Publications by authors named "Agnieszka Lipiec"

39 Publications

Sensitisation to airborne allergens as a risk factor for allergic rhinitis and asthma in the Polish population.

Postepy Dermatol Alergol 2020 Oct 9;37(5):751-759. Epub 2019 Apr 9.

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland.

Introduction: The patterns of sensitisation to airborne allergens and their association with allergic diseases have been analysed in different geographical regions.

Aim: To analyse the impact of sensitisation to airborne allergens on allergic rhinitis (AR) and asthma in different age groups of the Polish population.

Material And Methods: Completed questionnaires of 18,617 subjects (53.8% females), collected within the ECAP, a cross-sectional multicentre study, were analysed. Three groups of respondents were included: 6-7-year-olds (24.2%), 13-14-year-olds (25.4%), 20-44-year-olds (50.4%). The clinical part (an anamnesis, physical examination, spirometry, skin prick tests and an assay of major airborne allergen-specific IgE) was attended by 25.7% of the respondents.

Results: The AR was most strongly related to sensitisation to , with the highest odds ratios of 10 in two younger groups and of 16 for persistent AR in children. It was also the most important risk factor for allergic asthma, with odd ratios from 8.34 in children to 6.40 in adolescents. Sensitisation to grass pollen allergens was a major risk factor for both AR, with odds ratios from 9.16 in adults to 7.87 in adolescents, and asthma, with odds ratios from 6.16 in adolescents to 5.67 in adults.

Conclusions: AR and asthma shared common risk factors, independently of age. Sensitisation to airborne allergens was significantly associated with asthma and, even more strongly, with AR, across all age groups. The AR was the strongest risk factor for allergic asthma in the youngest group. Persistent AR increased asthma risk more than intermittent AR in all age groups.
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http://dx.doi.org/10.5114/ada.2019.84231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675083PMC
October 2020

Extension of WRF-Chem for birch pollen modelling-a case study for Poland.

Int J Biometeorol 2021 Apr 11;65(4):513-526. Epub 2020 Nov 11.

Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Kraków, Poland.

In recent years, allergies due to airborne pollen allergens have shown an increasing trend, along with the severity of allergic symptoms in most industrialized countries, while synergism with other common atmospheric pollutants has also been identified as affecting the overall quality of citizenly life. In this study, we propose the state-of-the-art WRF-Chem model, which is a complex Eulerian meteorological model integrated on-line with atmospheric chemistry. We used a combination of the WRF-Chem extended towards birch pollen, and the emission module based on heating degree days, which has not been tested before. The simulations were run for the moderate season in terms of birch pollen concentrations (year 2015) and high season (year 2016) over Central Europe, which were validated against 11 observational stations located in Poland. The results show that there is a big difference in the model's performance for the two modelled years. In general, the model overestimates birch pollen concentrations for the moderate season and highly underestimates birch pollen concentrations for the year 2016. The model was able to predict birch pollen concentrations for first allergy symptoms (above 20 pollen m) as well as for severe symptoms (above 90 pollen m) with probability of detection at 0.78 and 0.68 and success ratio at 0.75 and 0.57, respectively for the year 2015. However, the model failed to reproduce these parameters for the year 2016. The results indicate the potential role of correcting the total seasonal pollen emission in improving the model's performance, especially for specific years in terms of pollen productivity. The application of chemical transport models such as WRF-Chem for pollen modelling provides a great opportunity for simultaneous simulations of chemical air pollution and allergic pollen with one goal, which is a step forward for studying and understanding the co-exposure of these particles in the air.
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http://dx.doi.org/10.1007/s00484-020-02045-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985125PMC
April 2021

Prevalence of allergic rhinitis and asthma in Poland in relation to pollen counts.

Postepy Dermatol Alergol 2020 Aug 27;37(4):540-547. Epub 2019 Mar 27.

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland.

Introduction: Despite the known role of pollen allergens in causing allergy symptoms in sensitized individuals, there are few publications investigating the relationship between pollen exposure in different regions and the prevalence of inhalant allergy.

Aim: To assess the association between the prevalence of allergic rhinitis and asthma and the degree of exposure to pollen in various regions of Poland.

Material And Methods: Completed questionnaires of 9,443 subjects living in four urban centres (Wroclaw, Katowice, Warsaw, Bialystok), collected within part of the ECAP project, were analyzed. Children aged 6-7 ( = 2,278), adolescents aged 13-14 ( = 2,418), and adults aged 20-44 ( = 4,747) constituted 24.2%, 25.6% and 50.3% of the respondents, respectively. The clinical part (including skin prick tests, an assay of Timothy grass-specific IgE), was attended by 24% of the respondents. Data from 6-year pollen monitoring served to characterize birch and grass pollen seasons.

Results: We found insignificant negative associations between the duration of birch pollen season and the prevalence of declared allergic rhinitis and asthma during the season across all age groups. There were insignificant inverse associations between the number of days with above-threshold and high grass pollen concentrations, total grass pollen count and the prevalence of declared allergic rhinitis and asthma during the season across all age groups. Associations noted in the clinical part were also non-significant; however, these trends were not uniform across the age groups.

Conclusions: Our findings do not confirm the hypothesis of a positive association between pollen exposure and the prevalence of allergic rhinitis and asthma.
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http://dx.doi.org/10.5114/ada.2019.83624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507156PMC
August 2020

Exposure to pollen allergens in allergic rhinitis expressed by diurnal variation of airborne tree pollen in urban and rural area.

Otolaryngol Pol 2019 Apr;74(5):1-6

Faculty of Biology, University of Szczecin, Szczecin, Poland.

Exposure to airborne pollen allergens results in allergic symptoms in subjects who are sensitized. The paper presents diurnal variation in the counts of airborne allergenic pollen of selected trees (Betula L., Alnus Mill., Corylus L., Fagus L. and Ulmus L.) in two localities differing in the degree of urbanization: the city of Szczecin (urban) and the village of Gudowo, West Pomerania in northwest Poland (rural) in the years 2012-2014. The measurements were made by the volumetric method using a Burkardtype sampler operating in a continuous mode. The greatest similarities in the beginning of the main pollen season between the two sites studied were observed for birch and elm trees, while in the length of the main pollen season, for birch and alder trees. Pollen counts of alder and hazel reached higher levels in the rural area, while the levels of ash tree pollen counts were higher in the urban area. The level of birch tree pollen counts was similar in the two sites studied. For the majority of taxons observed in the urban and rural areas the dynamics of hourly changes in tree pollen counts were similar. The pollination peak was noted in the daytime, usually in the afternoon. For ash and elm trees increased pollen counts were observed at nighttime, while the birch tree pollen counts were at a high level for most of the 24 h cycle. The knowledge of seasonal and diurnal variations in tree pollen counts is crucial for prevention in patients with allergic rhinitis, sensitized to tree pollen allergens.
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http://dx.doi.org/10.5604/01.3001.0013.1532DOI Listing
April 2019

Dissociating polysensitization and multimorbidity in children and adults from a Polish general population cohort.

Clin Transl Allergy 2019 11;9. Epub 2019 Feb 11.

1Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland.

Background: Links between multimorbidity of allergic diseases and allergen sensitization are still under debate, especially in adults. This study aimed to establish a relationship between polysensitization and allergic multimorbidity in children and adults and the allergens involved in multimorbidity.

Material And Method: A cross-sectional multicentre study enrolled children aged 6-7 and 13-14 years and adults aged 20-44 years from a Polish national cohort. The diagnosis of allergic diseases was made by a physician. Skin prick tests to 13 allergens and serum IgE levels to 4 allergens were tested.

Results: Among the 3856 participants, single disease (asthma, allergic rhinitis or atopic dermatitis) was diagnosed in 27.7% subjects and allergic multimorbidity in 9.3%. Allergic multimorbidity occurred more commonly in children than in adults (p < 0.01). Asthma or atopic dermatitis alone were not associated with polysensitization. Rhinitis and multimorbidity were associated with polysensitization. Allergic multimorbidity occurred in 2.2% of participants with negative skin prick tests, 9.8% of those with one positive prick test (SPT ≥ 3 mm) and 20.6% of polysensitized ones (p < 0.001). There was an increasing risk of multimorbidity depending on the number of positive prick tests for both SPT ≥ 3 mm (OR 9.6-16.5) and SPT ≥ 6 mm (OR 5.9-13.7). A statistically significant relationship was found between allergic multimorbidity and sensitization to cat and mite allergens.

Conclusions: Multimorbidity is associated with polysensitization especially in children compared with adults in Polish population cohort. New insights into single disease patterns were found: bronchial asthma is the strongest risk factor for the development of multimorbidity in comparison with allergic rhinitis and atopic dermatitis.
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http://dx.doi.org/10.1186/s13601-019-0246-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369558PMC
February 2019

A study on the spatial and temporal variability in airborne Betula pollen concentration in five cities in Poland using multivariate analyses.

Sci Total Environ 2019 Apr 11;660:1070-1078. Epub 2019 Jan 11.

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland.

During the spring period, Betula pollen is the main cause of inhalant allergies in Poland and therefore it is important to monitor and forecast airborne pollen concentrations of this taxon. This study conducted a comparative analysis of the basic characteristics of Betula pollen seasons at the regional scale. The study was carried out from 2001 to 2016 in five cities in Poland: Lublin, Warsaw, Cracow, Sosnowiec, and Szczecin. To find the attributes of birch pollen seasons that mostly differentiated the individual cities, a general discriminant analysis (GDA) was performed, while a principal component analysis (PCA) allowed us to reduce the data space and present a scatterplot of PCA scores in order to compare pollen seasons in the individual cities. The contingency table was also analyzed to check whether there was a significant relationship between pollen counts in the studied years and cities. At most of the sites, biennial cycles of low and high pollen concentrations can be observed. Due to the high variation in seasons in each of these cities, two data groups were distinguished: Group 1 was composed of seasons with high pollen deposition (2001, 2003, 2006, 2008, 2010, 2012, 2014, 2016), and Group 2 comprising the other seasons. Multivariate analyses were performed on both these groups as well as in the entire dataset. End98, Peak Value, and Annual Total had the highest discriminant power. In Group 1, Warsaw and Sosnowiec differed the most in the investigated parameters, while Cracow and Szczecin differed the least. In both groups, most seasons with the highest pollen birch concentration were observed in Lublin, followed by Warsaw, while in Cracow, the number of such seasons was the smallest.
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http://dx.doi.org/10.1016/j.scitotenv.2019.01.098DOI Listing
April 2019

The dynamics of pollen seasons of the most allergenic plants - 15-year observations in Warsaw.

Otolaryngol Pol 2018 Sep;72(6):44-53

Military Institute of Medicine, Warsaw, Poland; Department of Otolaryngology with Division of Cranio-Maxillo-Facial Surgery, Warsawa, Poland.

Introduction: Allergic rhinitis concerns nearly 25% of the Polish population. Among pollen allergens, the most common reasons for allergic rhinitis are: grass, birch and mugwort. Knowledge of the characteristics of pollen seasons is necessary in diagnostics, monitoring of therapy and prevention of allergic rhinitis. P urpose: This work aims to analyze pollen seasons of the most allergenic plants in the Polish population; grass, birch and mugwort in the years 2003-2017 in Warsaw. M aterial and methods: Measurements of pollen concentration were carried out using Burkard volumetric spore trap operating in continuous mode. Analysis of pollen seasons was conducted based on the following characteristics: beginning, end, and length of season, the seasonal pollen index (SPI), defined as the sum of average daily pollen concentrations over the year, maximum daily concentration, number of days with maximum and threshold concentration. Linear regression together with the Pearson correlation coefficient were used in statistical analysis to study the relationship between variables; furthermore, descriptive characteristics of distributions studied were determined. R esults: The average beginning of the birch pollen season in the analyzed period is April 10th, and it belongs to seasons of average length (47 days on average). Birch pollen count above 75 grains/m3, when most allergic people develop symptoms, was recorded for an average of 18 days. The highest daily birch pollen count reaching 6321 grains/m3 (2012) exceeded the lowest value of the maximum concentration by almost 20 times (2015). Among the taxa analyzed, the highest values of daily counts and annual sums were recorded for birch pollen. The average date for the beginning of grass pollination season is on May 13th. It is the longest pollen season (on average 134 days), and the period when concentration exceeded 50 grains/m3 covered an average of 26 days. The highest daily grass pollen counts reaching 496 grains/m3 (2007) exceeded the lowest value of maximum concentration by 3.5 times (2016). The average date of the beginning of mugwort pollen season is July 16th. The season lasts 65 days on average, when concentration exceeding 30 grains /m3 was registered for an average of 12 days. The highest daily mugwort pollen count reaching 154 grains/m3 (2007) exceeded the lowest value of maximum concentration by 4 times (2013). For all analyzed taxa, the strongest correlated variables are the sum of average daily pollen concentrations over the year (SPI ) and daily maximum concentration (correlation for birch pollen = 0.92, for grass pollen = 0.88, and for mugwort pollen = 0.91).

Conclusions: Periods of pollen in the air show certain variation in the analyzed 15-year period. The maximum concentration in the pollen season for the analyzed taxa and the the sum of average daily pollen concentrations over the year show the highest variability, particularly strongly expressed in the case of birch pollen. There is a linear relationship between the sum of average daily pollen concentrations over the year and the maximum concentration value as well as the number of days with the threshold concentration for all analyzed taxa. Variability of parameters describing the dynamics of pollen seasons indicates the need to monitor, both by patients with hay fever and physicians, the current information on the concentration of pollen in the air during the pollen season.
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http://dx.doi.org/10.5604/01.3001.0012.4664DOI Listing
September 2018

Efficacy and safety of birch pollen allergoid subcutaneous immunotherapy: A 2-year double-blind, placebo-controlled, randomized trial plus 1-year open-label extension.

Clin Exp Allergy 2019 04 27;49(4):516-525. Epub 2019 Feb 27.

Department of Lung Diseases and Clinical Allergology, University of Turku, Turku, Finland.

Background: Previous clinical trials with birch pollen subcutaneous immunotherapy have been conducted over a 1- to 2-year treatment period and involved mostly a single geographic location.

Objective: This study (EudraCT-Number: 2005-000025-35) intended to evaluate the effect of subcutaneous immunotherapy with high-dose hypoallergenic birch pollen allergoid in patients with confirmed moderate to severe seasonal allergic rhinitis/rhinoconjunctivitis over a 3-year course in 19 European centres.

Methods: Adults with confirmed birch pollen allergy (n = 253) were randomized to preseasonal placebo (n = 129) or active treatment (n = 124). Primary endpoint was change in Symptom Medication Score after 2 years treatment (2007).

Results: The change in Symptom Medication Score of active- vs placebo-treated patients for the Full Analysis Set (n = 227, 15.2% reduction, P = 0.0710) and Per-Protocol Set (n = 216, 16.7% reduction, P = 0.0523) showed a positive trend, although significance was not achieved. The primary endpoint, assessed in 2007, coincided with the lowest pollination during the study period. In a subgroup analysis of patients in the north-eastern region (n = 102), where birch is the major tree and consequently patients' exposure is higher, changes in Symptom Medication Score (32.7% reduction, P = 0.0034) and median number of well days (P = 0.0232) were highly significant in favour of the active group. During the open-label third year of treatment, the mean Symptom Medication Score of active-treated patients was further reduced despite an increased pollen count. Subcutaneous immunotherapy was well tolerated and consistent with the known safety profile.

Conclusions And Clinical Relevance: Although the primary endpoint was not reached for the Full Analysis Set, a significant and clinically relevant effect on Symptom Medication Score was clearly demonstrated for the subgroup of patients in the north-eastern region of Europe, where birch is the predominant tree species. Proving efficacy of birch allergen subcutaneous immunotherapy is challenging due to the numerous factors influencing birch pollen allergen exposure in field studies.
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http://dx.doi.org/10.1111/cea.13331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849700PMC
April 2019

A multigene typing system for human adenoviruses reveals a new genotype in a collection of Swedish clinical isolates.

PLoS One 2018 14;13(12):e0209038. Epub 2018 Dec 14.

Department of Clinical Microbiology, Virology, and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.

Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal, urogenital, and ocular infections. They are divided into seven species containing 85 genotypes. Straightforward typing systems might help epidemiological investigations. As homologous recombination frequently shapes the evolution of HAdVs, information on a single gene is seldom sufficient to allow accurate and precise typing, and complete genome-based methods are recommended. Even so, complete genome analyses are not always easy to perform for practical reasons, and in such cases a multigene system can provide considerably more information about the strain under investigation than single-gene-based methods. Here we present a rapid, generic, multigene typing system for HAdVs based on three main deterministic regions of these viruses. Three PCR systems were used to amplify the genes encoding the DNA polymerase, the penton base hypervariable Arg-Gly-Asp-containing loop, and the hexon loop 1 (hypervariable region 1-6). Using this system, we typed 281 clinical isolates, detected members of six out of seven HAdV species (Human mastadenovirus A-F), and could also detect not only divergent strains of established types but also a new recombinant strain with a previously unpublished combination of adenovirus genomes. This strain was accepted by the Human Adenovirus Working Group as a novel genotype: HAdV-86. Seven strains that could not be typed with sufficient accuracy were also investigated using a PCR based on part of the fiber gene. By analysis of corresponding sequences of the 86 known HAdV genotypes, we determined that the proposed typing system should be able to distinguish all non-recombinant types, and with additional fiber information, all known HAdV genotypes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209038PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294355PMC
May 2019

The importance of specific IgE antibodies in epidemiology of allergic rhinitis and asthma - the Epidemiology of Allergic Diseases in Poland (ECAP) survey: part one. Influence of allergy risk factors on concentration of specific IgE antibodies in serum.

Postepy Dermatol Alergol 2018 Oct 19;35(5):520-526. Epub 2018 Jul 19.

Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland.

Introduction: Specific immunoglobulins E (sIgE) are important parameters to estimate severity of allergic diseases.

Aim: To determine the influence of allergy risk factors on the concentration of specific IgE antibodies in serum.

Material And Methods: The concentration of sIgE antibodies against allergens , cat dander, timothy grass, were determined in serum of 4077 respondents randomly selected from 9 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml) were correlated to answers in questionnaires ECRHSII and ISAAC.

Results: sIgE are more frequently detected in respondents declaring an allergic disease of a father than of a mother ( < 0.05, < 0.01). An early beginning to attend school, kindergarten or nursery increases the frequency of sIgE detection ( < 0.05). If the number of children who slept in the same room as a respondent before the respondent was five years old, was lower, sIgE antibodies are more frequently detected ( < 0.05). Relating to: 1) all 4 allergens, sIgE are the most frequently detected in respondents declaring absence of a carpet/rug at home ( < 0.05), 2) cat dander - less frequently detected in respondents who have a cat at home at the age of 1-4 years ( < 0.005).

Conclusions: Carpets/rugs capture a portion of mite, epidermal, mould allergens located at home, wherefore absence of a carpet or rug causes greater stimulation of an immune system by these allergens; as a consequence, IgE antibodies are the most frequently detected in respondents. Household contacts of the respondents, at the age of 1-4 years, with cats induced partial immune tolerance to cat dander.
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http://dx.doi.org/10.5114/pdia.2017.70894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232542PMC
October 2018

Effect of indoor air quality on the natural history of asthma in an urban population in Poland.

Allergy Asthma Proc 2018 Nov;39(6):e64-e70

From the Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Pol.

Indoor air pollution may have an impact on asthma. To evaluate the influence of indoor air pollution on the natural history of asthma. Data collection by using the European Community Respiratory Health Survey and International Study of Asthma and Allergies in Childhood standardized questionnaire (N = 18,617) and medical examinations (N = 4783) in selected Polish regions was used. Statistical analysis was performed by using the χ² test. A value of p < 0.05 was considered statistically significant. Questionnaire results demonstrated that people who used the central heating system were less likely to declare the occurrence of asthma (odds ratio [OR] 0.84) and were corroborated with clinical findings of moderate asthma (OR 0.35). Symptomatic asthma occurred more frequently in people who used a solid-fuel heating device (OR 1.36) and electric heaters (OR 1.54). The use of cooking appliances with municipal natural gas (OR 1.77) and gas storage tanks (OR 2.03) was correlated with more frequent declarations of asthma. Symptomatic asthma was more common among people who smoked for at least 1 year (OR 2.26) and those who smoked over the course of the preceding month (OR 1.60). Passive exposure to tobacco smoke provided for a 1.5-fold increase in the incidence of symptomatic asthma (OR 1.53), regardless of the time of exposure. Both active and passive tobacco smoke exposure as well as the use of certain types of heating and cooking appliances have a significant impact on the incidence of asthma and the intensification of its symptoms in rooms with limited air exchange. Highlights of the study included the following: (1) central heating had an amelioratory effect on asthma, (2) heating technologies used at home had a significant impact on the incidence of asthma, and (3) devices used for cooking (municipal and cylinder gas stoves) played an important role in the intensification of asthma symptoms.
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http://dx.doi.org/10.2500/aap.2018.39.4176DOI Listing
November 2018

The association between paracetamol use and the risk of asthma, rhinitis and eczema in the Polish population.

Ann Agric Environ Med 2018 Sep 17;25(3):428-432. Epub 2018 Apr 17.

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland.

Introduction: A growing number of epidemiological studies suggest that paracetamol, which is commonly used in children, may be a risk factor for asthma, allergic rhinitis, and atopic eczema.

Objective: The aim of this study was to determine and characterize the correlation between paracetamol use and asthma, allergic rhinitis, and atopic eczema symptoms in the Polish population.

Material And Methods: The study is part of the ECAP project involving the use of the ISAAC and ECRHS questionnaires. Completed questionnaires of 18,617 subjects, including 10,011 (53.8%) females, were analyzed. Children aged 6-7 (n=4,510), adolescents aged 13-14 (n=4,721), and adults aged 20-44 (n=9,386) constituted 24.2%, 25.4%, and 50.4% of respondents, respectively. Study subjects lived in 8 major urban centres and one rural area. The frequency of paracetamol use during the previous 12 months and symptoms of asthma, allergic rhinitis, and atopic eczema during that period were analyzed.

Results: The use of paracetamol was associated with a significant dose-dependent increase in the risk of asthma symptoms in all evaluated age groups. This was demonstrated via odds ratios (OR) for developing asthma symptoms, including wheezing or whistling in the chest in 6-7-year-olds and exercise-induced shortness of breath in 13-14-year-olds and adults, depending on the frequency of paracetamol use in the previous 12 months, compared to no paracetamol intake during that period.

Conclusions: The use of paracetamol in the last 12 months was associated with a significant dose-dependent increase in the risk of rhinitis and skin allergy symptoms, as demonstrated by the odds ratio. Therefore, frequent paracetamol use may be a risk factor for symptoms of asthma, rhinitis, and skin allergy in the Polish population.
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http://dx.doi.org/10.26444/aaem/86336DOI Listing
September 2018

Treatment strategy of allergic rhinitis in the face of modern world threats.

Otolaryngol Pol 2018 Apr;72(2):1-12

Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland.

Allergic rhinitis (AR) is the most common form of allergy, which - as epidemiological research has shown - applies to nearly 25% of the population. AR significantly affects the quality of life of the patient, and the more severe the disease, the greater the risk of developing bronchial asthma. One of the factors affecting the severity of symptoms and the degree of their control is air pollution. In some patients, despite proper treatment, persistence or only partial remission of symptoms (uncontrolled allergic rhinitis) is observed. This can lead to an increase in comorbidities - inflammation of the paranasal sinuses, otitis media and asthma - both in children and in adults. The treatment of allergic rhinitis, in accordance with the standards, consists in: education of the patient, elimination of the allergen from the environment and factors intensifying the course of the disease, selection of proper pharmacotherapy and specific allergen immunotherapy. Many factors influence the selection of the antihistamine used, e.g., the opportunity of safe increase of the dosage.
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http://dx.doi.org/10.5604/01.3001.0011.8057DOI Listing
April 2018

Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56.

J Gen Virol 2018 Jan 20;99(1):135-147. Epub 2017 Nov 20.

Batavia Biosciences BV, Leiden, The Netherlands.

The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase 'antigen'-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications.
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http://dx.doi.org/10.1099/jgv.0.000978DOI Listing
January 2018

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

PLoS One 2017 8;12(9):e0183922. Epub 2017 Sep 8.

Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183922PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590850PMC
November 2017

Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae.

PLoS Negl Trop Dis 2017 03 23;11(3):e0005451. Epub 2017 Mar 23.

Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Warsaw, Poland.

Background: Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica (CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli. In this study, we explore oral vaccination, which may be the desired method of delivery and is potentially capable of preventing infections at the site of helminth entry. To provide antigen encapsulation and to protect the vaccine antigen from degradation in the intestinal tract, transgenic plant-based systems are used.

Methodology: In the present study, we aimed to evaluate the protective ability of mucosal vaccinations of 12-week-old rats with CPFhW produced in a transgenic-plant-based system. To avoid inducing tolerance and to maximise the immune response induced by oral immunisation, we used the hepatitis B virus (HBV) core protein (HBcAg) as a carrier. Animals were immunised with two doses of the antigen and challenged with 25 or 30 metacercariae of F. hepatica.

Conclusions: We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%) was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly-rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responses to CPFhW for 4 consecutive weeks after the challenge.
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http://dx.doi.org/10.1371/journal.pntd.0005451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383346PMC
March 2017

Persons with allergy symptoms use alternative medicine more often.

Pneumonol Alergol Pol 2016 ;84(5):251-7

Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland.

Introduction: The aim of the study is to indicate the relation between the use of alternative medicine and the occurrence of allergic diseases in the Polish population of adults in the age of 20-44 years. Moreover the additional aim of the study is to define the relation between the sex, age and place of living and the use of alternative medicine.

Material And Methods: The data from the project Epidemiology of Allergic Diseases in Poland (ECAP) has been used for analysis. This project was a continuation of the European Community Respiratory Health Survey II. The questions on alternative medicine were asked to the group of 4671 respondents in the age of 20-44 years. Additionally outpatient tests were performed in order to confirm the diagnosis of allergic diseases.

Results: The total of 22.2% of respondents that participated in the study have ever used alternative medicine (n = 4621). A statistically significant relation between the use of alternative medicine and declaration of allergic diseases and asthma symptoms has been demonstrated (p &amp;amp;amp;amp;amp;lt; 0.001). No statistically significant relation between the use of alternative medicine by persons diagnosed by a doctor with any form of asthma or seasonal allergic rhinitis (p &amp;amp;amp;amp;amp;gt; 0.05) has been demonstrated.

Conclusions: The occurrence of allergic diseases and asthma influences the frequency of alternative medicine use. However the frequency of alternative medicine use does not depend on allergic disease or asthma being confirmed by a doctor.
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http://dx.doi.org/10.5603/PiAP.2016.0031DOI Listing
April 2017

Nasal patency in Poles in the light of research as part of the project on Epidemiology of Allergic Diseases in Poland.

Ann Agric Environ Med 2016 Sep;23(3):487-90

1. Department of Prevention of Environmental Hazards and Allergology, Faculty of Health Sciences, Medical University of Warsaw, Poland; 2. Department of Pediatric and Neonatology, Central Clinical Hospital of Ministry of Internal Affair, Warsaw, Poland.

Objective: The aim of this study was to estimate the reference values for nasal inspiratory flow in the study population in Poland as part of the project on Epidemiology of Allergic Diseases in Poland (ECAP).

Materials And Method: The study subjects were a group of 4,137 people: 1,136 children aged 6-7 years (561 girls and 575 boys), 1,123 adolescents aged 13-14 years (546 girls, 577 boys) and 1,878 adults (1,145 women, 733 men), residing in seven large Polish cities. The method used in the study was the measurement of the peak nasal inspiratory flow (PNIF) using a special mask for rhinomanometry tests, with a measurement scale of 20-350 L/min. Measurements were conducted twice: once before and once after nasal mucosa vasoconstriction with a 0.1% xylometazoline (Xylometazolinum) solution.

Results: Nasal patency rates increased with age in healthy subjects (children aged 6-7 years: 75.95 L/min; teenagers aged 13-14 years: 91.44 L/min and adults: 97.13 L/min (P<0.05). Similarly significant correlations were observed in the study group based on the region of residence (P<0.05). A moderate correlation was observed between PNIF and height as well as weight (with correlation coefficients r=0.51, P<0.05; and r=0.49, P<0.05, respectively). Interestingly, the observed difference in nasal vasoconstriction varied considerably between study subgroups with respect to the pre-determined criteria of age, gender, place of residence, and clinical diagnosis (allergic rhinitis vs. healthy controls), with the mean rates of 25-28%.

Conclusions: Any attempt to determine reference values for a given study population should include a number of variables, such as age, height, body weight, which can noticeably affect study results.
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http://dx.doi.org/10.5604/12321966.1210746DOI Listing
September 2016

The Effect of Preventive Immunization on the Incidence of Allergic Conditions.

Iran J Allergy Asthma Immunol 2015 Aug;14(4):402-9

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland.

The purpose of this study was to assess the effect of preventive immunization on the incidence of allergies in Poland. 18,617 (53.8% female, 24.2% 6-7 years old, 25.4% 13-14 years old, 50.4% 20-44 years old) were selected by stratified cluster sampling method in 8 cities and 1 rural area. 4783 of whom underwent objective outpatient screening assessments. Study subjects were evaluated for any association between preventive immunization against rubella, measles, typhoid fever, smallpox and incidence of atopic dermatitis, allergic rhinitis, and asthma. There was no increased risk of allergy incidence in the majority of vaccinated subjects against rubella, measles, typhoid fever, or smallpox (OR from 0.42 (p<0.0001) to 1.34 (p<0.0001) with 95% CI from 0.27-0.65 to 1.19-1.50). Slightly increased risk of asthma was after vaccination against typhoid (OR=1.27; p<0.0001) and smallpox (OR=1.21; p=0.02). The risk of atopic dermatitis (AD) was also evaluated following vaccination against rubella (OR=1.34; p<0.0001), typhoid (OR=1.13; p=0.005), varicella (OR=1.18; p=0.003); rhinitis and AR following vaccination against measles (respectively OR=1.22; p<0.0005 and OR =1.21; p=0.0002). No higher risk of allergic diseases was demonstrated in vaccinated individuals diagnosed by doctor in an outpatient setting. These data do not demonstrate a causal relationship between vaccinations and allergic conditions.
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August 2015

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

Allergy Asthma Proc 2015 Sep-Oct;36(5):e81-5

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland.

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.
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http://dx.doi.org/10.2500/aap.2015.36.3882DOI Listing
June 2016

Atopic dermatitis is a serious health problem in Poland. Epidemiology studies based on the ECAP study.

Postepy Dermatol Alergol 2015 Feb 2;32(1):1-10. Epub 2015 Feb 2.

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland. Head of Department: Prof. Bolesław Samoliński MD, PhD.

Introduction: Global epidemiological studies have revealed considerable geographical differences in prevalence of atopic dermatitis (AD).

Aim: To present the epidemiology of AD, risk factors and co-occurrence of allergic diseases in the Polish population.

Material And Methods: The present paper is a part of the Epidemiology of Allergic Disorders in Poland study. We studied 22 703 participants by ECRHS/ISAAC questionnaire; 18 617 (53.8% female, 24.2% 6-7 y.o., 25.4% 13-14 y.o., 50.4% 20-44 y.o.) completed questionnaires were accepted. Four thousand seven hundred and eighty-three participants (25.7%) have undergone a medical examination.

Results: Atopic dermatitis was diagnosed in 3.91% (6-7 y.o. 5.34%, 13-14 y.o. 4.3%, adults 3.02%), more often in females (OR = 1.52; 95% CI: 0.56-0.77), in the cities (OR = 2.23; 95% CI: 1.61-3.09), in mothers (OR = 2.07; 95% CI: 1.72-2.48) and fathers (OR = 2.00; 95% CI: 1.61-2.49) with atopy, higher education (OR = 1.61; 95% CI: 1.11-2.32) and economic status (OR = 1.35; 95% CI: 1.04-1.74). The highest prevalence was found in Katowice (4.89%) and lowest in rural areas (1.9%). Coexisting AD and allergic rhinitis (AR) was found in 26.17%, AR and asthma in 9.09% and AD, AR and asthma in 14.6%. Atopic dermatitis was diagnosed by allergologists in 6.5% (6-7 y.o. 8.7%, 13-14 y.o. 9.0%, adults 3.6%). Most diagnoses were made in Poznan (16.76%) and smallest in rural area (3.67%). 78.8% of subjects were diagnosed with AD for the first time although they had earlier experienced its symptoms.

Conclusions: Atopic dermatitis prevalence in Poland is below the mean rate for Europe, but the risk factor profile is similar to other countries. Atopic dermatitis is more frequent in well-educated females with atopic parents and high socioeconomic status and who live in a city.
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http://dx.doi.org/10.5114/pdia.2014.40935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360000PMC
February 2015

The effects of disease awareness on lifestyle changes and the use of preventive measures in asthma patients.

Allergy Asthma Proc 2015 Mar-Apr;36(2):e14-22

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland.

Reduction in asthma incidences and mortality, as well as improved quality of life, can be achieved via a wide use of prevention methods. A number of randomized cohort studies demonstrated the effectiveness of such management and the need for multiple treatments. Here, we evaluate whether asthma awareness influences the lifestyle and the use of prevention, as well as the effects of age, sex, economic status, and education on the use of prophylaxis. A total of 18,617 (53.8% female; 24.2% 6-7 years old, 25.4% 13-14 years old, and 50.4% 20-44 years old) were selected by a stratified cluster sampling method in eight cities and one rural area, each over 150,000 citizens. The sample was selected based on the methods and questionnaires of International Study of Asthma and Allergies in Childhood and European Community Respiratory Health Survey. Patients aware of asthma significantly less often (p < 0.05) reported owning asthma-inducing items and significantly more often reported behaviors minimizing the number of allergens (p < 0.05). Patients aware of asthma took all actions reducing their exposure to in-house allergens significantly more often than the healthy (p < 0.05) and individuals with symptoms only (p < 0.05). Allergy prevention was used more often in children (p < 0.0005), responders aware of diseases (p < 0.05), higher levels of education (p < 0.05), and higher household income (p < 0.05). The most common type of prophylaxis used is prophylactic actions, which are undertaken by patients diagnosed with asthma and who are aware of their disease. Adults do not use preventive measures as often as children or adolescents do. Higher rates of prevention-oriented behavior were observed in groups characterized by higher levels of education and higher household income.
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http://dx.doi.org/10.2500/aap.2015.36.3822DOI Listing
December 2015

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

J Dermatol 2015 Feb 6;42(2):140-7. Epub 2014 Dec 6.

Department of the Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland; Department of Pediatric and Neonatology, Central Clinical Hospital of Ministry of Internal Affair, Warsaw, Poland.

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.
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http://dx.doi.org/10.1111/1346-8138.12731DOI Listing
February 2015

The role of the SHH gene in prostate cancer cell resistance to paclitaxel.

Prostate 2014 Aug 12;74(11):1142-52. Epub 2014 Jun 12.

Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

Background: The increased activity of the Sonic Hedgehog (SHH) pathway has been demonstrated in many types of cancer including prostate cancer (PCa). It has been shown that SHH pathway is involved in tumor angiogenesis and in regulation of metabolism of cancer stem cells. The increased activity of the SHH pathway is responsible for generation and maintenance of the multidrug resistance in cancer cells. A key role in the development of this insensitivity to cytotoxic drugs play ATP-binding cassette (ABC) transporters.

Methods: SHH encoding plasmid was stably transfected into PCa cell lines DU145 and LNCaP. The expression of SHH was silenced by shRNA and the level of SHH was tested by quantitative (q)PCR and western blot methods. The effect of SHH overexpression in cells after treatment with paclitaxel was measured by MTT assay, crystal violet assay and flow cytometry. The level of 44 ABC transporters was estimated by qPCR.

Results: Expression of exogenous SHH protein in DU145 and LNCaP cell lines enhanced their resistance to paclitaxel along with increased expression of ABC transporters transcripts. Paclitaxel treatment further enhanced the expression of increased ABC transporters transcripts in cells overexpressing SHH.

Conclusions: Overexpression of SHH enhances PCa cell lines resistance to paclitaxel. Higher level of SHH leads to increase in ABC transporters expression in a manner dependent on paclitaxel.
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http://dx.doi.org/10.1002/pros.22830DOI Listing
August 2014

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

Public Health Nutr 2015 Feb 17;18(3):530-6. Epub 2014 Apr 17.

1Department of the Prevention of Environmental Hazards and Allergology,Medical University of Warsaw,Warsaw,Poland.

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.
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http://dx.doi.org/10.1017/S1368980014000676DOI Listing
February 2015

Intranasal glucocorticosteroids - not only in allergic rhinitis In the 40th anniversary of intranasal glucocorticosteroids' introduction.

Otolaryngol Pol 2014 Mar-Apr;68(2):51-64. Epub 2014 Feb 5.

Department of Prevention of Environmental Hazards and Allergology WUM, Head: prof. dr hab. n. med. Bolesław Samoliński, Warszawa, Poland.

It has been 40 years since Niels Mygind's 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.
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http://dx.doi.org/10.1016/j.otpol.2013.12.003DOI Listing
December 2015

Challenges in manufacturing adenoviral vectors for global vaccine product deployment.

Hum Gene Ther 2014 Apr 2;25(4):318-27. Epub 2014 Apr 2.

1 Crucell Holland BV , 2333CN Leiden, The Netherlands .

Abstract Once adenovirus vector-based vaccines are licensed for the prevention of important infectious diseases, manufacturing processes capable of reliably delivering large numbers of vaccine doses will be required. The highest burden of disease for many infectious pathogens under investigation occurs in resource-poor settings. Therefore, the price per dose will be an important determinant of success. This review describes common practices for manufacturing replication-incompetent adenovirus vectors at clinical scale. Recent innovations and strategies aimed at improving the cost-effectiveness of manufacturing and ensuring high-volume vaccine production and purification are described. Hereto, technologies to increase bioreactor yields are reviewed. In addition, the use of single-use perfusion bioreactors, modification of some purification steps to avoid the use of expensive endonucleases, and use of charged filters during anion exchange all have the potential to bring down the cost of goods and are thus described. Finally, processes for ensuring quality throughout the manufacturing process, methods for testing viral identity, and safety of master seeds through to the end vaccine product are described.
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http://dx.doi.org/10.1089/hum.2014.007DOI Listing
April 2014

Innate immunity to adenovirus.

Hum Gene Ther 2014 Apr 8;25(4):265-84. Epub 2014 Apr 8.

1 Institute of Molecular Life Sciences, University of Zurich , CH-8057 Zurich, Switzerland .

Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate-adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features.
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http://dx.doi.org/10.1089/hum.2014.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996939PMC
April 2014

Sonic hedgehog stimulates the recruitment of endothelial progenitor cells.

Med Wieku Rozwoj 2013 Apr-Jun;17(2):151-6

Department of Applied Pharmacy and Bioengineering, Medical University of Warsaw, Warsaw, Poland.

Aim: The present work focused on the Sonic hedgehog (SHH) gene that stimulates angiogenesis in the skin. It is postulated that endothelial progenitor cells (EPCs) are responsible for skin angiogenesis. The recruitment of endothelial progenitor cells was verified in the mouse skin transfected with the pSHH gene construct using the quantitative PCR method.

Material And Methods: The tests were performed on male Balb/c mice. The SHH gene preparation was administered intradermally and/or intramuscularly. The assessment of the expression of EPCs angiogenic genes was performed using the qPCR method. The statistical analysis of the selected results was performed using the t-Student test. Differences were considered statistically significant when p<0.05.

Results: Studies indicate that the SHH gene administered to mouse skin as pSHH, pSHH/PEI/NaCl and pSHH/PEI/H20 formulations recruits endothelial progenitor cells to the sites of injection. The increased expression of genes specific to endothelial progenitor cells as CD34, CD44, CD133, KDR and others was observed.

Conclusions: The sonic hedgehog gene stimulates the recruitment to the skin the cells expressing EPCs markers. The mechanism of proangiogenic activity of SHH is linked to EPCs mobilization. SHH gene seems to be a potential gene-candidate to proangiogenic gene therapy applications.
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October 2013