Gianluigi Marseglia

Foreign body aspiration in children

Abstract Background : The aim was to investigate the role of physical and radiological findings before bronchoscopy in the diagnosis of foreign body aspiration (FBA).

A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network.

Transient hypogammaglobulinemia of infancy (THI) is a heterogenous disorder characterized by reduced serum IgG levels in early infancy. A putative diagnosis is initially made after exclusion of other causes of hypogammaglobulinemia while a definitive diagnosis of THI can only be made a posteriori in patients with normalization of IgG levels. The aim of this study is to characterize clinical and immunological features of children with an initial diagnosis of THI in correlation to natural outcome, and to assess predictive laboratory parameters of clinical evolution for this disorder. We prospectively analysed clinical and immunological characteristics of 77 THI children at initial diagnosis and of 57 patients at follow-up. Memory B cell subsets and in vitro immunoglobulin production were evaluated. Seventy patients (91%) showed clinical symptoms. Patients suffered from infections (91%), allergies (47%) and autoimmune disease (4%). During follow-up 41/57 children (72%) normalized IgG values, mostly within 24 months of age (p<0.001), allowing the diagnosis of THI. The 16 children who did not normalize their IgG levels showed a higher frequency of severe infections and autoimmune disease (p<0.01). Moreover, they expressed a reduced frequency of IgM and switched memory B cells (p<0.01) and an inability to produce IgG in vitro (p<0.02). We conclude that most patients with an initial diagnosis of THI spontaneously recover within 24 months of age and have a benign clinical course, while a subgroup of children with undefined hypogammaglobulinemia share a clinical and immunological profile with other primary immunodeficiencies. Early recognition of children with hypogammaglobulinemia during infancy who are likely to suffer from permanent immunodeficiencies later in life would allow prompt and appropriate laboratory and clinical interventions.

Phylogenetic characterization of enterovirus 68 strains in patients with respiratory syndromes in Italy.

Enterovirus 68 (EV‐D68) was associated with mild to severe respiratory infections. In the last 4 years, circulation of different EV‐D68 strains has been documented worldwide. In this study, the phylogenetic characterization of nine EV‐D68 strains identified in patients in the 2010–2012 period and 12 additional EV‐D68 Italian strains previously identified in 2008 in Italy was described. From January 2010 to December 2012, a total of 889 respiratory specimens from 588 patients stayed or visited at the Fondazione IRCCS Policlinico San Matteo were positive for HRV or HEV. Extracted nucleic acids were amplified by one‐step RT‐PCR with primer specific for VP1 region of EV‐D68 and purified positive PCR products were directly sequenced. Overall, 9/3736 (0.24%) patients were EV‐D68 positive. Of these, 7/9 (77.8%) were pediatric and two (22.2%) were adults. Five out of seven (71.4%) pediatric patients had lower respiratory tract infection with oxygen saturation <94%. Four cases were detected from August through October 2010, while five other cases from September through December 2012. The Italian EV‐D68 strains in 2008 belonged to clade A (n = 5) and clade C (n = 7). In 2010 all the Italian strains belonged to clade A (n = 4) and in 2012, four Italian strains belonged to clade B and one to clade A. In conclusion, we provide additional evidence supporting a role of EV‐D68 in severe respiratory infection in pediatric patients. In addition, all the three EV‐D68 clades circulating worldwide were identified in Italy in a 5‐year period of time. J. Med. Virol. 86:1590–1593, 2014.

In vitro activation of mononuclear cells by two probiotics: Lactobacillus paracasei I 1688, Lactobacillus salivarius I 1794, and their mixture (PSMIX).

Background: Most studies on probiotics have described their effects on the human immune system after ingestion of LAB, but little is known about their effect on in vitro stimulation of human immune cells. Aim of the study: Evaluate the “in vitro” activity of Lactobacillus paracasei (I 1688), Lactobacillus salivarius (I 1794), and a commercial mix of the two (PSMIX, Proge Farm), on immune cells from healthy individuals. Materials: Two probiotic strains, Lactobacillus salivarius (I 1794; Proge Farm, Italy) and Lactobacillus paracasei (I 1688; Proge Farm, Italy), which are contained in the functional food ENTEROBACILLI, were evaluated for their ability to stimulate peripheral blood mononuclear cells and modulate surface phenotype and cytokine production. Results: All subjects responded to the bacteria, with different levels of response. The cell populations that showed a significant percent increase were CD4+/CD25+ cells (T-helper activated regulatory cells), CD8+/CD25+ (T-suppressor/cytotoxic activated cells), and CD16+/CD56+ (NK cells) (p<0.05). IL-12 and IFN-γ in vitro production significantly increased with exposure to probiotics (p<0.05 for both). Conclusions: This study provides the first evidence that Lactobacillus paracasei and Lactobacillus salivarius are capable of inducing a specific immune response that may be useful in the clinical setting for improving innate and adaptive immune responses.

Allergic reactions to foods by inhalation in children.

This article focuses on hypersensitivity reactions after inhalation of food particles as primary cause for food allergy. This is an increasingly recognized problem in children. Reactions are commonly diagnosed in children who develop symptoms when the food is ingested. Some children tolerate the food when it is eaten but they experience reactions to airborne food particles such as peanut, cows milk, and fish. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. Usually, respiratory manifestations include rhinoconjunctivitis, coughing, wheezing, and asthma, but in some cases even anaphylaxis has been observed. Practical approaches concerning diagnosing clinical reactivity including skin tests, serum IgE antibodies, specific provocation tests, and management have been identified. Studies are warranted to establish the accuracy of diagnostic tests as well as incidence, prevalence, and natural history of food allergy through inhalation route.

Deficiency of INFgamma producing cells in adenoids of children exposed to passive smoke.

Exposure to passive smoke is a very common event associated with increased susceptibility to respiratory tract infections. Many related adverse effects result from the ability of cigarette smoke extracts to interfere with the immune system, but the mechanism is not yet completly understood. The aim of the present study is to evaluate the intracellular cytokine profile in adenoids and peripheral blood cells of children exposed to passive smoke. Children undergoing adenoidectomy exposed or not exposed to passive smoke were studied. The intracellular cytokine profile of lymphocyte subsets in adenoids and in peripheral blood were evaluated by flow cytometry analysis. Children exposed to tobacco smoke showed a significantly lower percentage of INF-γ producing CD4+ and CD8+ cells in adenoids. Moreover a significant correlation was observed between the quantity of exposure and reduction in Th1 (CD4+INFγ+ and CD8+INFγ +) cells in adenoids. This reduction may be a contributing factor in the increasing susceptibility to respiratory tract infection in children exposed to tobacco smoke.

A forced expiratory flow at 25-75% value >65% of predicted should be considered abnormal: A real-world, cross-sectional study

Forced expiratory volume in 1 second (FEV1) is considered an important parameter for asthma diagnosis and follow-up. However, it has been proposed that forced expiratory flow at 25-75% (FEF(25-75)) could be more sensitive than FEV1 to detect slight airways obstruction. In this regard, a cutoff FEF(25-75) value has been recently established in a group of asthmatic children: FEF(25-75) < 65% of predicted has been considered impaired. However, the considered population was specifically selected. Therefore, the aim of the present study was to confirm an FEF(25-75) cutoff value in a large cohort of asthmatic children. Seven hundred allergic children (493 male subjects; median age, 11 years) with controlled and partly controlled asthma were evaluated by performing spirometry and skin-prick tests. Three hundred thirteen (44.7%) patients had FEF(25-75%) values of <65% of predicted. Two predictors were significantly associated with impaired FEF(25-75) values: (i) sensitization to perennial allergens (adjusted odds ratio [OR(Adj)], 3.4) and (ii) FEV(1) ≤ 86% of predicted (OR(Adj), 3.8). This study, conducted in real life, could suggest that FEF(25-75) value of <65% of predicted may be considered abnormal.

Long term persistence of anti-HBs protective levels in young patients with type 1 diabetes after recombinant hepatitis B vaccine.

The aim of the present study was to evaluate the persistence of anti-hepatitis B protective levels in young patients with type 1 diabetes, successfully immunised with a recombinant hepatitis B vaccine. We re-evaluated, after a 4 year follow-up, 54 patients and 70 age and sex-matched healthy subjects. Protective antibodies levels were found in 50/54 (92%) patients and in 67/70 (96%) controls. Moreover, anti-HBs levels were similar in diabetic patients and controls (means of log-titre and (sd); 1.95 (0.88) and 2.18 (0.64) patients and controls, respectively; P=0.11). No cases of clinical hepatitis were reported and all patients and controls remained HBc negative. These data demonstrate the persistence of anti-HBs levels in children, adolescents and young patients with type 1 diabetes after recombinant hepatitis B vaccine showing evidence of longterm immunogenity and protective effect.

Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.

Serum Leptin Levels in Patients with Pollen-Induced Allergic Rhinitis

Background: Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis. The aim of the study was to evaluate the serum leptin levels in a cohort of patients with pollen-induced allergic rhinitis, enrolled outside the pollen season, and in a group of healthy controls. Methods: The study included 75 subjects: 41 patients with moderate–severe persistent allergic rhinitis due to a pollen allergy and 34 normal subjects. All subjects were prospectively and consecutively evaluated. A skin prick test and blood sampling for assessing serum leptin levels, eosinophils, specific IgE, and nasal challenge were performed in all subjects. Results: After analyzing genders separately, female allergic patients showed significantly higher levels than normal females (p = 0.031), whereas the comparison between allergic and normal males was not significant (p = 0.9651). Leptin serum levels were significantly related with age in normal (p = 0.0059) and allergic (p = 0.0042) females. In addition, BMI and leptin levels were significantly correlated (p = 0.01) in all allergic patients; there were other significant relationships between leptin levels and symptom severity in females (p = 0063, r = 0.68), peripheral eosinophils in males (p = 0.023, r = 0.49), and allergen threshold dose at nasal challenge in both genders (males: p = 0.0001, r = –0.85; females: p = 0.0001, r = –0.95). Conclusions: This preliminary study provides the first evidence of significantly higher leptin serum levels in female patients with pollen-induced allergic rhinitis outside the pollen season.