bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low domestic exposure to house dust mite allergens (Der p 1) is associated with a reduced non‐specific bronchial hyper‐responsiveness in mite‐sensitized asthmatic subjects under optimal drug treatment
Authors: Maestrelli P. , Zanolla L. , Puccinelli P. , Pozzan M. , Fabbri L. M. 
Published: March 2003

Background Airway inflammation in asthma causes symptoms, airflow limitation and bronchial hyper‐responsiveness. The strategy of asthma management is to reduce airway inflammation by drug treatment and avoidance of triggers, including allergens.Objective We determined the effect of exposure to house dust mite (HDM) allergens on bronchial responsiveness in asthmatics sensitive to mites while under optimal drug treatment.Methods We studied 71 mild to moderate HDM‐sensitive asthmatics. Drug treatment sufficient to keep asthma under control was administered to each patient for 1 year. Subjects were divided into two groups, according to the amount of Der p 1 in their bedrooms measured after standard HDM reduction measures: low Der p 1 exposure (0.64 ± 0.5 µg/g dust) (Group 1, n = 34) and high Der p 1 exposure (12.5 ± 11.4 µg/g) (Group 2, n = 37). Bronchial responsiveness to methacholine (PD20FEV1) was determined at the beginning and end of the study.Results In Group 1, PD20FEV1 increased 2.15‐fold at the end of the study from 57 to 123 µg (P < 0.05), whereas in Group 2 no significant changes were observed. The subjects in Group 2 tended to increase the use of inhaled steroids and bronchodilators in the autumn months compared with subjects in Group 1, but the difference was not significant.Conclusion This long‐term study shows that exposure to lower levels of mite allergens in the bedroom is associated with a decrease of bronchial hyper‐responsiveness in sensitized asthmatic subjects under optimal drug treatment.
A simple diagnostic index for asthma
Authors: Bansal A. , Farnham J. M. , Crapo R. O. , Hughes D. C. , Jensen R. L. , Cannon‐Albright L. A. 
Published: March 2003

Background Asthma is becoming increasingly prevalent and a number of research groups are investigating its genetic and environmental basis.Objective To produce a brief screening tool suitable for determining phenotype in asthma research.Methods The scores from eight questions on symptoms and history were obtained from 678 adults and 244 children from high asthma‐incidence caucasian families. An independent physician diagnosis was also obtained with the use of a modified NHLBI‐CSGA questionnaire and pulmonary function test. Stepwise logistic regression was applied to determine which of the eight questions had greatest predictive value for asthma, and the quality of the resultant models was evaluated using an independent set of 643 adults and 239 children.Results For adults, the most parsimonious model used responses from three of the eight questions. It had sensitivity and specificity of 0.94 and 0.96, respectively. For children, responses to two questions gave a model with sensitivity and specificity of 0.97. For both age groups, negative predictive values were above 0.87. Positive predictive values were 0.58 and 0.78 for adults and children respectively. The latter emphasize the need for conformation, by physician, of ‘affected’ calls made by this initial screen.Conclusion The brief questionnaires described are potentially useful in a research setting, as a preliminary screening mechanism of low cost. Their use will reduce the numbers of subjects that must undergo detailed phenotyping.
Are children at high familial risk of developing allergy born into a low risk environment? The PIAMA Birth Cohort Study
Authors: Wijga A. , Smit H. A. , Brunekreef B. , Gerritsen J. , Kerkhof M. , Koopman L. P. , Neijens H. J. 
Published: March 2003

Background A family history of allergy, reflecting genetic risk factors, increases the risk of developing allergic diseases, but environmental factors, especially those present in early life, also contribute to the actual development of allergic phenomena.Objective To identify differences in lifestyle between allergic and non‐allergic parents, which may influence the prevalence of environmental risk factors in their homes.Methods Data were collected in a Dutch birth cohort study by postal questionnaire about 2 months before and 3 months after the birth of the child.Results Of the 3147 infants in the study 1910 (61%) had two non‐allergic parents, of 315 infants (10%) only the mother was allergic, of 787 infants (25%) only the father was allergic and 135 (4%) infants had two allergic parents. If both parents were allergic, 53% reported that allergy was taken into consideration when they furnished their home and significantly more of their homes were free of cats and free of cigarette smoke; adjusted odds ratio's for two allergic parents vs. two non‐allergic parents were 0.30 (confidence interval (CI) 0.17–0.50) for the presence of cats and 0.46 (CI 0.27–0.75) for smoking in the home. Parental allergy was also associated with having a smooth floor in the baby's bedroom and with postponement of the introduction of fruits and vegetables until the age of 26 weeks. The presence of dogs at home, the prevalence of mothers' smoking during pregnancy and the decision to breast feed were unrelated to parental allergy.Conclusion We conclude that studies on the relationship between allergy in parents and allergy in their offspring should always consider the home environment as a potential confounder. For allergy prevention our results imply that among allergic parents there is awareness and willingness to take measures that reduce exposure to indoor allergens.
Increased nitric oxide production in nasal epithelial cells from allergic patients – RT‐PCR analysis and direct imaging by a fluorescence indicator: DAF‐2 DA*
Authors: Takeno S. , Osada R. , Furukido K. , Chen J. H. , Yajin K. 
Published: March 2003

Background Nitric oxide (NO) is believed to participate in the regulation of airway clearance and non‐specific cellular immunity. Recent studies have suggested that airway epithelial cells of allergic and non‐allergic individuals may differ in their ability to produce this molecule.Objective The aim of this study was to detect the difference in NO production in human nasal epithelial cells between normal subjects and patients with perennial allergic rhinitis (AR), and to assess the relationship between the expression of nitric oxide synthase (NOS) isoforms and the severity of the disease.Methods Nasal epithelial cells were obtained from the inferior turbinate. The expression of mRNAs encoding constitutive endothelial NOS (eNOS) and inducible NOS (iNOS) was studied by reverse transcription‐polymerase chain reaction (RT‐PCR). Direct NO production in living cells was visualized and quantified by a fluorescent indicator, DAF‐2 DA.Results RT‐PCR analysis demonstrated that AR patients with a RAST score of 5 or 6 showed significant increases in the levels of iNOS mRNA and slight reductions in those of eNOS mRNA. Patients with a RAST score of 2–4 also revealed the same tendency however, the difference was not significant. DAF‐2 DA imaging demonstrated that epithelial cells, especially the ciliated cells, produced a larger amount of NO than non‐epithelial inflammatory cells. Preincubation with L‐NAME resulted in an approximate 40% decrease in both groups.Conclusion These results directly indicate that nasal epithelial cells of AR patients overall produce higher levels of NO through the concomitant expression of different NOS isoforms. Continuous NO production by the epithelial cells in normal subjects further support the hypothesis that NO derived from epithelium may play dual roles in the regulation of nasal airway clearance and in the host defense. In addition, the use of DAF‐2 DA provides a reliable method to visualize and quantify the direct NO production of living cells.
Evidence for an inflammatory pathophysiology in idiopathic rhinitis
Authors: Powe D. G. , Huskisson R. S. , Carney A. S. , Jenkins D. , Jones N. S. 
Published: March 2003

Background The pathophysiology of idiopathic rhinitis is unknown but the disease is classified as being non‐allergic on the basis of negative serum IgE radioallergosorbent assay (RAST) and skin prick tests. In contrast, allergic rhinitis has a Th2 type inflammatory pathology mediated by IgE and mast cells.Objective To test the null hypothesis that there would be no difference in the cellular infiltrate for key Th2‐associated inflammatory cells between allergic and idiopathic rhinitis.Methods We applied strict selection criteria in the recruitment of allergic and idiopathic rhinitis cases. In contrast to previous studies which used cytology or small biopsies, we studied all layers of the mucosa by using whole, full‐thickness nasal turbinate specimens with an average length of 2.5 cm. Immunohistochemistry and in situ hybridization techniques were used to compare the distribution and cell populations of mast cells, IgE positive (IgE+) cells, eosinophils and plasma cells in perennial allergic (n = 11) and idiopathic (n = 17) rhinitis, and control nasal mucosal tissue (n = 9).Results Mast cells and IgE+ cells were significantly increased within the epithelium of allergic and idiopathic mucosa compared to normal mucosa (P < 0.05). More IgE+ cells were present in the allergic group compared to the idiopathic group with the majority of IgE+ cells being mast cells. Both rhinitic groups showed increased eosinophilia localized to the superficial submucosa compared to normal mucosa (P < 0.05). More plasma cells were present in the allergic rhinitic tissue.Conclusion Idiopathic and allergic rhinitic mucosa show similarities in their inflammatory infiltrate suggesting that both groups share a highly localized Th2, IgE‐mediated cellular immunopathology.
Isolated airways from current smokers are hyper‐responsive to histamine
Authors: Schmidt D. T. , Jörres R. A. , Rühlmann E. , Rabe K. F. 
Published: March 2003

Epidemiological studies suggest that bronchial hyper‐responsiveness (BHR) and elevated levels of serum IgE are more frequently found in current smokers than in ex‐smokers.Since elevated serum IgE is associated with BHR under both in vivo and in vitro conditions, we aimed to assess whether smoking affects BHR independently from IgE.Lung resection material was obtained from 27 current smokers and 11 non‐smokers with low serum IgE (< 100 U/mL). Peripheral airways were cut into rings and incubated overnight in the presence (passively sensitized) or absence (non‐sensitized) of serum containing IgE levels above 250 U/mL. Isometric contractile responses to histamine were assessed in the organ bath.Compared with non‐smokers, isolated airways from smokers showed significantly increased responses to histamine (P < 0.05, anova). Passive sensitization enhanced responses in both groups by about the same amount (P < 0.05, both).In patients with low serum IgE current smoking is associated with increased bronchial responsiveness to histamine in vitro, which can be further enhanced by passive sensitization. These findings suggest that both smoking and serum IgE contribute to non‐specific airway hyper‐responsiveness.
Immunotherapy with a calcium phosphate‐adsorbed five‐grass‐pollen extract in seasonal rhinoconjunctivitis: a double‐blind, placebo‐controlled study
Authors: Leynadier F. , Banoun L. , Dollois B. , Terrier P. , Epstein M. , Guinnepain M.‐T. , Firon D. , Traube C. , Fadel R. , André C. 
Published: March 2003

Background Calcium phosphate‐adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants.Objectives A double‐blind, placebo‐controlled study was performed in order to confirm the safety and assess the efficacy of a standardized five‐grass‐pollen extract adsorbed onto calcium phosphate for specific immunotherapy (IT).Methods Twenty‐nine patients with seasonal rhinoconjunctivitis were randomized to receive either the active preparation (16 patients) or placebo (13 patients), in a 1‐year study. During the increasing dose phase, an extract ranging from 0.1 IR per ml to 50 IR per ml was administered at a rate of one subcutaneous injection per week until a maintenance dose was reached. The patients were assessed by symptom diary and rescue medications during seasonal exposure and specific nasal and skin reactivity before and after IT. Immunological parameters (specific IgE and IgG4 antibodies) were assessed before, during and after IT.Results The overall symptoms score (mean AUC) was not significantly different between the IT group and the placebo group during grass‐pollen exposure (49.6 vs. 56, respectively). The total medication score (mean AUC) was significantly lower in the IT group than in the placebo group (11 vs. 41, P < 0.01, Mann–Whitney U‐test). The cumulative symptom/medication score was significantly lower in the IT group than in the placebo group (64.5 vs. 102.3, P < 0.05, U‐test). A significant increase in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL before IT vs. 63.4 IR/mL after IT, P < 0.01, Wilcoxon), whereas no significant changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL after IT). IT induced a significant reduction in grass pollen cutaneous reactivity in the actively treated group (P < 0.001). A significant increase in serum‐specific IgG4 antibody response was observed in the IT group (3.1% before IT vs. 10.1% after IT, P < 0.001). Nine patients in the IT group developed moderate immediate systemic reactions vs. two patients in the placebo group.Conclusion Specific immunotherapy with calcium phosphate‐adsorbed standardized grass pollen extract was safe and effective for the treatment of patients with seasonal allergic rhinoconjunctivitis.
Identification of IgE and IgG binding epitopes on β‐ and κ‐casein in cow's milk allergic patients
Authors: Chatchatee P. , Järvinen K.‐M. , Bardina L. , Vila L. , Beyer K. , Sampson H. A. 
Published: March 2003

Background Cow's milk allergy (CMA) affects 2.5% of children aged less than 2 years of age. Although β‐ and κ‐casein are considered among the major allergens responsible for CMA, no data are available on their allergenic epitopes in humans.Objective The aim of the study was to identify IgE‐ and IgG‐binding epitopes on β‐ and κ‐casein and to determine whether the pattern of epitope recognition is associated with the natural history of CMA.Methods Overlapping decapeptides representing the entire length of β‐ and κ‐casein, respectively, were synthesized on a cellulose‐derivatized membrane. Sera from 15 milk‐allergic children, 4–18 years of age, with high levels of specific IgE antibodies to cow's milk were used to identify IgE‐ and IgG‐binding epitopes. In addition, IgE epitopes were screened with pooled or individual sera from younger patients aged less than 3 years and who had low levels of specific serum IgE, who are likely to outgrow CMA.Results Six major and three minor IgE‐binding epitopes, as well as eight major and one minor IgG binding regions, were identified on β‐casein. Eight major IgE‐binding epitopes, as well as two major and two minor IgG‐binding epitopes, were detected on κ‐casein. Three of the IgE binding regions on β‐casein and six on κ‐casein were recognized by the majority of patients in the older age group, but not by the younger patients.Conclusion Information regarding the immunodominant epitopes in β‐ and κ‐casein may be important for understanding the pathophysiology and natural history of CMA. Differences in epitope recognition may be useful in identifying children who will have persistent milk hypersensitivity.
Factors related to allergic sensitization to aeroallergens in a cross‐sectional study in adults: The Copenhagen Allergy Study
Authors: Linneberg A. , Nielsen N. H. , Madsen F. , Frølund L. , Dirksen A. , Jørgensen T. 
Published: March 2003

Background The factors underlying recent increases in the prevalence of respiratory allergy are largely unknown.Objective To assess the association between allergic sensitization and several lifestyle/environmental factors.Methods A cross‐sectional population‐based study of 15–69‐year‐olds in Copenhagen was carried out in 1990. The participation rate was 77.5% (1112/1435). Different lifestyle/environmental factors (explanatory variables) were defined based on questionnaire data. Dependent (outcome) variables were skin prick test (SPT) positivity or specific IgE positivity to common aeroallergens. Explanatory variables associated with outcome in univariate analysis (P < 0.25) were selected for multivariate analysis. Subsequently, a final model for each dependent variable was obtained by stepwise regression analysis (cut‐off for entry/removal of variables: P < 0.1).Results Male sex, young age, low number of siblings, a positive family history of hay fever and never smoking, were independently associated with both SPT positivity and specific IgE positivity. Furthermore, SPT positivity was positively associated with alcohol consumption (dose–response relationship only), and negatively associated with previous keeping of a dog in the household. The association between alcohol consumption and SPT positivity was mainly due to the consumption of wine and remained after adjustment for educational level. Specific IgE positivity was furthermore associated with body mass index with no apparent dose–response relationship.Conclusion Being male, young age, a positive family history of hayfever, low number of siblings and never smoking, were independently associated with allergic sensitization. In addition, the results indicated a possible relationship of alcohol consumption, body mass index and previous keeping of a dog in the household to allergic sensitization. There is a need for prospective studies of risk factors for respiratory allergy.
Heme oxygenase‐1 (HO‐1) protein induction in a mouse model of asthma
Authors: Kitada O. , Kodama T. , Kuribayashi K. , Ihaku D. , Fujita M. , Matsuyama T. , Sugita M. 
Published: March 2003

Background and objective Carbon monoxide (CO) is known to be present in measurable quantities in the exhalation of asthmatic patients. Corticosteroid treatment resulted in a decrease in exhaled CO levels in asthmatic patients, raising the possibility that an increase in exhaled CO concentration reflects inflammation of the asthmatic airway. Heme oxygenase‐1 (HO‐1) protein, also called HSP32, is the rate‐limiting enzyme in the catabolism of heme to biliverdin, free iron and CO. However, it is unknown whether an expression of HO‐1 within the lung tissue is related to allergic airway inflammation. We studied the expression of HO‐1 in lung tissue and bronchoalveolar lavage cells in a mouse model of asthma.Methods Ovalbumin (OVA)‐sensitized C57BL/6 mice were challenged with aerosolized OVA. HO‐1 positive cells were identified by immunostaining in lung tissue and bronchoalveolar lavage fluid (BALF) after the challenge.Results HO‐1 positive cell numbers increased in the subepithelium of the bronchi after OVA challenge. In cytospin preparations from BALF after OVA challenge, HO‐1 was localized to alveolar macrophages. Inside the macrophages, HO‐1 reactivity was expressed in the cytoplasm, and the perinuclear region in particular.Conclusion The expression of HO‐1 is increased within the lung tissue in allergic airway inflammation. Measurement of HO‐1 activity may be clinically useful in the management of asthma.
Novel dinucleotide repeat polymorphism in the first exon of the STAT‐6 gene is associated with allergic diseases
Authors: Tamura K. , Arakawa H. , Suzuki M. , Kobayashi Y. , Mochizuki H. , Kato M. , Tokuyama K. , Morikawa A. 
Published: March 2003

Background T helper‐type 2 cytokines, such as interleukin‐4 (IL‐4) and IL‐13, may play a central role in allergic diseases. The protein known as ‘signal transducers and activators of transcription 6’ (STAT‐6) is a key transcription factor involved in both IL‐4‐ and IL‐13‐mediated biological responses.Objective The objective of this study was to evaluate the possible role of the STAT‐6 gene in modulating atopy in the Japanese population.Methods We screened all 23 exons of the STAT‐6 gene from 10 subjects for mutations by direct polymerase chain reaction (PCR) sequencing. The STAT‐6 gene polymorphisms were genotyped by PCR fragment length polymorphism analysis and PCR‐SSCP analysis. The IL‐4 receptor Q576R polymorphism was also examined by PCR‐SSCP analysis.Results We found a novel dinucleotide repeat polymorphism in the first exon of the STAT‐6 gene. The genotypes were classified into four groups according to the number of GT repeats present, from 13 to 16. The frequency of the A1 allele (326 bp, containing 13 repeats of GT) was higher in children with allergic diseases (bronchial asthma, atopic dermatitis and/or food‐related anaphylaxis) than controls, although this was not statistically significant (P = 0.0158). In addition, a strong association between the A1 and A3 allele (containing 15 repeats of GT) heterozygote and allergic diseases was identified (P = 0.0002). However, the levels of IgE were not related to the GT repeat polymorphism in the allergic subjects. The GT repeat polymorphism was not associated with the polymorphism in the IL‐4 receptorachain gene (Q576R) and there was no association between the G2964A variant and allergic diseases.Conclusion This suggests that genetic variation in the STAT‐6 gene may be associated with predisposition to allergic diseases.
Lack of association between atopic eczema and the genetic variants of interleukin‐4 and the interleukin‐4 receptor α chain gene: heterogeneity of genetic backgrounds on immunoglobulin E production in atopic eczema patients
Authors: Tanaka K. , Sugiura H. , Uehara M. , Hashimoto Y. , Donnelly C. , Montgomery D. S. 
Published: March 2003

Background The genetic background of atopic eczema might be heterogeneous and there is a possibility that immunoglobulin (Ig)E responsiveness in patients with atopic eczema is controlled separately from the development of atopic eczema. Although both interleukin (IL)‐4 and the IL‐4 receptor α chain have an important role for IgE production and are therefore possible candidate genes for atopy, it has not been clarified whether these genes play any roles in atopic eczema patients who have normal IgE productivity.Objective We aimed to assess whether the polymorphisms of the IL‐4 gene and the IL‐4 receptor α chain gene play any roles in atopic eczema patients, particularly in patients who have normal IgE productivity.Method We determined the genotype with regard to polymorphisms in the genes for IL‐4 and the IL‐4 receptor α chain (− 589C/T of IL‐4; Ile50Val, Ala375Glu and Arg551Gln of IL‐4 receptor α chain) in patients with atopic eczema using the fluorogenic 5′ nuclease assay.Results IL‐4 and the IL‐4 receptor α chain genotypes were not significantly associated with either total patients with atopic eczema or atopic eczema patients who had normal IgE productivity. The distribution of genotypes of IL‐4–589C/T differed by the serum IgE levels in patients with atopic eczema.Conclusion These results suggest that the polymorphisms in the IL‐4 gene and the IL‐4 receptor α chain gene play no role in the development of atopic eczema in patients who have normal IgE productivity.