Riccardina Tesse

Efficacy of 1.25% and 1% topical cyclosporine in the treatment of severe vernal keratoconjunctivitis in childhood

Cyclosporine eyedrops 2% have been used for treatment of corticosteroid‐resistant vernal keratoconjunctivitis (VKC) cases. The purpose of our study was to verify the efficacy of 1.25% vs. 1% topical cyclosporine in improving severe form of VKC in childhood. Twenty children with severe VKC, were enrolled in a double‐blind, placebo‐controlled study and received cyclosporine 1.25% in one eye for 2 wk. Then an open trial was conducted during the next 3 months and 2 wk. Thirty‐two more patients were recruited the next year into a new open trial and they received cyclosporine 1% for 4 months. Ocular subjective symptoms and objective signs were scored in all children at entry, 2 wk and 4 months. Skin prick tests and conjunctival scraping tests were also performed; serum immunological and biochemical markers were assessed. The mean score values for severity of subjective symptoms and objective signs were significantly decreased after 2 wk, and 4 months, compared with those at entry (p < 0.001), in both groups of children who received cyclosporine eyedrops 1.25% and 1%, respectively. Serum markers did not differ from the beginning to the end of treatment. Conjunctival eosinophils and cyclosporine serum levels were not detectable at the end of therapy, nor were endothelial corneal cells damaged. Our findings suggest that 1% cyclosporine concentration might be the minimal effective treatment regimen to control symptoms and local inflammation in severe forms of VKC.

Exhaled breath condensate pH measurement in children with asthma, allergic rhinitis and atopic dermatitis.

Recent studies have shown that the pH of exhaled breath condensate (EBC) could be predictive of asthma exacerbation. Moreover, it has been documented that both allergic rhinitis and atopic dermatitis constitute risk factors for the occurrence of asthma in a progression of disease known as atopic march. The aim of our study was to establish if condensate pH could be used as a valuable mean of monitoring of asthma in atopic children. We studied 34 atopic children with acute asthma, 70 with stable asthma, 35 children with allergic rhinitis, and 17 with atopic dermatitis. Thirty healthy children were used as controls. All children underwent skin prick tests and lung function tests. Exhaled breath condensate samples were collected with a condensing device and de‐aerated with argon. The pH of EBC was measured using a pH meter. Children with acute asthma were treated with inhaled steroids and bronchodilators. We found that the pH of condensate in patients with acute asthma was lower than that of patients with stable asthma, rhinitis, and controls (7.25 vs. 7.32, p < 0.05; 7.25 vs. 7.48, p < 0.02; 7.25 vs. 7.78, p < 0.0001, respectively). Patients with stable asthma, rhinitis, and eczema had also lower pH than that of controls (7.32, 7.48, and 7.44 vs. 7.78; p < 0.0001, p < 0.006, p < 0.04, respectively). Patients with acute asthma normalized their pH after treatment (7.82 vs. 7.25; p < 0.0001). Finally, patients with acute asthma showed a positive correlation between pH and lung functional parameters (forced expiratory volume in 1 s; r = 0.39, p = 0.04). Our study shows that EBC pH measurement may be a promising marker for assessing airway inflammation and monitoring response to anti‐inflammatory treatment in asthmatic children. Furthermore, we report the first evidence of airways acidification in children with allergic rhinitis and atopic dermatitis. Therefore, EBC pH assessment may be useful in the evaluation of progression of the atopic march toward the development of asthma later in life. Further studies are recommended in order to confirm this indication.

Adequacy and tolerance to ass's milk in an Italian cohort of children with cow's milk allergy

BackgroundThe therapy for cows milk proteins allergy (CMPA) consists in eliminating cows milk proteins (CMP) from the childs diet. Asss milk (AM) has been recently considered as substitute of CMP. This prospective study investigated tolerance and nutritional adequacy of AM in children with CMPA from Southern Italy.MethodsThirty children (aged 6 months to 11 years) with suspected CMPA were enrolled. They underwent skin prick tests and bouble-blind, placebo controlled food challenge to CMP. After confirming the diagnosis of CMPA, patients received fresh AM in a open challenge. Specific serum CMP and AM IgE, and biochemical parameters in blood were also assessed. Auxological evaluations were performed in all subjects at entry (T0) and after 4–6 months (T1) of AM intake.ResultsTwenty-five children resulted elegible for the study, and 24 out of 25 subjects (96%) tolerated AM at the food challenge. Auxological data resulted improved by the end of the study in all patients, while blood biochemical parameters did not vary during the follow-up.ConclusionOur data confirm the high rate of AM tolerability in children with moderate symptoms of CMPA. Moreover, we found that AM seems to have nutritional adequacy in subjects with a varied diet.

Lactobacillus reuteri modulates cytokines production in exhaled breath condensate of children with atopic dermatitis.

We measured the concentration of interferon-γ and interleukin-4 in the exhaled breath condensate of children with atopic and nonallergic dermatitis receiving a probiotic supplementation (Lactobacillus reuteri ATCC 55730) or placebo for 8 weeks. We demonstrated that the levels of these cytokines increased and decreased respectively only in atopic subjects receiving active treatment. Our data suggest that the oral administration of a specific probiotic strain in patients with atopic dermatitis can modulate in vivo the cytokine pattern at a different site from intestine.

Exhaled breath condensate cytokines and pH in pediatric asthma and atopic dermatitis.

Some studies have proposed exhaled breath condensate (EBC) as a noninvasive tool for monitoring airway inflammation in children. Moreover, atopic dermatitis (AD) has been considered a risk factor for the development of asthma. This study was designed to assess the EBC pH and the exhaled concentration of cytokines produced by T-helper (Th) 1, Th2, and T regulatory cells in asthmatic children and AD and to verify if their concentrations are affected by a short course of treatment with inhaled corticosteroids (ICS). We assessed the mean levels of pH, interferon (IFN) gamma, interleukin (IL)-4, and IL-10 in EBC of children with asthma (n=20) and AD (n=12) and healthy controls (n=20) by enzyme-linked immunosorbent assay (ELISA). Variations of pH and cytokine concentration in response to ICS (flunisolide, 500 microg/day, for 2 weeks), were also investigated in asthmatic patients. We found that the mean condensate pH value in patients with asthma and AD was significantly lower when compared with that of controls (6.9+/-0.2 and 7.0+/-0.2 versus 7.4+/-0.4; p<0.0001) and it significantly increased in asthmatic patients after treatment (7.2+/-0.2 versus 6.9+/-0.2; p=0.003). In addition, the IL-4/IFN-gamma ratio was significantly higher in children with asthma and in those with AD when compared with controls (9.72+/-2.00 and 9.70+/-2.0 versus 8.04+/-2.6; p<0.001) and that it decreased in asthmatic patients after ICS (6.4+/-5.4 versus 9.72+/-2.00; p<0.01). We observed that exhaled IL-10 levels were significantly higher in children with asthma compared with those of controls (18.8+/-8.9 versus 4.2+/-1.0; p<0.002). IL-10 did not significantly increase after treatment with steroids. No such finding was documented in children with AD. Our data suggest that EBC IL-10 levels are different in asthmatic patients compared with healthy children, but they are insensitive markers in monitoring therapy with ICS. Moreover, children with AD show an EBC pH and an exhaled pattern of Th2/Th1 cytokines similar to that of asthmatic patients.

Treatment of severe vernal keratoconjunctivitis with 1% topical cyclosporine in an Italian cohort of 197 children

Tesse R, Spadavecchia L, Fanelli P, Rizzo G, Procoli U, Brunetti L, Cardinale F, Miniello VL, Bellizzi M, Armenio L. Treatment of severe vernal keratoconjunctivitis with 1% topical cyclosporine in an Italian cohort of 197 children. 
Pediatr Allergy Immunol 2010: 21: 330–335.
© 2009 John Wiley & Sons A/S

Risk Factors for Subclinical Atherosclerosis in Diabetic and Obese Children

Background. Increased carotid intima-media thickness (cIMT) is considered a marker of early-onset atherosclerosis and it seems to predict cardiovascular events both in obese and diabetic subjects. We aimed to evaluate early signs of atherosclerosis and investigate for predisposing factors in children and adolescents affected by type 1 diabetes (T1DM) or obesity, comparing them with healthy controls. Methods. Out of 71 enrolled subjects (mean age 12.8 ± 2.3 years), 26 had T1DM and 24 were obese, while 21 age- and sex-matched subjects acted as controls. cIMT was measured using standardized methods. Serum glucose, insulin, cholesterol, triglycerides and C-reactive protein levels were evaluated. An oral glucose tolerance test (OGTT) was performed in obese subjects. Results. Diabetic and obese individuals showed higher cIMT mean values than healthy controls (p<0.005). cIMT of the three examined segments correlated positively with fasting glucose levels and negatively with units of insulin/kg/day administered in T1DM individuals. A positive correlation between insulin levels (basal and after oral glucose load) and cIMT of common, internal and external carotid artery was found in obese subjects (p<0.03). High density cholesterol levels represented a protective factor for cIMT in this latter group of the study population. Conclusions. Our findings show that cIMT correlates with high insulin levels (a sign of insulin resistance) in obese patients and with high fasting glucose levels (a sign of relative insulin deficiency) in T1DM subjects, confirming the need of reducing hyperinsulinism and monitoring blood glucose levels in these subjects to prevent atherosclerosis.

Sleep-Disordered Breathing in Obese Children: The Southern Italy Experience

BACKGROUND The association of obesity with sleep-associated respiratory disturbances, which has traditionally been described as a problem in adults, actually originates in childhood. We sought an association between sleep-disordered breathing (SDB) and overweight and/or obesity in a large cohort of school- and preschool-aged children in Southern Italy. METHODS One thousand two hundred seven children (612 girls and 595 boys; mean age 7.3 years) were screened by self-administered questionnaires. According to answers, subjects were divided into three groups: nonsnorers (NS), occasional snorers (OS), and habitual snorers (HS). All HS, who also failed an oximetry study at home, underwent polysomnographic monitoring for the definition of SDB. BMI was calculated according to Italian growth charts. RESULTS A total of 809 subjects (67.0%) were eligible for the study. Of them, 44 subjects (5.4%) were classified as HS, 138 (17.0%) as OS, and 627 (77.5%) as NS. Fourteen subjects (1.7%) were given a diagnosis of obstructive sleep apnea syndrome (OSAS). Sixty-four subjects (7.9%) were defined as obese, 121 (14.9%) as overweight, and 624 (77.2%) as normal weight. The frequency of HS was significantly higher in obese subjects than in overweight and normal-weight subjects (12.5% vs 5.8% vs 4.6%, respectively; P = .02), whereas the frequency of OSAS was 1.6% in normal-weight, 1.6% in overweight, and 3.1% in obese subjects (P = not significant). CONCLUSIONS Our findings in a large sample of Italian children suggest that obesity is associated with snoring.

Clinical significance of serum cytokine levels and thrombopoietic markers in childhood idiopathic thrombocytopenic purpura.

BACKGROUND Biological markers useful for defining children with newly diagnosed immune thrombocytopenic purpura (ITP) who are likely to develop the chronic form of the disease are partially lacking. The purpose of this study was to assess the clinical role of both immunological and thrombopoietic markers in children with ITP and correlate their levels with different disease stages. MATERIALS AND METHODS We enrolled 28 children with ITP at the onset of their disease, who were followed-up for a whole year and divided according to whether their disease resolved within the 12 months (n=13) or became chronic (n=15), 11 subjects with chronic ITP off therapy for at least 1 month at the time of enrolment, and 30 healthy matched controls. Serum levels of T helper type 1 and 2 and T regulatory-associated cytokines, such as interferon γ, tumour necrosis factor α, interleukin (IL) 2, IL6, IL10, and thrombopoietin were measured in all children using quantitative immunoenzymatic assays, while reticulated platelets were evaluated by flow cytometric analysis. RESULTS Serum IL10 levels were significantly higher in patients with an acute evolution of ITP than in either healthy controls (p<0.001) or patients with chronic progression of ITP (p<0.05). Reticulated platelet count and thrombopoietin levels were significantly higher in ITP patients at the onset of their disease, whether with acute resolution or chronic progression, than in healthy subjects (p<0.01; p<0.001), but did not differ between the groups of patients. CONCLUSION IL-10 seems to predict the clinical course of ITP, as it is significantly higher at the onset of disease in patients who obtain disease remission in less than 1 year.

Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura.

Derangement of genetic and immunological factors seems to have a pivotal role in the pathophysiology of immune thrombocytopenic purpura (ITP). We investigated interleukin(IL)-10 genetically determined expression in children with an acute progression of ITP (n=41) compared to young patients with chronic ITP (n=44) and healthy controls (n=60), and attempted to correlate IL-10 production with the course of the disease. We genotyped our study population for three single nucleotide polymorphisms at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the promoter region of the IL-10 gene. IL-10 levels were measured by enzyme-linked immunoassay. The IL-10 production in our study population was significantly higher in patients carrying the GCC haplotype than those bearing ACC and ATA haplotypes (6.9 ± 1.5 vs 3.6 ± 0.8 vs 3.3 ± 0.3, p=0.03). The serum concentration of IL-10 was significantly higher in patients with an acute course of their disease, who mainly carried the GCC haplotype (92%), compared to chronic subjects, bearing the non-GCC haplotypes, and controls [17 pg/mL (1.7-18) vs 3.5 pg/mL (0.6-11) vs 3 pg/mL (1-7), p<0.01)]. Our findings show that patients carrying the GCC-high producer IL-10 haplotype have an acute development of ITP and that IL-10 levels might represent a useful predictive biomarker of the disease course.