bluuebunny/crossref_metadata_2025_split huggingface dataset:
NAC Manchester Asthma and Allergy Study (NACMAAS): risk factors for asthma and allergic disorders in adults
Authors: Simpson B. M. , Custovic A. , Simpson A. , Hallam C. L. , Walsh D. , Marolia H. , Campbell J. , Woodcock A 
Published: March 2003

Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates.To investigate the risk factors for asthma and allergic diseases in a large number of adults who are the parents of children in the National Asthma Campaign Manchester Asthma and Allergy Study.All pregnant women and their partners attending ‘Booking’ antenatal clinics were invited to take part in the study. Questionnaire data were collected including the history of asthma and other atopic diseases, pet ownership and smoking habits, and skin prick tests were performed. The prevalence of atopy and the risk factors for asthma and allergic disorders were investigated in all subjects who completed the questionnaire and underwent skin testing. Statistical analysis was carried out using logistic regression. Initially, risk factors were assessed by univariate analysis to see how each potential explanatory variable affected the probability of having allergic disease. Variables were then tested in a forward stepwise multivariate analysis.In 5687 adult subjects there was a very high (48.2%) prevalence of atopy, and 9.7% of subjects had a diagnosis of asthma. In a multivariate regression analysis sensitization to dust mite, cat, dog and mixed grasses were all independently associated with asthma. The odds ratios for current asthma increased with the increasing number of positive skin tests (any two allergens – OR 4.3, 95% CI 3.3–5.5; any three allergens – OR 7.0 95% CI 5.3–9.3; all four allergens – OR 10.4, 95% CI 7.7–14; P < 0.00001). Dog ownership (OR 1.31, 95% CI 1.10–1.57; P = 0.003) and current smoking (OR 1.36, 95% CI 1.15–1.62; P = 0.0004) were significantly and directly associated with ’asthma ever’. Thirteen per cent of participants reported a history of eczema. In the multivariate analysis the strongest independent associate of eczema was sensitization to dog (OR 1.37, 95% CI 1.14–1.63, P < 0.0001). Apart from dog, the strength of the association between sensitization to common allergens and eczema appeared to be much lower than in the case of asthma. The prevalence of hay fever was high (20.6%), and in the multivariate analysis the association between sensitization to pollen and hay fever was extremely strong (OR 13.6, 95% CI 11.3–16.3; P < 0.0001).The results of the current study emphasize the importance of sensitization to indoor allergens in asthma. However, evidence of a possible direct role of allergen exposure in asthma causation remains unclear.
Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents
Authors: Hjern A. , Hedberg A. , Haglund B. , Rosén M. 
Published: March 2003

Background Earlier studies have given conflicting results regarding the effect of exposure to tobacco smoke on atopic sensibilization.Methods A cross‐sectional study of present and former smoking habits in relation to atopic disorders from data on 6909 young and middle‐aged adults (16–49 years) and their 4472 children (3–15 years) from the Swedish Survey of Living Conditions in 1996–97.Results The prevalence of allergic asthma and allergic rhino‐conjunctivitis decreased, in a dose–response manner (P = 0.03 and P = 0.004, respectively), with increasing exposure to tobacco smoke in the adult study population. This pattern was little changed when potential confounders (sex, age, education, domicile, country of birth) were entered into a multivariate analysis: the adjusted odds ratio (OR) for allergic rhino‐conjunctivitis was 0.5 (0.4–0.7) for those who smoked at least 20 cigarettes a day and OR 0.7 (0.6–0.9) for those smoking 10–19 cigarettes, compared with those who reported that they never had smoked Former smokers had a tendency for a slightly lower risk: OR 0.9 (0.8–1.0). In a multivariate analysis, children of mothers who smoked at least 15 cigarettes a day tended to have lower odds for suffering from allergic rhino‐conjunctivitis, allergic asthma, atopic eczema and food allergy, compared to children of mothers who had never smoked (ORs 0.6–0.7). Children of fathers who had smoked at least 15 cigarettes a day had a similar tendency (ORs 0.7–0.9).Conclusions This study demonstrates an association between current exposure to tobacco smoke and a low risk for atopic disorders in smokers themselves and a similar tendency in their children. There is a need for further studies with a prospective design to certify the causal direction of this association. Smoking habits and atopic disorder in parents should not be considered independent variables in epidemiological studies of the connection between exposure to tobacco smoke and atopy in children.
The importance of housing characteristics in determining Der p 1 levels in carpets in New Zealand homes
Authors: Wickens K. , Mason K. , Fitzharris P. , Siebers R. , Hearfield M. , Cunningham M. , Crane J. 
Published: March 2003

Background A previous study of homes in Wellington, New Zealand showed that having carpets on floors was the most important determinant of floor Der p 1 levels, but there was much unexplained variability between houses in carpet levels.Objective To determine to what extent housing characteristics might explain this variability in Der p 1 levels between houses.Methods We returned to a selection of houses with carpets and sampled living room dust from 1 square metre for 1 min and from the whole floor at 5 m2 per min. Der p 1 levels were estimated by double monoclonal antibody ELISA and are expressed as geometric mean µg/g and µg/m2 (95% confidence intervals). Questionnaires were used to collect information on housing characteristics.Results Der p 1 levels were significantly higher in the 1 square metre sample (40.0, 31.9–50.2 µg/g; 53.4, 41.4–68.9 µg/m2) than in the whole room (25.8, 21.3–31.1 µg/g; 5.3, 3.8–7.4 µg/m2). However, results from the different sampling methods were correlated (r = 0.51, P = 0.001 for µg/g and r = 0.58, P = 0.001 for µg/m2). After controlling for possible confounders, houses with insulation or a room or garage below the living room had approximately half the Der p 1 concentration (P = 0.05 for both samples) and the amount of Der p 1 per m2 (P = 0.004 for the 1 square meter sample, P = 0.06 for the whole room sample) than houses without these features. Having more than two children was associated with higher levels of Der p 1 in 1 square meter, significant (P = 0.05) for µg/m2. Carpet underlay less than 8 mm thick was associated with an almost 3‐fold increase in ug/m2 Der p 1 (P = 0.03) and a 1.6‐fold increase in ug/g Der p 1 (P = 0.08) in the whole room sample, when compared with thicker carpet underlays.Conclusion The presence of insulation is the single most important housing characteristic explaining the between‐house variability in Der p 1 levels on carpeted living room floors.
Increased expression of cytosolic phospholipase A2, 5‐lipoxygenase and 5‐lipoxygenase‐activating protein in rat peritoneal macrophages during ovalbumin‐induced sensitization
Authors: Escoubet‐Lozach L. , M'Rini C. , Rey A. , Béraud M. , Lepert J.‐C. , Courtade M. , Frisach M.‐F. , Pipy B. 
Published: March 2003

Background Macrophages are involved in immediate hypersensitivity reactions by their ability to release leukotrienes involved in the symptomatology of allergy. To date it is unknown whether this ability to secrete leukotrienes has been favoured by modifications, occurring during the sensitization phase, of the enzymes involved in leukotriene metabolism.Objective We used ovalbumin‐sensitized rats to study the expression of cytosolic phospholipase A2 (cPLA2), 5‐lipoxygenase (5‐LO) and 5‐lipoxygenase‐activating protein (FLAP) in peritoneal macrophages during active sensitization. We compared basal and challenged (PMA, A23187 and allergen) arachidonic acid (AA) metabolism of macrophages from control (cPM) and sensitized (sPM) rats. Then we tested, in cultured cPM, whether IL‐4, the predominant cytokine of sensitization process, could reproduce the enzymatic modifications occurring in macrophages during sensitization.Methods cPLA2, 5‐LO and FLAP expression was assessed by Western blotting. The arachidonic acid (AA) metabolism study was performed after incorporation of tritiated AA in macrophages and analysis of secreted tritiated eicosanoids.Results Ovalbumin‐sensitization of rats increased cPLA2, 5‐LO and FLAP expression in peritoneal macrophages. These increased expressions were not paralleled by modifications of basal and PMA‐ or A23187‐stimulated AA metabolism of sPM. However, when macrophages encountered the specific allergen for a second time, sPM secreted higher levels of leukotrienes than cPM. IL‐4 induced FLAP expression in cPM but had no effect on cPLA2 and 5‐LO expression.Conclusion Active sensitization of rats induces an increase, in peritoneal macrophages, of the enzymes involved in leukotriene metabolism. The increased leukotriene secretion of sPM in response to ovalbumin challenge may be favoured by this increased expression of cPLA2, 5‐LO and FLAP that, however, is not able to lead to modifications of macrophage AA metabolism in any circumstance. Our results also suggest that IL‐4 is not the major element originating the enzymatic modification induced by sensitization in peritoneal macrophages.
IL‐6 attenuates apoptosis, while neither IL‐6 nor IL‐10 affect the numbers or protease phenotype of fetal liver‐derived human mast cells
Authors: Kambe M. , Kambe N. , Oskeritzian C. A. , Schechter N. , Schwartz L. B. 
Published: March 2003

Background The combination of recombinant human stem cell factor (rhSCF), rh interleukin (IL)‐6 and rhIL‐10 was reported to be optimal for mast cell development from cord blood progenitors and to induce chymase expression in all such mast cells earlier in their development than tryptase.Objective The effects of rhIL‐6 and rhIL‐10 in various combinations on the rhSCF‐dependent development of human mast cells from fetal liver progenitors were examined in serum‐free media.Methods Dispersed fetal liver cells were cultured in serum‐free AIM‐V medium with rhSCF alone, or with combinations of rhIL‐6 and rhIL‐10. Tryptase and chymase expression, surface Kit expression, metachromasia with toluidine blue and apoptosis were measured.Results Neither rhIL‐6 nor rhIL‐10 nor the two interleukins together, when included from day 0 of culture, affected the number or protease phenotype of mast cells at 1 or 3 weeks. Expression of tryptase paralleled the appearance of metachromasia and surface Kit, both of which preceded chymase expression, regardless whether a rabbit polyclonal or mouse monoclonal anti‐chymase antibody preparation was used. On the other hand, rhIL‐6 markedly attenuated baseline levels of apoptosis in the presence of rhSCF as well as apoptosis occurring after withdrawal of rhSCF, whereas rhIL‐10 had no effect.Conclusion RhIL‐6 protected fetal liver‐derived mast cells from apoptosis, particularly after withdrawal of rhSCF, but neither rhIL‐6 nor rhIL‐10 nor the combination of these interleukins affected the numbers or protease phenotype of these mast cells.
An annexin 1 (ANXA1)‐derived peptide inhibits prototype antigen‐driven human T cell Th1 and Th2 responses in vitro
Authors: Kamal A. M. , Smith S. F. , De Silva Wijayasinghe M. , Solito E. , Corrigan C. J. 
Published: March 2003

Background Annexin‐1 (ANXA1, lipocortin 1) is a pleiotrophic protein produced by many cell types including peripheral blood leucocytes. Although it has been shown to inhibit ‘macroscopic’ inflammatory processes in animal models, its direct effects on antigen‐activated human T cells have not been studied.Objective To test the hypothesis that ANXA1‐derived peptides inhibit antigen‐driven prototype Th1 and Th2‐type human T cell responses of clinical relevance and lectin‐driven responses in vitro.Methods Peripheral blood mononuclear cells (PBMC) were isolated from 14 atopic subjects sensitized to house dust mite allergen (Dermatophagoides pteronyssinus, Der p) and purified protein derivative (PPD) of Mycobacterium tuberculosis. PBMC (1 × 106/mL) were cultured with phytohaemagglutinin (PHA; 5 µg/mL; 4 days), Der p (25 µg/mL; 6 days), PPD (10 µg/mL, 6 days) or medium control. Two ANXA1‐derived peptides, Ac2–26 and AF‐2 (5–500 µm), were assessed for possible inhibition of PHA‐and antigen‐induced T cell proliferation (measured by 3H‐thymidine uptake), while Ac2–26 was assessed for inhibition of Der p‐induced interleukin (IL)−5 release and PPD‐induced interferon‐γ (IFN‐γ) release (measured by ELISA). Comparison was made with dexamethasone as an established inhibitory control. Endogenous production by PBMC of cell surface‐associated and intracellular ANXA1 in response to PHA, Der p and PPD in the presence and absence of dexamethasone was measured by specific ELISA.Results Both PHA‐ and antigen‐induced T cellular proliferation were inhibited by dexamethasone. Although neither ANXA1‐derived peptide significantly altered PHA‐induced proliferation, both effected concentration‐dependent reductions in antigen‐induced proliferation, Ac2–26 being the more potent. Peptides of identical amino acid composition to Ac2–26 and AF‐2, but of random sequence, were ineffective at equivalent concentrations. In addition, Ac2–26 and dexamethasone inhibited Der p‐induced IL‐5 release and PPD‐induced IFN‐γ release in a concentration‐dependent fashion. Endogenous ANXA1 was detectable in PBMC, but at concentrations approximately 104‐fold lower, in molar terms, than the effective concentrations of the exogenously added, ANXA1‐derived inhibitory peptides. Endogenous production was not significantly altered by any of the T cell stimuli employed in this study, in the presence or absence of dexamethasone.Conclusion In prototype Th1 and Th2‐type human T cell responses, ANXA1‐derived peptides can inhibit antigen‐driven cellular proliferation and cytokine production.
Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils
Authors: Mita H. , Hasegawa M. , Saito H. , Akiyama K. 
Published: March 2003

Background Cysteinyl leukotrienes (CysLTs) have been implicated as important contributors in the pathophysiology of asthma and their biological effects are mediated by at least two distinct G‐protein‐coupled receptors. cDNA sequences of cysteinyl leukotriene receptor 1 (CysLTR1) and cysteinyl leukotriene receptor 2 (CysLTR2) have recently been elucidated.Objectives Our aim is to explore gene expression and the comparative expression of CysLTR1 mRNA and CysLTR2 mRNA in human peripheral blood leucocytes.Methods Gene expression of CysLTR1 and CysLTR2 mRNAs in human peripheral blood eosinophils, neutrophils, monocytes and T lymphocytes has been measured by competitive reverse transcription‐polymerase chain reactions using RNA or DNA competitors.Results (a) When cellular levels of CysLTR1 mRNA were normalized to those of G3PDH mRNA, the relative concentration of CysLTR1 mRNA in eosinophils (43.8 ± 37.2, n = 29) was significantly higher than that in neutrophils (18.7 ± 23.3, n = 11), monocytes (0.93 ± 1.1, n = 10) and T lymphocytes (3.4 ± 2.4, n = 11). (b) When measured using each DNA competitor, mRNAs for both types of CysLTR coexisted in each type of leucocyte. The ratio of CysLTR1 mRNA to CysLTR2 mRNA was significantly lower in eosinophils (0.65 ± 0.42, n = 12) than in neutrophils (6.9 ± 4.9, n = 12), monocytes (1.8 ± 0.9, n = 10) and T lymphocytes (4.5 ± 5.7, n = 10). (c) Human umbilical vein endothelial cells expressed CysLTR2 mRNA, but not CysLTR1 mRNA.Conclusion These studies reveal that CysLTR1 mRNA and, in particular, CysLTR2 mRNA are abundantly expressed at high levels in eosinophils, raising the possibility that CysLTR2 may have an important physiological role in eosinophils and a CysLTR2 antagonist may be a good target for preventing signal transduction by CysLTs in eosinophils.
Exposure to wheat allergen and fungal α‐amylase in the homes of bakers
Authors: Vissers M. , Doekes G. , Heederik D. 
Published: March 2003

Background Few data are available on exposure to occupational allergens in dwellings occupied by inhabitants with occupational exposure to allergens. In small bakeries working and living often takes place in the same building. It is possible that allergens from the bakery can be transported into the homes of the bakers, via the clothes or shoes of the baker.Objective The aims of this study were to investigate exposure to occupational allergens, wheat and fungal α‐amylase in the homes of bakers, and evaluate potential determinants of exposure. Sensitization in family members to occupational allergens was investigated in a small preliminary survey.Methods Floor dust samples were collected in the homes of 34 bakers. Levels of wheat and fungal α‐amylase allergens were determined in an extract of the dust samples. Blood samples were collected from bakers and their family members to determine the prevalence of sensitization to occupational allergens.Results The concentration of wheat and α‐amylase allergens ranged from 38.9 to 172.4 µgeq/m2 (GM), to 10.5–76.7 ngeq/m2 (GM). Higher levels of dust and allergens were measured when the house could be reached directly through the bakery, and in houses with textile floor covers. Higher concentrations were also measured when bakers brought their work clothes and shoes into the house and when textiles from the bakery were laundered at home. Some family members appeared to be sensitized to wheat flour and α‐amylase, but it cannot be excluded that they became sensitized because of their incidental presence in the bakery.Conclusions Occupational allergens can be found in house dust from the homes of bakers and levels are associated with hygienic behaviour and distance to the bakery.
The Western blot is a highly sensitive and efficient technique in diagnosing allergy to wasp venom
Authors: Zollner T. M. , Spengler K. , Podda M. , Ergezinger K. , Kaufmann R. , Boehncke W.‐H. 
Published: March 2003

Background Diagnosis of allergy to wasp venom and decision to perform immunotherapy are based on the patient's history, along with skin and in vitro tests.Objective Given the high prevalence of specific IgE also in non‐allergic individuals, we evaluated the sensitivity and specificity of Western blots as a possible alternative to serum analyses of venom‐specific IgE.Methods Skin prick and/or intracutaneous tests were performed in 30 patients with allergy to wasp venom (generalized reaction following sting) along with serum analysis of venom‐specific IgE (AlaSTAT microplate) and Western blots. Western blots were subsequently scanned and evaluated qualitatively and semiquantitatively by means of densitometry. Bands were scored ‘positive’ in cases of signal intensities beyond the mean plus 3 standard deviations of control sera. Twenty newborns (age 2–7 days) and 30 adults without systemic or increased local reactions to hymenoptera stings served as controls.Results Western blot sensitivity reached 100% in the samples studied and was thus superior to the sensitivities of serum analysis of venom‐specific IgE using AlaSTAT microplate assay (90%) and skin tests (87%). The sensitivity of detection of a phospholipase A1 and antigen 5‐specific band was higher compared with a hyaluronidase‐specific band (97%, 97% and 86%, respectively). Twenty‐four out of twenty‐nine (83%) patients exhibited specific IgE antibodies against at least three distinct allergens. With regard to the specificities, skin tests as well as AlaSTAT microplate assays were comparable (90% and 93%, respectively), whereas the specificity of the Western blots was 70% if the appearance of any single band was regarded as a positive result. However, when analysing the appearance of a specific band for antigen 5 or hyaluronidase the specificity and overall diagnostic value increased markedly, making it the most efficient test (specificity 97% and 100%, efficiency 96.8% and 93.2%, respectively).Conclusion As allergy to wasp venom is a severe and potentially life threatening disease, false‐negative test results need to be minimized. Therefore, the superiority of the Western blot with regard to sensitivity, specificity and overall efficiency makes this technique a valuable tool for its diagnosis.
Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy
Authors: Vila L. , Beyer K. , Järvinen K.‐M. , Chatchatee P. , Bardina L. , Sampson H. A. 
Published: March 2003

Background Cow's milk (CM) is one of the leading causes of food allergy in children. However, approximately 85% of milk‐allergic children become clinically tolerant to CM within the first 3 years of life. The mechanisms involved in the achievement of tolerance remain unknown.Objective To study whether IgE antibodies from children with persistent cow's milk allergy (CMA) differ from children who become clinically tolerant in their ability to recognize linear and conformational epitopes of αs1‐ and β‐casein.Methods Thirty‐six milk‐allergic children were included in the study: 11 of the children became clinically tolerant, and 25 had persistent CMA. Blood was obtained from all patients during the time they showed clinical reactions to milk challenge. Six non‐milk‐allergic children served as controls. Specific IgE antibodies against linear (denatured) as well as conformational (native) milk proteins were determined by probing dot‐blots with patients' sera. In addition, selected decapeptides from αs1‐ and β‐casein, previously found to be suggestive of persistent CMA, were synthesized on a cellulose‐derivatized membrane and probed with individual sera from 10 patients who outgrew CMA and from 10 patients with persistent CMA.Results Analysis of immunodot‐blots showed that, in comparison to tolerant patients, milk‐allergic children with persistent symptoms had a significantly higher ratio of specific IgE antibodies to linearized than to native α‐ and β‐casein (P < 0.005 and P < 0.02, respectively). Comparing the selected decapeptides, six of the 10 patients with persistent allergy recognized the peptide corresponding to amino acids 69–78 from αs1‐casein while none of the patients who outgrew CMA had IgE binding to this epitope.Conclusion Patients with persistent milk allergy possess higher detectable levels of IgE antibodies to linear epitopes from αs1‐ and β‐casein than children who have achieved tolerance. Specific IgE binding to particular linear epitopes in αs1‐casein may be a predictive factor for persistence of CMA.