) today represents a therapeutic practice for the treatment of allergic diseases such as rhinitis or asthma and is recognized as the only treatment able to modify the natural history of the disease. Administering gradually increasing doses of the causative allergen, AIT, has the objective of achieving immune tolerance against allergens. One of the administration routes most used in clinical practice is represented by the sublingual route. Current research on sublingual immunotherapy (SLIT) is focused on confirming the efficacy for all the different relevant allergens, on a better definition of allergen extracts and the improvement of their immunological properties and safety, on the identification of best treatment regimens, and on the possibility of extending the clinical indications. The aim of this review is to describe the most recent step in the field of SLIT development.

ß2-AGONISTS IN CHILDHOOD ASTHMA.

ß2-agonists reduce airflow limitation by improving airway diameter as a consequence of a direct action on airway smooth muscle. ß;2-agonists can be broadly classified according to their duration of action: short-acting ß2-agonists (SABAs), including albuterol, terbutaline and fenoterol, have pharmacodynamics half–lives between 2 and 6 h and long-acting ß2-agonists (LABAs), including salmeterol and formoterol, require twice daily treatment. SABAs are often used “as needed” for asthma exacerbations and before exercise in the presence of exercise-induced bronchospasm. LABAs provide longer symptom control, which is a particularly useful feature for preventing night-time symptoms. There are two main LABAs, salmeterol and formoterol. This review focused on the recent data published on this topic.

LABAs in asthmatic children: highlights and new inside.

International asthma guidelines recommend increasing the dose of ICS or adding leukotriene modifiers or the use of long-acting inhaled beta2-agonists (LABAs) in combination with inhaled corticosteroids (ICS) when uncontrolled asthma occurs in adult and children in treatment with low-dose inhaled corticosteroids. However, in children, the effects of this last treatment option are unclear because there are few studies on the efficacy and safety of these drugs in pediatric age. Furthermore, salmeterol is licensed for use in children over 4 years and formoterol in children of more than 6 years. Finally, recent data provides evidence that repeated bronchoconstriction induces epithelial cell stress that may lead to remodeling and these findings may have potential implications for asthma management, particularly for LABAs treatment in the future.

Nasal high-mobility group box-1 protein in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is characterized by an inflammatory reaction. High-mobility group box-1 protein (HMGB1) has many characteristics similar to classic proinflammatory cytokines. No study has yet investigated its role in AR. The aim of this study was to measure HMGB1 levels in the fluid recovered from nasal lavage in children with untreated AR and in control subjects. MATERIALS: The study was conducted on 104 AR subjects (48 males and 56 females, median age 10.3 ± 3.4 years) and 97 healthy children (42 males and 55 females) who were age-matched (median age 9.8 ± 4.1 years). Total serum immunoglobulin E, peripheral eosinophils and nasal symptoms assessed by visual analog scale (VAS) were considered. HMGB1 was measured using an ELISA assay. RESULTS: HMGB1 levels in nasal lavage fluid were higher in AR children than in the control group (96.9 ± 19.3 vs. 9.27 ± 4.01 ng/ml; p < 0.001). There was a very strong relationship between HMGB1 levels and VAS values in AR children (r = 0.919). Considering the symptom severity assessed by VAS, there was a relationship between HMGB1 and VAS in all AR subgroups: more evident in the severe subgroup (r = 0.727). CONCLUSIONS: Nasal HMGB1 has significantly increased in children with AR and is significantly related to symptom severity.

Impaired spirometry may suggest sensitization.

The present study confirms that sensitization is very frequent in the general population and suggests that impaired FEF25-75 may be a marker of sensitization. Therefore, when spirometry is abnormal, mainly concerning FEF25-75, sensitization should be suspected.