Search

Difficult asthma is rare in childhood; when child's asthma is difficult to control, review of the diagnosis and evaluation of the different risk factors for exacerbations are recommended. The relationship between rhinosinusitis and bronchial asthma is provided by epidemiologic data. Doubts persist as to whether rhinosinusitis worsens asthma, or whether these are manifestations in different parts of the respiratory tract of the same underlying disease process. However, nasal sinus disease may contribute to less control in asthma, and patients with severe asthma appear to have the most prominent abnormalities on computed tomography scanning of the paranasal sinuses. From a pathogenetic point of view, many inflammatory mediators and the cellular infiltrate are often the same in the two entities, with a relevant role probably played by eosinophils. Antibiotic treatment of chronic sinus disease in asthmatic children may improve subjective asthmatic symptoms, lung function, and decrease bronchial hyperreactivity. Scientific evidence confirms that there may be an association between asthma and sinusitis even in childhood asthma: this could be relevant for diagnostic and therapeutic purposes.

Interleukin (IL)-8 is a major factor in inflammatory response and the IL-8 levels in exhaled breath condensate (EBC) may be used as a marker of airway inflammation. Airway acidification is implicated in the pathophysiology of obstructive airway diseases and pH EBC values have been used as a marker of airway acidification. The aim of our study is to investigate whether IL-8 and pH levels in EBC of cystic fibrosis (CF) children with respiratory exacerbations change after antibiotic treatment. Lung function, IL-8 and pH EBC values were measured in fifteen CF children (mean age 11 years) with acute exacerbation before (T0) and after two weeks (T1) of antibiotic treatment. IL-8 and pH values were compared by paired t-test. A p less than 0.05 was considered significant. IL-8 EBC levels decreased after antibiotic treatment (T0 0.36+/-0.03pg/ml vs T1 0.28+/-0.03pg/ml; p=0.03) and pH values increased (T0 7.36+/-0.09 vs T1 7.61+/-0.08; p=0.04). Results suggest possible application of EBC as a non-invasive tool to monitor efficacy of antibiotic treatment in CF patients.

The aim of this study was to evaluate the presence and the degree of reversible airflow obstruction as detected by forced expiratory volume in 1 second (FEV1), forced oscillometry (FOT), and interrupter technique (resistance measured by the interrupter technique [Rint]) in mild asthmatic children compared with controls. FOT, Rint, and FEV1 were evaluated before and after albuterol (200 microg) administered by metered-dose inhaler and spacer in 28 asthmatic children (mean age +/-SD, 9.1 +/- 1.9 years) and in 20 healthy children (mean age +/-SD, 8.5 +/- 2.1 years). No correlation was found between FEV1, FOT, and Rint values either before or after albuterol. FOT and Rint values were highly correlated pre- and postbronchodilatation. An improvement in FEV1 > or =12% after albuterol was observed in 11 (39%) asthmatic subjects. As suggested using the cutoff value at R6 > or =29%, significant bronchodilatation was observed in 20 (71%) children with FOT and using a reduction > or = 0.20 kPa or 2 cm of H2O, 22 (78%) subjects showed significant bronchodilatation with Rint. No significant changes were observed after albuterol in controls. FOT and Rint techniques showed a greater sensitivity in detecting reversibility of bronchoconstriction in mild asthmatic patients. Prospective studies are needed to clarify the possible advantages of these findings in mild-moderate asthmatic children.

Background: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case-control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery., Methods: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3(+) T, CD4(+) T, CD8(+) T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months., Results: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3(+) T and CD4(+) T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients., Conclusions: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis.

Background: Exhaled breath temperature has been proposed as a surrogate marker for the evaluation of airway inflammation in asthmatic patients., Objective: The aim of the present study was to extend the investigation of exhaled air temperature as a means for the evaluation of airway inflammation using a professionally developed instrument., Methods: Fifty-seven children, 41 allergic mild asthmatics and 16 healthy controls have been evaluated. They underwent exhaled air temperature and lung function measurement. The asthmatic children also underwent exhaled nitric oxide measurement, and hypertonic saline sputum induction for the evaluation of eosinophil (EOS) percentage., Results: The level of exhaled temperature was significantly higher in asthmatics than in controls, being 30.18+/-0.14 degrees C vs. 27.47+/-0.24 degrees C (P<0.001). In asthmatic children, a positive relationship was observed between exhaled air temperature and both exhaled nitric oxide (r=0.39; P=0.01) and EOS percentage in samples from induced sputum (rho=0.53; P=0.04)., Conclusion: The data from the present study support the hypotheses that exhaled breath temperature is related to the degree of airway inflammation in asthma.

Congenital heart defects (CHDs) are the most common birth defects in humans and over the last 20 years significant progress has been made in the understanding of the molecular and genetic determinants of an increasing number of CHDs. Fundamental to this progress has been the contribution of five fields of research: the epidemiological results of the Baltimore-Washington Infant Study (BWIS); the pathogenetic classification introduced by Clark; the Human Genome Project; genotype-phenotype correlation and familial recurrence studies; and transgenic animals. The recently advanced cytogenetic techniques can now detect subtle rearrangements in chromosomes, which may be overlooked by standard methods and, more recently, molecular instruments such as linkage analysis and positional cloning are being used to identify genes causing Mendelian monogenic syndromes with CHDs, such as Holt-Oram, Ellis-van Creveld and Noonan/LEOPARD syndromes. Finally, useful information is yet available with regard to genes causing isolated CHDs in individuals who do not have a genetic syndrome (an example is the mutation of NKX2.5 and GATA4 genes causing atrial septal defect). The future perspectives for the genetics of CHDs will involve three fields of interest: diagnosis; therapy; and prognosis.

A review concerning some embryogenetic aspects of the cardiac outflow tract is presented. Two main topics are discussed: the truncal septation and the secondary heart field. In the context of the septation of the truncus arteriosus, the development of the arterial valves is largely discussed, particularly in reference to the sinuses of Valsalva. Emphasis is also given to the fate of the external myocardial wall of the truncus arteriosus, as this primordial myocardial surface disappears later in the development. Molecular genetics data concerning Sox4 and NF-Atc transcription factors are correlated in the present review with rare forms of truncus malformations encountered in human pathology. The roles exerted by the secondary heart field and the neural crest on the development and growth of the conotruncal musculature are largely discussed. Reported experimental ablations of both secondary heart field and neural crest, showed conotruncal defects such as persistent truncus arteriosus, tetralogy of Fallot, and double-outlet right ventricle, which were considered as the result of a short outflow tract causing, ultimately, a lack of conotruncal rotation. In this regard, some morphologic correlations are carried out, in the present review, between these experimental animal models and human malformations, and it is thought that this sort of conotruncal defects cannot be explained always in terms of conotruncal hypoplasia. Finally, influence of Pitx2c, a left-right laterality signaling gene, on the modulation of the conotruncal rotation, as most recently reported, is emphasized in terms of very likely multifactorial contributions in the embryogenesis of the conotruncal region of the heart., ((c) 2006 Wiley-Liss, Inc.)

Background: Precise relationship between breastfeeding and infant allergy is poorly understood. Objective Aim was to quantify TGF-beta(1) and IL-10 in colostrum and mature milk from allergic and non-allergic mothers and to verify relationship with allergic disease development., Methods: Mothers (13 allergics, nine controls) of 22 newborns participated to prospective study on development of children atopy. Colostrum and mature milk were assayed for TGF-beta(1) and IL-10 by ELISA. Children underwent paediatrician evaluation at 6 months of life., Results: Data are presented as median values and range. A significant difference in concentration of TGF-beta(1) between colostrum (330, range 0-3400 pg/mL) and mature milk (215, range 0-2400 pg/mL) was observed in samples from allergic mothers (P=0.015). In mature milk TGF-beta(1) was significantly lower in allergic (215, range 0-2400 pg/mL) than in non-allergic mothers (1059, range 0-6250 pg/mL) (P=0.015). IL-10 was weakly expressed without significant differences between allergic (4.8, range 0-42 and 9.5, range 0-42 pg/mL in colostrum and in mature milk) and non-allergic mothers (0, range 0-42 pg/mL in colostrum and 0, range 0-42 pg/mL in mature milk). After 6 months 46% infants from allergic mothers, but none from controls, presented atopic dermatitis., Conclusion: TGF-beta(1) was significantly less secreted in mature milk of allergic mothers, while no difference in IL-10 was found. Particular cytokine patterns in milk could influence development of atopic diseases. Further immunological studies in this field are necessary.

Familial recurrence of congenitally corrected transposition of the great arteries (CCTGA) is considered uncommon. Most of the previous familial studies involved a small number of patients and referred to all situs and looping anomalies including single ventricle, heterotaxia, and other cardiac defects different from CCTGA. We performed a large, consecutive clinical case series study in order to detect the recurrence of congenital heart defects in families of children with the classic form of CCTGA. From January 1997 through December 2004, 102 consecutive patients with CCTGA were evaluated in four institutions. There were 59 male (57.8%) and 43 female (42.2%). Mean age was 8.6 +/- 7.8 years. Eighty-eight patients (86.3%) had situs solitus of the atria, 14 (13.7%) situs inversus. The cardiac and extracardiac anomalies among relatives and the patterns of familial recurrence were investigated. Relatives with congenital heart defects were found in 16/102 families (15.7%). Transposition of the great arteries (TGA) was the most common recurrent defect (6/102 families). Consanguinity was identified in the parents of three probands. Six probands had an unaffected twin-sib. Recurrence risks for congenital heart defects were calculated at 5.2% (6/116) for siblings. In conclusion, CCTGA is not always sporadic in families. The pattern of inheritance, the presence of consanguinity among parents and the recurrence of situs inversus could suggest, in some families, an autosomal recessive mechanism with similarities with that occurring in some pedigrees with heterotaxia. The recurrence of TGA and CCTGA in the same family suggests a pathogenetic link between these two anatomically different malformations., ((c) 2005 Wiley-Liss, Inc.)

Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 +/- 1.1% at T0 and 3.5 +/- 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 +/- 0.5% at T0 and 1.5 +/- 1.0% at T1 (ns). Cys-LTs mean level was 14.24 +/- 4.53 pg/ml at T0 and 4.65 +/- 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 +/- 0.19 pg/ml at T0 and 2.41 +/- 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 +/- 3.18 pg/ml at T0 to 7.36 +/- 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.

Background: Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress., Objective: The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity., Methods: EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children., Results: In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01)., Conclusions: Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.

Background: The aim of our study was to assess the prevalence of rhinitis, sneezing, runny or blocked nose apart from colds in a pre-school children population and to evaluate the risk factors and relationship with allergic diseases and sensitization., Methods: Eighteen nursery schools were randomly selected. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire (WQ) was distributed and filled by parents of pre-school children (3-5 years). The allergic sensitization to common aeroallergens and foods was evaluated by skin prick test (SPT). chi2 tests were used to compare proportions between rhinitic and non-rhinitic children., Results: One thousand four hundred and two (92%) valuable questionnaires were returned. Prevalence of rhinitis in the last 12 months was 16.8%. Rhinitic children compared to non-rhinitic children presented a significant increase of diagnosed asthma (20.8% vs. 6.2%, P<0.001), lifetime wheezing (43.2% vs. 21.6%, P<0.001), wheezing in the last 12 months (25.0% vs. 9.4%, P<0.001), atopic dermatitis (22.9% vs. 13.9%, P<0.001) and allergic sensitization (29.9% vs. 13.7%, P<0.001). Sensitization to grass pollen and house dust mites were significant risk factors for rhinitis (P<0.01). A family history of atopy, having pets at home, male gender and greater age were significant risk factors for rhinitis, but not smoking exposure, sharing a bedroom or breastfeeding., Conclusions: In pre-school children rhinitis has a strong association with wheezing symptoms, asthma and atopic dermatitis. Allergic sensitization is a risk factor for rhinitis and should be evaluated even in pre-school children.

Aim: In advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period, is often found and is associated with poor prognosis. Cortisol is strictly involved in the response to major surgical stress, is an immunosuppressor and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status., Methods: In 21 patients with colorectal cancer undergoing surgery we evaluated the assessment of total lymphocytes, CD4+, cortisolemia, circadian rhythm of cortisol (11 p.m. and 8 a.m.) at baseline and in 3(rd) and 7(th) postoperative days., Results: Increase of cortisolemia, as decrease of total and CD4+ lymphocytes in the postoperative period versus baseline was statistically significant. Patients with an altered circadian rhythm were 47% and 36% at 3rd and 7th postoperative days, respectively. At baseline 19% of patients had an altered cortisol circadian rhythm and it was more frequent in patients with nodal involvement (p<0.05) and with metastasis (p<0.01). No relations between lymphocytopenia and alteration of cortisolemia and cortisol circadian rhythm were found, either at baseline or postoperatively (p<0.05)., Conclusion: Lymphocytopenia in cancer patients seems not to be associated with cortisol level and circadian rhythm alteration, either at baseline or after surgical stress. An impairment of circadian rhythm of cortisol was found at baseline in 19% of patients. It was significantly associated with the presence of metastatic disease.

Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation., Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children., Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations., Conclusion: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Cell-mediated immunodeficiency is known to occur in advanced cancer patients, but it is less characterized in earlier stages. Pre-existing immunodeficiency may impair the recovery of postoperative lymphocytopenia, occurring generally within 8-14 days after surgical stress. This study was aimed to verify whether immunodeficiency exists in patients with operable gastric adenocarcinoma and whether radical surgery may restore a count of peripheral blood T helper cells (CD4) and CD4/CD8 ratio within physiological normal values in the late postoperative period. Thirty-five consecutive patients (M/F 18/17; mean age 67 years, range 42-82) with histologically proven gastric adenocarcinoma, undergoing surgery with radical intent, were studied. Assessment of total lymphocyte count and lymphocyte subsets was performed by FAC scan at baseline, then postoperatively 14 and 50 days after surgery. Normal reference values were according to CDC criteria for HIV immunodeficiency (total lymphocyte > 1500/mmc; CD4 cells > 500/mmc; CD4/CD8 > 1.2). Surgical interventions, including D2 locoregional lymphadenectomy, were as follows: 19 Roux Y total gastrectomies; 3 Roux Y subtotal gastrectomies and 13 Billroth II subtotal gastrectomies. Pathological nodal staging was pN0 in 18 and pN+ in 17 cases. Hystotype was intestinal in 14 patients, diffuse in 14 and unclassifiable in 7. Grading was G1 n = 7; G2 n = 7; G3 n = 21. Lymphocyte immunodeficiency was found at baseline in 41% of patients and at 14 days after surgery in 67% of patients. Recovery of postoperative surgery-induced lymphocytopenia occurred on the 50th day only in those patients with normal values at baseline (59%). CD4 deficiency was significantly more frequent in pN+ vs. pN0 patients, either at baseline (p < 0.001 ), on the 14th day (p < 0.02) and on the 50th day (p < 0.007) postoperatively. Cancer-related CD4 deficiency was a frequent finding in our consecutive series of gastric cancer patients; this systemic immune impairment was not restored after complete tumor removal, even in late postoperative period (50th day ). Further studies on a larger number of cases may confirm the prognostic value of lymphocyte count in early gastric cancer stages, and to verify whether early and late postoperative immunodeficiency may be prevented by IL-2 administration.

Nasal brushing has sometimes been used to characterize some affections of the respiratory tract, but seldom employed in chronic diseases such as asthma, for the possible presence of cellular inflammation in the small specimens used for electron microscopy. The present study evaluated the ultrastructure of epithelial cells obtained by nasal brushing in 11 allergic children with asthma, before and after staying in an environment free of allergens, usually implicated in the genesis of inflammatory events. The ultrastructural alterations of the nasal mucosa have been graded on the basis of their severity. Grade I lesions were characterized by well-differentiated mucous and ciliated cells. The ciliated cells appeared usually well preserved but decreased in number. In grade II lesions, most of the epithelial surface was covered by mucous cells. A further phenotype composed of poorly differentiated ciliated or mucous cells was detected. Grade III lesions showed aspects of depletion of the ciliated and mucous cells. The epithelium was largely composed of undifferentiated cells. Furthermore, the comparison of specimens at 2 different times of sampling did not differ. The data demonstrate that in allergic children with asthma, the nasal mucosa showed ultrastructural changes, which appeared to be unmodifiable during a prolonged stay in an environment free of allergens. Moreover, the nasal epithelium may provide a convenient sampling site, allowing grade of mucosal damage, with the benefit that the brush method is minimally invasive and avoids complications related to bronchoscopic examination.

Background: The measurement of exhaled nitric oxide (NO) has recently been proposed as a useful technique for the evaluation of airway inflammation in asthma. The purpose of this study was to determine the effect of methacholine bronchial provocation on the levels of exhaled NO in asthmatic children., Method: Exhaled NO was measurement immediately before and after methacholine provocation in 51 children with mild to moderate asthma., Results: A significant decrease occurred in the level of exhaled NO (p<0.0001) after methacholine bronchial provocation which was not correlated with the percentage fall in forced expiratory volume in 1 second (FEV(1))., Conclusions: The methacholine test should not be used immediately before measurement of exhaled NO in children with asthma.

Laparoscopic splenectomy is performed with increasing acceptance for hematologic disorders, with low complication rates reported. Splenoportal thrombosis following splenectomy is a rare complication, anecdotally reported after laparoscopic procedures. We here describe a case of thrombosis of the spleno-mesenteric-portal axis 14 days after a laparoscopic splenectomy using Ligasure. Abdominal ultrasound scans and Doppler examination allowed us to diagnose this event, and an angio-MR scan performed afterward confirmed the diagnosis. Heparin therapy was promptly begun. The patient was then switched to oral anticoagulant therapy, with resolution of the clinical features. The patient was discharged after 1 week of anticoagulant therapy with a stable Doppler ultrasound pattern. Early diagnosis and prompt initiation of anticoagulant therapy associated with careful surgical technique may reduce the risk of this life-threatening complication.

Airway inflammation is a characteristic of asthma. Exhaled nitric oxide (eNO) has been demonstrated to be related to actual levels of airway inflammation in asthmatic patients. The purpose of this study was to investigate whether the temperature of exhaled air is related to eNO levels. Temperature of exhaled air and eNO were measured in 52 asthmatic children with a cross-sectional design. A significant relationship was demonstrated between eNO and temperature of peak and plateau exhaled air temperature. The relationship between both the peak and the plateau values and eNO was more evident when it was corrected for environmental temperature. These results suggest a relationship between exhaled nitric oxide and the temperature of exhaled air in asthmatic patients not treated with systemic steroids.

The aim of the study was to evaluate the protective effect of single-dose, combination treatment comprising montelukast (5 mg) and loratadine (10 mg), on exercise-induced bronchoconstriction in asthmatic children. The combination was compared to placebo, loratadine and montelukast alone. Nineteen children were enrolled in a double-blind randomised, single-dose, crossover study. For each treatment patients undertook two treadmill exercise tests, 2 and 12 h respectively after single-dose administration. No significant differences were seen in the maximum fall in forced expiratory volume in one second (FEV1) 2 h after treatment and placebo. Whereas significant differences in maximum fall in FEV1 were observed between treatment groups 12 h after administration. Loratadine alone did not show any significant protection or any additional effect in comparison with montelukast alone. Single doses of montelukast and montelukast plus loratadine were significantly more effective than loratadine at 12 h. The present study, performed using single-dose treatments, demonstrated that maximal protective effect by montelukast was obtained 12 h after dosing and that montelukast plus loratadine did not result in significant additive bronchoprotective effects on exercise-induced bronchoconstriction.

Background: We investigated the effects of prolonged allergen avoidance in 18 house dust mite-sensitized asthmatic children during a prolonged residential period at a high altitude, allergen-free environment., Methods: Evaluations of residual volume (RV) and exhaled nitric oxide (eNO) were performed (i) at admission to the residential house in September, (ii) in December after 3 months of stay, (iii) in January after 15 days at home, exposed to allergens, and (iv) in June after 9 months of stay., Results: During the study period RV showed a significant decrease in December (from 117.5 +/- 7.7% to 96.5 +/- 3.2%) (P < 0.02) and a following increase in January (126.2 +/- 17.2%), after allergen re-exposure (P < 0.03). RV decreased again in June at the end of the study period (91.1 +/- 6.0%) (P = 0.001). FEV(1), FEF(25-75) and VC values did not present significant variations. ENO showed a significant decrease in December after 3 months at high altitude (from 21.3 +/- 3.9 p.p.b. to 11.9 +/- 1.7 p.p.b.) (P = 0.03), but no further significant change. No correlation was found between lung volumes and eNO, probably reflecting different aspects of asthma., Conclusions: Results suggest that RV may be more sensitive than other respiratory function parameters in identifying children with air trapping, being influenced significantly as the inflammatory indices by effective allergen avoidance/exposure regimen.

Background: Recent evidence suggests that asthma is not invariably related to atopy. The aim of this study was to evaluate the frequency of atopy, asthma and sensitization to eight common allergens in a large group of children with allergic symptoms., Methods: 1426 children referred to our Paediatric Asthma and Allergy Center because of allergic symptoms were examined. Bronchial asthma, allergic rhino-conjunctivitis, food allergy and atopic dermatitis were diagnosed with standardized methods. Atopy was diagnosed if at least one skin test was positive., Results: Of the 1426 children examined, 629 (44%) were atopic and 769 (56%) were non-atopic. Asthma was diagnosed in the same proportion (i.e., 64%) of atopic and non-atopic children. However, after division into age groups, non-atopic asthma was significantly more prevalent (chi2 = 8.46) in children between 0 and 3 years old (group 1). On the other hand, atopy was significantly associated with asthma only in group 3 (odds ratio 1.85). Furthermore, a significant association with asthma symptoms was found for house dust mite (HDM) in group 3 (odds ratio 4.8)., Conclusions: Asthma is related to atopy in pre-selected children only from the age of 7 years. House dust mite sensitization seems to be an important determinant of asthma in these "older" children.

Diet composition, in particular fat intake, has been suggested to be a risk factor for obesity in humans. Several mechanisms may contribute to explain the impact of fat intake on fat gain. One factor may be the low thermogenesis induced by a mixed meal rich in fat. In a group of 11 girls (10.1 +/- 0.3 yr), 6 obese (body mass index, 25.6 +/- 0.6 kg/m(2)), and 5 nonobese (body mass index, 19 +/- 1.6 kg/m(2)), we tested the hypothesis that a mixed meal rich in fat can elicit energy saving compared with an isocaloric and isoproteic meal rich in carbohydrate. The postabsorptive resting energy expenditure and the thermic effect of a meal (TEM) after a low fat (LF; 20% fat, 68% carbohydrate, and 12% protein) or an isocaloric (2500 kJ or 600 Cal) and isoproteic high fat (HF; 48% fat, 40% carbohydrate, and 12% protein) meal were measured by indirect calorimetry. Each girl repeated the test with a different, randomly assigned menu (HF or LF) 1 week after the first test. TEM, expressed as a percentage of energy intake was significantly higher after a LF meal than after a HF meal (6.5 +/- 0.7% vs. 4.3 +/- 0.4%; P < 0.01). The postprandial respiratory quotient (RQ) was significantly higher after a LF meal than after a HF meal (0.86 +/- 0.013 vs. 0.83 +/- 0.014; P < 0.001). The HF low carbohydrate meal induced a significantly lower increase in carbohydrate oxidation than the LF meal (20.3 +/- 6.2 vs. 61.3 +/- 7.8 mg/min; P < 0.001). On the contrary, fat oxidation was significantly higher after a HF meal than after a LF meal (-1.3 +/- 2.4 vs. -15.1 +/- 3.6 mg/min; P < 0.01). However, the postprandial fat storage was 8-fold higher after a HF meal than after a LF meal (17.2 +/- 1.7 vs. 1.9 +/- 1.8 g; P < 0.001). These results suggest that a high fat meal is able to induce lower thermogenesis and a higher positive fat balance than an isocaloric and isoproteic low fat meal. Therefore, diet composition per se must be taken into account among the various risk factors that induce obesity in children.

This study reports a 12-year-old girl who developed an anaphylactic reaction following snail ingestion during house dust mite (HDM) immunotherapy treatment. Radioallergosorbent (RAST) inhibition showed cross-reactivity between the two allergens, leading to consideration of HDM as the sensitizing agent. Children undergoing HDM immunotherapy treatment should be aware of the potential risks of hypersensitivity reactions to invertebrate foods.

The aim of this study was to evaluate the effectiveness of sentinel node (SN) biopsy in breast cancer. Twenty-five female patients classified as T1N0 according to the TNM system of the UICC were evaluated with this procedure from April to October 1999. The day before surgery a subdermal injection of 99mTc-nanocoll within the tissue overlying the neoplastic lesion and subsequent lymphoscintigraphy were performed. In all patients the SN was detected with a radioguided probe during scintigraphy and surgery. Histological examination of the SN for detection of metastases was positive in four patients who subsequently underwent axillary dissection. In the remaining patients with normal SNs no axillary dissection was performed. The preliminary results confirm the validity of the sentinel node procedure.

Exhaled nitric oxide (ENO) and eosinophil sputum markers are considered noninvasive markers of airway inflammation in asthma. The aim of this study was to evaluate whether the procedure of sputum induction can affect the level of ENO. We measured ENO before and after sputum induction by inhalation of hypertonic saline solution in 22 asthmatic children and 9 healthy controls. The ENO mean (+/- S. E.M.) value in the group of asthmatic children was reduced from a baseline value of 20.8 (+/- 3.0) ppb to 17.4 (+/- 2.4) ppb after sputum induction (P = 0.0012). In the healthy controls, the mean baseline value of ENO was 9.1 (+/- 2.1) ppb and it was reduced to 4. 8 (+/- 1.1) ppb after induction of sputum (P < 0.01). We suggest that measurements of ENO should be performed after the induction of sputum in asthmatic patients whenever both tests are done in sequence., (Copyright 2000 Wiley-Liss, Inc.)

The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy. In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6-13 yrs). ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011). The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroid-treated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood.

The level of exhaled nitric oxide (NO) has been demonstrated to reflect the degree of airway inflammation in patients with asthma and to be related to the severity of asthma, as well as to the efficacy of treatment. In contrast, lung function tests provide information about airway volumes and flows reflecting the level of airway obstruction, but do not allow any direct information about the degree of airway inflammation. Several studies have evaluated the relationships between the level of airway inflammation assessed by exhaled NO and the levels of airway obstruction and/or bronchial hyperresponsiveness in asthmatic adults and children. These studies highlight the complex pathophysiology of asthma and suggest that exhaled NO may have a promising role in addition to lung function measurement in the evaluation of asthma severity in children.

Inhaled corticosteroids are capable of reducing the level of exhaled nitric oxide (expiratory nitric oxide fraction (FE,NO)) in asthmatic patients in a dose-dependent fashion. The aim of this study was to evaluate whether or not treatment with an inhaled steroid can prevent changes in FE,NO after the exposure to relevant allergens, following avoidance, in asthmatic children allergic to house dust mite. Thirty-two house dust mite-allergy asthmatic children were randomly allocated to treatment with inhaled flunisolide (500 microg b.i.d) or placebo and evaluated before and 2 weeks after a period of natural exposure to mite antigens. Lung function and FE,NO were evaluated. FE,NO was increased in the placebo-treated group after antigen exposure. Treatment with inhaled flunisolide prevented such increase in FE,NO (p<0.001). No change was observed in lung function parameters. Inhaled flunisolide is effective in preventing the increase in airway inflammation observed in allergic asthmatic children re-exposed to allergens.

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.

Exposure to allergens has been shown to lead to sensitization and to the subsequent development of airway hyperresponsiveness in genetically predisposed individuals. Increasing interest is being devoted to mechanisms for the prevention of allergen sensitization and asthma development. Primary prevention (avoiding the sensitization to allergens) requires a large effort as the majority of atopic sensitizations occur in children with no demonstrable risk at the birth. Secondary prevention (deterrence of disease expression despite prior IgE sensitization) requires methods for detecting the population at risk by means of large population screening. Tertiary prevention (minimizing the morbidity for those who already have the disease) may be achieved by allergen avoidance, which has been demonstrated to effectively decrease inflammation in symptomatic patients.

Measurement of levels of exhaled nitric oxide (NO) has been proposed as a noninvasive method for evaluating the degree of airway inflammation in asthmatic patients. Some concern in the interpretation of results of such measurement may arise from possible interference by high environmental concentrations of NO inhaled by these patients. The aim of this study was to verify whether environmental concentrations of NO in the range from 0 to 150 ppb can influence levels of exhaled NO. We tested two groups of subjects. The first group, consisting of 16 subjects, was tested when environmental levels of NO were from 0 to 3 ppb and from 20 to 60 ppb, and exhaled NO mean ppb (+/- SEM) levels were 9.81 +/- 1.43 and 9.78 +/- 1.47 (p = ns) (mean +/- SEM), respectively. The second group, consisting of 30 subjects, was tested at ambient NO concentrations of 0 to 3 ppm, 80 to 100 ppm, and 120 to 150 ppb, and for 18 of these subjects who underwent testing under all three conditions investigated, the mean levels of exhaled NO were 9.23 +/- 1.51, 7.78 +/- 1.19, and 9.33 +/- 1.55 ppb (p = ns), respectively. The results of this study suggest that significantly different ambient levels of NO have no effect on levels of exhaled NO.

Background: Asthma is characterized by bronchial hyperresponsiveness (BHR), bronchial mucosa inflammation and airway epithelial damage., Objective: This study was designed to evaluate the effect of mite avoidance on bronchial epithelial shedding in asthmatic children sensitized to Dermatophagoides., Methods: The percentages of airway epithelial cells and eosinophil have been counted in samples obtained by hypertonic saline-induced sputum before and after a period of antigen avoidance in an Alpine environment (1756 m). The degree of bronchial hyperresponsiveness to methacholine was also evaluated., Results: After avoidance the median (lower, Q1, and upper, Q3, quartile) percentage of epithelial cells in the sputum decreased significantly from 3.50 [0.50;6.98] to 0 [0;0.5] (P=0.012) and eosinophil percentage decreased from 1 [0;5.25] to 0 [0,1.5] (P<0.05). Median (Q1,Q3) PC20 increased significantly from 2.75 [1.53;7.5] to 3.25 [1.65;15.25] mg/ mL (P=0.038). After 3 weeks of re-exposure to mite the epithelial median (Q1,Q3) percentage raised to 3.90 [1.5;6] (P = 0.027), eosinophils to 1.5 [0;3.00] (NS) and PC20 was 5.25 [1.68;14.50] (NS)., Conclusion: Exposure to house dust mite antigen can induce airway epithelial shedding even in subjects with low eosinophil airway infiltration, thus supporting the idea that epithelial damage in asthmatics sensitized to Dermatophagoides may be due to a proteolytic activity of the mite major antigens.

In the present study we have assessed the prevalence of asthma-related symptoms in school children resident in the urban area of Verona, in the north east of Italy, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The entirely of the population of children aged 6-7 yrs (total 2,350, from 64 schools) and 13-14 years (total 2,500 from 42 schools) living in the area was selected. A questionnaire was distributed at school. This was addressed to the parents of the younger population and distributed directly to the older children. In the two groups 2,091 (89%) and 2,179 (87%) questionnaires were returned, respectively. The results obtained show a more frequent history of "wheeling ever" in the young population compared to the older group (23.2 versus 7.9%, respectively) (p < 0.001). There was no difference in the prevalence of wheezing in the last 12 months (7.3 and 7.4%, respectively), and of asthma (4.6 and 3.5%, respectively). In the older group there was a higher incidence of exercise-induced wheezing (12.0 versus 3.2%), which was particularly significant in the females compared to males (14.2 versus 10.0, respectively; p < 0.01). Our data confirm that there is a marked variation in the prevalence of asthma and asthma-related respiratory symptoms in different centres throughout the world, since we obtained a lower percentage of reported symptoms in comparison to other ISAAC centres.

The pathogenesis of otitis media with effusion is still under debate, but allergic sensitization has been suggested in some cases. We investigated whether nasal cytology may indicate an allergic pathogenesis for otitis media with effusion. Atopic symptoms, results of skin prick tests to common aeroallergens, and nasal cytology by nasal scraping were evaluated in 40 children with current otitis media with effusion and compared with findings in a group of 40 healthy children. The presence of nasal eosinophils was significantly more frequent in children with otitis media with effusion than in the control group (p < 0.05). Nasal eosinophils were significantly associated with both allergic rhinitis (p < 0.001) and positive skin prick test results (p < 0.001). Allergic rhinitis with nasal eosinophilia was found in six children of the study group and in one child of the control group (p < 0.05). Our data suggest that nasal allergic inflammation may play a role in a subset of patients with otitis media with effusion. Therefore the possibility of allergic sensitization must always be considered in patients with serous otitis media.

Background: Exposure to relevant allergens causes an increase in bronchial hyperresponsiveness, as well as an inflammatory reaction at the site of the bronchial mucosa in patients with asthma., Objective: The purpose of this study was to determine whether antigen avoidance can exert an antiinflammatory effect on the eosinophil phase of airway inflammation in children with asthma., Methods: The level of bronchial hyperreactivity and the percentage of eosinophils in sputum samples obtained by inhalation of hypertonic saline solution, were evaluated in a group of asthmatic children allergic to house dust mite before and after a period of antigen avoidance in an Alpine environment (1756 m)., Results: At the end of the avoidance period PC20 increased from a median value (lower and upper quartile: Q1, Q3) of 1.17 (0.74, 4.75) to 3.5 (1.18, 8.87) mg/ml (p = 0.02), and eosinophil percentage in the sputum decreased from a median value (Q1, Q3) of 14.02 (3.34, 28.24) to 2.08 (0, 7.4) (p less than 0.01)., Conclusion: A 3-month period of antigen avoidance can significantly reduce the eosinophil phase of airway inflammation, along with bronchial hyperresponsiveness, in patients with asthma.

It has been proposed that cetirizine inhibits eosinophil migration and adherence. We evaluated the possible effect of cetirizine on integrin-induced eosinophil proinflammatory activation. Normodense eosinophils were triggered with monoclonal antibodies to integrins in the presence of different concentrations of certirizine. Proinflammatory activation was measured by evaluation of O2- production. Only at high concentrations (250 micrograms/ml) and in the first 15 min did certirizine significantly inhibit (p < 0.02) the eosinophil respiratory burst. No effect was shown for lower concentrations (50 and 100 micrograms/ml) or after 15 min. These data suggest that, only at very high concentrations, cetirizine may induce a transient inhibition of the integrin-induced eosinophil respiratory burst.

The contribution of beta 2-agonist treatment per se and the effect of beta 2-agonists plus allergen exposure was evaluated in two groups of thirteen asthmatic children being treated respectively at sea level during the period of maximal allergen exposure and at high altitude in an environment free of the offending allergens. Bronchial hyperreactivity was evaluated by standardised exercise tests before and after treatment with salbutamol controlled release tablets (4 mg). Challenges were performed at the beginning and after 2 and 4 weeks of treatment. A fourth test was performed 2 days after stopping the treatment. Children treated with salbutamol at sea level (exposure to allergen) showed baseline delta PEF of 16.9 +/- 3.4 and 13.7 +/- 4.2, 20.7 +/- 4.3, 26.0 +/- 5.1 respectively for the second, third and fourth test. Children treated at high altitude showed respectively delta PEF of 34.9 +/- 5.1, 31.1 +/- 4.9, 26.5 +/- 5.4, 27.9 +/- 5.0. These data suggest that oral salbutamol per se is not responsible for an increase in bronchial responsiveness, but eventually suggest that treatment with beta 2-agonists at the same time as continued allergen exposure may be responsible for an increase in bronchial hyperresponsiveness.

Inhaled steroids may control bronchial inflammation in asthmatics exposed to allergens. In this study we evaluated whether prophylactic budesonide would prevent relapse of asthma in children re-exposed to offending allergens at sea level, after a period of antigen avoidance at high altitude. Thirty children received either budesonide (200 micrograms b.i.d.) or placebo (double-blind). Following a 4-wk baseline period and 2 wk of treatment at high altitude, children were treated for 3 mo at sea level. Methacholine challenge and pulmonary function studies were performed before and after baseline period, after the 2 wk of treatment in the mountain environment, and at the end of treatment. ECP serum levels were evaluated after the baseline period and at the end of treatment. PEFR and symptoms were recorded in a diary card during the study. The increase in methacholine provocative dosage was greater, although not significant (p = 0.096), in the budesonide than in the placebo group after the treatment at high altitude and remained higher at the end of the treatment (p = 0.04). ECP levels increased in both the groups with no significant difference. Our results confirm that budesonide, in addition to its efficacy in treating pre-existent airway inflammation, is effective in preventing the increase of reactivity in asthmatic children re-exposed to allergens.

The introduction of infant formulas represents an important result in the field of the newborn and infant artificial feeding, reducing the gap with maternal feeding. In the last decade technological evolution allowed to obtain milk formulas which became more and more similar to human milk starting from cow's milk, thus obtaining a composition adequate to the digestive and nutritional requirements of the newborn and of the infant, starting from the model of the breast feeding (infant formulas). The major differences between human and cow's milk have been corrected by dilution, skimming, addition of carbohydrates, acidification. From an allergenic viewpoint, in a recent study, we observed that no significant differences can be observed in the development of atopic symptoms for children supplemented with different substances in the first 5 days of life or receiving cow's milk infant formulas in the first three months of life, compared to those breast fed. In the case of the development of intolerance or allergy to cow's milk proteins, the substitution of the cow's milk based formula with hydrolysed or soy formulas is required. Maternal feeding represents the best choice for the nutrition of the newborn; however, when it is not possible, milk formulas despite they still show marked differences with human milk, concerning both nutrients and defensive factors, allow to reach satisfactory results about both nutrition and health.

Home mattresses of 24 asthmatic children with house dust mite allergy were sprayed with either benzyl-benzoate foam or placebo in a double blind fashion, 10 days before the children left the residential house for asthmatic children Istituto Pio XII (located in the Italian Alps in an environment free of mites) and went back to their own home for the Christmas and Easter holidays. A further group of 8 children, whose mattresses received no treatment, was kept as an absolute control. Two days after spraying, benzyl-benzoate or placebo were vacuumed from the mattresses. Acarex test was performed immediately before spraying and at the end of each holiday period of 20 and 10 days, respectively. Bronchial hyperreactivity as well as serum and nasal secretory specific IgE for Dermatophagoides pteronyssinus were assessed in all children immediately before leaving and within 48 hr after returning to the residential house. The results of the study show that sprayed benzyl-benzoate foam was no more effective than placebo in reducing the level of house dust mite recovered from patients' mattresses, or in reducing bronchial hyperreactivity and IgE concentration in serum and nasal secretions.