bluuebunny/crossref_metadata_2025 huggingface dataset:
Disodium octaborate tetrahydrate (DOT) application and vacuum cleaning, a combined strategy to control house dust mites
Authors: Codina R. , Lockey R. F. , Diwadkar R. , Mobly L. L. , Godfrey S.
Published: December 2004

Background: The effectiveness of acaricides in homes is controversial.

Objective: To determine whether disodium octaborate tetrahydrate (DOT) combined with vacuuming lowers dust mite numbers and their allergens in carpets and sofas.

Methods: A 6‐month study was carried out with 93 homes, which were randomized into three groups: (i) active, received DOT; (ii) placebo, received water; and (iii) control, received no application. Active and placebo homes were vacuumed weekly. Dust was collected from carpets and sofas at the start of the study and every 2 months thereafter and quantified for live, total mites, and mite allergen levels.

Results: At 2 months, live mite numbers in active carpets were 3 ± 1, in placebo carpets 129 ± 48, and in control carpets 177 ± 39 mites/g. The corresponding numbers in sofas were 3 ± 2, 81 ± 31, and 134 ± 45 mites/g, respectively (P < 0.001 active vs placebo and vs. control). Live mites in carpets and sofas remained lower in the active group at 6 months (P < 0.001). Total mites in active carpets decreased from 555 ± 69 at baseline to 223 ± 32 mites/g at 6 months (P < 0.001) and mite allergen levels from 1.36 ± 0.13 to 0.85 ± 0.16 μg/g (P < 0.001). Total mites in active sofas remained unchanged, but mite allergen levels decreased from 1.48 ± 0.25 at baseline to 0.7 ± 0.15 μg/g at month 6 (P < 0.05).

Conclusion: DOT kills mites in carpets and sofas, and, combined with vacuuming, effectively reduces total mites in carpets and mite allergen levels in carpets and sofas.
Allergy to millet: another risk for atopic bird keepers
Authors: Bohle B. , Hirt W. , Nachbargauer P. , Ebner H. , Ebner C.
Published: December 2004

Background: Millet has been reported to induce not very frequent but severe anaphylactic reactions following ingestion. Seven individuals who all kept cage birds experienced allergic reactions after ingestion of millet‐containing food.

Methods: We investigated the immunoglobulin E (IgE)‐reactivity of these individuals to millet employing immunoblotting, RAST and skin prick tests. As the sensitization possibly occurred via the inhalant route we investigated millet‐specific IgE levels of 16 additional sera from bird keepers with proven atopy, in retrospect.

Results: All patients who had experienced reactions after ingestion of millet displayed millet‐specific IgE. Sixty‐three percent of the atopic bird keepers possessed millet‐specific IgE. By means of immunoblotting three major allergens in millet extract were detected.

Conclusions: Our results indicate that millet plays an important role as inhalant allergen for atopic bird keepers. A sensitization to millet may subsequently also elicit food allergy.
Association between infections and signs and symptoms of ‘atopic’ hypersensitivity – results of a cross‐sectional survey among first‐year university students in Germany and Spain
Authors: Uter W. , Stock C. , Pfahlberg A. , Guillén‐Grima F. , Aguinaga‐Ontoso I. , Brun‐Sandiumenge C. , Krämer A.
Published: December 2004

Background: This study assessed the hypothesis that a decreased exposure to childhood infectious diseases is associated with signs and symptoms of ‘atopic’ hypersensitivity diseases.

Methods: A cross‐sectional survey was performed among 1368 Spanish and German first‐year university students between 1997 and 1999, including self‐administered questionnaire data and serological tests.

Results: No association between the disease outcomes and hepatitis A, Helicobacter pylori infection and herpes simplex infection was observed in logistic regression analyses, adjusting for potential confounders (centre, sex, smoking, parental education). In contrast, vaccination against hepatitis B was associated with a decreased risk for the outcomes allergic rhinitis (OR 0.63, 95% CI: 0.42–0.95) and total serum IgE above 100 U/ml (OR 0.56, 95% CI: 0.39–0.81). Conversely, seropositivity to HBc antigen was significantly associated with high total serum IgE (OR 2.04, 95% CI: 1.34–3.06).

Conclusions: Our study partly confirmed and partly contradicted previous evidence and hypotheses, respectively, concerning the role of the infections considered. The observation of a decreased risk in persons vaccinated against hepatitis B warrants further, prospective investigation.
Comparative allergenicity studies of native and recombinant Blomia tropicalis Paramyosin  (Blo t 11)
Authors: Ramos J. D. A. , Teo A. S. M. , Ou K. L. , Tsai L. C. , Lee B. W. , Cheong N. , Chua K. Y.
Published: December 2004

Background:
The complementary DNA (cDNA) encoding for Blo t 11, a 102 kD allergen from Blomia tropicalis (Bt) was isolated, expressed and characterized previously. This study aimed to isolate the native Blo t 11 allergen and compare its allergenicity with the recombinant forms.

Methods: Native Blo t 11 (nBlo t 11) was isolated from crude Bt extract by immuno‐affinity chromatography, analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and Western blot, and verified by MALDI‐TOF MS. Recombinant full‐length Blo t 11 (rFL‐Blo t 11) and its immunodominant peptide (fD) were expressed as glutathione S‐transferase (GST)‐fusion proteins in Escherichia coli. Immunoglobulin E (IgE) reactivity of the Blo t 11 allergens were determined by enzyme‐linked immunosorbent assay (ELISA) and skin prick test. The inhibition capacity of the nBlo t 11 against fD and vice versa was determined by absorption studies.

Results: Affinity purified nBlo t 11 was susceptible to degradation with the major degraded product resolved at ∼66 kD. The nBlo t 11 was confirmed by immunoblot analysis and MALDI‐TOF MS that generated 13 peptides with complete identity to the deduced amino acid sequence of Blo t 11. Comparative in vitro and in vivo allergenicity tests and the cross inhibition studies between the native and recombinant Blo t 11 showed that recombinant fD, but not the rFL‐Blo t 11, has comparable IgE reactivity with the native counterpart.

Conclusions: This comparative study confirmed that the recombinant peptide fD contains the main immunodominant region of Blo t 11. This recombinant peptide, instead of the full‐length protein, is a good candidate for diagnostic and therapeutics development for mite allergy.
Enhanced soluble interleukin‐5 receptor alpha expression in nasal polyposis
Authors: Gevaert P. , Bachert C. , Holtappels G. , Novo C. P. , Van der Heyden J. , Fransen L. , Depraetere S. , Walter H. , van Cauwenberge P. , Tavernier J.
Published: December 2004

Background: Alternative splicing of the interleukin‐5 receptor alpha (IL‐5Rα)‐subunit leads to the generation of a signalling, membrane‐anchored (TM) isoform, or a secreted [soluble (SOL)], antagonistic variant. Given the key role of IL‐5 in eosinophil function, we investigated SOL IL‐5Rα expression pattern in an eosinophil‐associated disease such as nasal polyposis (NP).

Methods: An SOL IL‐5Rα enzyme‐linked immunosorbent assay and quantitative real‐time polymerase chain reaction (PCR) were established and applied in serum, nasal secretion and nasal tissue of controls (n = 12), and NP patients (n = 42) with or without asthma.

Results: Analysis of serum, nasal secretion, and nasal tissue samples revealed that SOL IL‐5Rα protein concentrations were significantly increased in NP vs control tissue. Within the NP group, there was a significant up‐regulation of SOL IL‐5Rα in patients with systemic airway disease. These findings were confirmed at the mRNA level, using an optimized real‐time reverse‐transcriptase PCR procedure.

Conclusions: This report demonstrates SOL IL‐5Rα transcript and protein up‐regulation in NP. Soluble IL‐5Rα differentiates nasal polyps with or without concomitant asthma. As SOL IL‐5Rα is strongly up‐regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti‐IL‐5.
In utero exposure to lead and cord blood total IgE. Is there a connection?
Authors: Annesi‐Maesano I. , Pollitt R. , King G. , Bousquet J. , Hellier G. , Sahuquillo J. , Huel G.
Published: December 2004

Background: Lead exposure and total immunoglobulin E (IgE) have been shown to be positively related in animals and humans even at lead levels below those recognized as toxic. In the last decades, exposure to lead has become more frequent in urban areas of industrialized as well as of developing countries where IgE‐mediated allergy prevalence has also increased.

Methods: We examined for the first time the relationship between in utero exposure to lead and cord blood total IgE in two samples of 137 and 237 mother–newborn pairs, respectively, recruited in Paris.

Results: Cord blood IgE was positively related to hair lead level at birth, providing an integrated measure of long‐term exposure in utero, in each cohort (Spearman's coefficient r = 0.32, P < 0.001 and r = 0.19, P < 0.01, respectively) and in the combined cohort (r = 0.21; P < 0.01). The relationship appeared to be more pronounced in newborns of nonallergic mothers (r = 0.24; P < 0.01) than in those of allergic mothers (r = 0.12). This could be due to the fact that familial history of allergy, the strongest determinant of IgE development, may overshadow the influence of lead on IgE in the offspring.

Conclusions: Our findings suggest a possible intervention of environmental exposure besides genetic factors in early life development of IgE production. Further studies are needed to confirm the finding.
The epidemiology of atopic dermatitis in Italian schoolchildren
Authors: Girolomoni G. , Abeni D. , Masini C. , Sera F. , Ayala F. , Belloni‐Fortina A. , Bonifazi E. , Fabbri P. , Gelmetti C. , Monfrecola G. , Peserico A. , Seidenari S. , Giannetti A.
Published: December 2004

Background: Atopic dermatitis (AD) is common in children in industrialized countries. Only one large population study on its prevalence has been conducted in Italy, based on self‐report questionnaire. The present study was designed to estimate the prevalence of AD in schoolchildren in Italy by dermatologists’ assessment and by UK Working Party criteria, and to investigate associated symptoms and factors.

Methods: Cross‐sectional survey on a random sample of 9‐year‐old schoolchildren from seven Italian cities. Children were examined by experienced dermatologists. Parents and teachers answered standardized questionnaires.

Results: Of the 1369 children examined, 88 had a diagnosis of AD, with an estimated point prevalence of 5.8% (95% CI 4.5–7.1) in the reference population. The reported lifetime prevalence was 15.2 (95% CI 12.2–18.2) for AD, 11.9% (95% CI 9.0–14.8) for asthma, and 17.6% (95% CI 14.6–20.7) for rhino‐conjunctivitis. The strongest associated factor was the presence of AD in at least one parent. No association of AD with maternal smoking during pregnancy, birth weight, maternal age at the time of the child birth and breast‐feeding was observed. The environmental characteristics of the house and the school did not correlate with the prevalence of AD. Episodes of lower respiratory tract infections were associated with asthma, and to a lower extent also with AD and rhinitis.

Conclusions: The prevalence of doctor‐diagnosed AD in Italian schoolchildren is comparable to those reported for other developed countries. Family history of atopy was the single most important associated factor, while the complex interplay of environmental factors remains to be elucidated.
Allergen‐reactive antibodies are found in nasal fluids from patients with birch pollen‐induced intermittent allergic rhinitis, but not in healthy controls
Authors: Benson M. , Reinholdt J. , Cardell L. O.
Published: December 2004

Background: Increased levels of allergen‐reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen‐induced IAR.

Methods: Nasal fluids were obtained from 23 patients with birch pollen‐induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1‐reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively.

Results: Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S‐IgA) and IgG. Most of the IgA, including Bet v 1‐reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1‐reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1‐reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2‐reactive IgE were nondetectable in most samples.

Conclusions: Nasal fluid Bet v 1‐reactive IgA and IgG were found in all patients with birch pollen‐induced IAR, but not in controls. However, no significant differences were found between patients during and after the birch pollen season.
Distinct delayed T‐cell response to β‐methasone and penicillin‐G in the same patient
Authors: Scala E. , Giani M. , Pastore S. , Pallotta S. , Guerra E. C. , Pirrotta L. , Locanto M. L. , Frezzolini A. , De Pità O. , Puddu P.
Published: December 2004

Background: Multiple drug allergy syndrome is a clinical condition characterized by reactions against more than one different class of, both pharmacologically and structurally, unrelated drugs. Scanty data are available to date about a multiple drug delayed hypersensitivity syndrome. Our aim was to report the case of a delayed reaction to both β‐methasone (β‐MT) and penicillin‐G (pen‐G) occurring in the same patient, and analyse β‐MT‐ and pen‐G‐specific T‐cell Lines (TCLs) with regard to their specificity, phenotype and cytokine profile.

Methods: We generated two drug‐specific TCLs from biopsies at the site of positive intradermal reactions, and analysed their immunophenotype, T‐cell receptor Vβ (TCR‐Vβ) domains expression and cytokine profile.

Results: We demonstrated the specificity of the T cells isolated from positive intradermal test reactions to pen‐G and β‐MT through the strict dose‐dependent proliferation in response to drug‐pulsed autologous antigen presenting cells. Fluorescence activated cell sorter (FACS) analysis revealed a predominance of CD4+ cells in the inflammatory cell infiltrate of intradermal test with β‐MT, while a predominance of CD8+ T cells in the site of delayed reaction to pen‐G was found. The drug specific CD4+ and CD8+ T cells were heterogeneous, with regard to TCR‐Vβ usage. CD8+ pen‐G‐TCL displayed a preferential T helper 2 (Th2) profile, while a substantially heterogeneous pattern of cytokine production characterized specific β‐MT TCL.

Conclusion: The study describes the coexistence in the same patient of a delayed hypersensitivity to both penicillin G and β‐MT, driven, respectively, by pen‐G‐specificTh2‐skewed CD8+ and β‐MT specificTh0 CD4+ T cells. This case further support the existence of a multiple drug allergy syndrome also for delayed hypersensitivity.
The IL1A genotype is associated with nasal polyposis in asthmatic adults
Authors: Karjalainen J. , Joki‐Erkkilä V‐P. , Hulkkonen J. , Pessi T. , Nieminen M. M. , Aromaa A. , Klaukka T. , Hurme M.
Published: December 2004

Background: Nasal polyposis (NP) is a chronic inflammatory disease often found coexisting with asthma. As this disorder tends to cluster in families, a genetic predisposition has been suggested. Interleukin‐1 (IL‐1) has been proposed to play a role in the pathogenesis of NP.

Methods: We analysed the single G‐to‐T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL‐1α (IL1A) and the C‐to‐T base exchange polymorphism at −511 of the gene encoding IL‐1β (IL1B) in a population‐based sample of adult asthma patients (n = 245). The data were assessed for correlation with data on history of NP and other phenotype‐related characteristics.

Results: The prevalence of NP in our study group was 14.3%. The distribution of the IL1A genotype differed significantly between asthmatics with and without NP (P = 0.005). The risk of NP was markedly increased in allele G homozygous subjects (OR = 2.73; 95%CI = 1.40–5.32). In the case of IL1B we found no significant associations. Asthmatics with NP had more symptoms than others, but lung function and blood eosinophil counts were similar.

Conclusions: Our study demonstrates an association of IL1A with NP inasthmatic patients and addresses the role of IL‐1α as an inflammatory modulator in the pathogenesis of this disease.
Severe drug rashes in three siblings simultaneously
Authors: Johnson‐Reagan L. , Bahna S. L.
Published: December 2004

Background: Adverse reactions to drugs commonly occur sporadically. Certain individuals seem to have an increased susceptibility to develop reactions to multiple drugs. Genetic predisposition has not been elucidated. Our objective was to describe a case of three siblings who developed severe rashes to the same drug simultaneously.

Methods: Review of the patients’ medical records for information on the clinical course, and comparing their serum immunoglobulin (Ig) levels initially and during follow‐up.

Results: The rashes were compatible with erythema multiforme and Stevens‐Johnson syndrome and developed in the three siblings within 1–3 weeks after the intake of thiabendazole. Follow‐up of serum Ig levels did not show any particular pattern, except for an initial mild to moderate elevation in IgG, IgA and IgM.

Conclusions: The occurrence of such severe cutaneous drug reaction in the three siblings to the same drug suggests a genetic predisposition to adverse drug reactions.
Specific sensitization to the common housefly (Musca domestica) not related to insect panallergy
Authors: Focke M. , Hemmer W. , Wöhrl S. , Götz M. , Jarisch R. , Kofler H.
Published: December 2004

Background: Allergy to houseflies is rare. We report a case of respiratory allergy from occupational exposure to houseflies in a farmer.

Case report: A 30 year‐old female farmer with a long‐standing history of grass pollen allergy observed for 2 years rhino‐conjunctivitis and mild asthma when entering livestock stables and barns. Allergy retesting revealed sensitization to various pollens but not to animal danders. Houseflies (Musca domestica) occurring on the farm in great quantity were suspected by the farmer herself as the causative agent.

Results: Skin prick testing with housefly was positive in the patient and negative in four controls. Experimental radioallergosorbant test was class 3 positive. Sensitization to house dust mite, storage mites and cockroach was not detectable. Western blots with housefly extracts revealed immunoglobulin E (IgE)‐binding to bands of 70, 50, and approximately 16 kDa. Tropomyosin in the housefly extract (35 kDa) was recognized by a tropomyosin reference serum but not by the patient. In enzyme‐linked immunosorbent assay (ELISA) inhibition assays using housefly as the solid phase, IgE‐binding of the patient was inhibited by 75% by M. domestica and by 44% by the closely related lesser housefly (Fannia canicularis), but not by extracts from blowfly (Lucilia spp.), fruit fly (Drosophila spp.), horsefly (Haematopota pluvialis) and mosquito (Culex pipiens). The IgE‐binding of the tropomyosin control serum was inhibited by 60–80% by all species.

Conclusions: In accordance with previous reports, this case demonstrates that respiratory sensitization to insects may be highly specific. According to ELISA inhibition, cross‐sensitization in the present case was restricted to species of the family of true flies (Muscidae).
IgE‐mediated allergy to recombinant human insulin in a diabetic
Authors: Baur X , Bossert J , Koops F
Published: December 2004

A 63‐year‐old nonatopic female suffering from type II diabetes with severe local and systemic immediate‐type allergic reactions to injections of different recombinant human insulin products has been reported. Skin testing as well as IgE measurements not only proved immediate‐type sensitization to human insulin but also to porcine and bovine insulin which had never been administered and indicated immunological cross‐reactivity. Cross‐reactivity was proved by an IgE inhibition test. Independent of this reaction, the patient showed IgE‐mediated sensitization to protamine.
How long does the effect of birch pollen injection SIT on apple allergy last?
Authors: Asero R.
Published: December 2004

Background: Recent studies showed that injection specific immunotherapy (SIT) with birch pollen extract greatly reduces or cures the associated apple allergy in a large proportion of birch pollen‐allergic patients. However, the long‐term efficacy of SIT for apple allergy has not been assessed.

Objective: To evaluate the duration of the effect of injection SIT with birch pollen extract on apple allergy in birch pollen‐allergic patients.

Methods: Thirty birch pollen‐allergic patients showing both the clinical disappearance of apple allergy and a negative SPT with fresh apple at the end of their injection SIT course were followed‐up at 12‐month intervals from 6 months after SIT was stopped. Apple tolerance as well as SPT was assessed on all occasions. Fifty‐seven birch pollen‐allergic subjects without apple allergy and not submitted to SIT regularly followed‐up for the onset of oral allergy syndrome (OAS) were used as controls.

Results: The overall prevalence of OAS after 30 months of follow‐up did not differ between patients and controls. Although most patients became re‐sensitized to apple by SPT over time, >50% of them were still able to tolerate eating the fruit at the 30‐month follow‐up visit.

Conclusion: Although most patients show a ‘natural’, gradual propensity to apple re‐sensitization (a consequence of prolonged and repeated inhalation of birch pollen responsible for primary sensitization?), the clinical effects of injection SIT on food allergy seem rather long lasting.
Frequency and intensity of responses to mite patch tests are lower in nonatopic subjects with respect to patients with atopic dermatitis
Authors: Seidenari S. , Giusti F. , Pellacani G. , Bertoni L.
Published: December 2004

Background: So far the issue of patch tests with mite allergens in subjects not affected by atopic dermatitis (AD) has been poorly investigated. The aim of this study was to assess the frequency and intensity of responses to atopy patch tests with Dermatophagoides in non‐AD subjects, and to compare them to the ones observed in AD patients.

Methods: Patch tests were performed, employing a mixture of Dermatophagoides pteronyssinus and farinae at two different concentrations (20 and 40% pet.), on 75 non‐AD subjects, including 33 patients with allergic rhinitis and 42 healthy volunteers, and on 210 AD patients, as controls.

Results: Positive responses to 20% mite patch tests were observed in 17 non‐AD subjects (23%) and in 102 AD ones (49%). The former showed a lower intensity of the responses, with a mean score of 1.4 compared with 2.1 in atopics.

Conclusions: Although positive responses to mite patch tests are also observable in subjects without AD, their frequency and intensity are significantly lower compared with AD patients.
Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Münster, Germany
Authors: Maziak W. , Behrens T. , Brasky T. M. , Duhme H. , Rzehak P. , Weiland S. K. , Keil U.
Published: December 2004

Objective: To assess time trends in symptoms of asthma, allergic rhinitis, and atopic eczema among children in Münster, Germany.

Methods: Two cross‐sectional surveys 5‐years apart (1994/1995, 1999/2000) using ISAAC core written and video questionnaires and applying the ISAAC protocol. Two main age groups (6–7 and 13–14 year olds) were designated with information collected by parental and self‐report for both age groups, respectively. A school‐based sample of 7744 participants in the 1994/1995 survey and 7962 participants in the 1999/2000 survey was recruited. In the first and second surveys, response rates for the 6–7 year olds were 81 and 82%, respectively, while for the 13–14 year olds response rates were 94% in both. Analyses focus on the change in 12‐month prevalence of symptoms of asthma, rhinitis, and eczema.

Results: There is a tendency towards an increase in current symptoms for all three conditions and in both age groups, but more so among girls. Indices of diagnosis either remained the same or increased in parallel to the increase in symptoms. Indices of severity also showed a homogenous increase in the 5‐year study period.

Conclusions: Our study shows that symptoms of asthma, rhinitis, and eczema are increasing, reflecting a change in the morbidity of these conditions in our population.
Further characterization of IgE‐binding antigens from guinea pig hair as new members of the lipocalin family
Authors: Fahlbusch B. , Rudeschko O. , Schlott B. , Henzgen M. , Schlenvoigt G. , Schubert H. , Kinne R. W.
Published: December 2004

Background: Guinea pigs are important sources of inhalant allergens in home and working environments. However, little is known about the molecular characteristics and the relevant epitopes of guinea pig allergens. Recently, several allergens have been identified in hair extract and urine, and the major allergen Cav p 1 (20 kDa) has been characterized.

Objective: The aim of the present study was to isolate and to characterize a further major allergen from guinea pig hair with 17 kDa.

Methods: Guinea pig hair extract was fractionated using anion exchange chromatography and reverse‐phase high performance liquid chromatography. Analyses were carried out by sodium dodecyl sulphate–polyacrylamide gel electrophoresis, 2D‐PAGE, immunoblotting, immunoblot inhibition, glycoprotein detection, and N‐terminal amino acid sequencing.

Results: The nonglycosylated 17 kDa allergen, which was named Cav p 2, was purified to homogeneity. On the basis its 15 N‐terminal residues, there was 69% identity with a sequence of Bos d 2, an allergenic protein from cow dander belonging to the lipocalin family. The 2D‐immunoblotting analyses of guinea pig hair extract demonstrated that Cav p 2 and Cav p 1, contained several isoforms with pI values ranging from 3.6 to 5.3. The 2D‐immunoblot inhibition disclosed cross‐reactive IgE epitopes on the allergens Cav p 2 and Cav p 1. Furthermore, Cav p 1 can form both monomers (20 kDa) and dimers (40–42 kDa).

Conclusion: These studies provide important information on the isoallergen character of two relevant guinea pig allergens Cav p 1 and Cav p 2 as well as on their cross‐reactive properties.
Various factors (allergen nature, mouse strain, CpG/recombinant protein expressed) influence the immune response elicited by genetic immunization
Authors: Chatel J. M. , Song L. , Bhogal B. , Orson F. M.
Published: December 2004

Background:  Genetic immunization is a very promising therapeutic approach for allergy treatment. In the present study we investigate the influence of the nature of the allergen, the mouse strain, and the relative amount of CpG to expressed recombinant protein on immune responses using two major peanut allergens, Ara h 1 and Ara h 4.

Methods:  The cDNA of Ara h 1 and of an isoform of Ara h 4 were cloned and inserted in pcDNA3. Antigen specific IgG1, IgG2a and IgE were followed after genetic immunization with 100 μg of these clones in mouse strain SKH‐Hr1 or BALB/c and with 1 μg of the clones+99 blank plasmid in SKH‐Hr1.

Results:  Genetic immunization in SKH‐Hr1 with Ara h 1 elicited a classical Th1 type response, but Ara h 4 elicited a mixed Th1/Th2 response with high IgG1 and even IgE in some mice. In BALB/c both plasmids produced a high IgG1 level. Decreasing the amount of plasmid injected did not change the immune response profile. However, increasing the amount of CpG administered relative to the recombinant Ara h 4 protein expressed reversed the Th1/Th2 response pattern in SKH‐Hr1 mice.

Conclusions:  Immune responses after genetic immunization are strongly influenced by the nature of the allergen, the mouse strain, and the ratio of CpG to recombinant protein expressed.
Effects of low dose fluticasone/salmeterol combination on surrogate inflammatory markers in moderate persistent asthma
Authors: Currie G. P. , Syme‐Grant N. J. , McFarlane L. C. , Carey F. A. , Lipworth B. J.
Published: December 2004

Background: Noninvasive surrogate markers provide valuable information on the asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in moderate persistent asthma.

Methods: Twenty‐five moderate persistent atopic asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 μg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 μg/salmeterol 50 μg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods.

Results: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P < 0.05) in all surrogate markers of inflammation apart from serum ECP. Geometric mean fold changes were 4.3‐fold/1.3‐fold for sputum/blood eosinophils, 2.2‐fold/1.2‐fold for sputum/serum ECP, 2.3‐fold for methacholine PD20 and 1.8‐fold for exhaled nitric oxide.

Conclusions: Surrogate markers apart from serum ECP may be used as a guide to evaluate the anti‐inflammatory effects of low dose inhaled corticosteroids. Sputum markers tend to be more sensitive than blood when assessing the anti‐inflammatory response.
Effects on inflammation parameters of a double‐blind, placebo controlled one‐year course of SLIT in children monosensitized to mites
Authors: Marcucci F. , Sensi L. , Frati F. , Bernardini R. , Novembre E. , Barbato A. , Pecora S.
Published: December 2004

Background: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor.

Methods: Twenty‐four children (age range 4–16 years, average 8.5 years) monosensitized to house dust mites (HDMs) were randomized to receive active or placebo SLIT for this allergen according to a double‐blind, placebo‐controlled design. Before treatment and 10–12 months later the following parameters were checked: ECP and tryptase in sputum and nasal secretion, serum and nasal mite‐specific IgE (sIgE), allergen‐specific nasal challenge test (sNCT), nasal symptoms and tryptase after sNCT.

Results: Nasal tryptase and nasal IgE in basal conditions were unchanged in treated children but significantly increased in untreated children (P = 0.0156 and P = 0.0313, respectively). The threshold for sNCT was unchanged in both groups of children, but the symptom score after sNCT was unchanged in the placebo group and significantly decreased in the active group (P = 0.0084). The nasal tryptase after sNCT was unchanged in the active group and significantly increased in the placebo group (P = 0.0218). Intergroup comparison showed a significant difference in oral tryptase and nasal tryptase after sNCT in favour of the active group.

Conclusions: These interim results after only 1 year of treatment show that SLIT in children monosensitized to HDMs is able to avoid the spontaneous increase in both nasal sIgE antibodies and in local allergic inflammation in basal conditions. These outcomes are confirmed and supported by the decrease of symptoms in the active group combined with the increase of nasal tryptase only in the control group in both cases after sNCT.
Rhinoconjunctivitis, bronchial responsiveness, and atopy as determinants for incident non‐work‐related asthma symptoms in apprentices exposed to high‐molecular‐weight allergens
Authors: Gautrin D. , Ghezzo H. , Malo J.‐L.
Published: December 2004

Objective: The aim of this study was to explore the role of rhinoconjunctivitis (RC), taking into account atopy and the level of bronchial responsiveness to methacholine, on the incidence of respiratory symptoms and in the development and/or worsening of asthma.

Methods: We examined data from a prospective study in 769 students starting exposure to high‐molecular‐weight occupational allergens and who were serially followed for up to 44 months.

Results: The presence of RC symptoms at baseline was significantly associated with an increased risk of developing shortness of breath and wheezing in atopic subjects regardless of PC20 level and in subjects with a PC20 ≤ 32 mg/ml regardless of atopic status. RC symptoms were significantly associated with the development of exercise‐induced respiratory symptoms. Multivariate analyses indicated that having a measurable PC20 was significantly associated with the incidence of all respiratory symptoms studied, whereas baseline seasonal RC was associated only with incident exercise‐induced respiratory symptoms; atopy played a minimal role, and only through an interaction with seasonal RC.

Conclusion: Of the three potential factors for the development of respiratory symptoms that we considered, i.e. RC symptoms, having a measurable PC20 and atopy, having a measurable PC20 is the most significant one.
Peach profilin: cloning, heterologous expression and cross‐reactivity with Bet v 2
Authors: Rodríguez‐Perez R. , Fernández‐Rivas M. , González‐Mancebo E. , Sánchez‐Monge R. , Díaz‐Perales A. , Salcedo G.
Published: December 2004

Background: Peach is among the main foods causing allergic reactions in the Mediterranean adult population. Only a single peach allergen, named Pru p 3, has been characterized. However, a potential role of profilin has also been suggested in grass pollen‐associated allergy to peach.

Methods: Complementary DNA clones for two different peach profilin isoforms were obtained by reverse transcriptase polymerase chain reaction using non‐degenerated primers. Expression of recombinant peach profilin was performed in Escherichia coli, and confirmed using rabbit polyclonal antibodies to sunflower pollen profilin. Twenty‐nine individual sera from patients with peach allergy proved by double‐blind, placebo‐controlled food challenges (DBPCFC), either with (n = 15) or without (n = 14) specific IgE to Bet v 2, were used in immunodetection assays to test recombinant peach profilin reactivity.

Results: Each peach profilin cDNA included an open reading frame coding for a 131 amino acid protein. The peach profilin isoforms, designated Pru p 4.01 and Pru p 4.02, showed 80% of amino acid sequence identity, and were very similar (>70% identity) to allergenic profilins from plant foods and pollens. Recombinant Pru p 4.01 was expressed in E. coli as a nonfusion protein, displaying the expected molecular size and reacting with anti‐profilin antibodies. rPru p 4.01 was recognized by all sera (15 of 15) with specific IgE to Bet v 2, whereas no sera (zero of 14) without IgE to this birch allergen reacted with rPru p 4.01.

Conclusions: Peach profilin Pru p 4 is very closed to other allergenic profilins from plant foods and pollens. A complete correlation between reactivity to rPru p 4 and rBet v 2 has been found in sera from peach allergic patients.
High prevalence of IgG and IgA antibodies to 19‐kDa Helicobacter pylori‐associated lipoprotein in chronic urticaria
Authors: Bakos N. , Fekete B. , Prohászka Z. , Füst G. , Kalabay L.
Published: December 2004

Background: Chronic urticaria has been described in patients with Helicobacter pylori infection. We studied the titer of IgG and IgA type antibodies against H. pylori in patients with and without urticaria of unknown etiology. We also investigated the prevalence of antibodies against H. pylori‐associated lipoprotein 20 (lpp20) in patients with and without chronic urticaria.

Methods: The concentration of anti‐H. pylori antibodies (IgG and IgA) was determined by the RIDA test. The level of anti‐lpp20 antibodies was determined by Western blot using various H. pylori antigens (from 19 to 120 kDa).

Results: Patients with chronic urticaria and H. pylori infection (subgroup 1, n = 33) had high IgG and IgA titers whereas all patients with chronic urticaria and without H. pylori infection (subgroup 2, n = 23) were seronegative (P = 0.0128 for IgG and P = 0.003 for IgA). Titers in subgroup 1 did not differ significantly from a control group (n = 33) with severe H. pylori‐associated gastritis without urticaria. The prevalence of the anti‐lpp20 antibodies was significantly higher in subgroup 1 compared to the control group (93.9 vs 21.2%, P < 0.0001 for IgG, and 46.1 vs 6.3%, P < 0.0029 for IgA).

Conclusions: We suggest that IgG and IgA antibodies to H. pylori‐associated lpp20 may play role in the pathogenesis of chronic urticaria.
Egg white proteins as inhalant allergens associated with baker's asthma
Authors: Escudero C. , Quirce S. , Fernández‐Nieto M. , de Miguel J. , Cuesta J. , Sastre J.
Published: December 2004

Background:  Bakery workers may develop IgE‐mediated allergy to liquid and aerosolized hen's egg proteins that are commonly used in the baking and confectionery industries.

Methods:  We studied four bakery workers who had work‐related allergic respiratory symptoms upon exposure to egg aerosols. The causative role of egg proteins in their respiratory symptoms was investigated by immunologic and specific inhalation challenge (SIC) tests.

Results:  Skin prick tests to egg white extract and to lysozyme gave positives responses in all the subjects, to ovalbumin in two, to ovomucoid in one and to egg yolk in two subjects. They were also sensitized to wheat, rye and barley flours. Specific IgE determinations to egg white were positive in all patients, to lysozyme in two, to ovalbumin in three, to ovomucoid in two and to egg yolk in two of them. Methacholine inhalation tests revealed bronchial hyperresponsiveness in all workers (PC20 < 16 mg/ml). SICs were performed with aqueous extracts of lysozyme (n = 4), ovalbumin (n = 2) and ovomucoid (n = 1), which elicited isolated early asthmatic reactions in all subjects. Double‐blind, placebo‐controlled, oral challenge tests with raw egg white were positive in three subjects.

Conclusions:  These bakery workers had developed IgE‐mediated occupational asthma to hen's egg white proteins.
Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air
Authors: Jang A.‐S. , Yeum C.‐H. , Son M.‐H.
Published: December 2004

Background: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries.

Objective: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross‐sectional study of a cohort of 670 children, aged 10–13 years.

Methods: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR.

Results: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 ± 0.48] compared to those in rural [31.9% (52/163), 9.84 ± 0.83] and coastal [33.3% (67/201), 7.17 ± 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P < 0.007]. Schoolchildren with atopy had lower PC20 than those without atopy (5.98 ± 0.60 vs 8.15 ± 0.45, P < 0.001). Positive allergy skin tests and living in a polluted area were risk factors in multivariate analyses adjusted for sex, parents’ smoking habits, age, body mass index, nose symptoms and lung symptoms (odds ratio for location = 2.4875, confidence interval 1.6542–3.7406, P < 0.000; odds ratio for allergy skin test = 1.5782, confidence interval 1.1130–2.2379, P < 0.0104).

Conclusion: Our findings demonstrate that more children living in polluted areas have airway hyperresponsiveness than do those living in less polluted areas.
Immunoglobulin E is not required for but enhances airway inflammation and hyperresponsiveness
Authors: Itami D. M. , Latinne D. , Bazin H. , Garcia M. L. B. , Perini A. , Martins M. A. , Macedo M. S. , Macedo‐Soares M. F.
Published: December 2004

The aim of this study was to investigate the role of immunoglobulin E (IgE) in the late phase reaction (LPR) of murine experimental asthma. Our model consisted of an implant of DNP‐conjugated, heat‐coagulated hen's egg white (DNP‐EWI), followed 14 days later by an intratracheal challenge with aggregated DNP‐ovalbumin. Airway inflammation was analyzed 48 h after challenge and compared with a similarly immunized group of mice with highly suppressed humoral response due to anti‐μ and anti‐δ antibody treatment. Total number of cells in the bronchoalveolar lavage (BAL) (with predominance of eosinophils) and EPO activity in the lung homogenate were increased in the DNP‐EWI‐immunized group compared with immunosuppressed or nonimmunized mice. However, the cellular infiltration and EPO activity observed in the immunosuppressed group were still significantly above those obtained in the nonimmunized group, indicating that inhibition of antibody production did not completely prevent the inflammatory manifestations in BAL and lung. Airway hyperresponsiveness to methacoline was obtained in DNP‐EWI‐immunized mice, but the respiratory mechanical parameters returned to normal levels in the immunosuppressed group. When these mice were reconstituted with monoclonal anti‐DNP antibodies, only IgE, but not IgG1, restored lung inflammation and decreased the conductance of the respiratory system, therefore, increasing hyperresponsiveness. These results indicate that antibodies are not essential for induction of LPR in the lung. However, IgE enhances pulmonary inflammation and hyperresponsiveness.
Evaluation of asthma knowledge and quality of life in Hungarian asthmatics
Authors: Meszaros A. , Orosz M. , Magyar P. , Mesko A. , Vincze Z.
Published: December 2004

Background:  The objective was to develop an educational instrument, to assess its impact as an intervention instrument and to examine quality of life (QoL).

Methods:  119 asthmatics were randomized (64 in the intervention and 55 in the reference group). The education instrument was developed based on the EuroPharm‐Forum Guidelines and its impact assessed by a self‐developed questionnaire. Patients’ QoL, asthma knowledge was assessed twice, once before and after the education seminar, education was only provided for the intervention group. QoL was measured with the St George's Respiratory Questionnaire (SGRQ) and a visual analogue scale (VAS).

Results:  We found significant differences in answers to the asthma questions, by 40% improvement, but no changes in the control group. In inhaler‐use technique, we could not find significant changes neither in the intervention nor in the control group. There were no significant differences between the results of the two visits neither with the VAS nor with the SGRQ on the QoL data.

Conclusion:  The results indicate that asthmatics experience lower QoL. As the subjects were regularly controlled asthmatics they had better general knowledge and inhaler‐use technique was expected. The results suggest that it is necessary to regularly refresh asthma knowledge, to assess patients’ self‐management plans to achieve long‐term effectiveness of asthma management.
Computational tools for the study of allergens
Authors: Brusic V. , Petrovsky N. , Gendel S. M. , Millot M. , Gigonzac O. , Stelman S. J.
Published: December 2004

Allergy is a major cause of morbidity worldwide. The number of characterized allergens and related information is increasing rapidly creating demands for advanced information storage, retrieval and analysis. Bioinformatics provides useful tools for analysing allergens and these are complementary to traditional laboratory techniques for the study of allergens. Specific applications include structural analysis of allergens, identification of B‐ and T‐cell epitopes, assessment of allergenicity and cross‐reactivity, and genome analysis. In this paper, the most important bioinformatic tools and methods with relevance to the study of allergy have been reviewed.
IVIG – mechanisms of action
Authors: Simon H. U. , Späth P. J.
Published: December 2004

Intravenous immunoglobulin (IVIG) preparations are fractionated from a plasma pool of several thousand donors. IVIG contain immune antibodies and physiologic autoantibodies. Immune antibodies reflect the immunologic experience of the donor population. This fraction of IVIG preparations is useful for replacement therapy and passive immunisation. Natural autoantibodies are able to react with the immune system of the recipient of IVIG and are suggested to help to correct immune deregulation. Immunomodulatory and anti‐inflammatory properties are based on multiple mechanisms of action which are described. These mechanisms are effective concomitantly and synergistically at every occasion of use of IVIG in inflammatory and autoimmune disorders.
Analysis of the CD4+ T cell responses to house dust mite allergoid
Authors: Kalinski P. , Lebre M. C. , Kramer D. , De Jong E. C. , Van Schijndel J. W. P. M. , Kapsenberg M. L.
Published: December 2004

Background: Modified allergen extracts (allergoids) with reduced IgE‐binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T‐cell stimulatory capacity is less well studied and is a subject of the present study.

Methods: We compared the ability of native house dust mite extract (Dermatophagoides pteronyssinus; HDM) and the glutaraldehyde‐modified allergoid (HDM‐GA) to induce the proliferation and cytokine production by fresh PBMC and by DC‐stimulated polyclonal Th cells and HDM‐specific Th cell clones.

Results: Freshly isolated T cells showed a partially reduced responsiveness to HDM‐GA, differentially pronounced in different donors. HDM‐specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM‐GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor‐dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM‐specific T cell clones.

Conclusions: The reduced stimulatory potential of HDM‐GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid‐nonreactive HDM‐specific Th cells may result in differential responses of individual patients to immunotherapy.
Effects of BCG revaccination on asthma
Authors: Choi I. S. , Koh Y. I.
Published: December 2004

In a study conducted 1 year ago, we found that Th1 immune enhancement following Bacille Calmette–Guérin (BCG) vaccination effectively suppressed human asthma. To investigate whether revaccination would further improve lung function, BCG vaccine was given again. Current lung function tended to improve in the Repeated BCG group (n = 9), but not in the Single BCG group (previously the placebo group) (n = 11), compared with that 1 year ago. The BCG vaccination improved lung function in both groups, and the Repeated BCG group showed a significant increase in the peripheral blood interferon γ/interleukin 4 ratio. These findings suggest that repeated BCG vaccinations might be effective in asthma therapy.