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Biomedical subjects

A L Boner

Publications and source records attributed to A L Boner.

At least 19 recordsLinked to original sources

Chromosome 7p linkage and GPR154 gene association in Italian families with allergic asthma.

BACKGROUND: Several genome scans have reported linkage of markers on chromosome 7p with asthma and related phenotypes in different populations. A fine mapping in Finnish and French-Canadian populations has associated the GPR154 gene (also known as G-protein-coupled receptor for asthma susceptibility, GPRA) with elevated IgE or asthma. OBJECTIVE: To confirm chromosome 7p linkage and candidate gene association in Italian families with atopic asthma. METHODS: In a two-phase approach, we first performed a linkage analysis of chromosome 7, and then a family-based association study on the GPR154 gene for allergic asthma phenotypes in the Italian population. RESULTS: The screening of 117 families with 19 microsatellite markers showed potential linkage for elevated IgE (P<0.002 at 22 cM from p-ter), asthma (P<0.005 at 44 cM), or atopy (P<0.005 at 54 cM). In the second phase of the present study, candidate gene GPR154, which is located in the phase one-linked region, was investigated in 211 families with seven single nucleotide polymorphisms (SNPs) that tag most haplotype variability, by the pedigree disequilibrium test. Elevated IgE levels were associated with two GPR154 gene SNPs (SNP 546333, P=0.0046; rs740 347, P=0.006), and with haplotypes in the global test (P=0.013). Haplotype analysis performed in nuclear families having at least 1 asthmatic parent showed a significant association with asthma (P=0.0173), atopy (P=0.0058), SPT (P=0.0025), and bronchial hyper reactivity (P=0.0163). CONCLUSION: These results support a susceptibility locus for asthma and related phenotypes on chromosome 7, and are in agreement with recent reports suggesting that a common susceptibility factor for atopic manifestations in asthma is likely conferred by the locus containing the GPR154 gene.

Asthma↗

Transforming growth factor-beta and interleukin-10 in breast milk and development of atopic diseases in infants.

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.

Breast Feeding↗

Flunisolide decreases exhaled nitric oxide and nitrotyrosine levels in asthmatic children.

BACKGROUND: Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. METHODS: This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. RESULTS: The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). CONCLUSIONS: This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects.

Administration, Inhalation↗

Adipose tissue and metabolic effects: new insight into measurements.

BACKGROUND: Epidemiologic evidence supports the theory that the relation between obesity and disease risk begins early in life, and those risk factors for disease track, or remain at a similar level, with advancing age, growth, and development. The fat tissue, once considered as a depot for energy substrate, is a metabolically active tissue. The fat cells produce agents that regulate a host of physiological processes directly related to carbohydrate and fat metabolism and the development of cardiovascular disease and type 2 diabetes. AIM: To discuss fat tissue, and fat distribution in relation to body composition measurements, with particular emphasis on imaging techniques (ie, dual energy X-ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI)) and its relationship with metabolic and cardiovascular heath variables mediated by the metabolic characteristics of the adipose tissue. DISCUSSION: In sum, the medical and physiological health complications of childhood obesity are well documented. Imaging methods are considered the most accurate means available for in vivo quantification at the tissue-organ level and the methods of choice for calibration of field methods designed to measure adipose tissue.

Absorptiometry, Photon↗

Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens.

BACKGROUND: Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re-exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens. METHODS: Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC(20)), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated. RESULTS: Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase (P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen. CONCLUSIONS: The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re-exposed to relevant allergens.

Acetates↗

Exaled nitric oxide and air trapping correlation in asthmatic children.

Exhaled nitric oxide (eNO) levels have been shown to correlate with atopy and with airway hyperresponsiveness but not with standard spirometry. The aim of our study was to evaluate the correlation between eNo levels and functional residual capacity (FRC), residual volume (RV), RV to total lung capacity (TLC) ratio, and pulmonary resistances in asthmatic children ages 6-13 years. Forty-nine patients (35 males) were enrolled in the study. Nineteen of them were not receiving inhaled corticosteroids. The eNO levels were measured by chemiluminescence's analyzer and lung function study were performed by body box plethysmography. As expected, there was no correlation between eNO levels and forced vital capacity (FVC); forced expiratory volume in the first second (FEV1); mid respiratory flow between 25 and 75% of the vital capacity (MEF(25 -75)), FEV1/FVC, and pulmonary resistances. Instead a correlation was found between eNO level and RV both considering all the study population together (r = 0.51, P = 0.001) and separately the asthmatic children not receiving ICS (r = 0.6, P = 0.003). In the patients receiving ICS the correlation was still present (r = 0.43, P = 0.01). The correlation between eNo levels and RV may reflect the effect of airway inflammation on NO production and diffusion as well as peripheral airway trapping and consequent RV.

Administration, Inhalation↗

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: a pilot study.

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.

Adolescent↗

Environmental prevention in atopic eczema dermatitis syndrome (AEDS) and asthma: avoidance of indoor allergens.

Indoor allergens represent an important precipitating factor for both asthma and atopic eczema dermatitis syndromes (AEDS). There is also accumulating evidence that sensitization to those allergens is associated with the onset of atopic disorders. Patients with AEDS present aeroallergen-specific T-cell responses associated with worsening of symptoms when exposed to specific aeroallergens. Furthermore, application of indoor allergens to the skin of patient with AEDS induces a local eczematous response in one-third of these patients. Exposure to high concentrations of mite allergens in early infancy have been demonstrated to be a risk factor for developing atopic dermatitis during the first 3 years of life. Moreover, a clear dose-response relationship has been documented between mite exposure and disease activity. Primary prevention of AEDS by avoiding indoor allergen exposure has been proved to be effective only when allergenic foods have also been avoided. Mite allergen avoidance in infants with AEDS and food allergy may however, prevent mite sensitization and the onset of asthma. Indoor allergen avoidance has been demonstrated to be effective in the majority of studies performed in patients with established AEDS. Negative results may be explained either by individual susceptibility variation, by long duration of disease with the consequent irreversible pathological changes in the target tissue or by exposure to allergens outside the house. Education of the patients and public consciousness of the problems are crucial for the efficacy of indoor allergen avoidance in allergic diseases.

Air Pollution, Indoor↗

"Cyst-like" structures within the ciliary shafts in children with bronchiectasis.

"Cyst-like" structures within the ciliary shafts were considered in four adults as a primary defect involved in the development of bronchiectasis. In this study, the presence and the primary or secondary nature of this abnormality were assessed in children with bronchiectasis. High resolution computed tomography (HRCT) and nasal biopsies for motion analysis and transmission electron microscopy (TEM) evaluation of cilia were obtained in 45 children with recurrent lower airway infections and abnormal chest radiography. HRCT disclosed bronchiectasis in 35 out of 45 (77.8%) children and cyst-like structures were demonstrated with TEM in 29 out of 45 (64.4%) patients. Cyst-like structures were constantly associated with other ultrastructural abnormalities commonly observed in chronic inflammation, and were found both in subjects with primary and with secondary ciliary dyskinesia. When considering only patients with bronchiectasis, a significant correlation between prevalence of cyst-like structures and the severity of bronchiectasis was demonstrated. Follow-up (2-22 months) of seven patients demonstrated that in the five children with secondary dyskinesia, the ultrastructural defect completely disappeared and there was a small reduction in the abnormality in the two patients with primary dyskinesia. In contrast to one previous report, the reversibility of the defect suggests its secondary origin, which is most likely related to chronic airway inflammation.

Adolescent↗

Rhinitis in pre-school children: prevalence, association with allergic diseases and risk factors.

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.

Age Factors↗

No linkage or association of five polymorphisms in the interleukin-4 receptor alpha gene with atopic asthma in Italian families.

The literature contains conflicting reports on the association of common variants of the interleukin (IL)-4 receptor alpha (IL4RA) gene with atopic asthma. The purpose of the present study was to investigate the linkage and association of several gene polymorphisms with atopic asthma in a large series of well-characterized individuals. Analysis of five polymorphisms (I50V, E375A, C406R, S478P and Q551R) of the IL4RA gene was performed in 823 individuals from 182 families with atopic asthmatic children from north-east Italy. The subjects were tested for clinical asthma, total serum IgE level, skin prick test positivity to common aeroallergens, and bronchial hyperresponsiveness to methacholine. The frequency of the polymorphisms was similar to that reported for other populations. The 375, 406, 478 and 551 polymorphisms were in linkage disequilibrium, as previously reported. No linkage or transmission disequilibrium was observed in the families between any mutation and any of the phenotypes investigated. No multipoint haplotype was associated with any phenotype. In conclusion, the IL4RA gene does not seem to play an important role in genetic predisposition to atopic asthma in the population tested.

Adolescent↗

Systemic activity of inhaled corticosteroid treatment in asthmatic children: corticotrophin releasing hormone test.

BACKGROUND: A study was undertaken to assess the function of the hypothalamic-pituitary-adrenal axis (HPA) in a group of asthmatic children before and after treatment with inhaled corticosteroids. METHODS: Thirty prepubertal patients of mean (SD) age 6.7 (1.8) years were treated with inhaled corticosteroids. All children underwent a corticotrophin releasing hormone (CRH) test with evaluation of serum cortisol and adrenocorticotrophin hormone (ACTH) levels before and after 3 months of treatment. Twenty four hour urine samples were also collected to measure free cortisol (UFC) excretion. RESULTS: Subjects showed no difference between basal serum cortisol levels (mean change -18; 95% CI -41 to 5; p=0.118) and delta (peak minus basal) levels (mean change -13; 95% CI -38 to 12; p=0.308) before and after treatment, whereas the peak cortisol level (mean change -31; 95% CI -55 to -7; p=0.013) and area under the curve (AUC) (mean change -175; 95% CI -288 to -63; p=0.003) after CRH were significantly lower following treatment. Basal, peak and AUC ACTH were significantly lower after treatment (p<0.05, p=0.004 and p=0.003, respectively), while delta ACTH was similar before and after treatment ((mean change -12; 95% CI - 31 to -7; p=0.199). No significant reduction in 24 hour UFC was observed after the treatment period (before 14.9 (7.1), after 15.0 (11.6); mean change 0.1, 95% CI -5.2 to 5.4; p=0.967). No correlation was found between UFC and any of the parameters of cortisol excretion following the CRH test, either before or after treatment. CONCLUSIONS: These data suggest that, at the dosage and for the treatment period used, inhaled steroids do not seem to suppress the HPA axis in the majority of patients. The CRH test may be more sensitive than 24 hour UFC and morning plasma cortisol levels in evaluating systemic activity of inhaled corticosteroid treatment.

Administration, Inhalation↗

Efficacy of sublingual immunotherapy in asthma and eczema.

Sublingual immunotherapy (SLIT) is the local route of administration of allergen extracts investigated in several controlled clinical trials. In a number of countries, particularly Italy, France and Spain, this has become common in office practice. At variance with subcutaneous immunotherapy, the knowledge of mechanisms of action of SLIT is still at the beginning: some studies, in animal models, provided interesting information: the dendritic cells of oral mucosa act as efficient antigen-presenting cells and produce IL-12, which directs the immune response towards a Th1 profile away from IgE-Th2 profile. Its clinical efficacy (improvement of symptoms and reduction of drug intake) for both asthma and rhinitis has been assessed in detail for the most common allergens: house dust mites, grass pollen, Parietaria, birch pollen and olive tree. SLIT requires further evaluation concerning the treatment of the extrinsic form of atopic dermatitis. The induction of immunologic tolerance rather than immunoreactivity should be worth pursuing due to the immunologic pathway involved in the pathophysiology of atopic dermatitis. The safety profile of SLIT, derived from the clinical trials and postmarketing surveillance studies, turned out to be satisfactory in adults and children. SLIT represents an important step towards an efficacious and safe treatment of patients with allergic respiratory diseases; nevertheless, further studies are necessary to establish it as a viable alternative to subcutaneous immunotherapy.

Administration, Sublingual↗

Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study.

BACKGROUND: Although widely practiced for over 80 years, the role of specific immunotherapy (SIT) in pediatric asthma treatment is still controversial. We assessed the effects of a 3-year period of subcutaneous administration of a standardized preparation of Dermatophagoides pteronyssinus (D pt) on the respiratory health in a group of asthmatic children monosensitized to house dust mite (HDM). METHODS: A randomized clinical trial was performed after 1-year run-in period. Fifteen children receiving SIT for HDM and 14 controls (four drop-outs), matched for age, allergen sensitization, asthma severity, lung function, and non-specific bronchial reactivity (BHR), were studied during the 3-year treatment period. During the whole trial, respiratory symptoms, pharmacological and respiratory function parameters were regularly evaluated. Skin prick tests and methacholine challenge were performed at the beginning and end of the study. RESULTS: In the SIT group significant improvement in asthmatic symptoms and marked reduction in drug intake was observed. The SIT group also showed a significant decrease in non-specific bronchial BHR. No new sensitivity occurred during the study period in the SIT group only. No major local or systemic side-effects were reported during the study. CONCLUSIONS: Our results confirm that SIT is effective in asthmatic children sensitive to mites. It is associated with a decrease in BHR and it may prevent the development of new sensitizations in monosensitized subjects.

Adolescent↗

Mite avoidance can reduce air trapping and airway inflammation in allergic asthmatic children.

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.

Adolescent↗

Reduction in exhaled nitric oxide immediately after methacholine challenge in asthmatic children.

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.

Adolescent↗