Gabriella Gálffy

Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation.

BackgroundAlthough patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS) and long acting beta-agonists (LABA).MethodsThis real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits.Results111 patients were analyzed: 53 (47.7%) received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F) pressurized metered dose inhaler (pMDI), 25 (22.5%) fluticasone-salmeterol (FP/S) dry powder inhaler (DPI), and 33 (29.7%) budesonide-formoterol (BUD/F) DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively) and the mean daily ICS dose were significantly lower.ConclusionspMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.

Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA). This method uses Bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the Bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated. With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2–1.8); p = 3×10−4). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics. In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

Prevalence and risk factors for allergic rhinitis in primary schoolchildren in Budapest

OBJECTIVE There is growing evidence that the prevalence of allergic diseases is increasing, especially among children. The aim of this study was to evaluate the incidence and risk factors of allergic rhinitis in 6-12-year-old schoolchildren in Budapest. METHODS A total of 6335 children aged between 6 and 12 years attending 21 randomly selected primary schools in Budapest were surveyed in September 2007 by using a questionnaire consisting in part of questions compiled by the International Study of Asthma and Allergies in Childhood and in part of questions based on our own experience. RESULTS 3933 of the questionnaires (1976 M/1957 F) were appropriately completed by the parents. The prevalence of current allergic rhinitis was 14.9% (n=530), that of physician-diagnosed allergic rhinitis was 11.6% (n=413), and that of cumulative allergic rhinitis was 26.5% (n=943). Male gender (p<0.001), family history of atopy (p<0.001), eczema (p<0.001), urticaria (p<0.001), itchy-watery eyes (p<0.001), coughing (p<0.001), wheezing (p<0.001), a hearing impairment (p<0.001), itching of the palate (p<0.001), frequent upper airway infection (p<0.001), frequent rhinosinusitis (p<0.001), a history of tonsillectomy (p<0.01), a history of adenoidectomy (p<0.001), antibiotics given in the first year of life (p<0.001), paracetamol given in the first year of life (p<0.001), living in a green area (p<0.001), the consumption of soft drinks containing preservatives or colourants (p<0.04), feather bedding (p<0.01), living in a house made of concrete (p<0.001), living not far from an air-polluting factory or mine (p<0.001), and long-lasting disease before the appearance of the allergy (p<0.001) were all significant factors involving an increased risk of allergic rhinitis symptoms. The frequent consumption of tomatoes, nuts, margarine and butter significantly affected the cumulative allergic rhinitis prevalence. RESULTS Overall, the 12-month prevalence of allergic rhinitis in these 6-12-year-old children in Budapest was 14.9%, which is higher than reported from other European countries. Our findings differ from those on other cohorts in that exposure to ragweed and to indoor environmental factors in concrete housing estates in Budapest may be of particular importance as concerns allergic sensitization.

Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease

In this study, we aimed to identify novel genes involved in experimental and human asthma, importance of which has not yet been recognized. In an ovalbumin-induced murine model of asthma, we applied microarray gene expression analysis at different time points after allergen challenges. Advanced statistical methods were used to relate gene expression changes to cellular processes and to integrate our results into multiple levels of information available in public databases. At 4 h after the first allergen challenge, gene expression pattern reflected mainly an acute, but non-atopic, inflammatory response and strong chemotactic activity. At 24 h after the third allergen challenge, gene set enrichment analysis revealed significant over-representation of gene sets corresponding to T(h)2-type inflammation models. Among the top down-regulated transcripts, an anti-oxidant enzyme, paraoxonase-1 (PON1), was identified. In human asthmatic patients, we found that serum PON1 activity was reduced at exacerbation, but increased parallel with improving asthma symptoms. PON1 gene polymorphisms did not influence the susceptibility to the disease. Our observations suggest that an altered PON1 activity might be involved in the pathogenesis of asthma, and serum PON1 level might be used for following up the effect of therapy.

Exhaled breath condensate pH decreases during exercise-induced bronchoconstriction

Exercise‐induced bronchoconstriction (EIB) is the temporary narrowing of the airways caused by physical exercise. Its exact pathophysiology is unclear; however, acute changes in airways pH may play a role. Exhaled breath condensate (EBC) pH was suggested as a surrogate indicator for airway acid–base status, but its value is also affected by volatile molecules and respiratory droplet dilution. The aim of the study was to assess changes in EBC pH during EIB.

Implication of BIRC5 in asthma pathogenesis

In the last few years, it has been recognized that the unbalanced regulation of survival and apoptosis of bronchial inflammatory cells is a key component in the development of asthma. Baculoviral IAP repeat containing 5 (BIRC5) (also known as survivin) is an important anti-apoptotic protein that has been implicated in many cancer types, and recent studies provide evidence for its role in controlling inflammatory disorders as well. Our aim was to investigate at both genetic and transcriptional levels if BIRC5 has an impact on asthma development. We found that induced sputum samples of patients with bronchial asthma contained elevated levels of BIRC5 mRNA compared with healthy subjects and its level was in correlation with sputum eosinophil percentages. Furthermore, in a case-control study examining single nucleotide polymorphisms (SNPs) in the BIRC5 regulatory regions, the minor alleles of rs8073903 and rs8073069 were found to be significantly associated with asthma and especially non-allergic asthma phenotypes, which associations were more prominent among women. Two marker haplotype analyses further strengthen the impact of these two polymorphisms on both asthma and non-allergic asthma. In the female cohort, rs1508147 was also significantly associated with increased risk of non-allergic asthma. Additionally, with linear regression analysis, we showed that rs9904341 was significantly correlated with both absolute and relative serum eosinophil levels. In conclusion, our results suggest that possibly by inhibition of the eosinophil apoptosis, BIRC5 might be an important regulator of the asthmatic processes and we provide some evidence that its effect might be affected by SNPs located in the gene regulatory regions.

Effector and Regulatory Lymphocytes in Asthmatic Pregnant Women

Citation Bohács A, Cseh Á, Stenczer B, Müller V, Gálffy G, Molvarec A, Rigó J Jr, Losonczy G, Vásárhelyi B, Tamási L. Effector and regulatory lymphocytes in asthmatic pregnant women. Am J Reprod Immunol 2010; 64: 393–401

Exhaled breath condensate pH is influenced by respiratory droplet dilution

Several studies support that airway acid stress plays a role in the pathophysiology of asthma. Exhaled breath condensate pH (EBC pH) was suggested as a surrogate marker of airway acidification. The dilution of airway lining fluid (ALF) acids and bases by alveolar water may influence condensate pH, but it has not been studied yet. The aim of our study was to investigate the relationship between EBC pH and ALF dilution in EBC samples obtained from asthmatic and healthy subjects. EBC was collected from 55 asthmatic and 57 healthy subjects for pH and conductivity measurements. Fractional exhaled nitric oxide (FE(NO)) and lung function tests were also performed in asthmatic patients. EBC pH was determined after 10 min of argon deareation and the dilution was estimated by the measurement of conductivity in vacuum-treated samples. There was no difference either in EBC pH or dilution between the two groups. However, a significant relationship was found between EBC pH and dilution in both groups (p < 0.05, r = -0.35 and r = -0.29, asthmatic and healthy groups, respectively). Our results suggest important methodological aspect indicating that EBC pH is affected by respiratory droplet dilution, and this effect should be taken into consideration when interpreting EBC pH data.

A survey of the burden of allergic rhinitis in Hungary from a specialist's perspective

BackgroundThe casual and severity distribution of allergic rhinitis (AR) in Hungary is unknown.The aim of this survey was to evaluate symptom perception, disease severity, concomitant asthma frequency and the impact of AR on everyday life activities in a cross-sectional, multicenter study in Hungary under the supervision of Hungarian Respiratory Society.MethodsData were recorded by 933 AR patients (65.93% women) and their treating specialists. The perceptions of patients regarding the symptoms (nasal, ocular and others) of AR and its severity, together with its impact on everyday life were assessed. Physicians recorded data regarding the diagnosis and severity of AR, and comorbidities.Results52.5% of patients suffered from seasonal AR, 35.1% from perennial AR. A large proportion of patients had moderate to severe disease (MS-AR) (57.34%), persistent disease (98.0%) and concomitant asthma (53.32% in the mild, 57.52% in the MS-AR group). MS-AR was more frequent among women. Despite the treatment used, in MS-AR the proportions of patients reporting moderate to severe rhinorrhoea, nasal obstruction, ocular itching/redness, watering, itchy throat and sneezing were as high as 52.0%, 54.0%, 33.8%, 26.5%, 44.0% and 31.2%, respectively. Overall, there was a poor agreement between disease severity reported by patients and specialists. The adherence to oral antihistamines and intranasal corticosteroids was found to be between 50 and 65%; mostly depending on the dosage form.ConclusionsAR remains a significant health problem in Hungary because of the burden of symptoms, high rate of concomitant asthma and the significant proportion of MS-AR affecting general well being.

Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

Purpose Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma. Methods In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreover, gene expression levels were measured by RT PCR in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi-square tests, and logistic regression were carried out in order to assess associations of SNP frequency and expression level with asthma. Permutation tests were performed to account for multiple hypothesis testing. Results The frequency of 4 SNPs in 2 genes differed significantly between asthmatic and control subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds ratio of 0.64 (0.51-0.80; P=7×10-5) in SCIN and 0.56 (0.42-0.76; P=1.2×10-4) in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were significantly lower in the sputum of asthmatics. Conclusions Three potentially novel asthma-associated genes were identified based on mouse experiments and human studies.