Prevalence of Asthma and Its Associating Environmental Factors among 6-12-Year-Old Schoolchildren in a Metropolitan Environment-A Cross-Sectional, Questionnaire-Based Study.

We aimed to evaluate the prevalence of asthma and its associating environmental factors within a 6-12-year-old population. A cross-sectional, questionnaire-based study was conducted in primary schools located in the capital of Hungary; 3836 eligible parent-reported questionnaires were evaluated. Besides the International Study of Asthma and Allergies in Childhood (ISAAC) phase three core questions for asthma, the survey also assessed various potential risk factors. We introduced the umbrella term cumulative asthma as the union of physician-diagnosed asthma and current wheezing to estimate the lifetime prevalence of asthma. Current wheezing and physician-diagnosed asthma showed a frequency of 9.5% and 6.3%, respectively. They contributed to a cumulative asthma prevalence of 12.6% among the sampled population, with a girl-boy percentage of 37.4% to 62.6%. Air-pollution and weedy areas were associated with greater risk for asthma, while a suburban residence showed lesser odds. Indoor smoking, visible mold, and keeping a dog were defined as risk factors for asthma, while the presence of plants in the bedroom and pet rodents were associated with lower odds ratios. The consumption of fast food, beverages containing additives and margarine were significantly higher in asthmatics, while we found frequent sport activity and cereal intake associated with lower odds ratios for asthma. In this urban environment, we identified an increased asthma prevalence compared to some previously published studies, but the cross-sectional design and the different methodology did not permit us to draw timeframe-dependent conclusions.

Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo.

INTRODUCTION: Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. METHODS: Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. RESULTS: We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. CONCLUSION: Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.

Prevalence of allergic rhinitis, related comorbidities and risk factors in schoolchildren.

BACKGROUND: The study aimed to determine the prevalence and risk factors of allergic rhinitis and related comorbidities in school-age children in Budapest, capital of Hungary. Data and epidemiological studies on this disease are still limited. METHODS: A cross sectional study was conducted in 21 representative and randomly selected primary schools in 2019. International Study of Asthma and Allergies in Childhood-based questionnaires (n = 6869) inquiring about prevalence and related risk factors of allergic rhinitis were distributed to all parents. The data were characterised with standard descriptive statistics: frequencies (percentages) and means for categorical and quantitative data, respectively. RESULTS: 3836 of the questionnaires (1857 M/1979F) were completed. The prevalence of current allergic rhinitis was 29.3% (1043), physician-diagnosed allergic rhinitis was 9.7% (373), cumulative allergic rhinitis was 36.2% (1289) and current allergic rhinoconjunctivitis was 16.2% (577). The presence of physician diagnosed atopic disease-asthma (p < 0.0001, OR = 4.398, 95% CI 3.356-5.807), food allergy (p < 0.0001, OR = 2.594, 95% CI 1.995-3.378), and eczema (p < 0.0001, OR = 1.899, 95% CI 1.568-2.300)-were significantly related to an increased risk of cumulative allergic rhinitis. Significant factors associated with allergic rhinitis include male gender (p < 0.0001), family history of atopy (p < 0.0001), frequent upper respiratory tract infections (p < 0.0001), tonsillectomy (p = 0.0054), antibiotics given in the first year of life (p < 0.0001), paracetamol given in the first year of life (p = 0.0038), long-lasting common infections caused by viruses and/or bacteria before the appearance of the allergy (p < 0.0001), consumption of drinks containing preservatives or colourants (p = 0.0023), duration of living in Budapest (p = 0.0386), smoking at home (p = 0.0218), smoking at home in the first year of life (p = 0.0048), birds at home (p = 0.0119), birds at home in the first year of life (p = 0.0052), visible mould in the bedroom (p = 0.0139), featherbedding (p = 0.0126), frequent or constant heavy-vehicle traffic (p = 0.0039), living in a weedy area (p < 0.0001) and living in the vicinity of an air-polluting factory or mine (p = 0.0128). CONCLUSIONS: The prevalence of allergic rhinoconjunctivitis in 6-12-year-old children in Budapest is higher than reported for most of the surrounding European countries. While asthma (OR = 4.398) is the most significant comorbidity, environmental factors such as birds at home in the first year of life (OR = 2.394) and living in a weedy area (OR = 1.640) seem to be the most important factors associated with AR. Strategies for preventive measures should be implemented. TRIAL REGISTRATION NUMBER: KUT-19/2019. The study was approved by the Ethics Committee at Heim Pál National Pediatric Institute.

Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years.

BACKGROUND: Recommendations in current guidelines for the treatment of chronic spontaneous urticaria (CSU) in infants and children are mostly based on extrapolation of data obtained in adults. This study reports the efficacy and safety of rupatadine, a modern H1 and PAF antagonist recently authorized in Europe for children with allergic rhinitis and CSU. METHODS: A double-blind, randomized, parallel-group, multicentre, placebo-controlled compared study to desloratadine was carried out in children aged 2-11 years with CSU, with or without angio-oedema. Patients received either rupatadine (1 mg/ml), or desloratadine (0.5 mg/ml) or placebo once daily over 6 weeks. A modified 7-day cumulative Urticaria Activity Score (UAS7) was employed as the primary end-point. RESULTS: The absolute change of UAS7 at 42 days showed statistically significant differences between active treatments vs. placebo (-5.5 ± 7.5 placebo, -11.8 ± 8.7 rupatadine and -10.6 ± 9.6 desloratadine; p < 0.001) and without differences between antihistamines compounds. There was a 55.8% decrease for rupatadine followed by desloratadine (-48.4%) and placebo (-30.3%). Rupatadine but not desloratadine was statistically superior to placebo in reduction of pruritus (-57%). Active treatments also showed a statistically better improvement in children's quality of life compared to placebo. Adverse events were uncommon and non-serious in both active groups. CONCLUSION: Rupatadine is effective and well tolerated in the relief of urticaria symptoms, improving quality of life over 6 weeks in children with CSU. This is the first study using a modified UAS to assess severity and efficacy outcome in CSU in children.

Inhaler competence and patient satisfaction with Easyhaler®: results of two real-life multicentre studies in asthma and COPD.

OBJECTIVE: The aim of this study was to investigate patients' inhaler competence and satisfaction with the Easyhaler(®) dry powder inhaler. DESIGN: Two open, uncontrolled, non-randomised studies. SETTING: Real life based on patients attending 56 respiratory clinics in Hungary. PARTICIPANTS: Patients with asthma or chronic obstructive pulmonary disease (COPD) (n = 1016). INTERVENTION: In a 3-month study, adult patients (age range 18-88 years; n = 797) received twice-daily inhalations of formoterol via Easyhaler(®), and in a consequential study (from one visit to another, with 3-12 months in-between) children and adolescents (age range 4-17 years; n = 219) received salbutamol via Easyhaler(®) as needed. MAIN OUTCOME MEASURES: Control of six Easyhaler(®) handling steps and patients' satisfaction with Easyhaler(®) based on questionnaires. RESULTS: Correct performances (minimum and maximum of the six steps) were noticed after one demonstration in 92-98% of the adults, 87-99% of the elderly, 81-96% of the children and 83-99% of the adolescents. These figures had markedly increased at the last visit. Repeat instructions were necessary in 26% of the cases. Investigators found Easyhaler(®) easy to teach in 87% of the patients and difficult in only 0.5%. Patients found Easyhaler(®) easy to learn and use, and the patients' (and parents') satisfaction with the inhaler was very high. Lung function values [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)] improved statistically significantly during the studies, indicating good inhaler competence and treatment adherence. CONCLUSION: Investigators found Easyhaler(®) easy to teach and patients found it easy to use, and their satisfaction with the device was high.

Tear film function in patients with seasonal allergic conjunctivitis outside the pollen season.

BACKGROUND: Seasonal allergic conjunctivitis can manifest itself through tear film instability and symptoms of eye discomfort during the pollen season. This study investigated whether seasonal allergic inflammation defines tear film instability outside the season. METHODS: Twenty-three control subjects and 13 ragweed-allergic patients were involved (21 female, 15 male; mean age 26.6 ± 5.4 years). Outside the pollen season, subjective ocular symptoms, non-invasive tear film break-up time, lower tear meniscus height and the tear lipid layer's interference pattern grade were recorded. C3a complement activation level was also measured in collected tear samples. RESULTS: Non-invasive tear film break-up time, lower tear meniscus height, C3a complement activation level and the incidence of the different grades of tear lipid pattern did not differ significantly in the two examined groups (p ≥ 0.223). The mean eye symptom score outside the season was greater in the allergic group, but the difference was not significant (p = 0.062). The C3a complement activation level showed a significant and inverse correlation with the lipid layer grade (r = -0.343, p = 0.017). Among the participants with thinner tear lipid layers, the complement activation in the tear samples was higher than among those patients with normal tear lipid layers. CONCLUSION: Seasonal allergic inflammation did not cause permanent tear film instability and eye symptoms were not observed outside the pollen season.

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.

[Comparing the young asthmatics running fitness]. / Asztmás fiatalok összehasonlító futás-állóképesség vizsgálata.

INTRODUCTION: Nowadays, doctors strongly recommend physical activity for asthmatic children, since the resulting improved physical fitness and psychological change also raise the quality of life. AIMS: The aim of this study was to compare the physical fitness of asthmatic children who regularly participate in therapeutic swimming, with asthmatic children who do not participate in this training and with non-swimming, healthy children using the 12 minute free running, Cooper test. METHOD: The children from the swimmer asthmatic group (n= 51, age = 9-22 yrs) took part in a special, long term, swimming exercise program (Gyene method). Whereas, the non-swimmer asthmatics (n = 28, age = 8-22 yrs) and the healthy children (n: 179, age: 9-22 yrs) only took part in the normal school physical education classes. Fitness was measured using the Cooper test. RESULTS: Data was collected from 258 subjects and showed that the fitness of swimmer asthmatics is significantly better than that of the non-swimmer asthmatics and even better than that of the healthy subjects (swimmer/ non swimmer asthmatic p = 0.01; swimmer asthmatic/ healthy p < 0.0001 Chi(2) test). The difference in the fitness acquired from swimming was the most pronounced for the 8-11 years old asthmatics, presumably because of greater motivational factors. No differences were found between genders for the two asthmatic groups, whereas healthy boys were found to have significantly greater levels of fitness than healthy girls. CONCLUSIONS: Fitness is substantially increased with regular swimming. The favourable effects of swimming are expressed not only in comparison with the non-swimmer asthmatics but with the healthy subjects too. The regular therapeutic swimming program helps the formation of running fitness too.

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.