Association of PPAR polymorphisms with cytokine levels in allergic rhinitis.

Our aim was to study the association of Pro12Ala and exon6 C161T polymorphisms of PPARgamma and intron7 G/C polymorphisms of PPAR-alpha with clinical symptoms, peak nasal inspiratory flow values, serum soluble TNF-alpha, TNF-R1, Fas, Fas ligand and IgE concentrations in patients with seasonal allergic rhinitis during and after pollen season. We performed a follow-up study of 66 Hungarian patients with seasonal allergic rhinitis and 180 healthy referent subjects. We used PCR-RFLP technique and ELISA. The distribution of mutant alleles of PPAR-gamma and -alpha did not differ in patients and referent subjects. Patients carrying the mutant 12Ala, exon6 161T alleles of PPAR-gamma and intron7 C allele of PPAR-alpha had significantly higher clinical symptom score values, TNF-alpha and IgE levels and lower peak nasal inspiratory flow values during and after pollen season. The results indicated that nuclear receptors PPAR-gamma and PPAR-alpha are involved in the regulation of inflammatory mediator production in patients with seasonal allergic rhinitis and polymorphisms of the receptors are very likely to contribute to the heterogeneity of clinical and immunological parameters of allergic patients.

Association of TLR-4 and TNF-alpha polymorphisms with clinical symptoms and cytokine levels in patients with allergic rhinitis.

Our objective was to determine the frequency of TNF-alpha -238, -308 G/A promoter and TLR-4 299 D/G and 399 T/I polymorphisms in healthy population and in patients with seasonal allergic rhinitis, and to examine its influences on serum TNF-alpha, TNF receptor-1, Fas, Fas-ligand, IgE levels and on clinical symptoms. A pilot study was performed in 66 patients with seasonal allergic rhinitis to ragweed pollen and 161 non-allergic subjects using PCR-RFLP technique and ELISA. Carriers of the -238A and -308G alleles have significantly higher TNF-alpha and IgE levels, clinical score values and lower peak nasal flow (PNIF) values during and after ragweed pollen season. Patients with the 299G/399I alleles of the TLR-4 gene have significantly lower TNF-alpha, Fas, FasL and IgE levels, clinical scores and higher PNIF values during and after pollen season. The -238A and -308G polymorphisms of the TNF-alpha promoter and 299D/399T polymorphisms of the TLR-4 gene are associated with more pronounced clinical symptoms, higher cytokine and IgE levels, and low PNIF values. These polymorphisms are very likely to contribute to the heterogeneity of clinical and laboratory parameters of patients.

Depressive symptoms amongst asthmatic children's caregivers.

We wanted to find out, whether the number of depressive symptoms is higher amongst asthmatic children's caregivers, compared to international data, to the Hungarian population average, and to parents of children with chronic renal disease. Are these depressive symptoms connected to the children's psychological status, asthma severity or current asthma symptoms? One-hundred and eight, 7- to 17-yr-old asthmatic children were enrolled, who have been treated at the Semmelweis University, First Department of Pediatrics. Children were suffering from asthma for at least 1 yr, with a median of 8 yr (1-16 yr), they started to develop asthmatic symptoms between the age of 0.5-14 yr (median: 3 yr). We also identified 27 children with chronic renal diseases and their caregivers, who functioned as a control group. Children were asked to complete the Hungarian-validated versions of the Child Depression Inventory, the Spielberger State Anxiety Inventory for Children and the Juniper Pediatric Asthma Quality of Life Questionnaire. Asthma severity and current symptoms were also documented, 56% had no symptoms on the preceding week. Caregivers were asked to complete the Hungarian versions of the Beck Depression Inventory (BDI) short form, the Spielberger Anxiety Inventory and the Juniper Pediatric Asthma Caregivers' Quality of Life Questionnaire. Caregivers of asthmatic children had significantly more depressive symptoms (7.73 +/- 6.69 s.d.) than the age-specific normal population (p < 0.01). Caregivers of renal patients also experience more depressive symptoms (9.61 +/- 7.43 s.d.) than their healthy peers, but difference between the two chronic diseases' group did not prove to be significant. Asthmatic children's caregivers who scored more points on the BDI than the population average suffer from more anxiety symptoms, but their quality of life is not worse than the caregivers' with less depressive points. Depressive symptoms were neither connected to the children's psychological and asthmatic symptoms nor quality of life. Amongst caregivers of asthmatic children, at least mild depressive symptoms were represented amongst 39% of men and 33% of women. Gender difference was not significant, despite observations in the normal Hungarian population. Amongst caregivers of renal patients, depressive symptoms were represented in 14% of men and 50% of women. Gender difference was significant. (p = 0.05). Significant difference was observed between male asthmatic and renal caregivers, albeit difference was not significant between the female groups. No difference was found in depressive symptoms according to caregivers' level of education. Caregivers of children with asthma have more depressive symptoms than the average Hungarian population, but their results do not differ from caregivers taking care of children with chronic renal diseases. Caregivers of asthmatic children having at least mild depressive symptoms tend to have higher anxiety symptoms as well. Up to date, childhood chronic disease management and long-term care should also focus on parental psychology, mainly on depression and anxiety, as prevalence is higher than in the average population.

[Depression, anxiety and quality of life in pediatric asthma]. / Depresszió, szorongás, életminoség gyermekkori asztmában.

AIMS: The study's objective was to examine depression, anxiety and quality of life according to age and asthma status in pediatric asthma in a pediatric university department. METHODS: 108 patients, age: 11.75 +/- 3.10 (mean +/- SD) years (boys 11.6 +/- 2.8 years and girls 12.1 +/- 3.7 years) completed the Child Depression Inventory, the State Trait Anxiety Inventory for Children, the Pediatric Asthma Quality of Life Questionnaire, and a symptom score. Forced expiratory volume in one second was also measured. RESULTS: Mean forced expiratory volume in one second percent was 97.4 +/- 12.8. 23 patients (21%) had intermittent asthma, 40 patients (37%) had mild persistent, 43 patients (40%) had moderate persistent, 2 patients (2%) had severe persistent asthma. Pediatric asthma patients scored 9.36 +/- 5.57 points in the depression questionnaire. Patients showed as many depressive symptoms as the Hungarian average population, pre-adolescent boys with asthma showed even less. Children with asthma scored 31.16 +/- 4.61 points on the anxiety questionnaire; (boys 30.64 +/- 4.29, girls 32.67 +/- 5.27). Children with asthma have the same anxiety level as their healthy peers. On the quality of life questionnaire asthmatic children reached 6.18 +/- 1.00 (2.87-7.00); adolescent girls scored the worst (5.62 +/- 1.28). Adolescent asthmatic girls have the worst quality of life. Boys reach better quality of life scores as they grow older ( p = 0.02). Girls with adolescence have a tendency of decreasing quality of life, although the difference is not significant. In adolescence, asthmatic girls experience more quality of life deprivation than boys ( p = 0.013). Depression score, anxiety, or quality of life showed no difference between the intermittent and persistent asthmatic groups. Children in the symptomatic subgroup experienced poorer quality of life. Depression and anxiety were not affected by current asthma symptoms. There was no significant difference in depression, anxiety or quality of life scores according to age. CONCLUSION: The psychological status of children with asthma is fairly good. One should concentrate more on the quality of life of girls in adolescence. The good pediatric care of childhood asthmatics helps to avoid the psychological consequences of the disease.

Seasonal changes of proapoptotic soluble Fas ligand level in allergic rhinitis combined with asthma.

The function of apoptosis is to eliminate unnecessary or dangerous cells. The balance between production and death is important in the control of cell numbers within physiological ranges. Cells involved in allergic reactions may have altered apoptosis. The aim of this study was to examine the seasonal changes of programmed cell death in children with pollen allergy. We measured serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL), and examined whether there was any correlation between soluble apoptosis markers and development of asthma and or rhinitis in children with pollen allergy. We examined two groups of patients with ragweed pollen allergy. The first group consisted of 17 children with 'rhinitis only'. The second group consisted of 16 children with 'asthma + rhinitis'. For seasonal analysis we pooled the two groups and termed this the 'ragweed sensitive' group (n = 33, 5-18 yr, 25 boys, eight girls). Measurements (sFas and sFasL) were taken during the ragweed pollen allergy season, while control measurements were performed during the symptom-free period. There was no difference in sFas levels measured during and after [1941 +/- 68, 1963 +/- 83 pg/ml (mean+/-s.e.m, respectively)] the pollen season in the 'ragweed sensitive' group. The sFasL level showed seasonal change, which was significantly higher (p = 0.0086) in the symptomatic period compared to the symptom-free state (99 +/- 13 and 53 +/- 16 pg/ml, respectively). There was a difference between the 'rhinitis only' and the 'asthma + rhinitis' groups in the measured parameters of apoptosis. Children having allergic rhinitis combined with asthma had a significantly (p = 0.03) higher sFas level in the symptom-free state than the 'rhinitis only' group did (2115 +/- 156 and 1820 +/- 52 pg/ml, respectively). During the allergic symptom state the sFasL level of the 'asthma + rhinitis' group was significantly higher (p = 0.025) than that of the 'rhinitis only' group (125 +/- 20 and 75 +/- 14 pg/ml, respectively). In conclusion, the increased level of sFasL during the pollen season may signal its role in the pathogenesis of allergic airway diseases. There was no seasonal change in sFas levels in the examined ragweed allergic group, however in the symptomatic period we observed a diminished level of antiapoptotic factor (sFas) and an elevated level of proapoptotic factor (sFasL) if there was a combined disease with pollen allergic asthma. We suggest that there is a deviation in the apoptotic reaction in children that may increase the seasonal allergic inflammation.

Bronchial asthma and the short-term quality of life: follow-up study of childhood bronchial asthma in Hungary.

The aim of our study is to determine and describe the current short-term health-related quality of life of recent adult patients who had bronchial asthma in childhood. Our objective was to investigate if symptom control in bronchial asthma could be in conflict with general quality of life. We made a follow-up study of 152 patients (105 male, 47 female) over the age of 30 (31-55 yr) who were allergic asthmatics in childhood. The patients' current symptoms and short-term quality of life were evaluated by a questionnaire. The patients developed asthmatic symptoms by age 4.4 (0.5-13) years on the average. Now 60% (91 persons) have no symptoms. They became symptom-free between 3 and 41 yr of age (mean = 14.2 +/- 8.2). Amongst the currently asthmatic patients (58 patients, 38%), 34 patients (22%) belong to the Global Initiative for Asthma (GINA) I, nine patients (6%) to the GINA II, five patients (3.3%) to the GINA III, and five patients (3.3%) to the GINA IV classification. Five patients (3.3%) did not specify their own symptoms. Three persons (2%) did not answer this question. Symptomatic patients reached 5.28 on the Juniper Asthma Quality of Life Questionnaire, while their asymptomatic peers scored statistically higher with 6.8 on the scale. Amongst the symptomatic patients, the most limited areas were: 'bothered by heavy breathing', 'had to avoid a situation or environment because of dust', 'experienced difficulty breathing out as a result of asthma', 'experienced asthma symptoms as a result of the weather or air pollution outside'. They were least 'concerned about medication', 'frustrated as a result of their asthma', they were least limited in 'going outside because of the weather or air pollution'. The most problematic areas for the symptom-free patients were 'had to avoid a situation or environment because of dust', 'had to avoid a situation or environment because of cigarette smoke', 'experiencing asthma symptoms as a result of being exposed to dust and the 'need to clear throat'. It seems that having no asthma symptoms is not equal to having a good quality of life for asthmatic patients. Moreover, symptom control in bronchial asthma is in conflict with quality of life, as many prophylactic measures to prevent exposure to allergens also restrict the patient's life.

[Therapy of bronchial asthma in childhood]. / Az asthma bronchiale kezelése gyermekkorban.

The aim of the study is to summarize the up-to-date therapy of bronchial asthma in childhood. Many children in the world (1-30%) suffer from this disease. The essence of it is the special allergic inflammation of the bronchi, so the chief aim of the therapy is the diminution of this inflammation and the ceasing of the actual symptoms. The therapy is based on three possibilities: diminution of the causative allergens and trigger factors in the environment, drug therapy, and allergen vaccination (immunotherapy). The drug therapy is considered on the four step severity criteria of the WHO. The study makes known the basic properties of the important drugs and the practice of the therapy; gives a list of elimination possibilities and mentions the chief features of immunotherapy.

Slight decrease in bone mineralization in cow milk-sensitive children.

BACKGROUND: Patients with cow milk allergy (CMA) are potentially at risk for osteopenia because their milk-free diet usually contains a low calcium content. In our study, different parameters of bone mineralization in children with CMA were investigated. PATIENTS AND METHODS: Twenty-seven CMA patients (mean age, 4.3 years; range, 3-8 years) were enrolled in the study. During a mean milk-free diet period of 11.8 months, children were fed extensively hydrolyzed or soy-based formulas. After a milk challenge test, 7 patients showed allergic symptoms, and the other 20 children had transient CMA. From the sera of all patients, the levels of sodium, potassium, chloride, calcium, phosphate, and magnesium ions, as well as alkaline phosphatase (AP), parathyroid hormone (PTH), osteocalcin, and beta-crosslaps, were determined. These values were compared with those of 20 healthy age-matched controls. Bone mineral density was measured as well. RESULTS: The AP and PTH concentrations were higher in CMA patients than in the control group (AP: 610.2 U/L vs. 499.7 U/L, P < 0.01; PTH: 1.56 pmol/L vs. 0.83 pmol/L, P< 0.03), but all values were in the normal range. The osteocalcin concentration was similar in both groups, and the beta-crosslaps concentration was lower in CMA patients than in controls (0.92 vs. 1.47 ng/mL, P< 0.001). The mean Z score of bone mineral density in patients with CMA was -0.6. In 10 cases, the Z score was less than the -1 SD value. On the basis of the Z score, CMA patients were divided into two groups. The PTH concentration was significantly elevated in the group with lower Z score (2.24 pmol/L vs. 1.16 pmol/L; P< 0.03). CONCLUSION: The results suggest that, in children with CMA who are on a cow milk-free diet, slight disturbances of bone mineralization can be observed by osteodensitometry.

Serum immunoglobulin E, IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: association with prognosis and clinical manifestations.

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1-34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk-specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme-linked immunosorbent assay (ELISA). The results were compared to those of 30 non-atopic age-matched control children. On average, after 9.2 months (range 2-31 months) on a milk-free diet, a repeated challenge was performed in 38 children. At the re-challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom-free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti-alpha-casein IgG level (of 2.10) in children with a positive reaction at the re-challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re-challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti-BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti-alpha-casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.

Budesonide aqueous nasal spray is an effective treatment in children with perennial allergic rhinitis, with an onset of action within 12 hours.

BACKGROUND: Budesonide aqueous nasal spray is a topical corticosteroid which at doses of 64 to 256 microg once daily has been found to be effective in the treatment of seasonal allergic rhinitis in adults and children. OBJECTIVE: This study was conducted to determine the efficacy of budesonide aqueous nasal spray, 128 microg once daily, in children with perennial allergic rhinitis. METHODS: This double-blind, randomized, placebo-controlled, parallel-group, multicenter study compared the efficacy and safety of budesonide aqueous nasal spray, 128 microg once daily intranasally, with placebo in 202 patients (aged 6 to 16 years) with perennial allergic rhinitis. Efficacy was evaluated daily by measurement of peak nasal inspiratory flow (PNIF), nasal symptom scores over 12 hours, and an overall evaluation of treatment efficacy. In a subset of patients (n = 76), quality of life was measured by validated questionnaires. RESULTS: Budesonide, 128 microg once daily, was significantly more effective than placebo in improving the PNIF, combined and individual nasal symptom scores, and the overall evaluation of treatment efficacy. The onset of action was found to occur within the first 12-hour time interval evaluated for combined nasal symptoms and within 48 hours for PNIF. Budesonide was associated with reduced percentage of eosinophils in brush samples and reduced intake of rescue medication in comparison with placebo. Quality of life scores were reduced, but the differences did not reach significance. CONCLUSIONS: Budesonide aqueous nasal spray, 128 microg once daily, is effective in children with perennial allergic rhinitis. Efficacy was demonstrated within 12 hours.

[Role of the TNF system in the pathomechanism of bronchial asthma]. / A tumornecrosis faktor (TNF) rendszer szerepe az asthma bronchiale patomehanizmusában.

INTRODUCTION: The activation of the TNF system during asthmatic attack has already been proved. AIMS: The aim of the study was to reveal the role of the tumor necrosis factor (TNF) system in the pathomechanism of bronchial asthma. PATIENTS/METHODS: Childhood asthmatic lately symptom-free adults (n:39) and their non-asthmatic offspring were examined (n:42). According to the methacholin airway challenge test, patients were divided into bronchial hyperreactive (n:44) and non-hyperreactive (n:37) groups. Tumor necrosis factor alpha (TNF-alpha) and its soluble receptors 55 (sTNF-R1) and 75 kDa (sTNF-R2) were measured by ELISA. RESULTS: Among the hyperreactive patients (n:44) significantly higher TNF-alpha (mean +/- SD: 5.13 +/- 1.37 vs. 3.91 +/- 0.61 pg/ml, p < 0.0001), sTNF-R1 (mean +/- SD: 1.37 +/- 0.28 vs. 1.16 +/- 0.13 ng/ml, p = 0.0002) and sTNF-R2 (mean +/- SD: 0.78 +/- 0.42 vs. 0.43 +/- 0.41 ng/ml, p < 0.0001) values were measured compared to the non-hyperreactives (n:37). In hyperreactive patients there was a significant correlation between the cytokine and cytokine receptor levels (TNF-alpha-sTNF-R1 p = 0.0184, r = 0.3541; TNF-alpha-sTNF-R2 p < 0.0001, r = 0.6468). Significant negative correlation was detected between the serum TNF-alpha and sTNF-R2 concentrations and PD20 FEV1 methacholin (dose of methacholin resulting in a 20% reduction of forced exspiratory volume in 1 second) in hyperreactive patients. CONCLUSION: According to our results the activation of the TNF system may contribute to the bronchial hyperreactivity. It can be observed in asthmatic patients having been symptom-free for years and in their non-asthmatic offspring as well. These results refer to the presence of a minimal allergic inflammation.

The prognosis of bronchial asthma in childhood in Hungary: a long-term follow-up.

The aim of this study was to determine the prognosis of bronchial asthma in childhood in Hungary. One hundred and forty five adults (96 men and 49 women) with a clinical history of childhood bronchial asthma were examined at the age of 28 years or above (mean age 37.6, SD 5.9 years). The patients completed questionnaires concerning their asthmatic and accompanying allergic symptoms in childhood, at the age of 18 and at present. They were all prick-tested with 12 inhalant allergens. The results showed that 42.8% of the patients had become symptom-free, but 57.2% still had intermittent or persisting asthmatic symptoms in adulthood. More patients had intermittent day-time (59%) and night-time (67%) asthmatic symptoms than persistent symptoms (41% and 33%). Accompanying allergic diseases (rhinitis, conjunctivitis, dermal and gastrointestinal diseases, and drug andfood allergies) in childhood did not definitely affect the prognosis of the bronchial asthma. The proportion of females with allergic diseases increased, and among patients with skin diseases it was significantly higher than the proportion of affected males. At the age of 18, allergic rhinitis was more frequent than in childhood. The frequencies of other allergic disorders did not change significantly. In the patients with asthmatic symptoms, molds and cat-hair allergies were more frequent than in the symptom-free group. The long-term prognosis of bronchial asthma in childhood in Hungary is relatively good, but fewer than half of the patients became symptom-free. The complaints of most of the patients were mild, but one in seven of all the adults suffered from moderate or serious bronchial asthma. Household allergens may contribute to the persistence of asthmatic symptoms.