Gian Luigi Marseglia

Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences

ABSTRACT In order to evaluate the infectious agents associated with the first episode of severe acute wheezing in otherwise healthy infants and to define the role of each of them in recurrences, 85 patients in Italy, aged <12 months, hospitalized because of a first acute episode of wheezing, were prospectively enrolled between 1 October 2005 and 31 March 2006. Upon enrolment, nasopharyngeal swabs were collected for the real-time PCR detection of respiratory syncytial virus (RSV) types A and B, influenza virus types A and B, adenovirus, parainfluenza viruses types 1, 2, 3 and 4, rhinovirus, human metapneumovirus, human coronavirus types 229E, OC43, NL63, and HKU1, bocavirus, enterovirus, and paraechovirus; nasopharyngeal aspirates were also obtained to detect atypical bacteria. At least one infectious agent was identified in 76 children (89.4%). RSV was the most frequently detected pathogen and its prevalence was significantly higher than that of the other pathogens in both age groups, and significantly higher in the children aged 3–12 months than in those aged <3 months. Only the children with RSV infection experienced recurrent wheezing. Viral load was significantly higher in children with than in those without recurrent wheezing. This study shows that RSV is the main reason for hospitalization during the first wheezing episode in infants, and that it appears to be the only pathogen associated with a high frequency of recurrences. A high viral load seems to be strictly related to the likelihood of recurrence.

Role of FEF25-75 as an early marker of bronchial impairment in patients with seasonal allergic rhinitis.

Background Allergic rhinitis may be associated with asthma. Forced expiratory flow between 25 and 75% of vital capacity (FEF25–75) is a measure of small airways narrowing. The aim of this study was to evaluate whether patients with seasonal allergic rhinitis (SAR) without symptoms of asthma might, nevertheless, have airways obstruction both in and out of the pollen season. Methods Fifty patients (mean age, 23.7 ± 4.9 years) with SAR were evaluated both during and outside the pollen season. All of them had moderate–severe grade of nasal obstruction. Total symptom score, rhinomanometry, nasal lavage, nasal scraping, spirometry, and methacholine (MCH) bronchial challenge were assessed in all subjects. Results Although data on forced vital capacity and response to MCH were similar in and out of the pollen season, all other parameters were markedly different. The major finding of the study was that FEF25–75 was significantly associated with nearly all of the parameters considered, including bronchial hyperreactivity, with Pearson R ranging from 31 to 75% and differences in mean FEF25–75 ranging between 14.5 and 16.5% of predicted. The more significant association was with nasal airflow in the pollen season (R = 82.8%; p < 0.001). A significant association persisted for all parameters while controlling for season. Conclusion This study highlights the link between upper and lower airways and the role of FEF25–75 as an early marker of bronchial impairment in those patients with SAR alone.

Safe administration of an inactivated virosomal adjuvanted influenza vaccine in asthmatic children with egg allergy

In order to evaluate whether the virosomal adjuvanted influenza vaccine that has been shown to have the lowest egg protein content (Inflexal V, Berna Biotech) could be administered to children with even severe egg allergy without any risk of allergic reactions, we used epicutaneous skin testing with the undiluted vaccine in 88 asthmatic children (44 with and 44 without egg allergy), none of whom had a positive response. They were then vaccinated with the whole dose of Inflexal V intramuscularly in a one-dose protocol, and the occurrence of any immediate or delayed adverse events were actively monitored for 28 days. The results showed the safety of the administration, and demonstrated that Inflexal V can be safely given without performing a vaccine skin test in children with any kind of egg allergy.

Chromosome Instability and Nibrin Protein Variants in NBS Heterozygotes

The frequency of spontaneous chromosome abnormalities in peripheral blood lymphocytes and the X-ray G2 sensitivity in lymphoblastoid cell lines (LCL) have been evaluated in heterozygous subjects from three unrelated Nijmegen Breakage Syndrome (NBS) families, characterised by different mutations in the NBS1 gene. In all the 13 NBS heterozygotes analysed, we found spontaneous chromosome instability consisting in chromosome and chromatid breakages and rearrangements, while radiosensitivity was similar to that of control LCLs in seven out of eight tested NBS heterozygotes. The densitometric analysis of nibrin by immunoblotting indicated only a slight reduction in some of the LCLs from NBS carriers, whereas the immunoprecipitation assay appears a more reliable tool to detect NBS carriers. By means of immunoprecipitation, we investigated two homozygous and four heterozygous subjects. In the cells of the NBS patient 668, with the mutation 900del25, an alternative form of nibrin with a molecular weight of approximately 55 kDa has been detected. This variant protein, together with the normal p95, was also found in the LCL 34 established from a carrier of the same family. Signals of nibrin with a molecular weight lower than 95 kDa, but higher than that observed in LCLs 668 and 34, were detected also in three carriers from the family with mutation 835del4.

Different maturation of neutrophil chemotaxis in term and preterm newborn infants

N EW BORN I N FAN TS are known to be particularly susceptible to bacterial infections1-2; the preterm infant is even more susceptible than the term neonate? Impairment of neutrophil functions (chemotaxis, chemolumineseence production, hexose monophosphate shunt activity, and intracellular microbicidal activity) has been found in healthy and stressed newborn infants and related to the susceptibility to infections in these subjects. .6 Miller 4 has suggested that defective neutrophil chemotaxis is one of the main causes of frequent neonatal infections, and this finding has been confirmed by in vivo data. 7 Laurenti et al s have reported that the defect of chemotaxis in preterm infants is similar to that in normal neonates. Up to now, however, only cross-sectional data are available and no longitudinal Studies have been Carried out. The purpose of the present study was to establish the duration of the defect in term and preterm infants.

Role of FEF25%–75% as a predictor of bronchial hyperreactivity in allergic patients

BACKGROUND The small airways may play an important role in the clinical manifestations of asthma. Forced expiratory flow between 25% and 75% (FEF25%-75%) has been proposed as an approximate measure of the caliber of distal airways. Bronchial hyperreactivity (BHR) is a feature of asthma. OBJECTIVE To evaluate the possible role of FEF25%-75% as a predictor of BHR in allergic patients with asthma and rhinitis. METHODS A total of 726 patients (mean +/- SD age, 24.7 +/- 6.3 years) were evaluated. Spirometry and methacholine bronchial challenge were evaluated in all the participants. RESULTS A difference between forced expiratory volume in 1 second and FEF25%-75% greater than 20 or a ratio between these variables greater than 1.24 discriminates between patients with no response to a mild response to methacholine vs patients with a moderate-to-severe response with high sensitivity (P < .001). CONCLUSION This study highlights the possible role of FEF25%-75% in predicting BHR in allergic individuals with airway disorders.

Nasal Obstruction is the Key Symptom in Hay Fever Patients

BACKGROUND: Allergic rhinitis is characterized by a Th2-dependent inflammation. Nasal obstruction largely depends on allergic inflammation. OBJECTIVE: The aim of this study was to evaluate the possible role of the symptom nasal obstruction in assessing patients with hay fever. METHODS: Fifty patients (mean age, 23.7 ± 4.9 years) with hay fever were evaluated both during and outside pollen season. All of them had moderate-severe grade of nasal obstruction. Total symptom score (TSS), rhinomanometry, nasal lavage, nasal scraping, spirometry, and methacholine bronchial challenge were performed in all subjects. RESULTS: During the pollen season, patients with severe nasal obstruction showed significantly higher values of TSS, IL-4, IL-5, IL-8, nasal eosinophils and neutrophils, and significantly lower values of nasal airflow, IFNγ, FEV1, FVC, and FEF 25-75 in comparison with patients with moderate nasal obstruction. Twenty (83%) patients with severe nasal obstruction showed bronchial hyperreactivity (BHR), whereas only 6 (25%) patients with moderate nasal obstruction had BHR. Outside the pollen season overlapping results were observed. CONCLUSIONS: This study provides evidence about the key role played by nasal obstruction in assessing patients with allergic rhinitis.

Probiotics and food allergy.

The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the “hygiene hypothesis” low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions.Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells.Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.

Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: A pilot study

Abstract Aim: To unravel the potential idiopathic intracranial hypertension (IIH) endocrine-metabolic comorbidities by studying the natural (and targeted drug-modified) history of disease in children. IIH is a disorder of unclear pathophysiology, characterized by raised intracranial pressure without hydrocephalus or space-occupying lesion coupled with normal cerebrospinal fluid (CSF) composition. Methods: Retrospective study (years 2001–2010) of clinical records and images and prospective follow-up (years 2010–2013) in 15 children (11 girls, 4 boys; aged 5–16 years) diagnosed previously as “IIH”, according to the criteria for pediatric IIH proposed by Rangwala, at four university pediatric centers in northern, central, and southern Italy. Results: We identified six potential endocrine-metabolic comorbidities including, weight gain and obesity (n=5), recombinant growth hormone therapy (n=3), obesity and metabolic syndrome (n=1), secondary hyperaldosteronism (n=1), hypervitaminosis A (n=1), and corticosteroid therapy (n=1). Response to etiologically targeted treatments (e.g., spironolactone, octreotide) was documented. Conclusions: IIH is a protean syndrome caused by various potential (risk and) associative factors. Several conditions could influence the pressure regulation of CSF. An endocrine-metabolic altered homeostasis could be suggested in some IIH patients, and in this context, etiologically targeted therapies (spironolactone) should be considered

Omalizumab in Children

Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of circulating immunoglobulin E (IgE) and expression of IgE high-affinity receptors on mast cells and basophils, interrupting the subsequent allergic inflammatory cascade. Current indications for treatment with omalizumab in pediatric patients are clearly defined and are confined to moderate-to-severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU). Any other prescription can only be off label. Data available from clinical trials conducted in children suggest that omalizumab is clinically effective and generally well tolerated. Given its mechanism of action, recent reports have suggested its possible clinical use in other IgE-mediated disorders, such as allergic rhinitis, food allergy, and anaphylaxis. In recent years, several studies have also investigated the possible applications of omalizumab in a number of non IgE-mediated diseases. The aim of the present review is to assess all applications of omalizumab as therapy in the pediatric population. The approved indications—allergic asthma and CSU—are reviewed. Moreover, further potential applications of omalizumab are discussed in both IgE-mediated and non-IgE-mediated diseases.