Edyta Krzych-Fałta

Filaggrin Gene Defects Are Independent Risk Factors for Atopic Asthma in a Polish Population: A Study in ECAP Cohort

Background FLG null variants of which 2282del4 and R501X are the most frequent in Caucasians are established risk factors for atopic dermatitis (AD) with an effect probably mediated through impairment of epidermal barrier. Among subjects with AD FLG defects are also consistently associated with asthma and allergic rhinitis (AR) but it is less clear to what extent these associations are also present independently from skin disease. The aim of the present study was to evaluate the role of 2282del4 and R501X in predisposing to these allergic phenotypes in a Polish population. Methodology 2282del4 and R501X were typed among 3,802 participants of the Epidemiology of Allergic Diseases in Poland (ECAP) survey, a cross-sectional population-based study using ECRHS II and ISAAC questionnaires, and ambulatory examination. Principal Findings The FLG null variants were associated with AD (OR = 2.01, CI: 1.20–3.36, P = 0.007), allergic rhinitis (in particular persistent form, OR = 1.69, CI:1.12–2.54, P = 0.011), and asthma (in particular atopic asthma, OR = 2.22, CI:1.24–3.96, P = 0.006). Association with atopic asthma (but not persistent allergic rhinitis) was also present in the absence of AD, (OR = 2.02, CI: 1.07–3.81, P = 0.027) as well as in the absence of AD and history of broadly defined inflammatory skin disease (OR = 2.30, CI: 1.07–4.93, P = 0.03). Association to atopic asthma would have not been found if diagnosis was made by questionnaire only (OR = 1.15, CI: 0.58–2.32, P = 0.8). We did not observe an association between FLG variants and allergic sensitizations (P = 0.8) or total IgE. (P = 0.6). Conclusions/Significance In a Polish population FLG 2282del4 and R501X carriage increases risk for development of AD and atopic asthma (also in the absence of AD or history thereof). This suggests that interventions aimed at restoring epidermal barrier may have a general role in asthma prophylaxis/treatment.

Obesity--a risk factor for asthma, but not for atopic dermatitis, allergic rhinitis and sensitization.

OBJECTIVE To analyse the relationship between obesity and overweight and the prevalence of allergic diseases and sensitization, and the impact of gender and place of residence. DESIGN Questionnaire based on those used in ISAAC (International Study of Asthma and Allergies in Childhood) and ECRHS (European Community Respiratory Health Survey). SETTING Our study involved populations of the eight largest cities and one rural region in Poland (each with over 150,000 inhabitants). SUBJECTS The study included 18,617 participants (24·2% aged 6-7 years, 25·4% aged 13-14 years, 50·4% adults aged 20-44 years) in eight cities and one rural area. The out-patient study involved 4783 patients (25·7%); we performed skin prick testing with fifteen aeroallergens. RESULTS Overweight was found in 16·13% of participants (9·11% of 6-7-year-olds, 4·90% of 13-14-year-olds and 25·61% of adults), obesity in 6·41% (7·16%, 2·45% and 8·36%, respectively). In adults, overweight (OR=1·34) and obesity (OR=1·80) increased the prevalence of asthma, especially in women (OR=1·53, OR=2·01). Among 13-14-year-olds the prevalence was higher only in the obese (OR=1·76). Overweight (OR=1·99) and obesity (OR=2·17) affected the incidence of doctor-diagnosed asthma in 6-7-year-olds. Overweight (OR=0·81) and obesity (OR=0·76) reduced the prevalence of allergic rhinitis in men. There was no relationship between BMI and asthma in people from rural areas. Obesity and overweight did not affect the frequency of sensitization to aeroallergens. CONCLUSIONS Overweight and obesity increased the prevalence of symptomatic asthma in adults, especially in women. In 13-14-year-olds, only obesity increased the prevalence of asthma. In children, overweight was associated with increased prevalence of clinically diagnosed and declared asthma and a trend towards atopy. Higher BMI was negatively associated with the prevalence of allergic rhinitis in overweight and obese man. There was no correlation between BMI and sensitization to aeroallergens.

Epidemiology of atopic dermatitis in Poland according to the Epidemiology of Allergic Disorders in Poland (ECAP) study.

Epidemiological studies (International Study of Asthma and Allergies in Childhood [ISAAC], The European Community Respiratory Health Survey [ECRHS]) revealed considerable geographical differences in prevalence of atopic dermatitis (AD). The aim of our study is to present the epidemiology and the risk factors of AD in a Polish population. A total of 18 617 subjects were selected. The sample included respondents in eight cities and one rural area each over 150 000 citizens. The study had two parts: (i) questionnaire survey conducted among all respondents (response rate, 64.4%); and (ii) allergological examination performed among 25.7% with skin prick test (SPT) with 15 aeroallergens. AD was identified in 3.91% of subjects, more often in females, living in the cities, with a mother and/or father with atopy and with a higher education and higher economic status. Comorbidities of AD were atopic rhinitis (AR) in 26.17% and AR and asthma in 14.6%. AD was diagnosed by allergologists in 311 subjects (6.5%). Positive SPT occurred in 66.9% persons with AD (house dust mite, 33.1%; grasses/crop plants, 30.6%). Of the patients, 9.5% with perennial versus 9.3% seasonal and 9.6% with polyvalent versus 9.0% monovalent sensitization had AD. AD prevalence in Poland is below the mean rate for Europe, but risk factor profile is similar to other countries. AD is more frequent in female, well‐educated individuals, of high socioeconomic status, with atopic parents and who live in a city. Seasonal and monovalent atopy play a more essential role in subjects with AD compared with AR and asthma.

The prevalence of sensitization to inhalant allergens in children with atopic dermatitis.

BACKGROUND The role of sensitization to inhalant allergens in atopic dermatitis (AD) in children is uncertain. The aim of our study was to assess the relationship of AD symptoms with sensitization to aeroallergens in Polish children ages 6-7 and 13-14 years. MATERIAL AND METHOD Epidemiology of Allergic Disorders in Poland is a randomized study with medical examination according to the ECRHS II and the International Study of Asthma and Allergies in Childhood standards in nine selected regions of Poland. We studied 6-7-year-old (n = 4510) and 13-14-year-old children (n = 4721). A total of 1583 children (25%) had a medical examination and a skin-prick test (SPT) with the 15 most common aeroallergens. RESULTS AD was diagnosed in 235 children (8.9%) (8.7%, 6-7-year-old children; 9.0%, 13-14-year-old children; 8.6% boys and 9.1% girls). AD was more frequent in urban versus rural habitants (9.6% versus 3.7%; p < 0.05) and in participants with a positive atopy history versus those without atopy (9.4% versus 5.1%; p < 0.05). Positive SPT was found in 1165 children (43.9%) (38.5% boys, 49.5% girls) and 64.72% with AD versus 41.9% without AD (p < 0.05) and more common in the rural region versus urban setting among 6-7 year-olds (71.8% versus 35.0%; p < 0.05). The most frequent allergic reaction was Dermatophagoides pteronyssinus (13.5%), Dermatophagoides farina (11.7%), and grasses/crop plants (11.8%). The same pattern was seen in participants with and those without AD. Children with AD had more frequent positive SPT for all aeroallergens (p < 0.05). CONCLUSION AD should be more frequent in children with a positive atopy history and in children who live in the city. Aeroallergens play an essential role in pathogenesis of eczema in children. House-dust mites and grass pollen proved to be the most common relevant aeroallergens.

Intranasal glucocorticosteroids – Not only in allergic rhinitis In the 40th anniversary of intranasal glucocorticosteroids’ introduction

It has been 40 years since Niels Myginds publication in British Medical Journal on intranasal application of beclomethasone dipropionate aerosol in allergic rhinitis (AR). Since then a new era in treatment of allergic and nonallergic upper airway diseases began. This publication presents current concepts on application of intranasal glucocorticosteroids (inGCS) in treatment of upper airway diseases and in particular of AR and rhinosinusitis. Nonquestionable advantage of inGCS is their strong anti-inflammatory local action with little impact on general health responsible for few and benign side effects. Main way of action of glucocorticosteroids is connected with binding to the intracellular glucocorticosteroid receptor and its impact on nuclear cytoplasmic transcriptional factors. Glucocorticosteroids suppress gene expression of factors responsible for generating and supporting inflammatory processes, proinflammatory cytokines and chemokines production, and adhesive molecules expression. It appears that glucocorticosteroids have also other mechanisms of action, non-involving intracellular receptors, leading to inhibition of early and late phase of allergic reaction. At the moment the following glucocorticosteroids are registered in Poland: beclomethasone, budesonide, fluticasone propionate, fluticasone furoate, and mometasone furoate. Furoates earn special attention as their lateral furoate ester chain makes the molecules highly lipophilic, and hence easily absorbed by nasal mucous membranes, epithelium and cell membrane phospholipids. This minimizes their general action and maximizes local action. According to current state of knowledge topical glucocorticosteroids are used in the following upper airway diseases with different inflammatory mechanisms: AR, non-AR, particularly NARES, acute rhinosinusitis, chronic rhinosinusitis with and without nasal polyps, adenoid hypertrophy and rhinitis in bronchial asthma.

Specificity and sensitivity assessment of selected nasal provocation testing techniques

Introduction Nasal provocation testing involves an allergen-specific local reaction of the nasal mucosa to the administered allergen. Aim To determine the most objective nasal occlusion assessment technique that could be used in nasal provocation testing. Material and methods A total of 60 subjects, including 30 patients diagnosed with allergy to common environmental allergens and 30 healthy subjects were enrolled into the study. The method used in the study was a nasal provocation test with an allergen, with a standard dose of a control solution and an allergen (5,000 SBU/ml) administered using a calibrated atomizer into both nostrils at room temperature. Early-phase nasal mucosa response in the early phase of the allergic reaction was assessed via acoustic rhinometry, optical rhinometry, nitric oxide in nasal air, and tryptase levels in the nasal lavage fluid. Results In estimating the homogeneity of the average values, the Levene’s test was used and receiver operating characteristic curves were plotted for all the methods used for assessing the nasal provocation test with an allergen. Statistically significant results were defined for p < 0.05. Of all the objective assessment techniques, the most sensitive and characteristic ones were the optical rhinometry techniques (specificity = 1, sensitivity = 1, AUC = 1, PPV = 1, NPV = 1). Conclusions The techniques used showed significant differences between the group of patients with allergic rhinitis and the control group. Of all the objective assessment techniques, those most sensitive and characteristic were the optical rhinometry.

Optical rhinometry in nasal provocation testing

Introduction Optical rhinometry (ORM) is a technique that allows for direct continuous measurement of changes in blood flow (optical density) in nasal vessels, at the same time analyzing changes per unit of time in the evaluated variable: intravascular blood flow and oxygen saturation. Aim To assess the extent to which ORM can be used as an objective measure of nasal mucosal edema following a nasal allergen provocation test in a group of patients with allergic rhinitis versus healthy controls. Material and methods The study group included 60 subjects: 30 patients diagnosed with an allergy to common environmental allergens (dust mites/grasses) and 30 healthy controls. The method used in the study was a nasal provocation test with an allergen, with a standard dose of a control solution and an allergen (5,000 SBU/ml) administered using a calibrated atomizer into both nostrils in room temperature. Results The mean delay to the onset of nasal mucosal response as measured by ORM was 3.15 min and the level of light extinction returned to baseline after 28.15 min (change in optical density 0.431). These objective changes in optical density strongly correlated with subjective perception measured via a visual analog scale. Conclusions Optical rhinometry is a valuable tool for nasal allergen provocation testing.

Probiotics: Myths or facts about their role in allergy prevention

BACKGROUND The hygiene hypothesis proposed by Strachan in the 1980s clearly emphasized the role of microorganisms in atopy prevention. OBJECTIVES The study objective was to assess the preventive role of probiotics in patients with allergic rhinitis, bronchial asthma, atopic dermatitis, and/or food allergy. MATERIAL AND METHODS The methods used in the study were the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires for 6-7- and 13-14-year-olds and the European Community Respiratory Health Survey II (ECRHS II) questionnaire targeted for the 20-44 age group. The study was conducted as part of the cross-sectional Epidemiology of Allergic Diseases in Poland study conducted in 9 Polish regions (8 urban: Warszawa, Lublin, Białystok, Gdańsk, Poznań, Wrocław, Katowice, Kraków, and the rural regions of Zamojski and Krasnostawski counties). The study material was a group of patients diagnosed with food allergy (n = 407), atopic dermatitis (n = 311), allergic rhinitis (n = 1.353), bronchial asthma (n = 505), and healthy volunteers (n = 2,403). RESULTS Genetic factors play an important role in the allergy development. A family history positive for chronic skin disorders increased the risk of atopic dermatitis and food allergies (OR = 1.456, CI = 1.14-1.85, p = 0.002; and OR = 1.378, CI = 1.05-1.81, p = 0.02, respectively). The consumption of products containing live bacterial cultures showed no preventive effects in any of the evaluated disorders in early childhood. Conversely, over the age of 14 years, probiotic formulations exhibit health-promoting effects and may lower the risk of allergic diseases. CONCLUSIONS The use of probiotics in the Polish population showed no protective effect in the first years of life. The changes in dietary habits introduced during late adolescence demonstrated significantly greater preventive effects of live bacterial cultures against the development of allergic diseases.

Haplotype dependent association of rs7927894 (11q13.5) with atopic dermatitis and chronic allergic rhinitis: A study in ECAP cohort

The T allele of rs7927894 (at 11q13.5) was associated with atopic dermatitis and other allergic diseases. Our purpose was to replicate the association with allergic phenotypes and explore the role of rs7927894 in predisposing to persistent allergic rhinitis and atopic asthma. We also wanted to explore if other SNPs at 11q13.5 contributed to effect of rs7927894. We studied patients with atopic dermatitis (N = 270), atopic asthma (N = 486), persistent allergic rhinitis (N = 589) and controls matched for age, sex and region (N = 540, N = 372 and N = 1178, respectively). We found that rs7927894 T was associated with atopic dermatitis (OR = 1.39, CI: 1.12–1.73, P = 0.003) and independently with persistent allergic rhinitis (OR = 1.24, CI:1.07–1.43, P = 0.0043, Pcorrected = 0.013) but not atopic asthma. Analysis of additional tagging SNPs (rs7930763, rs2513517, rs7125552) showed that effect of rs7927894 T was limited to haplotypes encoding G at rs7125552. In conclusion, rs7927894 T is associated not only with atopic dermatitis but also persistent allergic rhinitis. Since these effects are haplotype dependent rs7927894 alone does not account for the association between 11q13.5 and atopic dermatitis/persistent allergic rhinitis.

Extent of protective or allergy-inducing effects in cats and dogs

OBJECTIVE The study aimed to assess the effect of fur-bearing pets, including cats and dogs, on the health of individuals with allergic conditions. MATERIAL AND METHODS The study group comprised 18,617 individuals (16,562 from urban and 2,055 from rural areas). The tool used in the study was the European Community Respiratory Health Survey (ECRHS) and International Study of Asthma and Allergies in Childhood (ISAAC) study questionnaire, adapted to European conditions (Middle and Eastern Europe) and used as part of the study Implementation of a System for the Prevention and Early Detection of Allergic Diseases in Poland. RESULTS The factors determining the keeping of fur-bearing pets in a household included a larger living space and the number of cigarettes smoked, which were observed especially in urban settings. The keeping of fur-bearing animals in rural areas acts preventively against allergic conditions, while in urban areas, these animals were a factor clearly aggravating symptoms of bronchial asthma - the risk of cough (OR 1.921; CI 10-3.36; P=0.02) and wheezing (OR 2.60; CI 1.22-5.54; P=0.01). CONCLUSIONS Fur-bearing animals kept in rural settings exhibit preventive effects on the development of allergies; whereas in urban areas they exacerbate allergic symptoms, especially the symptoms of bronchial asthma.