ADENOID HYPETROPHY: DEFINITION OF SOME …S)JBRHA26-1.pdf · de amici m1, ciprandi g2, marseglia a 3, licari a, matti e4, caputo m 4,benazzo m, castellazzi am3, pusateri a4 , pagella

JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS

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Vol. 26, no. 1 (S), 1-7 (2012)

Adenoids removed for airway obstruction and/or recurrent infections have been studied to identify a possible mechanism to explain chronicity. In this regard, macrophages may play a relevant pathogenic role as well as neutrophils during bacterial infections and eosinophils in allergic inflammation. Therefore, this study aimed at investigating some mediators as surrogate markers of inflammation in children who had to undergo to adenoidectomy. Globally, 67 children (25 females, 42 males, mean age 4.9 years), affected by persistent obstruction caused by adenoid hypertrophy were consecutively enrolled into the study. Blood samples were collected from patients and controls to determine serum CD163, Myeloperoxidase (MPO) and ECP. There were significant differences between patients and controls for serum CD163 (p<0.0001); MPO (p<0.0001); serum ECP (p<0.0001). This study demonstrated some risk factors for severe AH: apnoea, recurrent respiratory infections, and high serum CD163 levels.

Key-words: Adenoidectomy, Adenoids hypertrophy, CD163, Children, Risk Factors

Corresponding author: Gian Luigi MarsegliaDepartment of Pediatrics, University of PaviaFondazione IRCCS Policlinico San MatteoP.le Golgi, 2 – 27100 Pavia (PV) ItalyPhone +39.0382.502818FAX +39.0382.527976E-mail: [email protected]

ADENOID HYPETROPHY: DEFINITION OF SOME RISK FACTORS

DE AMICI M1, CIPRANDI G2, MARSEGLIA A3, LICARI A3, MATTI E4, CAPUTO M4, BENAZZO M4, CASTELLAZZI AM3, PUSATERI A4 , PAGELLA F4, MARSEGLIA GL3.

1 Pediatric Unit, Foundation IRCCS Policlinico San Matteo, Pavia, Italy 2 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy3 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

4 ENT Department, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

Adenoids with obstructive hypertrophy are considered to be one of the most ancient and common problem in Paediatrics. Anatomically, adenoids are part of the Waldeyer’s ring and, since they may create mechanical Eustachian Tube (ET) obstruction, they are relevant in the pathogenesis of Otitis Media (OM). In addition, to diagnose adenoid hypertrophy, nowadays nasal endoscopy is considered to be the gold standard even in young kids, as this technique is also able to detect a possible association between adenoid inflammation/infection and OM, especially during infancy and early childhood (1).

Nasal-associated lymphoid tissues are major inductive organs in the mucosal immune system of the upper respiratory tract (2). These tissues are localized in a strategic position, in order to mediate local and regional immune functions, as they are exposed both to outside air antigens and to alimentary antigens. Adenoids have characteristics similar to lymphoid glands, and, together with tonsils, are part of the mucosa-associated lymphoid tissues, having a major role in the induction of immunity. Indeed, they actually play a main role as effector organs in

both mucosal-type and systemic-type adaptive immunity (3).

Approximately one million adenoidectomy procedures were performed in the United States in the 1970s, but, in the last 20 years, the number of such operations has dramatically decreased, mainly because of the several discussions over the pros and cons for this procedure (4). Nevertheless, adenoidectomy remains one of the most commonly performed paediatric surgical procedures in the world (5). In Paediatrics, the most common indications for such procedure include airway obstruction (often combined with tonsillectomy), chronic otitis media (often combined with bilateral myringotomy and tubes), and medically refractory chronic rhinosinusitis (6). In patients with healthy ears and adenoid hypertrophy, history of apnoea is the main indication for adenoidectomy, together with a high frequency of upper respiratory tract infections (7). Adenoids removed for airway obstruction and/or recurrent infections have been studied to identify a possible mechanism to explain chronicity, and they have shown the presence of bacterial organized into biofilms






Vol. 26, no. 1 (S), 9-14 (2012)

Key words: Thyroid autoimmunity, Atopy, Children

Corresponding Author: Michele Miraglia del Giudice MD, Department of Pediatrics, Second University of Naplese-mail: [email protected]

Recently, there has been considerable interest in the relationship between allergic and autoimmune diseases. We evaluated the prevalence of thyroid autoimmunity in 566 children affected by atopic dermatitis (AD), urticaria, rhinitis, chronic cough, and asthma. Our results suggest that allergy and autoimmunity can be two potential outcomes of dysregulated immunity. It is tempting to speculate that NK Th2 cells can favour asthma onset and at the same time improve thyroid autoimmunity.

ATOPY AS A RISK FACTOR FOR THYROID AUTOIMMUNITY IN CHILDREN

PEDULLÀ M1, MIRAGLIA DEL GIUDICE M1, FIERRO V1, ARRIGO T2, GITTO E2, SALPIETRO A2, LIONETTI E3, SALPIETRO V2, LEONARDI S3, SANTANIELLO F1, PERRONE L1

1 Department of Pediatrics, Second University of Naples, Italy2Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy

3Department of Pediatrics, University of Catania, Italy

Recent observations have challenged the validity of the Th1/Th2 paradigm. The new paradigm identifies additional lymphocyte subsets, such as Th17 cells (1), soluble factors such as IL-9 (2), and regulatory T cells (T reg) (3). Consequently, there has been considerable interest in defining the relationship between the expression of allergic and autoimmune disease in patient populations.

A series of clinical reports addressed the coincidence or co-prevalence of atopy with autoimmune disease such as psoriasis, rheumatoid arthritis, multiple sclerosis and type 1 diabetes mellitus (4). Nevertheless recent studies suggest that IL-4 and IgE may be involved in the development, progression, and maintenance of Graves’ disease (5) and a role for Treg in the natural progression of hyperthyroid Graves’ disease to Hashimoto’s thyroiditis and hypothyroidism in humans (6), the occurrence of a possible association between thyroid autoimmunity and atopy has not been extensively investigated.

In order to evaluate the independent effects of atopy on the development of thyroid autoimmunity we describe our experience concerning atopic and non atopic children affected by atopic dermatitis, urticaria, rhinitis, chronic cough and asthma, and associated thyroid autoimmunity.

MATERIALS AND METHODS

From January 2007 to December 2010, 756 children were consecutively referred to the Pediatric Clinic of the Pediatric

Department at the Second University of Naples for evaluation of atopic symptoms. Because of immunological immaturity 190 children younger than 24 months were excluded from our analysis Informed consent was obtained from all the patients and their parents.

We included in the study children in whom a diagnosis of asthma, chronic cough, allergic rhino-conjunctivitis, atopic dermatitis and urticaria was confirmed by a paediatric allergist. We defined bronchial asthma as one episode from 2 years of age or any episodes of wheezing independent of age if combined with atopic symptoms in the family or others atopic symptoms in the child and/or a bronchodilator-test confirmation of the positive response of a 12% increase in the forced expiratory volume (FEV1) in 1 sec (7). Chronic cough was defined as a cough of >4 weeks duration (9). Allergic rhino-conjunctivitis was diagnosed if sneezing nasal obstruction watery rhinorrhoea, nasal itching, conjunctival hyperemia and photophobia appeared at least twice after exposure to a particular allergen and was unrelated to infection. Atopic dermatitis was defined according to Hanifin and assessed with the Scorad index (8). Urticaria was defined as wheals consisting of three features: (I) central swelling of various sizes, with or without surrounding erythema; (II) pruritus or occasional burning sensations; and (III) the skin returning to normal appearance, usually within 1-24 hours. (10).

The diagnosis of atopy based on clinical history was confirmed by skin-prick test (SPT) as well as by measuring serum specific IgE levels concentration (ImmunoCAP Specific IgE-Phadia).

SPTs were performed using a standard battery of allergens: house dust mite (HDM), Parietaria officinalis, grasses, mould






Vol. 26, no. 1 (S), 15-25 (2012)

Key Words: spirometry, FEF25-75, sensitisation

Corresponding Author:Giorgio Ciprandi, M.D.Viale Benedetto XV 6, 16132 Genoa, ItalyPhone 00 39 10 35331820FAX 00 39 10 3538664E-mail: [email protected]

IMPAIRED SPIROMETRY MAY SUGGEST SENSITIZATION.

CIPRANDI G1, SALPIETRO A2, LEONARDI S3, TOSCA MA4, MIRAGLIA DEL GIUDICE M5, SALPIETRO C2, LA ROSA M3, CIRILLO I6, SIGNORI A7, MARSEGLIA GL8.

1 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 2 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy

3 Department of Pediatrics, University of Catania, Italy4 Pneumology and Allergy Pediatric Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

5 Department of Pediatrics, Second University of Naples, Italy6 Navy Medical Service, La Spezia, Italy

7 Department of Health Sciences, Genoa University8 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

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.

The prevalence of allergic rhinitis, conjunctivitis, and asthma is worldwide high: up to 40% of the general population in some countries (1-3). Moreover, there is a close association between allergic rhinitis and asthma and allergic rhinitis may be a risk factor for the onset or the worsening of asthma (4-5). Both disorders are characterized by an airflow limitation. Functional evaluation of bronchial airflow is mainly based on performing spirometry. The gold standard parameter to evaluate bronchial obstruction is forced expiratory volume/1 second (FEV1) (6). However, it has been proposed that the forced expiratory flow at the 25 and 75% of the pulmonary volume (FEF25-

75) might be useful in predicting airway responsiveness, bronchial reversibility, and early bronchial involvement in patients with allergic rhinitis. (7).

Usually, the diagnosis of allergic disease is based on the concordance between the allergen-specific IgE production (i.e. sensitization) and the symptom occurrence following the exposure to the sensitizing allergen. On the other hand, spirometry is a routine procedure requested for several occupational and/or sportive rules. In this regard, Italian Navy Medical Service has stated that all military people, who has to obtain a professional certificate (e.g. frogman, combat diver, etc), must perform spirometry; if spirometry

is impaired, subjects should be carefully evaluated.


The aim of this study was to analyze the findings of a session of certificate visits in a cohort of 778 (680 males, mean age 25.1 years) Italian Navy military personnel, who performed spirometry for periodic fitness visit in order to be allowed to maintain the qualification certificate. The visits were performed during the spring. The Navy Review Board approved the study procedures and written informed consent was obtained from each subject. It should be noted that all subjects included in this study had never symptoms of lower airway disease or asthma: in fact, the military service does not accept subjects who have asthma or other known lung diseases. In addition, only no smokers were enrolled in the study.

Spirometry was performed by using a computer-assisted spirometer (Pulmolab 435-spiro 235, Morgan, England), with optoelectronic whirl flow meter. It was performed as stated by the European Respiratory Society (6). Skin prick test was performed in all subjects as stated by the European Academy of Allergy and Clinical Immunology (8). The panel consisted of: house dust mites

JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS Vol. 26, no. 1 (S), 0-0 (2012)





Keywords: allergic asthma, rhinitis, children, FEV1, FEF25-75, spirometry, reversibility, bronchodilation test.

Corresponding Author:Giorgio Ciprandi, M.D.Viale Benedetto XV 6, 16132 Genoa, ItalyPhone 00 39 10 35338120 FAX 00 39 10 3538664E-mail [email protected]

IMPAIRED FEF25-75 VALUES MAY PREDICT BRONCHIAL REVERSIBILITY IN ALLERGIC CHILDREN WITH RHINITIS OR ASTHMA.

CIPRANDI G1, CAPASSO M2, LEONARDI S3, LIONETTI E3, LA ROSA M3, SALPIETRO C4, MIRAGLIA DEL GIUDICE M5, CIRILLO I6, TOSCA M7, MARSEGLIA GL8.

1 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 2 Department of Paediatrics, Ospedale Civile “Ave Gratia Plena”, Piedimonte Matese (CE), Italy

3 Department of Pediatrics, University of Catania, Italy4 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy

5 Department of Pediatrics, Second University of Naples, Italy6 Navy Medical Service, La Spezia, Italy

7 Pneumology and Allergy Pediatric Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy8 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

FEV1 is considered an important parameter for asthma diagnosis and follow-up. However, it has been proposed that FEF25-75 could be more sensitive than FEV1 to detect slight airways obstruction. Bronchial reversibility defined by positive response to bronchodilation test. The aim of the present study was to define whether an impaired FEF25-

75 value (< 65% of predicted) may be predictive for reversibility in a large cohort of allergic children with rhinitis or asthma. Six hundred allergic children were recruited: 300 with controlled asthma and 300 with allergic rhinitis. All of them were evaluated by performing spirometry, bronchodilation test, and skin prick test. Two predictors were significantly associated with bronchial reversibility: i) an impaired FEF25-75 value (< 65% of predicted), and ii) sensitization to perennial allergens. It was more relevant in children with rhinitis (ORAdj:8.9 and 2.2 respectively). In conclusion, this study, conducted in real life, could suggest that an impaired FEF25-75 value (<65% of predicted) may be considered a reliable marker of bronchial reversibility, mainly in children with allergic rhinitis

Numerous epidemiological studies have demonstrated that allergic rhinitis may be closely associated with asthma (1-4). In addition, allergic rhinitis may be considered a risk factor for both onset and worsening of asthma (5). Reversible airflow obstruction, bronchial inflammation and hyper-reactivity characterize asthma. Asthma diagnosis is based on clinical and functional evaluation. Spirometry is mandatory in asthmatic patients and GINA (Global Initiative for Asthma) guidelines (6) state that the forced expiratory volume/1 second (FEV1) represents the gold standard lung function measurement to evaluate bronchial obstruction. Spirometric parameters are well standardized and their interpretation is commonly

recognized (7,8). In addition, reversibility of airflow obstruction is considered a main functional characteristic of asthma. This reversibility may be spontaneous or induced by drugs, such as bronchodilators, mainly b2-agonists. The bronchodilation test is usually prescribed to demonstrate the reversibility of bronchial obstruction and a positive response defines a correct asthma diagnosis.

On the other hand, asthmatic patients may often have normal FEV1 values when they are clinically stable (9). Moreover, small airways are deeply involved in the pathogenesis of asthma. Even though there is no direct marker for obstruction/inflammation of small airways, it has been proposed that the forced expiratory flow






Vol. 26, no. 1 (S), 27-33 (2012)

Key words: allergic rhinitis, asthma, FEF25-75, children, nitric oxide

Corresponding Author:Giorgio Ciprandi, M.D.Viale Benedetto XV 6, 16132 Genoa, ItalyPhone 00 39 10 35331820FAX 00 39 10 3538664E-mail [email protected]

IMPAIRED FEF25-75 MAY PREDICT HIGH EXHALED NITRIC OXIDE VALUES IN CHILDREN WITH ALLERGIC RHINITIS AND/OR ASTHMA.

CIPRANDI G1, TOSCA MA2, CIRILLO I3, LIONETTI E4, LEONARDI S4, MIRAGLIA DEL GIUDICE M5, LA ROSA M4, SALPIETRO A6, CAPASSO M7, MARSEGLIA GL8.

1 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 2 Pneumology and Allergy Pediatric Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

3 Navy Medical Service, La Spezia, Italy4 Department of Pediatrics, University of Catania, Italy

5 Department of Pediatrics, Second University of Naples, Italy6 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy

7 Department of Paediatrics, Ospedale Civile “Ave Gratia Plena”, Piedimonte Matese (CE), Italy8 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

Allergic rhinitis and asthma are closely associated. Inflammation is a common pathological characteristic shared by both disorders. The measure of the fractional concentration of exhaled nitric oxide (FeNO) may be considered a surrogate marker for airway inflammation. Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) has been previously demonstrated to be able to predict BHR and bronchial reversibility. The aim of this study was to evaluate whether impaired FEF25-75 values may be related to FeNO values in a pediatric cohort of allergic subjects. 850 children with allergic rhinitis, allergic asthma, or both, were evaluated. Bronchial function (FEV1, FVC, and FEF25-75), FeNO, and sensitizations were assessed. Bronchial function and FeNO were significantly different in the 3 groups (p<0.001). A strong inverse correlation between FeNO and FEV1was found in patients with rhinitis, asthma and asthma with rhinitis (r= -0.72, r=-0.70 and r= -0.70, respectively). Impaired FEF25-75 values (such as <65% of predicted) were significantly associated with high FeNO levels (such as > 34 ppb). In conclusion, this study provided evidence that FEF25-75 is strongly and inversely related with FeNO and FEF25-75 may predict high FeNO levels in children with allergic rhinitis, asthma or both.

Asthma is characterized by airway inflammation, reversible bronchial obstruction, and bronchial hyperreactivity (BHR) (1). Allergic rhinitis is similarly characterized by mucosal inflammation and may be frequently associated with asthma (2). Hence, airway inflammation represents a common pathogenic pathway for both diseases.

Accurate measurement and monitoring of inflammatory airways state is a crucial issue in managing allergic patients (3), but a correct assessment of airway inflammation needs invasive methods (bronchial biopsy and/or lavage) or sputum analysis, both are complex and require adequate structures. It is now possible to assess airway inflammation by measuring the fractional

concentration of exhaled nitric oxide (FeNO) during an office visit and there is international consensus on this testing methodology (4,5). There is evidence that the FeNO level is well correlated to BHR degree, bronchial reversibility, and peripheral or bronchial eosinophils (6,7).

On the other hand, bronchial obstruction is a paramount characteristic of asthma and can be accurately measured by the forced expiratory volume/1 second (FEV1) (8.9). Nevertheless, the forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) has been proposed as more sensitive indicator of persistent airflow obstruction than FEV1 (10). Recently, it has been defined that FEF25-

75 may predict the response to bronchodilation test and a value < 65% of predicted should be considered abnormal






Vol. 26, no. 1 (S), 35-40 (2012)

Key words: asthma, probiotics, L.Reuteri DSM 17938, FeNO

Corresponding Author:Michele Miraglia del Giudice MDDepartment of Pediatrics, Second University of Naplese-mail: [email protected]

Recently, it has been hypothesized that the oral administration of specific live probiotic strains may have therapeutic potential in the treatment of allergic inflammation. The aim of this study was to evaluate the effect of the oral L. reuteri DSM 17938 administration (1X108CFU), in airways allergic inflammation in mild persistent asthmatic children. In this DBPC randomized study we selected 50 children ( 6-14 years old), affected by mild persistent asthma (GINA step 2) and allergic to HDM. At the run-in period (T-2), the children were submitted to medical examination, prick tests for the main respiratory allergens, spirometry and children asthma control test (C-ACT). We selected only the children with well controlled asthma (C-ACT >19 and FEV1> 80%). After two weeks (T0) the children were allocated into two groups, the FeNO was measured and the breath condensate was collected. Group A children were treated with the placebo (5 drops per day) and Group B children with L. reuteri (108CFU =5 drops per day) for 60 days. After the treatment period (T1), all patients were evaluated by medical examination, C-ACT, spirometry, FeNO measurement and exaled breath condensate analysis. The FeNO values showed a significant reduction (p=0,045) in L. reuteri group but not in the placebo group at the end of the treatment (T1). Furthermore, the cytokines exam showed an increase in IL-10 levels (p<0.05) and a significant reduction in IL-2 levels (p<0.05) only in L. reuteri group at T1. No significant differences in FEV1 values and C-ACT score were found in both groups. In conclusion, these data showed that L. reuteri (108 CFU) was effective in reducing bronchial inflammation in asthmatic children. No significant effect was found on FEV1 values and C-ACT score, probably because we selected children with well controlled asthma.

AIRWAYS ALLERGIC INFLAMMATION AND L. REUTERII TREATMENT IN ASTHMATIC CHILDREN

MIRAGLIA DEL GIUDICE M1, MAIELLO N1, DECIMO F1, FUSCO N1, D’AGOSTINO B2, SULLO N2, CAPASSO M1, SALPIETRO V3, GITTO E3, CIPRANDI G4, MARSEGLIA GL5, PERRONE L1.

1 Department of Pediatrics, Second University of Naples, Italy2 Department of Experimental Medicine, Pharmacology Section, Second University of Naples, Italy

3 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy4Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy5Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

Over the past decades, an increase in the incidence of allergic diseases and asthma has been observed in pediatric patients, in particular in the industrial countries. For this reason, nowadays, allergies are the most common chronic diseases in children all over the world. Many theories have been suggested to explain this phenomenon and the most plausible hypothesis is the “hygiene hypothesis”, elaborated by Strachan in 1989 (1). According to the “hygiene hypothesis”, the immune system lack of exposure to microbial agents in the early years of life increases the risk of allergic diseases (1). Hence, children who live

in countries with the best hygienic-sanitary conditions have a predisposition to allergies, because of the reduced environmental antigen stimulation. In these patients the physiological immune system “switch” Th2-Th1 turns out to be damaged with a lack of immunological tolerance. Another theory, the “microflora hypothesis”, said that the overuse of antibiotics and changes in the diet typical of the industrial countries, have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, which has led to an increase in the incidence of allergic diseases (2). A lot of studies indicate






Vol. 26, no. 1 (S), 41-48 (2012)

Key Words: Airway epithelium, Airway inflammation, Asthma, Exacerbation, Immunity

Corresponding Author:Giovanna Vitaliti Via Santa Sofia 78 95100 Catania ItalyTel: 0039- 0953782939Fax: 0039-0953782385Email: [email protected]

Asthma is traditionally defined as a chronic disease characterized by bronchial hyper-responsiveness and lung inflammation. The airway inflammation and remodelling together likely explain the clinical manifestations of asthma. The mechanisms by which the external environmental cues, together with the complex genetic actions, propagate the inflammatory process that characterizes asthma are beginning to be understood. There is also an evolving awareness of the active participation of structural elements, such as the airway epithelium, airway smooth muscle, and endothelium, in this process; these structural elements within the lung and the bone marrow serve as reservoirs for and the source of inflammatory cells and their precursors. Although often viewed as separate mechanistic entities, so-called innate and acquired immunity often overlap in the propagation of the asthmatic response. This review examines the newer information on the pathophysiologic characteristics of asthma and focuses on the role of airway epithelium in the exacerbation of the disease.

FUNCTION OF THE AIRWAY EPITHELIUM IN ASTHMA

LEONARDI S1, VITALITI G1, MARSEGLIA GL2, CAIMMI D2, LIONETTI E1,MIRAGLIA DEL GIUDICE M3, SALPIETRO C4, SPICUZZA L1, CIPRANDI G5, LA ROSA M1.

1 Department of Pediatrics, University of Catania, Italy2 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy


5 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy

Asthma is traditionally defined as a chronic disease characterized by bronchial hyper-responsiveness (BHR) and lung inflammation, particularly within the airways [1]. It manifests clinically with repeated, variable, episodic attacks of dyspnea, cough, and wheeze occurring secondary to bronchoconstriction in the setting of airway hyper-responsiveness and mucous hypersecretion. In both allergic and non-allergic forms of the disease, the airway is infiltrated by T-helper (Th) cells, which predominantly secrete characteristic cytokines such as interleukin (IL)-4, IL-5, and IL-13, the so-called Th2 cytokine milieu. These cytokines stimulate mast cells, cause eosinophilia, promote leukocytosis, and enhance B-cell IgE production, and may also participate in the characteristic airway remodelling of asthma. However, for an individual to develop an asthmatic phenotype is required the combination of both exposure to appropriate stimuli and a genetic predisposition [2, 3].

Histopathological analyses of bronchial biopsies from asthmatic subjects demonstrate that inflammatory cell infiltration is associated with airway remodelling

[4-7]. Among alterations in the structure of the airways that characterize airway remodelling, increased airway smooth muscle (ASM) mass may represent a key feature contributing to airflow obstruction observed in severe forms of asthma [8-11]. The relationship between ASM cells and resident cells, especially epithelial cells AND basal steam cells [12], may be an additional factor, which enhances or perpetuates the ASM remodelling process.

The aim of our review is to highlight the role of the airway epithelium in the development of asthma and bronchial hyperreactivity.

Asthma and the airway epithelial phenotypeAirway epithelium forms a continuous, highly

regulated physical barrier lining of the airway lumen, which prevents invasion of inhaled environmental agents such as aeroallergens, pollutants and pathogens. A number of observations suggest that airway epithelium is disrupted in asthma. These include the detachment of columnar ciliated cells, presence of epithelial cell aggregates in the






Vol. 26, no. 1 (S), 49-52 (2012)

Key Words: helicobater pylori infection, asthma, atopy, children.

Corresponding Author:Michele Miraglia del Giudice MDDepartment of Pediatrics, Second University of Naplese-mail: [email protected]

A potential role of Helicobater Pylori (HP) infection in several extra-intestinal pathologies has been recently suggested. The aim of our study was to assess the role of serology positive for HP in atopic and non atopic infants and children affected by atopic dermatitis, urticaria, rhinitis and asthma. We included 615 children affected by atopic diseases. According to prick test positivity and age, we divided the patients into two groups: atopic or non-atopic patients and infants (0-2 years) or children (2-12 years). The serum levels of antibodies for H. pylori immunoglobulin G were measured by using an ELISA test. We found a not significant difference between group 1 and group 2 about atopy. There was a significant higher frequency of HP positive serology in older children. As for infants, a higher significant prevalence of HP positive serology was found in non-atopic patients. HP positive serology was significantly higher only in non-atopic infants affected by atopic dermatitis and urticaria than in atopic. In group 2, non atopic children shown a significant increase in the prevalence of HP serum positivity than atopic children. As for asthma, there was an higher prevalence of HP serology positive in non atopic asthmatic children group than in atopic asthmatics. On the contrary, the prevalence of positive HP serology was not significantly different between atopic and non atopic children affected by dermatitis, urticaria, and rhinitis. The present data confirm an inverse association between HP positive serology and atopy in both groups. However, the higher prevalence of positive HP serology was observed in non atopic asthmatics children than in atopic asthmatics. We could speculate that HP infection can favour non atopic asthma onset.

COULD BE A LINK BETWEEN NON ATOPIC ASTHMA AND HP INFECTION?

PEDULLÀ M1, PERRONE L1, FIERRO V1, CAPRISTO C1, SALPIETRO C2, LEONARDI S3,LA ROSA M3, ARRIGO T2, LICARI A4, LONGARETTI P4, MIRAGLIA DEL GIUDICE M1



A potential role of Helicobater Pylori (HP) infection in several extra-intestinal disorders, such as anemia, failure to thrive, idiopathic thrombocytopenic purpura, asthma and allergic disorders has been recently suggested (1). The HP infection seems to be able to induce chronic inflammation which cause remote effects from the primary site of infection (2). Recent data suggest an inverse association between HP infection and asthma (3). Furthermore HP positive serology was inversely related to many allergic disease, as recent wheezing, allergic rhinitis, dermatitis and eczema (3).

The aim of this study was to assess the role of serology positive for HP in atopic and non atopic infants and children affected by atopic dermatitis, urticaria, rhinitis, and asthma.


From January 2008 to December 2010, 615 children consecutively referred to the Paediatric Department of the Second University of Naples for atopic dermatitis, urticaria, rhinitis and asthma. The criteria for asthma diagnosis were based on a history of two or more episodes of wheezing within the last 6 months if combined with atopic symptoms in the family or others atopic symptoms in the child and/or a positive response to the bronchodilation test, such as a > 12% increase in the forced expiratory volume (FEV1) in 1 sec (4). Allergic rhino-conjunctivitis was diagnosed if sneezing, nasal obstruction, watery runny nose, nasal itching, conjunctiva hyperemia and photophobia appeared at least twice after exposure to a particular allergen and were unrelated to infection (5). Atopic dermatitis was defined according to Hanifin and Rajka diagnostic criteria






Vol. 26, no. 1 (S), 53-61 (2012)

Keywords: Allergic children, Asthma, Respiratory function, IL-10, IL-23, IL-4

Corresponding Author: Carmelo Salpietro Department of Genetic and ImmunologyG. Martino Hospital MessinaE-mail: [email protected]

Asthma is characterized by airway inflammation that is controlled by a complex cytokine network. The Th1/Th2 imbalance has been well documented in the pathogenesis of allergic asthma. Recently, Th17 cells and regulatory T (Treg) cells have been found to participate in the pathogenesis of allergic asthma. This study aimed at verifying whether anti-inflammatory treatment could change serum IL-4, IL-10 and IL-23 in asthmatic children. Globally, 78 children (40 males and 38 females, median age 9.3±3.7 years), with asthma and monosensitized to house dust mites, were evaluated. Lung function (such as FEV1) and serum IL-4, IL-10 and IL-23 levels were measured at baseline (T0), after 4 weeks (T1) and after 12 weeks (T2) of inhaled corticosteroid (ICS) treatment. The control group consisted of 40 healthy children (22 males and 18 females) age matched. At baseline, IL-4 and IL-23 levels were higher in severe asthmatics than in control group (p < 0.001), while serum IL-10 levels were significantly lower in group of asthmatic children as compared to healthy control group (p < 0.001). At T2, IL-4 and IL-23 significantly diminished (p < 0.001), while IL-10 significantly increased. There was significant relationship between FEV1 and IL-4, IL-10 and IL-23 at T0 (r=-0.784; r=-0.735 and r=-0.787, respectively). Moreover, there were correlations between FEV1 and IL-4, IL-10 and IL-23 in patients at T1 (r=-0.563; r=-0.539 and r=-0.583, respectively) and at T2 (r=-0.549; r=-0.428 and r=-0.393, respectively). The present study provided evidence that: i) serum IL-23 was up-regulated also in asthmatic children, ii) ICS treatment was able of reducing IL-23, and iii) IL-23 change well related with lung function improvement. Thus, it is presumable that IL-23 could be a suitable marker of allergic inflammation in asthma.

SERUM IL-23 IN ASTHMATIC CHILDREN

CIPRANDI G1, CUPPARI C2, SALPIETRO A2, TOSCA M3, GRASSO L2, RIGOLI L2, LA ROSA M4, MARSEGLIA GL5, MIRAGLIA DEL GIUDICE M6, SALPIETRO C2.

1 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 2 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy3 Pneumology and Allergy Pediatric Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy


6 Department of Pediatrics, Second University of Naples, Italy

Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity as measured by school absences, emergency department visits, and hospitalizations (1). In asthma pathogenesis, the development of immune response depends on a repertoire of cytokines produced by numerous cells, mainly CD4+ helper T cells. These lymphocytes can be paradigmatically divided into two subsets: T helper type 1 (Th-1) and T helper type 2 (Th-2), based on their cytokine profiles (2). Effector Th1 cells are involved in delayed-mediated type hypersensitivity through their production of IFN-γ and IL-2, whereas Th2 cells secrete IL-4, IL-9, IL-10 and IL-13, and promote antibody-mediated humoral immune

responses (3). Upon airway allergen challenge in allergic patients, naïve CD4+ T cells differentiate to a prevailing Th2 effector phenotype characterized by IL-4, IL-5, and IL-13 secretion. Furthermore, these cytokines induce the recruitment of eosinophils, mast cells and lymphocytes, hyperplasia of smooth muscle and goblet cells, and airway hyperresponsiveness, associated with increased serum IgE concentration (4,5,6). Besides Th2/Th1 schema, other T sub-populations, such as regulatory T (Treg) cells and Th17 cells, play a role in atopic diseases (7). Treg may play a critical role in controlling the development of asthma, as they can suppress a potentially harmful immune response. There is evidence that the number and function of two






Vol. 26, no. 1 (S), 63-68 (2012)

Keywords: Celiac disease, echocardiography, gluten free-diet, hearth.

Corresponding Author: Elena LionettiDepartment of PaediatricsUniversity of CataniaVia Santa Sofia 78 95124 – Bari ItalyTel. ++39 095 3782684 Fax ++39 095 3781288E-mail: [email protected]

The aim of the present work was to assess the prevalence of early cardiac involvement in children with celiac disease (CD), and the impact of a gluten free diet (GFD) on this issue. Sixty CD children was compared with a control group of 45 healthy children by an echocardiographic examination. CD patients were re-evaluated 1-year after 1-year GFD. Main outcome measures were ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), any regurgitating valve lesions. Mild cardiac involvement was found in 13 CD children and in one control (21.7% vs. 2.2%; p=0.003), and was secondary to regurgitation of mitral valve, aortic valve, pulmonary and tricuspid valve, or to impaired ejection fraction. CD children as compared to controls had significantly lower contractility indices, and higher left ventricular dimensions. In patients adhering to the GFD all valve regurgitations resolved, and the echocardiographic parameters significantly improved. Subclinical cardiac involvement in CD children is quite frequent, and GFD may exert a beneficial effect on the overall cardiac performance.

SUBCLINIC CARDIAC INVOLVEMENT IN PAEDIATRIC PATIENTS WITH CELIAC DISEASE: A NOVEL SIGN FOR A CASE FINDING APPROACH.

LIONETTI E1, CATASSI C2,3, FRANCAVILLA R4, MIRAGLIA DEL GIUDICE M5, SCIACCA P1, ARRIGO T6, LEONARDI S1, SALPIETRO A6, SALPIETRO C6, LA ROSA M1.

1 Department of Pediatrics, University of Catania, Italy2 Department of Paediatrics, Università Politecnica delle Marche, Ancona

3Center for Celiac Research, University of Maryland School of Medicine, Baltimore4Department of Paediatrics, University of Bari


It is currently recognized that celiac disease (CD) can manifest with a wide range of clinical presentations, including the typical malabsorption syndrome (such as chronic diarrhoea, weight loss, abdominal distension) and a spectrum of symptoms potentially affecting any organ or system (1). Because CD presentation may be often atypical or even clinically silent, many patients remain undiagnosed and are exposed to the risk of long-term complications, such as osteoporosis, infertility, or cancer (2). The burden of illness related to CD is doubtless higher than previously thought (3) and there is growing interest on the social dimensions of this disorder.

Recently, several studies have demonstrated a close association between CD and heart diseases in adults (4-10). However, there is scarce information about cardiac involvement in CD in the paediatric age (11) and no study has prospectively evaluated cardiac function before and

after gluten-free diet (GFD).We therefore performed a prospective case-control

study in which the primary objectives were to assess the prevalence of early cardiac involvement in a population of CD children, and the impact of a GFD on the overall cardiac performance.


All consecutive children with CD diagnosed in the Department of Paediatric Gastroenterology of the University of Catania (Italy) between November 2008 and June 2009 were candidates for inclusion in the study. CD diagnosis was based on: i) positive serology (IgA and/or IgG antibodies to human tissue transglutaminase), ii) histological evidence of villous atrophy with crypt hyperplasia and increase in intraepithelial lymphocytes at the small intestinal biopsy, and iii) disappearance






Vol. 26, no. 1 (S), 69-76 (2012)

Key Words: Children, H. Pylori, Probiotics, Therapy

Corresponding Author: Elena Lionetti, MDDepartment of PaediatricsUniversity of CataniaVia S. Sofia, 7895125 – Catania, ItalyTel. ++39 095 3782684 Fax ++39 095 3781288E-mail: [email protected]

Approximately 50% of the world population is infected with Helicobacter pylori (H. pylori), with the highest prevalence rates in developing countries. The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30%. Current interest in probiotics as therapeutic agents against Helicobacter pylori is stimulated by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Available data in children indicate that probiotics seems to be efficacious for the prevention of antibiotic associated side-effects, and might be of help for the prevention of Helicobacter pylori complications by decreasing Helicobacter pylori density and gastritis, and for the prevention of Helicobacter pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the Helicobacter pylori eradication rate.

PROBIOTICS AND HELICOBACTER PYLORI INFECTION IN CHILDREN

LIONETTI E1, FRANCAVILLA R2, CASTELLAZZI AM3, ARRIGO T4, LABÒ E3, LEONARDI S1, CIPRANDI G5, MIRAGLIA DEL GIUDICE M6, SALPIETRO V4, SALPIETRO C4, LA ROSA M1.

1 Department of Pediatrics, University of Catania, Italy2 Department of Biomedicina dell’Età Evolutiva, University of Bari, Italy

3 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy4 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy

5 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 6 Department of Pediatrics, Second University of Naples, Italy

Probiotics were recently defined by FAO/WHO as “Live microorganisms which when administered in adequate amounts confer a health benefit on the host“ (1). Several controlled clinical trials have shown in children beneficial outcomes for the use of probiotics in some different conditions as rotavirus infections, antibiotic-associated diarrhoea, irritable bowel syndrome (2-4).

Microorganisms most commonly used in clinical practice are lactic acid-producing bacteria such as Lactobacillus spp, and microrganisms belonging to genus Bifidobacterium and Bacillus. Other less commonly used probiotic microorganisms are strains of Streptococcus, Escherichia coli, and Saccharomyces (3). Different biologic effects have been described for probiotics, including the synthesis of antimicrobial substances as lactic acid, hydrogen peroxide and bacteriocins, the competitive interaction with pathogens for microbial adhesion sites, and finally the modulation of the immune response of the host (5,6). Research efforts into the

clinical effects of probiotics in man are increasing rapidly. A field in which particular interest is arising represents the Helicobacter pylori infection.

Helicobacter pylori The gram-negative, spiral-shaped bacterium

Helicobacter pylori is a common human pathogen and public health problem that causes gastritis and peptic ulcers both in adults (7) and children (8) and is considered an important cofactor in the development of gastric cancer (9). It is well known that childhood is an important period for acquisition of Helicobacter pylori infection although several recent articles have reported a decline in the prevalence of Helicobacter pylori infection in children over the last 10 years (10). Intrafamiliar transmission of the infection, especially from mother to child, has been hypothesised as the major mode of dissemination (11). Poor socioeconomic conditions remain a significant risk factor for infection, while exclusive breast-feeding






Vol. 26, no. 1 (S), 77-83 (2012)

Key Words : antrochoanal polyp, children, cystic fibrosis, nasal endoscopy, nasal polyposis

Corresponding Author Gian Luigi MarsegliaDepartment of PediatricsFoundation IRCCS Policlinico San Matteo - University of Pavia, ItalyP.le Golgi, 2 - 27100 Pavia (PV) ItalyTel: +39.0382.502818 Fax: +39.0382.527976E-mail: [email protected]

Nasal polyposis is a chronic inflammatory disease affecting the nasal cavity and the paranasal sinuses. It is a relatively common disease, occurring in 1-4% of the general population, but it is rarely described in the pediatric population. Most of the published series include children presenting with other underlying systemic diseases, mainly cystic fibrosis. The aim of the present study was to describe the characteristics of the patients suffering from nasal polyposis, evaluated at the Pediatric Clinic of the University of Pavia (Italy) over the last 17 years. 56 consecutive pediatric patients referring to our Pediatric Department had a diagnosis of nasal poyposis over the last 17 years. All children underwent allergy evaluation, nasal endoscopy, CT scan of the paranasal sinus, and Functional Endoscopic Sinus Surgery. The mean age of the present cohort was of 11.8 years and most of the patients were male. 50% of the patients presented with unilateral, polyposis, mostly with a diagnosis of antrochoanal polyp. 4 patients presenting with bilateral polyposis suffered from cystic fibrosis. Main symptoms at diagnosis included nasal obstruction, snoring and rhinorrhea 32% of the patients presented at least a positivity to skin prick test, for major inhalant and food allergens. Nasal polyposis in children could represent an alert sign for other underlying systemic diseases. Nasal endoscopy should therefore be prescribed when a diagnosis is suspected. To properly treat a patient presenting with nasal polyposis, it is necessary to integrate medical and surgical skills through a multidisciplinary approach.

NASAL POLYPOSIS IN CHILDREN

CAIMMI D1, MATTI E2, PELIZZO G3, MARSEGLIA A1, CAIMMI S1, LABÒ E1, LICARI A1, PAGELLA F2, CASTELLAZZI AM1, PUSATERI A2, PARIGI GB3 , MARSEGLIA GL1.

1 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy2 ENT Department, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

3 Department of Pediatric Surgery, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

Nasal polyposis is a relatively common disease, occurring in 1-4% of the general population, especially in subjects older than 20 years, while it is less frequent in the pediatric population (< 1%) (3-5). It is to note, however, that most of the published studies are based on patient-reported data through questionnaires, missing though endoscopic results, which are essential for diagnosis, and the real prevalence of the disease might therefore be underestimated. Nasal polyposis affects mostly males, with a male-female ratio of up to 4:1 (6).

The nasal polyps may be either isolated or associated with other medical conditions. Isolated nasal polyposis in children is a rare condition, being most of the times associated with a systemic disease. Nasal polyps are found in 5-15% of asthmatic subjects, in 5-8% of patients with non-steroidal anti-inflammatory drugs (NSAIDs) hypersensitivity, and, less frequently (0.5-

Nasal polyposis is a chronic inflammatory disease affecting the nasal cavity and the paranasal sinuses, and characterized by the presence of mucosal congestion associated to the presence of edematous inflammatory growths: the nasal polyps. The polyps originate from the paranasal sinuses and protrude into the nasal cavity (1, 2). Through a mechanical barrier effect, the polyps alter and block the normal flow of air through the nose. Similarly, blocking the drainage pathways of the sinuses, they cause sinu-nasal congestion. Clinically, the patient experience a nasal airway obstruction, which sometimes is so severe that is accompanied by forced mouth breathing. Other common symptoms include rhinorrhea, postnasal drip, cough, facial pains, snoring at night, hypo/

anosmia. Possible complications, though uncommon, include periorbital or orbital cellulitis which, sub-periosteal abscesses, cerebral cavernous sinus thrombosis.






Vol. 26, no. 1 (S), 85-93 (2012)

Key Words: Allergy, Immune system, Mucosal immunity, Sublingual immunotherapy

Corresponding AuthorVitaliti GiovannaVia Santa Sofia, 78 - 95100 Catania - ItalyTel: 0039-0953782764Fax: 0039-0953782385Email: [email protected]

The increasing prevalence of allergy and its impact on individual quality of life underline the need of an improvement of the treatment options in order to modify the natural course of allergic diseases. In this context, specific sublingual immunotherapy (SLIT) represents an approach currently available to redirect inappropriate immune response in atopic patients. The immunological mechanism that underlies SLIT has only started to be investigated. Oral mucosal tissue displays high permeability for allergens. It is conceivable that the sublingual administration route might induce immunological tolerance towards allergens involving cells and mediators specific of oral and intestinal mucosa. Recent literature data stated the presence in oral mucosa of dendritic cells (DCs) which express the high-affinity receptor for immunoglobulin (Ig)E (FceRI). Moreover some studies indicated that the mechanism of immunotherapy might be based on the increase of number and activity of regulatory T cells. Accumulating evidences suggest that the generation of T regulatory cells in periphery is orchestrated by a particular subset of DCs. It seems that repeated stimulation of naïve CD4 T cells with allogenic immature DCs induce Tr1 cells maturation. Nevertheless other cells are involved in this process, such as TLR, MHC of I and II class and costimolatory molecules such as CD40, CD 80/B7.1 and CD 86/B7.2. An increase of serum IgG4 and IgA, a reduced number of inflammatory cells infiltrating target organs, as well as a reduction of eosinophilic cationic protein and a very heterogenous influence on T cells in the peripheral blood in terms of T cell suppression also occur with SLIT. All these molecules orchestrate the immune response within the regional immune system, recreating a favourite environment for the induction of tolerance operated by SLIT.

MUCOSAL IMMUNITY AND SUBLINGUAL IMMUNOTHERAPY IN RESPIRATORY DISORDERS

VITALITI G1, LEONARDI S1, MIRAGLIA DEL GIUDICE M2, SALPIETRO A3, ARTUSIO L4,CAIMMI D4, ARRIGO T3, SALPIETRO C3, CIPRANDI G5, LA ROSA M1.

1 Department of Pediatrics, University of Catania, Italy2 Department of Pediatrics, Second University of Naples, Italy

3 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy 4 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy5 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy

The increasing prevalence of allergy and its impact on individual quality of life and social costs underline the need of an improvement of the treatment options in order to modify the natural course of allergic diseases. In this context, specific immunotherapy (SIT) represents the only approach currently available to redirect inappropriate immune response in atopic patients and it has been shown to be safe and effective in the treatment of clinically significant respiratory IgE-mediated diseases (1).

For years the gold standard of SIT was represented by the subcutaneous immunotherapy (SCIT), but the risk of severe systemic side effects and the need for frequent

injections has limited the application of SCIT, especially in children. Nowadays, other kinds of immunotherapy such as sublingual-swallow immunotherapy (SLIT) may represent a valuable alternative to SCIT. SLIT has been shown to be safe and effective in several double blind placebo-controlled studies in children affected by asthma and rhinitis (2-3). In 2001, the allergic rhinitis and its impact on asthma (ARIA) extended the indications of SLIT also to children and a recent meta-analysis concluded that SLIT significantly reduces both symptoms and the requirement of medications. (4)

The immunological mechanism that underlies SLIT






Vol. 26, no. 1 (S), 95-103 (2012)

Key words: obesity, insulin, leptin, total ghrelin, obestatin.

Corresponding Author:Gian Luigi MarsegliaDepartment of Pediatrics, University of PaviaFondazione IRCCS Policlinico San MatteoP.le Golgi, 2 – 27100 Pavia (PV) ItalyPhone +39.0382.502818 FAX +39.0382.527976E-mail: [email protected]

The aim of the study was to evaluate fasting levels of glucose, insulin, leptin, total ghrelin, and obestatin in a group of prepubescent obese children before and after weight loss. We enrolled 64 prepubescent obese children, but only 35 completed the study (mean age 7.6 ± 0.9 years, 19 females) and 20 normal-weight prepubescent children as controls. Fasting plasma concentration of glucose, insulin, Homeostasis Model assessment for insulin resistance (HOMA-IR), and leptin, total ghrelin, and obestatin levels were measured at baseline and after a 6-month lifestyle intervention (i.e. improved nutrition and increased physical activity). At baseline, obese children showed significantly (p<0.001) higher leptin and obestatin levels, and lower total ghrelin concentrations than control subjects. Weight loss significantly (p<0.001) diminished plasma leptin and insulin levels and increased ghrelin and obestatin concentrations. Weight loss in prepubescent children is associated with a significant change in leptin, ghrelin and obestatin concentrations. These results confirm the hypothesis that levels of these hormones are closely associated with obesity in childhood and might take part, as consequence but not as a cause, in glucose, fat, and energy metabolism.

EFFECT OF WEIGHT REDUCTION ON LEPTIN, TOTAL GHRELIN AND OBESTATIN CONCENTRATIONS IN PREPUBERTAL CHILDREN.

ARRIGO T1, GITTO E1, FERRAÙ V1, MUNAFÒ C1, ALIBRANDI A1, MARSEGLIA GL2, SALPIETRO A1, MIRAGLIA DEL GIUDICE M3, LEONARDI S4, CIPRANDI G5, SALPIETRO C1.

1 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy2 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

3 Department of Pediatrics, Second University of Naples, Italy4 Department of Pediatrics, University of Catania, Italy

5 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy

It is widely known that the prevalence of childhood obesity is increasing in most industrialized countries and that it is associated a major risk factor for co-morbidity and mortality during the adult life (1). A recent representative survey, conducted in Italy, demonstrated that 24% of school children were overweight and 12% were obese.In addition, the prevalence of obesity and estimated metabolic diseases was about 2 times higher in the Southern Italy in comparison with the Northern Italy (2).

One of the largest health problems in obese adolescents and young adults is the development of type 2 diabetes mellitus, preceded by insulin resistance during childhood usually associated with visceral fat accumulation. Waist circumference correlates with cardiovascular morbidity as well as the body mass index (BMI) or percent body

fat. Adipose tissue and adipocytes are a site for storage of energy, and also a source of many adipokines and hormones (e.g. visfatin, adiponectin, leptin, resistin) (3).

There have been several studies reporting the role of insulin and leptin on energy homeostasis through control of appetite and energy expenditure: both hormones increase in direct proportion to adipose mass (4-7). Ghrelin, an endogenous ligand of the growth (GH) secretagogue receptor, is inversely correlated with BMI and insulin concentrations in normal children (8). Therefore, ghrelin, insulin and leptin represent afferent hormonal links between peripheral energy metabolism and central feeding behavior (9,10). Additionally, there is evidence that ghrelin and obestatin, derived from a common pro-hormone, are involved in appetite stimulation and suppression and in metabolism (11).






Vol. 26, no. 1 (S), 105-108 (2012)

Key words: atopic dermatitis, serum PTX3, symptom severitiy

Corresponding Author: Giorgio CiprandiDI.M.I.Viale Benedetto XV 6, 16132 Genoa, ItalyPhone + 39 10 35338120FAX + 39 382 527976E-mail [email protected]

PTX3 behaves as an acute-phase response protein as its blood levels rapidly and dramatically increase during endotoxic shock, sepsis, and other inflammatory and infectious conditions. Therefore, this study was designed to investigate a possible role of PTX3 in children with Atopic Dermatitis (AD). One-hundred-and-thirty-six patients (37 females, 99 males, mean age 10.4 years) were enrolled in the study. One hundred patients (74%) had only respiratory symptoms (allergic rhinitis and/or bronchial asthma); thirty-six patients (26%) showed dermatitis associated with respiratory allergy (allergic rhinitis and/or bronchial asthma). PTX3 levels were higher in children with AD and there was a significant correlation between serum PTX3 levels and SCORAD index (p-value=0.0001, rho=0.658). Therefore, this study may show that PTX3 might be a reliable marker for the severity of AD in children with respiratory allergy.

PENTRAXIN 3 SERUM LEVELS IN CHILDREN WITH ATOPIC DERMATITIS

MARSEGLIA GL1, DE AMICI M2, MARSEGLIA A1, CAIMMI S1, MIRAGLIA DEL GIUDICE M3, LEONI MC1, SALPIETRO C4, LEONARDI S5, BRAMBILLA I1, CIPRANDI G6.

1 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy2 Pediatric Unit, Foundation IRCCS Policlinico San Matteo, Pavia , Italy


5 Department of Pediatrics, University of Catania, Italy6 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy

Atopic dermatitis (AD) is an inflammatory skin disease characterized by pruritus and chronic or relapsing eczematous lesions that commonly present during early infancy and affect up to 16% of children (1). AD is thought to represent an interaction between both genetic and environmental influences with trigger factors, including irritants, allergens and microorganisms.

The immune response is impaired in AD patients and a pathogenic role exerted by T helper cells is certain as well as allergic reaction often is associated. Various populations of effector and regulatory T cells have been shown to play a crucial role in inflammation (2). Depending on the substances co-exposed with the allergen and the status of the cells and cytokines in the milieu, CD4+ naïve T cells can differentiate into Th1, Th2, Th9, or Th17 effector cells (2). Based on their respective cytokine profiles, responses to chemokines, and interactions with other cells, these T cell subpopulations can promote different types of inflammatory responses. In this regard, TGF-β in the presence of IL-4 reprograms Th2 cell differentiation and

leads to the development of a new population of Th9 cells producing IL-9 and IL-10 (3).

Therefore, an immune-mediated inflammatory reaction is involved in the pathogenesis of AD. In this regard, Pentraxins are acute-phase reactants and are classified as short and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are well known short pentraxins, mainly CRP is produced by hepatocytes in response to pro-inflammatory mediators (4).

PTX3 is the prototypic long pentraxin and is produced by resident and innate immunity cells in peripheral tissues, in response to inflammatory signals and TLR activation (5). PTX3 behaves as an acute-phase response protein as its blood levels rapidly and dramatically increase during endotoxic shock, sepsis, and other inflammatory and infectious conditions (5,6). Data collected in different pathologies suggest a relationship between PTX3 plasma levels and disease severity, so there might be a possible role of PTX3 as a novel marker of disease (7).

Therefore, this study was designed to investigate a






Vol. 26, no. 1 (S), 109-112 (2012)

Allergic disorders are typically characterized by an inflammatory response to allergen exposure. PTX3 behaves as an acute-phase response protein as there is a relationship between PTX3 plasma levels and disease severity. Therefore, this study was designed to investigate a possible role of PTX3 in children with allergic rhinitis. One hundred patients (28 females, 72 males, median age 11 years) were enrolled in the study. All patients were monosensitized: 43 (43%) to seasonal allergens (Graminaceae), 57 (57%) to perennial allergens (house dust mites, cat and dog epithelium, alternaria tenuis). Patients’ blood samples for assessing serum PTX3 levels were performed during the spring. Children with rhinitis had higher PTX3 levels and there was a significant relationship between symptom severity and serum levels. Therefore, this study shows that PTX3 serum levels could be a reliable marker for symptom severity in children with allergic rhinitis.

Key words: allergic rhinitis, serum Pentraxin 3, symptom severitiy


PENTRAXIN 3 IN CHILDREN SUFFERING FROM ALLERGIC RHINITIS

MARSEGLIA GL1, DE AMICI M2, LEONARDI S3, MIRAGLIA DEL GIUDICE M4, SALPIETRO A5, LA ROSA M3, CAIMMI D1, CAIMMI S1, LICARI A1, CIPRANDI G6.

1 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy2 Pediatric Unit, Foundation IRCCS Policlinico San Matteo, Pavia , Italy

3 Department of Pediatrics, University of Catania, Italy4 Department of Pediatrics, Second University of Naples, Italy

5 Department of Pediatrics, Genetics and Immunology Unit, University of Messina, Italy6 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy

The innate immunity represents the first line of defence towards pathogens, and exerts a pivotal role about the activation and orientation of adaptive immune response, and plays a key role in maintaining tissue integrity and repair. The innate immune system consists of a cellular and a humoral arm. About the humoral arm, Cell-associated pattern-recognition molecules (PRMs) possess the characteristic of being strategically localized in different cellular compartment (e.g. plasma membrane, endosomes, cytoplasm) . PRMs belong to several molecular classes: the Toll-like receptors, the NOD- and RIG-like receptors, and the scavenger receptors (1,2). PRMs may be also shed and detected in several fluids, including blood. Fluid-phase PRMs belong to different molecular families, including collectins, ficolins, and pentraxins (3). Humoral PRMs are functional ancestors of anticorpal response (ante-antibodies). It is to note that humoral PRMs share a basic, evolutionary conserved mode of action: such as activation of the complement, agglutination, neutralization, and opsonisation. In addition, there is a bidirectional cross-talk

between humoral and cellular compartment to regulate and amplify the innate immune response.

Pentraxins constitute a superfamily of evolutionary conserved (from arachnids and insect to humans) proteins, which have a cyclic multimeric structure and present 200 amino acid pentraxin domain in the C terminus (4). Pentraxins are acute-phase reactans and are classified as short and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are well known short pentraxins, maily CRP is produced by hepatocytes in response to pro-inflammatory mediators. Long pentraxins are: PTX3, the first identified in the ’90, guinea pig apexin, neuronal pentraxin 1 and 2.

PTX3 is the prototypic long pentraxin and is produced by resident and innate immunity cells in peripheral tissues, in response to inflammatory signals and TLR activation (5). PTX3 is present in a functional “ready-to-use” form in polymorphonuclear granules and is promptly released after adequate activation (6). PTX3 behaves as an acute-phase response protein as its blood levels rapidly and dramatically






Vol. 26, no. 1 (S), 113-117 (2012)

Key words: Birch allergy, Oral Allergic Syndrome, Bet v 1, proliferations.


Patients with pollen allergy may frequently present an additional food-related allergy (Oral Allergic Syndrome, OAS), as consequence of cross-reactivity between pollen allergens (mainly birch, hazelnut, alder, mugwort) and vegetable allergens. The aim of this study was to evaluate the effect on Bet v 1-induced T cell proliferation exerted by the presence of OAS in birch patients. Fourteen allergic patients were evaluated (6 males, mean age 35.8 years). All of them were monosensitized to birch and suffered from allergic rhinitis: 4 had also OAS to apple. Proliferation of peripheral mononuclear cells was evaluated using Bet v 1 and non-specific stimuli. OAS had higher proliferation than non-OAS patients. In addition, there were significant relationships between immunological and clinical parameters in OAS patients. This study evidences that OAS characterizes a more severe form of birch allergy: as OAS patients had higher SI, circulating eosinophils, and IgE levels. Thus, this study confirms the previous report and underlines the relevance of measuring recombinant birch allergen as higher values may suggest a reliable prediction of OAS.

PATIENTS WITH ORAL ALLERGIC SYNDROME TO APPLE HAVE INTENSE PROLIFERATIVE RESPONSE TO BET V 1

CIPRANDI G1, FENOGLIO G2, KALLI F2, DE AMICI M3, LEONARDI S4, MIRAGLIA DEL GIUDICE M5, SALPIETRO C6, LA ROSA M4, CAIMMI S7, MARSEGLIA GL7.

1 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 2 CEBR – University of Genoa

3 Pediatric Unit, Foundation IRCCS Policlinico San Matteo, Pavia , Italy4 Department of Pediatrics, University of Catania, Italy


7 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

allergen (5,6). Previously, it has been demonstrated that quantitative birch specific IgE level proved useful in predicting clinical allergic symptoms with birch exposure (7). In addition, it has been also reported that patients with severe birch allergy had higher levels of serum IL-17 in comparison with patients with mild form (8). Patients with severe birch allergy have also higher total IgE levels and circulating eosinophils than patients with mild birch allergy (9). Therefore, the aim of this study was to evaluate the effect on Bet v 1-induced T cell proliferation exerted by the presence of OAS in birch patients.


PatientsFour-teen allergic patients were evaluated (6 males, mean

Patients with pollen allergy may frequently present an additional food-related allergy, as consequence of cross-reactivity between pollen allergens (mainly birch, hazelnut, alder, mugwort) and vegetable allergens (1). The IgE cross-reactivity between pollen and food allergens constitutes the molecular basis for the Oral Allergy Sindrome (OAS); pollen allergy represents the basis for onset and maintenance of OAS (2). Moreover, apple sensitization has been identified as the unique predictive factor for OAS symptom occurrence with a 99% relative risk (3).

The genetic engineering applied to allergy has enabled the production of recombinant allergens (4). Most cross-reactions between birch pollen and apple are caused by the major birch allergen: Bet v 1, one of the most important pan-allergen with high homology with apple






Vol. 26, no. 1 (S), 119-123 (2012)

Key words: Allergy, IgE, Pediatrics, Tetanus toxoid


Hypersensitivity reactions after immunization with tetanus toxoid are occasionally observed in atopic and non-atopic individuals. High IgE levels in infancy may predict subsequent allergy. The aims of this study were: i) to evaluate the role of specific IgE to tetanus toxoid in children in response to tetanus immunization and the possible factors associated with specific IgE levels, and ii) to investigate the correlation between specific IgE levels to tetanus toxoid and the late development of allergy (up to 12 years). Initially, 278 healthy infants (152 males and 126 females, aged 12 months) living in an urban city were screened for serum total IgE and specific IgE to tetanus toxoid, after having obtained informed consent from parents. After 12 years, 151 children could be evaluated. Total IgE summed with tetanus specific IgE were significantly associated with allergy at 12 years. In conclusion, this study demonstrates that serum total IgE and tetanus specific IgE may be predictive of subsequent allergy onset.

TETANUS TOXOID IGE MAY BE USEFUL IN PREDICTING ALLERGY DURING CHILDHOOD

CIPRANDI G1, DE AMICI M2, QUAGLINI S3, LABÒ E4, CASTELLAZZI AM4, MIRAGLIA DEL GIUDICE M5, MARSEGLIA A4, BIANCHI L4, MORATTI R6, MARSEGLIA GL4,

and Workgroup “Allergy Project”*

1 Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 2 Pediatric Unit, Foundation IRCCS Policlinico San Matteo, Pavia , Italy

3 Department of Computer Engineering and Systems Science, University of Pavia, Italy 4 Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

5 Department of Pediatrics, Second University of Naples, Italy6 Scientific Direction, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

*The other members of the Workgroup “Allergy Project” are: Bosio M, Fiorentini ML, (Direzione Sanitaria, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy), Alesina R, Luisetti M., (Respiratory Diseases, Fondazione IRCCS Policlinico San Matteo,

Pavia, Italy), Borroni G, Vignini M (Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Univerità degli Studi di Pavia; Pavia, Italy), Spinillo A (Department of Obstretics and Ginecology, Fondazione IRCCS Policlinico San Matteo, Università degli

Studi di Pavia, Pavia, Italy), Perotti F (Department of Obstretics and Ginecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy), Stronati M, Bollani L (Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy), Cerra C,

Carugno B (ASL of Pavia, Sisetma Informativo Aziendale, Pavia, Italy)

Hypersensitivity reactions after immunization with tetanus toxoid are occasionally observed in atopic and non-atopic individuals. In the literature, a low incidence of serious side effects after T immunization has been reported (1,2). In young infants, preschool and school children reported side effects are mostly minor local reactions, while systemic reactions are quite rare (3, 4, 5). Elevated serum IgE antibody levels to tetanus toxoid may be observed after booster immunization with aluminum-adsorbed tetanus vaccine. In cross-sectional studies on atopic adults as well as 4 to 17-year-old atopic children, tetanus IgE antibody levels

were found to be higher compared to non atopic individuals (6, 7). Additionally, it was found that older children with markedly elevated total serum IgE levels synthesized anti-tetanus IgE antibodies (7).

Moreover, Dannemann et al (8), showed that 24-month-old children with and without early manifestation of atopic symptoms were capable of producing IgE antibodies in response to tetanus immunization. About 50% of the infants in that study developed detectable specific tetanus antibodies. Children with immunological indicators of atopy such as specific sensitizations already at the age of 2






Vol. 26, no. 1 (S), 125-131 (2012)

Key Words: asthma, comorbidity, endoscopy, pediatrics, sinusitis

Corresponding Author: Gian Luigi MarsegliaHead of the Department of PediatricsFoundation IRCCS Policlinico San Matteo - University of Pavia, ItalyP.le Golgi, 2 - 27100 Pavia (PV) ItalyTel: +39.0382.502818 Fax: +39.0382.527976E-mail: [email protected]

Sinusitis is frequently associated with asthma. The diagnosis and management of patients with asthma associated with sinusitis are often challenging, though sometimes unsatisfactory. Detection and treatment of sinusitis in asthmatics may lead to a better control of asthma symptoms. Most of the studies regarding the relationship between sinusitis and asthma have been conducted in adults. The aim of the present study was to evaluate the presence of sinusal comorbidity in children with un-controlled asthma both clinically and through nasal endoscopy after the first 6 months of treatment. The present study included 294 consecutive asthmatic children (97 males, mean age 7.3 years). Asthma diagnosis, severity assessment and treatment were performed according to GINA guidelines. Twenty-one patients with non-controlled asthma presented with endoscopic features of sinusitis, but without any clinical sign or symptom. We defined such condition occult sinusitis. Not only overt sinusitis, but also occult sinusitis could be a significant comorbidity in asthmatic patients. For this reason, it may be beneficial to determine the presence of sinus inflammation in children with non-controlled asthma, even when they don’t present clinical signs or symptoms of upper airways involvement.

OCCULT SINUSITIS MAY BE A KEY FEATURE FOR NON-CONTROLLEDASTHMA IN CHILDREN

MARSEGLIA GL1, CAIMMI S1, MARSEGLIA A1, PAGELLA F2, CIPRANDI G3, LA ROSA M4, LEONARDI S4 , MIRAGLIA DEL GIUDICE M5, CAIMMI D1.

1Department of Paediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy2ENT Department, Foundation IRCCS Policlinico San Matteo, University of Pavia, Italy

3Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy 4Department of Pediatrics, University of Catania, Italy

5Department of Pediatrics, Second University of Naples, Italy

Sinusitis represents a frequent co-morbidity in patients suffering from asthma and some studies pointed out that there could be an association between these two diseases (1-3). Upper respiratory airways diseases may induce a worsening of asthma because of different pathogenic mechanisms, including vaso-vagal reflex, oral breathing, post nasal drip, and inflammation continuity (4). The elevated incidence of upper respiratory tract infections in children may therefore lead to a less control of asthma in the pediatric population. Retrospective studies suggested that treatment of chronic upper airway diseases in patients suffering from asthma may lead to improved asthma outcomes (1,5).

Asthma is characterized by airway inflammation, reversible obstruction, and hyperrreactivity; diagnosis is based on typical symptoms, impaired lung function, and demonstration of reversibility and/or bronchial

hyperreactivity (6). Clinical manifestations include dry cough, expiratory wheezing, chest tightness and dyspnoea, which are triggered by several exogenous factors, such as allergens, infections, airways irritants and overall in children exercise (7). Severe forms of asthma interest only a small proportion of the asthmatic population. These patients may often require, despite new and improved inhalation therapies, a continuous and long-term treatment with oral steroids to achieve asthma control (8). Uncontrolled asthma may thus represent a serious problem in childhood, mainly in those cases in which steroidal dosage needs to be frequently increased to reduce asthma symptoms. Therefore, in uncontrolled patients, a careful re-evaluation should include the review of the accuracy of the diagnosis and of the compliance to the therapy, and the investigation for possible comorbidities (9). In particular, several authors have considered sinusitis as a

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