The comparison between children and adolescents with asthma provided by the real-world "ControL'Asma" study.

OBJECTIVE: Because asthma is a disease that changes over time, the Italian Society of Pediatric Allergy and Immunology launched a nationwide study on asthma control (the ControL'Asma study). The intent was to test the hypothesis that children with asthma could present a different pattern compared to adolescents. In the study, we compared children with adolescents in a real-world setting by analyzing the asthma control grade and other asthma-related parameters. METHODS: This cross-sectional real-world study included 471 asthmatic children (

Respiratory syncytial virus and airway microbiota - A complex interplay and its reflection on morbidity.

The immunopathology of respiratory syncytial virus (RSV) infection varies considerably, severe disease occurring only in a minority of the affected children. The variability of the clinical presentation is in part explained by viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiologic immaturity of the innate and adaptive immune system. There is evidence that the maturation of the host immune response is positively influenced by the composition of the nasopharyngeal microbiome that, promoting an efficient reaction, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional since microbial dysbiosis may also represent a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV can also increase the virulence of potential pathogens in nasopharynx, a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Moreover, if negative changes in microbial community composition in early life may constitute a heightened risk toward severe RSV respiratory infection, on the contrary specific groups of microorganisms seem to be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species on RSV infection may improve primary prevention and possibly care of this highly contagious disorder.

Recurrence of right lower lobe pneumonia 3 years after the first episode in an otherwise healthy 13-year-old girl.

Recurrent pneumonia is one of the most frequent reasons for referral to paediatric chest physicians. The diagnostic work-up is dependent on whether infection repeatedly occurs in the same lung lobe, or affects multiple lobes and/or different areas in different episodes. A 13-year-old girl was admitted with a second episode of right lower lobe pneumonia. The chest x-ray demonstrated an inhomogeneous opacity, without a clearly recognizable segmental distribution. A contrast-enhanced CT scan, was therefore performed that showed a polycyclic consolidation with blood supply from a systemic artery, originated from the thoracic aorta. A diagnosis of superinfection of an intralobar sequestration was made. The patient was treated with systemic antibiotics and, four weeks later, a segmental resection of the lesion was performed. The histological evaluation of the surgical specimen confirmed the diagnosis.

Exposure to vehicular traffic is associated to a higher risk of hospitalization for bronchiolitis during the first year of life.

BACKGROUND: The most common cause of hospitalization for children younger than age one is bronchiolitis. Several prenatal and environmental risk factors may affect the incidence of hospitalization for bronchiolitis. The aim of this study was to investigate the relation between exposure to vehicular traffic and the incidence of hospitalization for bronchiolitis in children during their first year of life in Italy. METHODS: A multicenter prospective birth cohort study, where equal numbers of newborns of 33-34, 35-37 and ≥38 wGA were recruited at birth (1814 children) in 30 Italian neonatology units. Two interviewer-administered questionnaires were used to collect data. The first interview was carried out at the end of the Italian epidemic season. The second interview was carried out when the child was one year old. Data on possible prenatal, perinatal, and postnatal/environmental risk factors and on vehicular traffic density in the zone of residence were collected. On each interview, parents were also asked about any hospitalizations of the child. The outcome measure was the hospitalization for bronchiolitis (International Health Service ICD-9 code 466). RESULTS: Univariate analysis demonstrated that exposure to air pollution due to vehicular traffic, was significantly associated with an increased risk of hospitalization for bronchiolitis. The adjusted risk from logistic regression model confirmed that children exposed to air pollution due to vehicular traffic were at increased risk of hospitalization for bronchiolitis. CONCLUSIONS: Exposure to air pollution due to vehicular traffic may increase the risk of hospitalization for bronchiolitis in the first year of life.

Prenatal tobacco smoke exposure increases hospitalizations for bronchiolitis in infants.

BACKGROUND: Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women's and children's health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. METHODS: From November 2009 to December 2012, newborns born at ≥ 33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. RESULTS: Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4%) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5-8.1) and of 1.7 (CI 1.1-2.6) respectively. CONCLUSIONS: These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants' respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of life.

Perception of bronchodilation assessed by Visual Analogue Scale in children with asthma.

BACKGROUND: Visual Analogue Scale (VAS) has been proposed as a useful tool for assessing the perception of asthma symptoms, a cornerstone in disease management. While airway flow limitation and its reversibility are thought to be a useful marker of disease severity, there are very few studies that evaluated the response to bronchodilation (BD) testing perception by VAS. To investigate whether VAS assessment of breathlessness perception could provide a useful tool to assess the response to BD testing in asthmatic children. METHODS: This cross-sectional study included a total of 150 children (96 males, mean age 11.05 years) with asthma, 50 had bronchial obstruction (i.e. FEV1 <80% of predicted). Perception of breathlessness was assessed by VAS; lung function was measured by spirometry. BD testing was performed in all children. RESULTS: In children with bronchial obstruction, VAS at baseline was 4.7 and significantly increased to 6.9 (p<0.001) after BD. In children without bronchial obstruction, VAS at baseline was 7.4, but further significantly increased to 8.4 after BD testing (p<0.01). There was a significant difference in Δ VAS between children with bronchial reversibility and children without it (p<0.0001). CONCLUSIONS: The present study demonstrates that VAS might be considered an initial tool to assess the BD response in children with asthma, mainly with overt bronchial obstruction.

Breathlessness perception assessed by visual analogue scale and lung function in children with asthma: a real-life study.

BACKGROUND: In children with asthma, discrepancies between objective indicators of airway obstruction and symptom perception are often observed. Although visual analogue scale (VAS) has been proposed as a useful tool for assessing accurate symptom perception, previous studies conducted in children with asthma included only small cohorts. A study was therefore designed to investigate the usefulness of VAS in establishing a reliable relationship between breathlessness perception and lung function in a large cohort of children with clinical diagnosis of asthma. METHODS: A total of 703 children [470 boys and 233 girls, median age 10.29 (8.33-12.58) yr] with asthma were included in this cross-sectional, real-life study. Perception of breathlessness was assessed by using VAS, and lung volumes and expiratory flows were measured by spirometry. RESULTS: Most children had intermittent or mild persistent asthma (93.3%), and only 46 children had a significant bronchial obstruction defined by FEV(1) values <80% of predicted. Globally, VAS was significantly, even though weakly, related to lung function. Analyzing children with bronchial obstruction, a moderate relationship between both FEV(1) (r = 0.47) and FEF(25-75) (r = 0.42) and VAS was detected. A VAS value of 6 was found to be a reliable cutoff for discriminating children with bronchial obstruction (AUC 0.83 at ROC curve; OR 9.4). CONCLUSION: The present study demonstrates that VAS might be considered a useful tool to assess symptom perception, mainly in children with airflow limitation.

Pharmacological modulation of the bradykinin-induced differentiation of human lung fibroblasts: effects of budesonide and formoterol.

OBJECTIVE: Bradykinin (BK) induces differentiation of lung fibroblasts into myofibroblasts, which play an important role in extracellular matrix remodeling in the airways of asthmatic patients. It is unclear whether this process is affected by antiasthma therapies. Here, we evaluated whether a glucocorticoid, budesonide (BUD), and a long-acting ß2-agonist, formoterol (FM), either alone or in combination, modified BK-induced lung fibroblast differentiation, and affected the BK-activated intracellular signaling pathways. METHODS: Human fetal lung fibroblasts were incubated with BUD (0.001-0.1 µM) and/or FM (0.0001-0.1 µM) before exposure to BK (0.1 or 1 µM). Fibroblast differentiation into α-smooth-muscle-actin-positive (α-SMA⁺) myofibroblasts, BK2 receptor (B2R) expression, extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation (p-ERK1/2), intracellular Ca²âº concentration ([Ca²âº]i), and p65 nuclear factor kappa B translocation were evaluated. RESULTS: BUD (0.1 µM) and FM (0.1 µM), either alone or in combination, completely inhibited BK-induced α-SMA protein expression and decreased the numbers of α-SMA⁺ fibroblasts, with a clear reduction in α-SMA stress fibers organization. BUD also completely inhibited the increase of B2R, whereas FM with or without BUD had no effect. BK-induced increases of [Ca²âº]i and p-ERK1/2 were significantly reduced to similar levels by BUD and FM, either alone or in combination, whereas p65 translocation was completely inhibited by all treatments. CONCLUSION: Both BUD and FM, either alone or in combination, effectively inhibited the BK-induced differentiation of fibroblasts into α-SMA⁺ myofibroblasts and the intracellular signaling pathways involved in fibroblast activation. These results suggest that BUD and FM combination therapy has potential to inhibit fibroblast-dependent matrix remodeling in the airways of asthmatic patients.

Determinants of exhaled nitric oxide levels (FeNO) in childhood atopic asthma: evidence for neonatal respiratory distress as a factor associated with low FeNO levels.

BACKGROUND: In allergic asthmatic children exhaled nitric oxide (FeNO) levels are related to eosinophilic inflammation by correlation analysis. Whether FeNO can be modified by factors potentially influencing the natural history of asthma in early life is not known. OBJECTIVE: To evaluate the frequency of anamnestic factors influencing the natural history of asthma and to identify potential determinants for elevated or low FeNO levels by multivariate analysis. METHODS: One hundred seventy-one children with mild-moderate asthma were stratified according to their FeNO levels into three groups: low (<20 ppb), mid (20-40 ppb), and high (>40 ppb). The frequency of nine anamnestic factors together with indices of allergic sensitization (total and allergen-specific immunoglobulin E [IgE], blood eosinophil counts) and of airflow limitation (forced expiratory volume in one second [FEV(1)]% predicted) were evaluated. Results. Among factors related to the patient history, neonatal respiratory distress was reported only in children with low FeNO levels, whereas this factor was never reported in children with mid-to-high FeNO levels (p = .008). As compared with low FeNO group, mid and high FeNO groups showed higher eosinophil counts and a tendency to have lower FEV(1) values. By multivariate analysis, four factors (eosinophils >300 cells/mm(3), cat-specific IgE, house dust mites [HDM]-specific IgE, FEV(1) ≤ 86% predicted) turned out to be significantly associated with mid-high FeNO levels and two factors (eosinophils >600 cells/mm(3), total IgE >355 kU/L) with high FeNO levels. CONCLUSIONS: Besides confirming the well-known tight association between blood eosinophilia and/or allergic sensitization and FeNO, these data provide new evidence for neonatal respiratory distress as potential factor associated with low FeNO levels in childhood atopic asthma.

Asthma in children and adolescents: the ControL'Asma project.

The control of asthma is the objective of asthma management. However, it is difficult to obtain in clinical practice. The Italian Society of Allergy and Clinical Immunology promoted the nationwide project "ControL'Asma" to investigate the real situation in a group of children and adolescents with asthma. The preliminary outcomes demonstrated that many asthmatic subjects do not achieve adequate asthma control. Moreover, asthma in Italian children and adolescents was usually more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled and partly controlled asthma affected about the half of subjects. However, this project suggested that the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.

Discrepancy between sensitization to inhaled allergens and respiratory symptoms in pediatric patients with type 1 diabetes mellitus.

According to the 'Th(1)/Th(2) paradigm', children with type 1 diabetes mellitus (T1DM) should have a lower risk of developing allergic sensitization and, because of the involvement of insulin in modulating airway inflammation, different frequency or severity in allergy-related respiratory manifestations. This article aims at evaluating the frequency and type of allergic sensitization and its respiratory manifestation, asthma and/or rhinitis, in a group of pediatric patients with T1DM. Patients (112) with T1DM, 7.8-16.9 yr of age (63 males and 49 females) were evaluated. Skin prick test (SPT) reactivity to the most common classes of aeroallergens were performed and compared with data obtained in 709 school-aged children. The frequency of sensitization was not different in the T1DM and in the control subjects (43.7% and 40.8%, respectively; p = 0.55), with similar proportions of individuals sensitized to one allergen (32.7% and 38.1%, respectively; p = 0.47). In both groups, sensitization to house dust mite allergens was the most frequently detected (69.4% and 65.4%, respectively; p = 0.59), with a higher proportions of individuals sensitized to Graminae (+Cynodon dactylon; p < 0.0001) and a lower, but weakly significant, proportion sensitized to Parietaria (p = 0.03) in the T1DM group, as compared with controls. No differences were found between T1DM and control groups in the proportion of individuals reporting rhinitis (26.8% and 29.2%; p = 0.60). However, comparing separately sensitized and non-sensitized subjects, a lower proportion of rhinitis subjects was detected in the non-sensitized T1DM patients, when compared with the non-sensitized control subjects (p = 0.01). In addition, no differences were detected between T1DM and control groups in frequency of symptoms related to 'lifetime asthma', i.e., asthma episodes during life (14.3% and 16.5%, respectively: p = 0.55), also when sensitized and non-sensitized subjects were evaluated separately (p = 0.12 and p = 1.00, respectively). However, no T1DM patient had 'actual asthma', i.e., asthma episodes in the last year, vs. 5.8% of the individuals in the control group (p = 0.009), the difference being mostly ascribed to sensitized subjects (p = 0.012). Finally, out of the 16 T1DM patients with 'lifetime asthma', 15 had mild intermittent disease and only one mild persistent disease. T1DM does not seem to play a downregulating role on the development of allergic sensitization to aeroallergens, but may lower the frequency or the severity of its clinical manifestations at respiratory level.

Could Bet v 1 affect sensitization molecular pattern in children?

BACKGROUND: Allergy is characterized by allergen-specific IgE production. Molecular-based allergy diagnostic allows to define the precise sensitization profile. Bet v 1 is the major allergen of the PR-10 family. It has been reported that pan-allergens could affect the sensitization panel in adults. OBJECTIVE: This study aimed to evaluate the impact of Bet v 1 sensitization on clinical presentation in a sample of children with Bet v 1-sensitization; oral allergy syndrome (OAS) or anaphylaxis (ANA) were considered. METHODS: Serum IgE molecular components were assessed by ISAC method. Sera and clinical data from 132 children, 91 males (68.94%) and 41 females (31.06%), mean age 9.08 years (3.45 years), were analyzed. RESULTS: Bet v 1-sensitized children were frequently, but not exclusively, sensitized to other molecules belonging to PR-10 family. However, there was no significant difference concerning IgE levels between children with or without food allergy and between children with OAS and ANA, but hazelnut only for generic food allergy. CONCLUSIONS: The present study demonstrates that Bet v 1 sensitization may affect the sensitization pattern in children living in Genoa, a Mediterranean city located in a birch-free area, but it is unable to discriminate patients from a clinical point of view. So, ISAC test should be integrated with more precise IgE assay.

Pru p 3 sensitization in children with allergy to Parietaria pollens.

BACKGROUND: Pru p 3 is the major allergen of the peach and belongs to the LTP family. Pru p 3 sensitization has been associated with severe allergic symptoms after eating LTP-containing foods. However, a previous experience partially downsized the potential danger of Pru p 3 sensitization in a group of adult rhinitics. This study aimed to evaluate the real impact of Pru p 3 sensitization in children in a real-world setting. METHODS: 82 consecutive paediatric patients (55 males and 27 females, mean age 8.19±4.23 years) with allergic rhinitis due to Parietaria pollen allergy and sensitization to Pru p 3, documented by ISAC test, were evaluated. Serum IgE was measured by ImmunoCap method. Allergic symptoms occurring after ingesting LTP-containing foods were considered and scored as oral allergy syndrome, food allergy, and anaphylaxis. RESULTS: About one-quarter of Pru p 3-sensitized children reported anaphylaxis after ingesting LTP-containing foods, about half reported food allergy or oral allergy syndrome. Only » was merely sensitized. CONCLUSIONS: Pru p 3 sensitization deserves careful attention in children contrary to what might occur in adult patients. It could depend on the age and the serum IgE level. Thus, Pru p 3 sensitization should be adequately interepreted and managed in clinical practice.