Lucio Armenio

Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis

Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy and inflammatory activity in the airways, but the relationship between eNO and total serum IgE has not been fully elucidated in the context of allergic sensitization. The aim of this study was to investigate the relationship between eNO, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non‐atopic children were recruited as controls. eNO levels (median) were significantly higher in patients with asthma (22.7 p.p.b.) and in those with allergic rhinitis (15.3 p.p.b.) than in healthy controls (5.9 p.p.b.). Children with allergic asthma had higher eNO levels than children with allergic rhinitis. A significant positive correlation was found between eNO and total serum IgE (asthma, r = 0.42, p < 0.0001; allergic rhinitis, r = 0.31, p < 0.01), and between eNO and the number of positive skin prick tests (asthma, r = 0.31, p < 0.0001; allergic rhinitis, r = 0.39, p < 0.01). eNO levels were better correlated with total IgE than with the number of positive skin prick tests. This correlation was independent of allergic sensitization. High total serum IgE represents a specific and predictive marker of eNO increase in children with asthma or allergic rhinitis. This finding adds further support to the hypothesis that increased serum IgE could be a marker itself of airway inflammation in patients with allergic disease.

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.

Respiratory symptoms in children living near busy roads and their relationship to vehicular traffic: results of an Italian multicenter study (SIDRIA 2).

BackgroundEpidemiological studies have provided evidence that exposure to vehicular traffic increases the prevalence of respiratory symptoms and may exacerbate pre-existing asthma in children. Self-reported exposure to road traffic has been questioned as a reliable measurement of exposure to air pollutants. The aim of this study was to investigate whether there were specific effects of cars and trucks traffic on current asthma symptoms (i.e. wheezing) and cough or phlegm, and to examine the validity of self-reported traffic exposure.MethodsThe survey was conducted in 2002 in 12 centers in Northern, Center and Southern Italy, different in size, climate, latitude and level of urbanization. Standardized questionnaires filled in by parents were used to collect information on health outcomes and exposure to traffic among 33,632 6–7 and 13–14 years old children and adolescents. Three questions on traffic exposure were asked: the traffic in the zone of residence, the frequency of truck and of car traffic in the street of residence. The presence of a possible response bias for the self-reported traffic was evaluated using external validation (comparison with measurements of traffic flow in the city of Turin) and internal validations (matching by census block, in the cities of Turin, Milan and Rome).ResultsOverall traffic density was weakly associated with asthma symptoms but there was a stronger association with cough or phlegm (high traffic density OR = 1.24; 95% CI: 1.04, 1.49). Car and truck traffic were independently associated with cough or phlegm. The results of the external validation did not support the existence of a reporting bias for the observed associations, for all the self-reported traffic indicators examined. The internal validations showed that the observed association between traffic density in the zone of residence and respiratory symptoms did not appear to be explained by an over reporting of traffic by parents of symptomatic subjects.ConclusionChildren living in zones with intense traffic are at higher risk for respiratory effects. Since population characteristics are specific, the results of validation of studies on self-reported traffic exposure can not be generalized.

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.

Mutations of the X-linked lymphoproliferative disease gene SH2D1A mimicking common variable immunodeficiency

Abstract. Common variable immunodeficiency (CVID) and X-linked lymphoproliferative (XLP) disease are two immunodeficiencies that may share a similar immunological phenotype making differential diagnosis difficult. We report two patients initially diagnosed as affected with CVID who, using molecular analysis, have been subsequently found to be affected with XLP disease. Distinguishing between these two diseases is essential since they have different prognosis, treatment and genetic counselling. Conclusion: current techniques, such as genetic analysis of the SH2D1A gene and expression of signalling lymphocyte activation molecule-associated protein, allow a definite diagnosis of X-linked lymphoproliferative disease.

Double blind, placebo controlled study of nedocromil sodium in asthma.

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.

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