bluuebunny/crossref_metadata_2025_split huggingface dataset:
In utero priming of allergen‐specific helper T cells
Authors: Devereux Graham , Seaton Anthony , Barker Robert N. 
Published: March 2003

Background Allergic diseases are major health problems in developed countries. Cord blood mononuclear cells (CBMC) at birth can proliferate after stimulation with allergen and this has led to the widespread view that the sensitization of the fetal immune system by allergens is a key determinant in establishing immunological bias towards allergy. However, the notion that the immune system can be primed by allergen in utero remains unproven. Determination of the CD45 isoform of responding T helper cells is an established method of determining the activation status of responding T helper cells because unsensitized cells express CD45RAhigh and previously sensitized cells CD45ROhigh.Objective To determine if sensitization of allergen‐specific T helper cells can occur in utero by determining the CD45 isoform of CBMC proliferating in response to allergen.Methods CBMC proliferative responses were measured after stimulation in culture with a panel of allergens, mitogen and control antigen. To ascertain whether any responding T helper cells had been primed in utero, depletion experiments established whether they carried the CD45ROhigh marker of previous activation or the CD45RAhigh marker of unstimulated T cells.Results CBMC from a high proportion of 223 randomly selected neonates were stimulated to proliferate in vitro by allergens, with 76% responding to timothy grass pollen. In 50% of such responses to timothy grass, the CD45 isoform of the T cells that proliferate indicated that they had been previously activated. However, the remaining 50% of responses to timothy grass were mediated by previously unstimulated T cells. Proliferative responses mediated by CBMC sensitized in utero tended to be greater in magnitude than those mediated by unsensitized cells (P = 0.08). Seventy‐five per cent of CBMC samples proliferated after stimulation with mycobacterial PPD and, as in BCG‐vaccinated adults, all such CBMC proliferative responses at birth were predominately mediated by sensitized cells.Conclusion Allergen‐ and antigen‐specific Th cells can be primed in utero.
Development of allergy and IgE antibodies during the first five years of life in Estonian children
Authors: Julge K. , Vasar M. , Björkstén B. 
Published: March 2003

Background Epidemiological studies have demonstrated a low prevalence of allergic diseases and atopic sensitization among schoolchildren and young adults in the formerly socialist countries of Central and Eastern Europe as compared to Western Europe.Objective The aim of our study was to prospectively investigate IgE responses to food and inhalant allergens and the development of allergy during early childhood in a population with a low prevalence of atopic disorders.Methods In a population‐based prospective study, 273 children were followed from birth through the first 5 years of life, recording manifestations of allergy by questionnaires and clinical examinations at 0.5, 1, 2 and 5 years (n = 213). Skin prick tests (SPT) were performed using natural foods (cow's milk, egg white) and commercial extracts of inhaled allergens (cat, dog, D. pteronyssinus, birch, timothy). In addition, serum IgE levels and circulating IgE antibodies against the seven allergens were determined.Results The prevalence of allergic diseases at 5 years of life was 19%. Atopic dermatitis was the most common allergic disease at all ages. The point prevalence of positive skin prick tests was 7% at 0.5, 1 and 2 years of age, and 3% at 5 years. Circulating IgE antibodies against food allergens were common at all ages, i.e. 13, 23, 36 and 36%, respectively, at 0.5, 1, 2 and 5 years. The prevalence of circulating IgE antibodies to inhalant allergens increased from 1.5% at 0.5 years to 11% at 1, 19% at 2 and 47% at 5 years. The antibody levels were generally low, however. The value of positive SPT and the presence of IgE antibodies in the diagnosis of clinical allergy were low.Conclusion The results of this prospective study carried out in a previously socialist country with a low allergy prevalence among schoolchildren and young adults indicate that transient sensitization in early childhood is followed by a down‐regulation of skin reactivity.
Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children
Authors: Anyo G. , Brunekreef B. , De Meer G. , Aarts F. , Janssen N. A. H. , Van Vliet P. 
Published: March 2003

Background Studies have suggested that early contact with pets may prevent the development of allergy and asthma.Objective To study the association between early, current and past pet ownership and sensitization, bronchial responsiveness and allergic symptoms in school children.Methods A population of almost 3000 primary school children was investigated using protocols of the International Study on Asthma and Allergies in Childhood (ISAAC). Allergic symptoms were measured using the parent‐completed ISAAC questionnaire. Sensitization to common allergens was measured using skin prick tests (SPT)s and/or serum immunoglobulin (Ig)E determinations. Bronchial responsiveness was tested using a hypertonic saline challenge. Pet ownership was investigated by questionnaire. Current, past and early exposure to pets was documented separately for cats, dogs, rodents and birds. The data on current, past and early pet exposure were then related to allergic symptoms, sensitization and bronchial responsiveness.Results Among children currently exposed to pets, there was significantly less sensitization to cat (odds ratio (OR) = 0.69) and dog (OR = 0.63) allergens, indoor allergens in general (OR = 0.64), and outdoor allergens (OR = 0.60) compared to children who never had pets in the home. There was also less hayfever (OR = 0.66) and rhinitis (OR = 0.76). In contrast, wheeze, asthma and bronchial responsiveness were not associated with current pet ownership. Odds ratios associated with past pet ownership were generally above unity, and significant for asthma in the adjusted analysis (OR = 1.85), suggesting selective avoidance in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only showed an inverse association with sensitization to pollen: OR = 0.71 for having had furry or feathery pets in general in the first two years of life, and OR = 0.73 for having had cats and/or dogs in the first two years of life, compared to not having had pets in the first two years of life.Conclusion These results suggest that the inverse association between current pet ownership and sensitization and hayfever symptoms was partly due to the removal of pets in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only seemed to offer some protection against sensitization to pollen.
Cytokine pattern in allergic and non‐allergic chronic rhinosinusitis in asthmatic children
Authors: Riccio A. M. , Tosca M. A. , Cosentino C. , Pallestrini E. , Ameli F. , Canonica G. W. , Ciprandi G. 
Published: March 2003

Background Rhinosinusitis represents one of the most common chronic diseases. The association of rhinosinusitis with asthma has been frequently reported. Eosinophils and Th2 cells play a pathogenic mechanism in asthma.Objective The aims of the study were to evaluate the cytokine pattern in chronic rhinosinusitis in asthmatic children and to compare the findings in allergic vs. non‐allergic asthmatics.Methods Thirty‐five asthmatic children were evaluated, 19 males and 16 females, with an average age of 8.7 years. All children were asthmatic and suffered from chronic rhinosinusitis. Twenty were allergic and 15 were non‐allergic. Ten healthy children were studied as normal controls. Evaluated parameters were the levels of the following cytokines: IL‐1β, IL‐4, IL‐6, IL‐8, IL‐12, IFN‐γ and TNF‐α. Cytokines were recovered from rhinosinusal lavage and measured by immunoassays. Nasal cytology was also performed in all subjects and inflammatory cells were counted by conventional staining.Results Allergic subjects showed a significant increase of IL‐4 (P < 0.01) and TNF‐α (P < 0.05) and a significant decrease of IL‐12 (P < 0.05) and of IFN‐γ (P < 0.0001), whereas IL‐1β, IL‐6 and IL‐8 were not significantly increased. Non‐allergic children showed a significant increase of IL‐4 (P < 0.05) and a significant decrease of IFN‐γ (P < 0.0001), IL‐12 was not significantly decreased, and IL‐1β, IL‐6 and IL‐8 were not significantly increased. A significant inflammatory infiltrate was present in all asthmatic children. Significant correlations were demonstrated between IL‐4 and IL‐12 (P < 0.001), IL‐12 and IFN‐γ (P < 0.001), IL‐8 and neutrophils (P < 0.01), and TNF‐α and monocytes/macrophages (P < 0.05), in allergic asthmatics. IL‐4 and IL‐12 were significantly correlated (P < 0.05) as well as IL‐8 and neutrophils (P < 0.01) in non‐allergic asthmatics.Conclusion This study shows that allergic asthmatic children with chronic rhinosinusitis have a typical Th2 cytokine pattern, but also non‐allergic asthmatic children share a similar pattern. These findings would suggest the existence of a common pathophysiological mechanism shared by upper and lower airways and are consistent with the concept of united airways disease.
The protective role of country living on skin prick tests, immunoglobulin E and asthma in adults from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper‐responsiveness and atopy
Authors: Kauffmann F , Oryszczyn M. P , Maccario J 
Published: March 2003

SummaryBackground  Farming environment and traditional lifestyle seem to protect from childhood allergy.Objective  The aim is to analyse the relationships of living in the country to asthma, positive skin prick tests and IgE among adults considering various windows of exposure over the life‐span.Methods  The study concerns 805 adults drawn from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper‐responsiveness and atopy (EGEA) (asthmatic cases, non‐asthmatic controls, and parents of cases with and without asthma). Ever living in the country concerned 55% of the subjects. Early (beginning < 1 years), childhood (beginning ≤ 16 years), prolonged (duration ≥ 10 years) and current life in the country were studied.Results  The results based on the case control and family components of the study show that IgE levels were significantly lower in those who ever lived in the country and in particular in those who lived for ≥ 10 years. Positive skin prick tests (SPT) were significantly less prevalent in those who ever lived in the country and in particular in those with childhood (≤ 16 years) exposure. These associations remained independent of age, sex, smoking or asthma with IgE levels of 64 vs. 88 IU/mL; P = 0.004 for those ever living in the country vs. others and odds ratio for SPT positivity of 0.72 (95% CI [0.53–0.98]). In the more specific group with traditional mode of heating in childhood (use of wood) associations were stronger. The association with asthma, studied in parents of asthmatic probands showed that fathers, but not mothers, of asthmatics were significantly less often asthmatic themselves in relation to country living.Conclusion  Country life protects from asthma and adulthood allergy. The protective effect is not restricted to exposure in early childhood.
Long‐term safety and efficacy of nevirapine tolerance induction
Authors: Messaad D. , Reynes J. , Fabre J. , Bousquet J. , Demoly P. 
Published: March 2003

SummaryBackground  The most frequent side‐effects due to nevirapine (Viramune®), the first non‐nucleoside HIV reverse transcriptase inhibitor introduced for clinical use, are cutaneous hypersensitivity reactions. In non‐serious cases, tolerance induction can be proposed.Objective  Describe the long‐term safety and efficacy of tolerance induction to nevirapine.Methods  Six HIV‐infected patients started a tolerance 1 to 2 months after an episode of nevirapine hypersensitivity. Increasing doses of nevirapine (2.5, 10, 25, 100, 250 and 750 μg and 2.5, 5, 10, 25, 50 and 100 mg) were given orally at half‐hour intervals under strict medical surveillance and patients were followed up regularly.Results  All but two of the patients tolerated this induction well. One had a mild and transient reaction on day 1; nevirapine was not stopped. One had a moderate to severe reaction one month later; nevirapine was stopped and he recovered fully. All other patients have been taking nevirapine for more than 3 months without any adverse reaction.Conclusion  Therefore, when no alternatives are available in severely ill and hypersensitive HIV‐infected patients, tolerance induction is a possible therapeutic option.
Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis?
Authors: Eaton T. E. , Weiner Miller P. , Garrett J. E. , Cutting G. R. 
Published: March 2003

SummaryBackground  Previous work suggests that cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations may be implicated in the aetiology of allergic bronchopulmonary aspergilosis (ABPA).Objective  To compare the frequency of CF gene mutations in asthmatics with ABPA of varying severity with asthmatics who were skin prick test (SPT)‐positive to Aspergillus fumigatus (Af) without evidence of ABPA and asthmatics SPT‐negative to Af.Methods  Thirty‐one Caucasian patients with ABPA were identified, together with asthmatics SPT positive to Af without evidence of ABPA (n = 23) and SPT negative to Af (n = 28). Genomic DNA was tested for 16 CF mutations accounting for approximately 85% of CF alleles in Caucasian New Zealanders.Results  Four (12.9%) ABPA patients were found to be carriers of a CF mutation (ΔF508 n = 3, R117H n = 1), one (4.3%) asthmatic SPT positive to Af without ABPA (ΔF508), and one (3.6%) asthmatic SPT negative to Af (R117H). All patients with a CF mutation had normal sweat chloride (< 40 mM). There was no significant difference between the frequency of CF mutations in the ABPA patients and asthmatics without ABPA. However, the frequency of CF mutations in the ABPA patients was significantly different (P = 0.0125) to the expected carrier rate in the general population.Conclusion  These results lend further support to a possible link between CF mutations and ABPA.
Prevention of sensitization to house dust mite by allergen avoidance in school age children: a randomized controlled study
Authors: Arshad S. H. , Bojarskas J. , Tsitoura S. , Matthews S. , Mealy B. , Dean T. , Karmaus W. , Frischer T. , Kuehr J. , Forster J. ,   the SPACE study group
Published: March 2003

SummaryBackground Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders.Objective To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children.Methods As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5–7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust‐mite allergen. Control group children were given non‐specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed.Results Ten children in the prophylactic group and 19 in the control group were lost to follow‐up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03–0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child.Conclusion Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.
Immunotherapy with keyhole lampet hemocyanin‐conjugated decapeptide vaccine in cypress pollen allergy
Authors: Demoly P. , Persi L. , Dhivert H. , Delire M. , Bousquet J. 
Published: March 2003

SummaryBackground Cupressaceae pollen allergy is a world‐wide pollinosis but immunotherapy has rarely been tested. Immunotherapy is usually allergen‐specific but new forms may be targeted towards IgE.Objectives A randomized, double‐blind, placebo‐controlled trial was carried out to assess the efficacy of a vaccine made of keyhole lampet hemocyanin (KLH)‐conjugated decapeptide from the Fcε4 domain of the IgE in cypress pollinosis.Methods Sixty patients with cypress pollen allergy were studied. They were included on a suggestive clinical history, positive skin tests and nasal challenge to cypress pollen extract. Three intramuscular injections of the vaccine (250 µg) or placebo were administered monthly with a booster injection 5 to 8 weeks later. The primary end‐point criterion was the threshold dose inducing a positive nasal challenge. The secondary end‐point was the symptom‐medication scores measured when cypress pollen grains were over 50 grains/m3.Results Nasal challenge before treatment was non‐significantly different between the placebo and vaccine groups. After treatment there was no significant difference between the two groups. Pollen counts were over 50 grains/m3 for 8 weeks during the trial. There was no significant difference in total symptom scores between the placebo and vaccine groups. The vaccine was safe.Conclusions The KLH‐conjugated decapeptide vaccine was not effective in cypress pollen allergy.
Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma
Authors: Meijer R. J. , Postma D. S. , Kauffman H. F. , Arends L. R. , Koëter G. H. , Kerstjens H. A. M. 
Published: March 2003

SummaryBackground There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response.Aim We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients.Methods One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 µg/day b.i.d. or fluticasone propionate 250 µg/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double‐blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% fall in FEV1 (PC20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response.Results We found that changes in FEV1, PC20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV1, but not for change in PC20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (≥ 3%) correctly predicted an improvement in PC20 Mch in only 65% of the patients.Conclusion Our findings show that baseline values of the clinical parameters used as outcome parameters are the major predictors of clinical response to corticosteroids. Eosinophil percentage in blood or sputum adds to this, whereas ECP provides no additional information. Correct prediction of clinical response in an individual patient, however, remains poor with our currently used clinical and inflammatory parameters.
Extractable latex allergens in airborne glove powder and in cut glove pieces
Authors: Kujala V. , Alenius H. , Palosuo T. , Karvonen J. , Pfäffli P. , Reijula K. 
Published: March 2003

SummaryBackground Quantification of natural rubber latex (NRL) allergens of NRL glove extracts has been reported in several studies. Similarly, immunoassay studies reporting the level of NRL aeroallergens in air samples have been published. When studying the NRL allergens of gloves, however, little attention has been focused on identifying the relationship between extractable NRL allergens of medical gloves and NRL aeroallergens in indoor air.Objective In an experimental study we analysed NRL aeroallergens of medical gloves in joint relation to total airborne dust concentration and NRL allergen concentration in gloves.Methods NRL aeroallergen level was measured using a chamber setting with 18 lots of powdered medical gloves. In each setting 10 pairs of powdered NRL gloves were swinging in an unventilated chamber (9 m3). Air samples were collected using airflow through Millipore filters (pore size 0.8 µm). The filters were weighed before and after the experiment, and total airborne dust concentration in the chamber was calculated. The filter samples were then extracted and the NRL allergen level measured by IgE ELISA‐inhibition assay. Furthermore, cut NRL gloves were extracted and analysed by the same method. Finally, levels of two major NRL allergens, Hev b1 and Hev b 6.02, were measured in three selected NRL glove brands.Results The NRL aeroallergen level in the chamber air ranged from < 0.9 to 2.9 allergen units (AU)/m3. The total airborne dust concentration in the chamber air remained low with all lots of gloves measured (range < 20 to 80 µg/m3). The NRL allergen level in cut glove extracts varied over 100‐fold (< 10 to 1050 AU/mL). Statistically significant correlation between aeroallergen concentration and airborne dust (r = 0.8, P = 0.0015) concentration was found. Moreover, significant correlation between aeroallergen levels and allergen content of cut glove pieces was observed (r = 0.59, P < 0.05). Hev b 1 levels varied from 9 to 25 ng/mL and the levels of Hev b 6.02 from 1720 to 14460 ng/mL in the glove extracts. In the extracts from airborne dust samples, Hev b 6.02 content varied from 61 to 183 ng/m3, whereas Hev b 1 levels were very low (0.4 to 3 ng/m3).Conclusion An elevated NRL aeroallergen level is rather related to a high level of airborne glove powder than to a high concentration of extractable NRL allergen in medical gloves.