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.

Lung clearance index evaluation in detecting nocturnal hypoxemia in cystic fibrosis patients: Toward a new diagnostic tool.

BACKGROUND: Nocturnal hypoxemia adversely affects outcomes in patients with cystic fibrosis (CF). Although an early detection of this abnormality may be desirable, still its predictability remains uncertain. The Lung Clearance Index (LCI) is a measure of lung ventilation distribution obtained from a multiple-breath washout technique (MBW), recently implemented in patients with CF. This study aimed to establish whether the LCI predicts nocturnal hypoxemia in patients with stable CF, with mild to moderate disease, and normal diurnal gas exchange. METHODS: 31 stable patients (15 males, mean age 17.4 ± 5.2 years) with mild to moderate CF, normoxic when awake, were enrolled. In all patients we performed nocturnal cardio-respiratory polygraphy, lung function measurement, and MBW test to derive LCI values. RESULTS: LCI was abnormal in most of the patients and inversely correlated with mean nocturnal SpO2 (r = -0.880 p < 0.01). A receiver operating characteristic (ROC) analysis, performed to assess whether LCI predicted nocturnal hypoxemia, revealed a high predictive accuracy of LCI for nocturnal desaturation (AUC = 0.96; Youden index = 0.79). Forced expiratory volume in 1 s (FEV1) was predictive only in patients with more severe airway obstruction, with a moderate degree of accuracy (AUC 0.71). CONCLUSIONS: The LCI showed a high effectiveness in predicting nocturnal hypoxemia in stable patients with CF, particularly when compared with a traditional parameter of lung function such as FEV1.

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.

A radio ridge connecting two galaxy clusters in a filament of the cosmic web.

Galaxy clusters are the most massive gravitationally bound structures in the Universe. They grow by accreting smaller structures in a merging process that produces shocks and turbulence in the intracluster gas. We observed a ridge of radio emission connecting the merging galaxy clusters Abell 0399 and Abell 0401 with the Low-Frequency Array (LOFAR) telescope network at 140 megahertz. This emission requires a population of relativistic electrons and a magnetic field located in a filament between the two galaxy clusters. We performed simulations to show that a volume-filling distribution of weak shocks may reaccelerate a preexisting population of relativistic particles, producing emission at radio wavelengths that illuminates the magnetic ridge.

Pilot study shows right ventricular diastolic function impairment in young children with obstructive respiratory disease.

AIM: This study determined cardiovascular impairment in young children with obstructive respiratory disease who were assessed using the opening interrupter technique (RINT). METHODS: This pilot study enrolled 41 children who had been referred to pulmonology and allergology specialists at the University of Catania, Italy, from March to July 2017: 23 (mean age 4.13 ± 0.62 years) had chronic coughs and wheezing and 18 controls (mean age 4.27 ± 0.66 years) had obstructive chest disease, but were otherwise healthy. Airway resistance was evaluated using RINT and cardiac function by studying the ejection fraction, pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion and tricuspid flow propagation velocity (TFPV). RESULTS: The RINT and PASP values were significantly higher in the patient group when compared to the controls, but the TFPV values were lower. A direct and significant Spearman's correlation coefficient (r) between RINT and PASP values was observed (r = 0.81). We found a significant inverse correlation between RINT and TFPV (r = -0.83), as well as TFPV and PASP (r = -0.78). CONCLUSION: This study showed that children with obstructive respiratory diseases had a major risk of cardiovascular impairment. Impaired diastolic function of the right ventricle occurred very early when airway resistance was abnormally increased.

Different concentration of human cord blood HMGB1 according to delivery and labour: A pilot study.

OBJECTIVE: Oxidative stress is involved in several maternal conditions characterized both by an increase in free radicals synthesis and a parallel decrease in the antioxidant activity. Parturition induces considerable oxidative stress and many inflammatory mediators, among which HMGB1, are involved from the beginning of pregnancy to the birth of the infant. We evaluated serum cord blood HMGB1 levels in a population of neonates to investigate correlation with mode of delivery, as well as the influence of labour. SETTING AND PATIENTS: The study subjects were 325 neonates delivered at University Hospital "G. Martino" of Messina over an 18-month period. Following cord separation, venous blood sampling was performed on umbelical cords. RESULTS: In the cord venous blood, we found HMGB1 values significantly more elevated in spontaneous vaginal group when compared to elective or emergency caesarean section group. Regarding labour, umbilical cord venous blood HMGB1 levels were significantly higher in the spontaneous and induced labour group, compared to non-labouring women. CONCLUSION: These results could highlight a possible role of HMGB1 during birth time related to mode of delivery and labour.

Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: A systematic review.

Familial Mediterranean fever (FMF) is the most common autosomal recessive autoinflammatory disease. To date, following the isolation of more than 280 MEFV sequence variants, the genotype-phenotype correlation in FMF patients has been intensively investigated; however, an univocal and clear consensus has not been yet reached. Thus, the aim of this systematic review was to analyze the available literature findings in order to provide to scientific community an indirect estimation of the impact of genetic factors on the phenotypic variability of FMF. This systematic review has been conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The p.M694V mutation was reported to have a relatively severe clinical course, similarly, patients homozygous for M694I and M680I, or carrying a combination of both at codons 694 and 680, have a severe disease. Also, patients homozygous for M694V and V726A variants experienced more severe clinical picture. Conversely, heterozygous p.V726A and p.E148Q genotypes have been correlated with a milder disease course. At present, doubts remain on the potential pathogenic role of E148Q variant. The heterogenity in clinical FMF manifestations reflects the changes occuring in repertoire of mutations. We believe that clinical criteria and gene tests, enhancing each other, could better support the diagnosis of FMF.

Inflammatory biomarkers and intellectual disability in patients with Down syndrome.

BACKGROUND: Intellectual disability (ID) is part of the Down syndrome (DS) phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals with DS is not yet fully understood, with many research hypotheses still unproven. Basing on previous studies (which suggested a possible role of altered inflammatory response in DS-related ID), we assessed the serum levels of a number of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP), high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy controls. METHODS: In total, 24 children diagnosed with DS and 12 healthy controls were enrolled, and all underwent detailed cognitive assessment. Also, serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and correlated to the severity of ID in the DS group. RESULTS: Serum SAA, C-RP and HMGB1 values were found to be significantly higher in the DS group compared with the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively correlated with C-RP and SAA in the DS group but not in the healthy controls. Only serum C-RP levels resulted inversely correlated (P < 0.01) with intelligence quotient (IQ); conversely, significant statistical correlations between serum SAA levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05). CONCLUSIONS: The levels of the determined markers were higher in DS individuals compared with (cognitively) healthy subjects, and CRP showed a negative correlation with IQ in children with DS.

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

BACKGROUND: Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. OBJECTIVE: To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. METHODS: A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. RESULTS: 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. CONCLUSIONS: The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF.

Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy.

BACKGROUND: Although several studies suggest a possible link between dyslipidemia and atopy, literature findings are still unclear. OBJECTIVE: The aim of the study was to investigate the relationship between dyslipidemia and atopy in a pediatric population affected by dyslipidemia or dyslipidemia/atopic predisposition. MATERIALS AND METHODS: Children with dyslipidemia, dyslipidemia and atopy as well as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23 levels as well as fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were performed on all enrolled children. RESULTS: The present study evaluated 23 patients affected by dyslipidemia, 26 patients affected by atopy and dyslipidemia and, 22healthy children. Serum total IgE levels significantly related also with serum cholesterol levels: positively with total cholesterol (p<0.05), LDL (p<0.05), and tryglicerides (p<0.001), but negatively with HDL (p<0.05). Serum levels of IL-10 were lower in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). Serum IL-10 levels significantly related also with serum cholesterol levels: negatively with total cholesterol (p<0.001), LDL (p<0.05), and triglycerides (p<0.05), but positively with HDL (p<0.05). Serum IL-17 and IL-23 levels showed the same trend. They were significantly higher in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). In particular, serum IL-17 and IL-23 values positively correlated with serum total IgE levels (p<0.05); serum total cholesterol levels (p<0.001); serum LDL levels (p<0.001); serum triglycerides levels (p<0.05). Although not statistically significant, an inverse correlation has been noted between serum IL-17, IL-23 and HDL levels. CONCLUSIONS: These findings support the notion that dyslipidemia and atopic predisposition share the same immune pathways as well as they offer new insights in the complex crosstalk between hyperlipidemia and atopy.

The Role of Neurotrophins in Inflammation and Allergy.

Allergic inflammation is the result of a specific pattern of cellular and humoral responses leading to the activation of the innate and adaptive immune system, which, in turn, results in physiological and structural changes affecting target tissues such as the airways and the skin. Eosinophil activation and the production of soluble mediators such as IgE antibodies are pivotal features in the pathophysiology of allergic diseases. In the past few years, however, convincing evidence has shown that neurons and other neurosensory structures are not only a target of the inflammatory process but also participate in the regulation of immune responses by actively releasing soluble mediators. The main products of these activated sensory neurons are a family of protein growth factors called neurotrophins. They were first isolated in the central nervous system and identified as important factors for the survival and differentiation of neurons during fetal and postnatal development as well as neuronal maintenance later in life. Four members of this family have been identified and well defined: nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 4/5. Neurotrophins play a critical role in the bidirectional signaling mechanisms between immune cells and the neurosensory network structures in the airways and the skin. Pruritus and airway hyperresponsiveness, two major features of atopic dermatitis and asthma, respectively, are associated with the disruption of the neurosensory network activities. In this chapter, we provide a comprehensive description of the neuroimmune interactions underlying the pathophysiological mechanisms of allergic and inflammatory diseases.

Human herpesviruses-6 and -7 encephalitis in immunocompetent infants: are they really so uncommon?

Human herpesviruses-6 and -7 (HHV-6 and 7) are considered uncommon causes of central nervous system infection and may occasionally cause encephalitis in young infants, however, the clinical syndrome and incidence are not well defined. In immunosuppressed hosts, reactivation is associated with a worse outcome such as encephalitis, hepatitis, or graft rejection. In immunocompetent hosts, this persistent infection is generally of no consequence. We report 4 cases of immunocompetent critically ill children, affected by HHV-6 and -7 encephalitis, admitted to our Pediatric Intensive Care Unit. In three patients, herpesvirus polymerase chain reaction in blood and cerebrospinal fluid was positive for HHV- 6, while one patient was positive for HHV-7. In our cases, a typical clinical picture of viral infection was not present but neurological symptoms were predominant. In all 4 children, neurological involvement rapidly regressed after acyclovir therapy. In this report, we offer evidence that HHV-6 and -7 primary infections can cause several clinical manifestations, such as encephalitis, also in immunocompetent hosts. In our experience, children with neurological symptoms suggestive of viral encephalitis should be fully investigated for these two viruses.

ALMOND MILK: A POTENTIAL THERAPEUTIC WEAPON AGAINST COW’S MILK PROTEIN ALLERGY.

Food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly following exposure to a given food. Cow’s milk protein allergy results from an immunological reaction to one or more milk proteins. The principle key in the treatment of cow’s milk protein allergy is the dietary elimination of cow’s milk protein. Although hydrolyzed and elemental formulas are appropriate replacements, other milk products, including almond milk adequately integrated, could be administered. Here, in the light of encouraging results from our study, we focused on the anti-inflammatory and anti-oxidant properties of almond milk and we also believe that almond milk might be considered as a potential alternative in cow’s milk protein allergy treatment.

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.

EXHALED BREATH TEMPERATURE IN ASTHMATIC CHILDREN.

Asthma is characterized by chronic inflammation of airways. Currently, no traditional method allows an easy daily evaluation of the degree of airway inflammation. Measuring inflammatory biomarkers in the breath is a very attractive approach to monitor asthma inflammation. In recent years, the measurement of exhaled breath temperature (EBT) has been proposed as a method capable of detecting the inflammatory status of the airways. The objective of this study is to strengthen the role of EBT in the diagnosis and monitoring of asthma. The study sample was represented by a group of 40 patients, of both sexes, aged 6-15 years. The elective criteria for submitting patients to EBT determination were abstaining from drugs in the preceding 24 h, fasting for at least 2 h, physical resting for at least 30 minutes, a body temperature between 35-37°C. The temperature in the room of the surveys ranged from 18 to 25°C. The EBT values of asthmatic patients were higher [(median (IQR): 29.77°C (30.67°C to 29.38°C) range 28.46°C min-max 34.78°C] than those of non-asthmatic ones (median (IQR): 28.22°C (29.09°C-27.7°C), range 27.09°C min-max 30.07°C] and this difference was highly significant (p less than 0.001). Furthermore, no significant difference was found between the EBT values of the following groups of patients: those exposed and not exposed to passive smoking, those receiving and not receiving leukotriene drugs, those receiving and not receiving specific immunotherapy, monoallergic patients and poliallergic ones, those sensitized and not sensitized to house dust, perennial allergic patients and seasonal allergic ones. In addition, the evaluation of the correlation of EBT values with body temperature (r=0.119, p=0.464) and ambient temperature (r=-304, p = 0.057) did not show any significant correlation. Finally, no statistically significant correlation was demonstrated between EBT values and FEV1 (r=-0055, p=0.81, Fig. 4). In conclusion, the data of the present study further support the hypothesis that EBT can be considered a good method for monitoring asthma.

PRIMARY NOCTURNAL ENURESIS IN CHILDREN WITH ALLERGIC RHINITIS AND SEVERE ADENOTONSILLAR HYPERTROPHY: A SINGLE CENTER PILOT STUDY.

Nocturnal enuresis is defined as intermittent urinary incontinence during sleep that occurs at least twice a week for three consecutive months. There is no unifying etiology for nocturnal enuresis in the pediatric population and the disorder is likely to be multifactorial. We aimed to investigate the relationship between primary nocturnal enuresis, allergic rhinitis, and related complications in a paediatric case series from a single Center. We retrospectively reviewed and prospectively followed-up at our Institution (i) 32 children (14 females, 18 males; mean age 6.31±1.21 yrs) affected by allergic rhinitis with adenoidal hypertrophygrade I-II (group A) and (ii) 27 children (11 females, 16 males; mean age 6.52±1.33 yrs) affected by allergic rhinitis with adenoidal hypertrophy grade III-IV (group B). Allergic rhinitis was diagnosed on the basis of (a) typical nasal symptoms due to atopic sensitization (e.g., rhinorrhea , itching, sneezing fits, and nasal congestion and obstruction) and (b) positive skin prick testing and/or increased level of total serum IgE. We identified discrepancies between group A and group B in terms of risk of primary nocturnal enuresis. In fact, only 1 child of group A (3.12%) reported uncomplicated primary nocturnal enuresis; conversely, 6 children of group B (22.22%) showed a history of uncomplicated primary nocturnal enuresis (p=0.040). There was no statistically significant difference between the two groups in terms of atopic sensitization and serum total IgE levels (p=0.43). Allergic rhinitis may potentially influence the onset and the natural history of nocturnal enuresis in some children. Children with allergic rhinitis and more severe respiratory manifestations, seem to be more prone to developing primary nocturnal enuresis, likely due to potential multi-factorial causes (e.g., sleep disorders, chronic phlogosis, immune deregulation).

HIGH-MOBILITY GROUP BOX 1 IN ALLERGIC AND NON ALLERGIC UPPER AIRWAY INFLAMMATION.

High mobility group box 1, an evolutionary ancient protein conserved in the eukaryotic kingdom, exerts intra- and extra- cellular functions, orchestrating a homeostatic defensive response in challenged tissues. Its action associated with various inflammatory cells is essential for the occurrence, progression, and persistence of asthma, rhinitis, and nasal polyposis. The recent discovery of High mobility group box 1, as a critical mediator of inflammation, stimulated an increasing interest in the field of inflammation research, suggesting new therapies for atopic and non-atopic inflammatory processes.

ATOPIC DERMATITIS: MELATONIN AS POTENTIAL TREATMENT.

Atopic dermatitis (AD) is a chronic relapsing-remitting inflammatory skin disorder, characterized by a skin barrier dysfunction resulting in epidermal damage and altered permeability to allergens and microbes. Traditionally, the immunological mechanism involving the Th1-Th2 paradigm is considered central in the pathogenesis of AD. However, oxidative stress is, currently, recognized as a fundamental predisposing stimulus for AD. Several therapeutic approaches have been proposed as treatment, including the use of melatonin. This indolamine, through widespread expression and pleiotropic activity of the cutaneous melatoninergic system, may counteract environmental and endogenous stressors, regulate the immune response, decrease oxidative stress, and, finally, promote skin integrity. In the light of its pleiotropic effects, melatonin could represent a potential and alternative therapeutic approach in patients with AD.