bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma
Authors: Hoshino M. , Takahashi M. , Takai Y. , Sim J. , Aoike N.
Published: March 2003

Background Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied.

Objective We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients.

Subjects and methods We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 µg/daily, or placebo, for 6 months in a double‐blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non‐asthmatic control subjects.

Results There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP‐treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP‐treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = −0.49, P < 0.05) and airway responsiveness (rs = −0.36, P < 0.05).

Conclusion These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.
A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma
Authors: Wilson A. M. , Dempsey O. J. , Sims E. J. , Lipworth B. J.
Published: March 2003

Background Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy.

Objective To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma.

Patients and methods A single‐blind double‐dummy placebo‐controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 µg inhaled plus 200 µg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1‐week placebo run‐in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms.

Results There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2–18.6) for placebo vs. budesonide, 2.9 (1.0–8.4) for placebo vs. montelukast, and 2.1 (1.1–4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms.

Conclusion Once‐daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.
Validation of the Chinese translated version of ISAAC core questions for atopic eczema
Authors: Chan H. H. , Pei A. , Van Krevel C. , Wong G. W. K. , Lai C. K. W.
Published: March 2003

Background The International Study of Asthma and Allergies in Childhood (ISAAC) was designed to allow international comparison of epidemiological data on atopic conditions in childhood. In so doing, further aetiological information would be obtained that in turn would provide a framework for future studies. The global ISAAC results on the prevalence of atopic dermatitis indicated a 60‐fold variation recorded in different countries. Such a degree of difference may be partially due to the translated questionnaires that were not validated in all of the involved countries.

Objective To validate the Chinese version of the ISAAC core questions for atopic eczema.

Methods One thousand nine hundred and twenty children aged between 3 and 5 were randomly recruited from 13 kindergartens in Hong Kong. Using a dermatologist's clinical examination as the gold standard, we validated the Chinese version of the ISAAC core questions for atopic eczema. The Youden's Indexes obtained in our study were compared with those obtained in the United Kingdom's validation study.

Results The Youden's Indexes obtained in our study were significantly lower than those from the United Kingdom. The low scores were likely to be due to a reduction in the sensitivity of the Chinese questionnaire, which ranged from 23.5% to 70.6%.

Conclusion Our findings indicate that the translated questionnaire is less effective than the English version in assessing the prevalence of atopic eczema. The indication of a low prevalence of atopic eczema among the Chinese population reported in previous studies was at least partially due to problems with the translated questionnaire.
Decreased T lymphocyte infiltration in bronchial biopsies of subjects with severe chronic obstructive pulmonary disease
Authors: Di Stefano A. , Capelli A. , Lusuardi M. , Caramori G. , Balbo P. , Ioli F. , Sacco S. , Gnemmi I. , Brun P. , Adcock I. M. , Balbi B. , Barnes P. J. , Chung K. F. , Donner C. F.
Published: March 2003

Background Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied.

Objective The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa.

Methods We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium.

Results Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P < 0.012, P < 0.02 and P < 0.02, respectively) and control smokers (P < 0.015, P < 0.005 and P < 0.015, respectively). In subjects with airflow limitation the number of CD3+ and CD8+ cells was inversely correlated with the degree of airway obstruction (r = 0.59, P < 0.015 and r = 0.52, P < 0.032, respectively).

Conclusions Bronchial inflammation in severe COPD is characterized by lower numbers of CD3+ and CD8+ cells and decreased numbers of CD3+ cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation.
Intravenous immune globulin effects on serum‐soluble CD5 levels in atopic dermatitis
Authors: Noh G. , Lozano F.
Published: March 2003

BackgroundIntravenous immune globulin (IVIG) therapy has been tried in the treatment of atopic dermatitis. Recently, the presence of serum‐soluble CD5 (ssCD5) in atopic dermatitis was reported.

ObjectiveIVIG effects on ssCD5 levels in atopic dermatitis were examined and the correlation of ssCD5 level changes with clinical and laboratory parameters were investigated.

MethodsIVIG therapy was tried on 40 atopic dermatitis and 17 recurrent spontaneous abortion patients. Five atopic dermatitis patients received normal saline as a placebo control group. The clinical and laboratory parameters were evaluated on day 0, 1, 7 and 21 after administering the IVIG therapy.

ResultsWith IVIG therapy, in atopic dermatitis, the ssCD5 level was 5.5 ± 6.2 ng/mL before infusion (day 0), 15.2 ± 12.1 ng/mL on day 1, 13.8 ± 14.1 ng/mL on day 7, and 3.9 ± 4.1 ng/mL on day 21. The clinical severity score was 350.5 ± 120.3 on day 0, 420.4 ± 174.8 on day 1, 250.0 ± 121.2 on day 7, and 115.5 ± 53.9 on day 21. White blood cell (WBC) counts and serum IgE levels showed a gradual decrease with IVIG infusions. Blood eosinophil fractions were 5.3 ± 2.8% on day 0, 8.6 ± 5.2% on day 1, 7.3 ± 3.7% on day 7, and 6.8 ± 4.0% on day 21. Changes in the total eosinophil count were insignificantly parallel with those of blood eosinophil fractions

ConclusionIn atopic dermatitis, IVIG therapy increased the ssCD5 levels. Further studies concerning the exact role of ssCD5 are needed.
Repeatability and validity of cell and fluid‐phase measurements in nasal fluid: a comparison of two methods of nasal lavage
Authors: Belda J. , Parameswaran K. , Keith P. K. , Hargreave F. E.
Published: March 2003

Background There is little information on the repeatability of cell counts and fluid‐phase measurements in nasal fluid obtained by different methods of nasal lavage.

Objective To compare the repeatability and validity of total and differential cell counts and eosinophil cationic protein (ECP) in nasal secretions obtained by two methods of nasal lavage.

Patients and methods Twelve healthy subjects and twelve subjects with clinically stable allergic rhinitis were randomly assigned to two nasal lavages (separated by 48 h), by one of two methods in the first week and by the second method in the following week. One method was a modification of the method described by Greiff et al. and Grunberg and coworkers and the other was that described by Naclerio and coworkers.

Results Both methods of nasal lavage gave poorly repeatable eosinophil counts and ECP in normal subjects but better repeatability in subjects with rhinitis. The modified Greiff/Grunberg method gave higher and more repeatable total cell count and, in subjects with rhinitis, more reproducible ECP levels compared with the Naclerio method. Both methods were able to discriminate between healthy and rhinitic subjects: mean ± SD eosinophil percentage count and eosinophil cationic protein differences were 4.5 ± 4% (P < 0.05) and 24.5 ± 46.9 µg/L (P < 0.05), respectively, with the modified method and 7.0 ± 4% (P < 0.05) and 26.9 ± 68 µg/L (P < 0.05), respectively, with the Naclerio method.

Conclusion Both methods are valid and discriminate between normal and rhinitic subjects. In subjects with rhinitis, although the repeatability of eosinophil counts is similar by both methods, the modified Greiff/Grunberg method gives more reproducible ECP measurements, compared with the Naclerio method.
Safety of sputum induction with isotonic saline in adults with acute severe asthma
Authors: Wark P. A. B. , Simpson J. L. , Hensley M. J. , Gibson P. G.
Published: March 2003

Background Sputum induction is a safe and effective technique to study airway inflammation in stable asthma. However, it has the potential to induce bronchospasm and the safety and efficacy of the technique in acute asthma has not been determined.

Objective The objective of this study was to evaluate the safety and efficacy of a protocol to induce sputum using isotonic saline in adults with acute exacerbations of asthma.

Methods Adults (n = 47) presenting to the emergency room with acute asthma and an FEV1 > 1.0 L underwent supervised sputum induction with 0.9% saline delivered by an ultrasonic nebuliser. Induction was ceased if there was a fall of 20% or greater from baseline FEV1.

Results Subjects had moderate to severe exacerbations of acute asthma. An adequate sputum sample was obtained in 87% of subjects. Four subjects ceased induction because of symptom distress. There was a fall ≥ 20% in 28% of subjects. Bronchoconstriction was successfully reversed by salbutamol in all subjects. Predictors of significant bronchoconstriction were older age, use of ingested corticosteroids, and a requirement for high‐dose nebulized salbutamol for the exacerbation. Maintenance long‐acting β2‐agonist therapy protected against bronchoconstriction during sputum induction.

Conclusions Sputum induction in acute asthma using isotonic saline is highly efficacious in obtaining an adequate sputum sample. There is the potential for significant bronchoconstriction to occur but this can be managed safely with minimal discomfort to subjects.
Farming, rural lifestyle and atopy in adults from southern Germany – results from the MONICA/KORA study Augsburg
Authors: Filipiak B. , Heinrich J. , Schäfer T. , Ring J. , Wichmann H.‐E.
Published: March 2003

Background and objective The increasing urbanization and the decrease in the numbers of farms in southern Germany might be associated with an increasing prevalence of allergic diseases. We compared the prevalence of allergic diseases in farmers, and rural, suburban and urban residents in the small geographical area of Augsburg in southern Germany.

Methods In a cross‐sectional survey adults, aged 25–75 years selected from the community population register were investigated. Rural, suburban and urban residents were defined by community size and farmers by occupation. Allergic respiratory disorders were assessed by self‐administered questionnaires and specific IgE antibodies to five common aeroallergens.

Results In comparison to rural residents the urban population had an increased risk of allergic rhinitis (OR = 1.5; 95% CI: 1.2–1.9), atopic sensitization (OR = 1.2; 95% CI: 1.0–1.4) and sensitization against pollen (OR = 1.5; 95% CI: 1.2–1.9). There was no difference in the risk of asthma (OR = 1.0; 95% CI: 0.6–1.6) and a decreased risk in the sensitization against house dust mite (OR = 0.8; 95% CI: 0.7–1.0). The suburban residents did not differ from urban residents. Farmers had lower risks in allergic rhinitis, atopic sensitization, sensitization against pollen and mites (OR = 0.63; 0.86; 0.51 and 0.80, respectively) than rural non‐farming residents, however, these differences were statistically not significant. Reported allergic rhinitis with sensitization to pollen was 2.5 times (95% CI: 1.8–3.6) more prevalent in urban than in rural residents.

Conclusion A farming environment and rural lifestyle might be associated with unknown protective factors impacting the prevalence of allergies.
Transforming growth factor‐bβ1 mediates coexpression of the integrin subunit aαE and the chymase mouse mast cell protease‐1 during the early differentiation of bone marrow‐derived mucosal mast cell homologues
Authors: Wright S. H. , Brown J. , Knight P. A. , Thornton E. M. , Kilshaw P. J. , Miller H. R. P.
Published: March 2003

Background

Mucosal mast cells (MMC) play a central role in gut hypersensitivities and inflammation. They are morphologically, biochemically and functionally distinct from their connective tissue counterparts. Massive hyperplasia of MMC occurs 7–10 days after intestinal infection with nematodes but it has never been possible to replicate this phenomenon in vitro.

Objective

(1) To determine whether mouse bone marrow‐derived mast cells (mBMMC) grown in the presence of transforming growth factor (TGF)‐β1 could develop over the same time frame (7–10 days) as MMC in parasitized mice. (2) To compare the early expression of surface receptors (integrins αE and β7, c‐kit and FcεR) with that of the MMC‐specific granule chymase mouse mast cell protease‐1 (mMCP‐1).

Methods

Mouse bone marrow cells were cultured in the presence of IL‐9, IL‐3 and Stem Cell Factor (SCF) with or without TGF‐β1. mBMMC were quantified after toluidine blue or Leishmans' staining. Expression of MMC‐specific mouse mast cell proteases was analysed by ELISA, immunohistochemistry and RT‐PCR. Surface antigen expression was characterized by flow cytometry and confocal microscopy.

Results

TGF‐β1 promotes the development of abundant MMC‐like mBMMC from bone marrow progenitor cells with kinetics, which closely parallel that seen in vivo. mRNA transcripts encoding mMCP‐1 and ‐2 are readily detectable by day 4 ex vivo in cultures grown in the presence of TGF‐β1. Between 30 and 40% and 75–90% of the cells in these cultures on days 4 and 7, respectively, have typical mast cell morphology, are c‐kit+, FcεR+, integrin αEβ7+, and express and secrete abundant mMCP‐1. The integrin αE subunit is coexpressed with mMCP‐1.

Conclusion

The kinetics of mMCP‐1+/αE+ mBMMC development, regulated by TGF‐β1, are consistent with that seen in vivo in the parasitized intestine. The normally down‐regulatory functions of TGF‐β1 in haematopoiesis are superseded in this culture system by its ability to promote the early expression of αE and mMCP‐1.
Cord blood mononuclear cell cytokine responses in relation to maternal house dust mite allergen exposure
Authors: Marks G. B. , Zhou J. , Yang H. S. , Joshi P. A. , Bishop G. A. , Britton W. J. ,   The Caps Investigators
Published: March 2003

Background Cord blood mononuclear cells have demonstrated specific immune responses to environmental allergens.

Objective To establish whether the nature of this response is related to the level of maternal antenatal exposure to house dust mite (HDM) allergen and, hence, whether antenatal allergen avoidance may have a role in the prevention of allergic sensitization in children.

Methods Children with a family history of asthma were recruited antenatally as subjects in a randomised controlled trial: the Childhood Asthma Prevention Study. HDM allergen (Der p 1) concentrations were measured in dust collected from the maternal bed at 36 weeks gestation. Cord blood mononuclear cells were stimulated in culture, separately, with phytohaemaglutinin (PHA) and HDM extract. Cytokine IL‐4, IL‐5, IL‐10 and IFN‐γ concentrations in supernatant were measured by ELISA. mRNA signals for these cytokines were measured using RT‐PCR.

Results The median concentration of HDM allergen was 18.4 µg/g (interquartile range 7.3–35.3 µg/g). Median concentrations of IL‐4, IL‐5, IL‐10 and IFN‐γ, after PHA stimulation were 4, 19, 401 and 1781 pg/mL, respectively. After HDM allergen stimulation the median concentrations were 0, 0, 20 and 14 pg/mL, respectively. The distribution of mRNA cytokine signals was similar. Neither cytokine protein concentrations nor cytokine mRNA signal levels were correlated with the concentration of HDM allergen in the mothers' beds at 36 weeks gestation.

Conclusion These findings do not support the view that the prevention of allergic disease in children requires the institution of HDM avoidance interventions during pregnancy.
DNA microarrays to study gene expression in allergic airways
Authors: Benson M. , Svensson P. A. , Carlsson B. , Jernås M. , Reinholdt J. , Cardell L. O. , Carlsson L.
Published: March 2003

Background Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample.

Objective To study gene expression in nasal mucosal biopsies from patients with allergic rhinitis using DNA micro‐arrays.

Methods Nasal biopsies were obtained from 14 patients with symptomatic birch pollen‐induced allergic rhinitis and five healthy controls. RNA was extracted from the biopsies and pooled into one patient pool and one control pool. These were analysed in duplicate with DNA micro‐arrays containing more than 12 000 known genes.

Results Approximately half of the genes were expressed in the patient and control samples. Guided by the current literature we chose 32 genes of possible relevance to allergic airway inflammation and investigated their relative expression. Among these, transcripts encoding immunoglobulins and their receptors were most abundant. The expression of cytokines and growth factors was low, whereas their corresponding receptors and cell surface markers displayed higher expression levels. IgA had the highest expression of all 12 626 genes. RT‐PCR showed that IgA1 was the predominant subclass. This was confirmed by the protein level in nasal fluids. Allergen‐specific IgA was significantly higher in patients than in controls and correlated significantly with eosinophil granulae proteins.

Conclusion DNA micro‐array analysis can be used to identify genes of possible relevance to allergic airway inflammation. In this study, the expression profile in the nasal mucosa was quantitatively dominated by immunoglobulins, particularly IgA. Protein analyses in nasal fluids indicated a role for allergen‐specific IgA in eosinophil degranulation.
Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate‐type reactions to betalactam antibiotics
Authors: Sanz M. L. , Gamboa P. M. , Antépara I. , Uasuf C. , Vila L. , Garcia‐Avilés C. , Chazot M. , De Weck A. L.
Published: March 2003

Background In this study, we used flow cytometry to determine the percentage of activated basophils that expressed the CD63 marker after in vitro stimulation by different betalactam antibiotics. The diagnostic reliability of the technique was assessed, as well as its correlation with specific IgE.

Methods Fifty‐eight patients with clinical allergy to betalactam antibiotics and presenting positive skin tests to at least one of the allergens (minor determinant mixture (MDM), benzylpenicilloyl‐polylysine (PPL), penicillin, ampicillin, amoxicillin, cephalosporins) were tested. Thirty subjects non‐allergic to betalactams were also studied as controls. The flow assay stimulation test (FAST) uses flow cytometry to determine the percentage of basophils that express CD63 as an activation marker after in vitro stimulation with allergen. Double labelling with monoclonal antibodies anti‐CD63‐PE and anti‐IgE FITC was used.

Results The allergic patients show a statistically greater number of activated basophils than the control subjects, after the incubation of cells with all the betalactams at various concentrations. The sensitivity of the technique is 50%, the specificity 93.3%, the likelihood ratio for a positive value 7.46 and the likelihood ratio for a negative value 0.54. In spite of having a greater sensitivity (37.9%) and specificity (86.7%) than CAP, differences between sensitivity and specificities of both techniques (CAP and FAST) do not reach statistical significance.

Conclusion The basophil activation test is a particularly useful technique in the diagnosis of patients with IgE‐mediated allergy to betalactams and allows the identification of 50% of patients. Used in conjunction with CAP, it allows the identification of 65.5% of such patients.
Pollutional and meteorological factors are closely related to complaints of non‐allergic, non‐infectious perennial rhinitis patients: a time series model
Authors: Braat J. P. M. , Mulder P. G. , Duivenvoorden H. J. , Gerth Van Wijk R. , Rijntjes E. , Fokkens W. J.
Published: March 2003

Background Epidemiological studies in the past have focused on meteorological conditions, pollution and pollen and their relationship with symptoms of bronchial hyper‐reactivity, however, there are no epidemiological studies which examine a wide range of such factors and determine their role in nasal hyper‐reactivity.

Objective To investigate whether environmental factors can influence symptomatology in non‐allergic non‐infectious perennial rhinitis (NANIPER) patients, who suffer primarily from nasal hyper‐reactivity symptoms.

Methods We studied 16 non‐smoking NANIPER patients and seven non‐smoking controls during a 218‐day study period (March–October) by means of daily symptom scores and visual analogue scales for the subsets patency, secretions and sneezing, and compared them to seven primary factors which affected ‘symptoms’ and 10 secondary factors which affected primary factors only.

Results The mean symptom scores in the NANIPER and control groups were 2.17 and 0.13, respectively. In NANIPER, the highest correlations of primary factors with symptomatology were found for symptom scores and sneezing with minimum daytime temperature (r = −0.62 and −0.45, respectively), ozone and NO concentrations. Patency and secretions were associated with minimum daytime temperature (r = −0.39 and 0.32, respectively). Time series analysis, however, correcting for several confounders such as autocorrelated symptomatology, showed that minimum daytime temperature and daytime relative humidity made an independent contribution to symptoms. In the control group, correlations were much lower, though present. Time series analysis was not possible.

Conclusions We conclude that in a mild climate with relatively low levels of pollution, minor pollution and meteorological disturbances result in substantial changes in nasal reactivity symptoms in NANIPER patients, but not controls, irrespective of other factors such as allergy or infection.
The allergen profile of ash (Fraxinus excelsior) pollen: cross‐reactivity with allergens from various plant species
Authors: Niederberger V. , Purohit A. , Oster J. P. , Spitzauer S. , Valenta R. , Pauli G.
Published: March 2003

Background Ash, a wind‐pollinated tree belonging to the family Oleaceae, is distributed world‐wide and has been suggested as a potent allergen source in spring time.

Objective The aim of this study was to determine the profile of allergen components in ash pollen in order to refine diagnosis and therapy for patients with sensitivity to ash pollen

Methods The IgE reactivity profile of 40 ash pollen‐allergic patients was determined by immunoblotting. Antibodies raised to purified pollen allergens from tree and grass pollens were used to identify cross‐reactive structures in ash pollen extract. IgE immunoblot inhibition studies were performed with recombinant and natural pollen allergens to characterize ash pollen allergens and to determine the degree of cross‐reactivity between pollen allergens from ash, olive, birch, grasses and weeds.

Results The allergen profile of ash pollen comprises Fra e 1, a major allergen related to the major olive allergen, Ole e 1, and to group 11 grass pollen allergens, the panallergen profilin, a two EF‐hand calcium‐binding protein, a pectinesterase‐like molecule and an allergen sharing epitopes with group 4 grass pollen allergens. Thus, the relevant allergens of ash are primarily allergens that share epitopes with pollen allergens from other tree, grass and weed species.

Conclusions Allergic symptoms to ash pollen can be the consequence of sensitization to cross‐reactive allergens from other sources. The fact that ash pollen‐allergic patients can be discriminated on the basis of their specific IgE reactivity profile to highly or moderately cross‐reactive allergens has implications for the selection of appropriate forms of treatment.
Human T cells that have been conditioned by the proteolytic activity of the major dust mite allergen Der p 1 trigger enhanced immunoglobulin E synthesis by B cells
Authors: Ghaemmaghami A. M. , Shakib F.
Published: March 2003

Background We have previously demonstrated that the proteolytic activity of Der p 1 selectively cleaves human CD25, the 55 kDa α subunit of the IL‐2 receptor. As a result of cleavage of surface CD25, peripheral blood T cells produce less IFN‐γ and more IL‐4, thereby leading to progressive polarization of the T cells towards a Th2 cytokine profile. Therefore, these observations underline the potential role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis.

Objective To study the effect of T cells that have been conditioned by the proteolytic activity of Der p 1 on IgE synthesis by B cells.

Methods We have examined this concept in experiments whereby T cells that have been exposed to either proteolytically active or inactive Der p 1 were cocultured with autologous B cells and IgE antibody synthesis was monitored.

Results Here we demonstrate for the first time that coculturing T cells that have been in contact with proteolytically active Der p 1 with autologous B cells leads to augmentation of IgE antibody responses.

Conclusions The proteolytic activity of Der p 1 conditions human T cells, which then become empowered to trigger enhanced IgE synthesis by B cells.
Determination of interleukin‐5 secretion from drug‐specific activated ex vivo peripheral blood mononuclear cells as a test system for the in vitro detection of drug sensitization
Authors: Sachs B. , Erdmann S. , Malte Baron J. , Neis M. , Al Masaoudi T. , Merk H. F.
Published: March 2003

Background In vitro detection of drug sensitization is still limited. The lymphocyte transformation test, which determines drug‐specific proliferation, is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's clinical phenotype. Accumulation of eosinophils following IL‐5 secretion from drug‐specific stimulated T cells is a characteristic histological feature of drug‐induced skin eruptions.

Objective We determined whether in vitro drug‐specific activation of ex vivo peripheral blood mononuclear cells from 10 patients with drug‐induced maculopapular exanthems and three patients with severe skin reactions results in secretion of IL‐5, IL‐10 or IFN‐γ and assessed the sensitivity and specificity of drug‐specific IL‐5 secretion as a test system compared with the lymphocyte transformation test and patch tests. Furthermore, the subsets of CD4+ and CD8+ T cells involved in drug‐specific proliferation, IL‐5 secretion and mRNA expression were examined in three patients.

Methods Drug‐specific proliferation of peripheral blood mononuclear cells in the lymphocyte transformation test was investigated by 3H‐thymidine uptake, and culture supernatants taken after 5 days were analysed for IL‐5, IL‐10 and IFN‐γ concentrations by ELISA technique. IL‐5 mRNA expression was determined by RT‐PCR.

Results Drug‐specific activation of peripheral blood mononuclear cells consistently resulted in IL‐5 and to a lesser extent in IL‐10 and IFN‐γ secretion. The sensitivities of the patch test, lymphocyte transformation test and assessment of drug‐specific IL‐5 secretion for the detection of drug sensitization were 55%, 75% and 92%, respectively.

Conclusion These data suggest a role for the determination of drug‐specific IL‐5 secretion by ex vivo peripheral blood mononuclear cells for the in vitro detection of drug‐sensitization in drug‐induced maculopapular exanthems.
Increased Th1 and Th2 allergen‐induced cytokine responses in children with atopic disease
Authors: Smart J. M. , Kemp A. S.
Published: March 2003

Background Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen‐induced T cell responses can provide information on cytokine production by allergen‐reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non‐specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN‐γ responses to allergens in atopic subjects.

Objective To examine childhood polyclonal and allergen‐induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease.

Methods PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non‐atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic).

Results Atopic children had significantly reduced IFN‐γ and increased IL‐4 and IL‐5 but not IL13 production to SEB superantigen stimulation when compared with non‐atopic children. HDM and RYE allergens stimulated significantly increased IFN‐γ, IL‐5 and IL‐13, while OVA stimulated significantly increased IFN‐γ production in atopic children.

Conclusion We show that a polyclonal stimulus induces a reduced Th1 (IFN‐γ) and increased Th2 (IL‐4 and IL‐5) cytokine pattern. In contrast, the allergen‐induced cytokine responses in atopic children were associated with both increased Th1 (INF‐γ) and Th2 (IL‐5 and IL‐13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.
The importance of maximal airway response to methacholine in the prediction of asthma development in patients with allergic rhinitis
Authors: Koh Y. Y. , Kang E. K. , Min Y‐G. , Kim C. K.
Published: March 2003

Background Allergic rhinitis is a known predictor and correlate of asthma incidence. However, it is not clear which patients with allergic rhinitis are at greater risk of the development of asthma.

Objective The aim of this study was to investigate whether airway hypersensitivity and/or increased maximal response on the dose–response curve to methacholine would predict the development of asthma in subjects with allergic rhinitis.

Methods One hundred and forty‐one children with allergic rhinitis were prospectively studied for 7 years. At the initiation of the study, bronchial provocation test with methacholine using a stepwise increasing concentration technique was performed to measure PC20 (provocative concentration causing a 20% fall in FEV1) and maximal response. Each subject was evaluated at least every 6 months and details of asthmatic symptoms or signs experienced during the intervening period were taken.

Results Twenty of 122 subjects available for the follow‐up developed asthma. Nine (19.6%) of 46 hypersensitive (PC20 < 18 mg/mL) subjects developed asthma, compared with 11 (14.5%) of 76 normosensitive subjects (P = 0.462). Eight (32%) of 25 subjects without maximal response plateau developed asthma, compared with 12 (12.4%) of 97 subjects with maximal response plateau (P = 0.018). Score test for trend revealed a significant association between the level of maximal response (P = 0.007), but not the degree of methacholine PC20 (P = 0.123), and the future development of asthma.

Conclusion An increased maximal airway response to methacholine is shown to be a better predictor for the future development of asthma in patients with allergic rhinitis, than airway hypersensitivity to methacholine.
An association study between the Clara cell secretory protein CC16 A38G polymorphism and asthma phenotypes
Authors: Mansur A. H. , Fryer A. A. , Hepple M. , Strange R. C. , Spiteri M. A.
Published: March 2003

BackgroundPreviously, an association has been reported between an increased risk of asthma and a polymorphism in the Clara cell secretory protein (CC16) gene [namely, an adenine to guanine substitution in the CC16 gene at position 38 (A38G) downstream from the transcription initiation site within the noncoding region of exon 1]. Homozygous individuals for the polymorphic sequence (AA genotype) were reported to have a significant (6.9 fold) increased risk of developing asthma. This finding has not been confirmed independently.

ObjectiveTo validate the association of CC16 A38G polymorphism to asthma in a separate well‐characterized population through a case–control study.

MethodsWe conducted an association study using a sample of 217 unrelated Northern European Caucasians. Individuals were clinically characterized by a validated respiratory questionnaire, spirometry and bronchial reactivity measurement, and genotyped for the A38G polymorphism using PCR and restriction digestion. Association analysis was performed using the nonparametric Chi‐squared tests.

ResultsIn the unselected population, 43.3% participants were homozygous for the CC16*G allele and 45.4% were heterozygous (AG). We observed no significant difference in the distribution of positive bronchial reactivity to methacholine (at FEV1PC20of ≤ 8 mg/mL) across the three genotypes. Homozygous individuals for the CC16*A allele did not demonstrate an increased risk of asthma when compared to heterozygous or GG homozygotes. In addition, no significant difference was observed in the distribution of the CC16*A or *G alleles in the asthmatics vs. non‐asthmatics.

ConclusionCC16 polymorphism A38G does not influence the predisposition to asthma in this sample.
High‐level expression of recombinant house dust mite allergen Der p 1 in Pichia pastoris
Authors: Jacquet A. , Magi M. , Petry H. , Bollen A.
Published: March 2003

Background The major house dust mite Der p 1 allergen is associated with allergic disease. Heterologous over‐expression of biologically active Der p 1 was previously attempted but with limited success.

Objective The aim of this study was to establish an efficient system for the production of recombinant Der p 1.

Methods The proform of Der p 1 was expressed in Pichia pastoris as a fusion with the α mating factor signal sequence. The recombinant product was purified from culture medium and compared to Der p 1 isolated from mite culture, in terms of enzymatic activity as well as IgE binding capacity.

Results ProDer p 1 was efficiently secreted into culture medium as a hyperglycosylated protein of 40–60 kDa. Postpurification dialysis in acidic buffer was required for the autocatalytic processing of Der p 1. During this treatment, the prosequence was efficiently removed to give highly glycosylated recombinant mature Der p 1. Competition ELISA experiments as well as cysteine proteinase activity assays indicated that recombinant processed Der p 1 was similar to natural Der p 1 isolated from mite cultures in terms of IgE binding and enzymatic activities. However, the histamine releasing activity of recombinant Der p 1 was slightly weaker than that of natural Der p 1.

Conclusion This efficient system for recombinant Der p 1 expression leads the way for the design of new diagnostics for house dust mite allergy, epitope mapping, allergen engineering, structural and immunological studies and new immunotherapeutic treatments.
The use of a neural network to forecast daily grass pollen concentration in a Mediterranean region: the southern part of the Iberian Peninsula
Authors: Sánchez‐Mesa J. A. , Galan C. , Martínez‐Heras J. A. , Hervás‐Martínez C.
Published: March 2003

BackgroundPollen allergy is a common disease causing hayfever in 15% of the population in Europe. Medical studies report that a prior knowledge of pollen content in the air can be useful in the management of pollen‐related diseases.

ObjectivesThe aim of this work was to forecast daily Poaceae pollen concentrations in the air by using meteorological data and pollen counts from previous days as independent variables.

MethodsLinear regression models and co‐evolutive neural network models were used for this study. Pollen was monitored by a Hirst‐type spore trap using standard techniques. The data were obtained from the Spanish Aerobiology Network database, University of Cordoba Monitoring Unit. The set of data includes a series of 20 years, from 1982 to 2001. A classification of the years according to their allergenic potential was made using a K‐mean cluster analysis with pollen and meteorological parameters. Statistical analysis was applied to all the years of each class with the exception of the most recent year, which was used for model validation.

ResultsIt was observed that cumulative variables and pollen values from previous days are the most important factors in the models. In general, neural network equations produce better results than linear regression equations.

ConclusionCo‐evolutive neural network models, which obtain the best forecasts (an almost 90%“good” classification), make it possible to predict daily airborne Poaceae pollen concentrations. This new system based on neural network models is a step toward the automation of the pollen forecast process.
Allergy development after bone marrow transplantation from a non‐atopic donor
Authors: Shalit M. , Amar A. , Or R.
Published: March 2003

Background Transfer of allergy from atopic bone marrow donors to recipients is known to occur. Development of allergy in a non‐atopic patient transplanted from a non‐atopic donor is an unfamiliar phenomenon in clinical practice.

Objectives To clarify the course of events causing a bone marrow recipient to acquire an allergic disease in such non‐conducive circumstances.

Methods Full medical history, prick and intradermal skin tests, and serum IgE levels were obtained from both donor and recipient patients. DNA and red blood cell phenotype analyses were used to detect the degree of chimerism.

Results Only the recipient patient showed positive specific IgE antibodies and skin tests to house dust mite. The recipient patient displayed 100% donor chimera, based on all engraftment markers sought.

Conclusion Full engraftment after allogeneic bone marrow transplantation may be associated with modulation ofT and B cell function, which in turn could cause the onset of allergic disease after bone marrow transplantation.
Polyclonal and allergen‐induced cytokine responses in children with elevated immunoglobulin E but no atopic disease
Authors: Smart J. M. , Tang M. L. K. , Kemp A. S.
Published: March 2003

Background Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease.

Objective To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non‐atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non‐atopic controls were compared.

Methods We examined allergen‐induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non‐atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years).

Results Symptomatic atopic children had reduced SEB‐induced IFN‐γ and increased SEB‐induced IL‐4 and IL‐5 as compared with non‐atopic controls. In contrast, SEB‐induced IFN‐γ, IL‐4 and IL‐5 production in asymptomatic atopics was not significantly different from the non‐atopic control subjects. Allergen‐induced Th1 (IFN‐γ) and Th2 (IL‐5 and IL‐13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non‐atopic controls.

Conclusion The defect in polyclonally induced IFN‐γ production was associated with the clinical manifestation of atopic disease but not the atopic state per se. This suggests that the global reduction in IFN‐γ is the key determinant of the development of overt atopic disease. In contrast, elevated allergen‐induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.
Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey
Authors: Jaén A. , Sunyer J. , Basagaña X. , Chinn S. , Zock J. P. , Antó J. M. , Burney P. ,   the European Community Respiratory Health Survey (ECRHS)
Published: March 2003

Background The role of atopy in the evolution to chronic obstructive disease remains controversial.

Aim We aimed to assess the association between individual sensitization to common allergens and lung function.

Method We analysed data from 12 687 subjects aged 20 to 44 years, from 34 centres in 15 countries participating in the European Community Respiratory Health Survey (ECRHS). Participants performed a blood test, lung function test, methacholine challenge, and answered an administered questionnaire. The relationships between specific IgE, FEV1 and FEV1/FVC ratio were assessed for each study centre stratified by sex, followed by random effects meta‐analysis.

Results Asthmatics sensitized to house dust mite had a lower FEV1 (− 119 mL in women and − 112 mL in men) and FEV1/FVC ratio (− 1.95%, and − 2.48%) than asthmatics without sensitization. Asthmatics sensitized to cat had a lower FEV1 (statistically significant for women only) and a lower FEV1/FVC ratio. Asthmatic women sensitized to grass had a lower FEV1 and a lower ratio, and those sensitized to Cladosporium had a lower FEV1. A weak association was found with sensitization to cat and to Cladosporium among non‐asthmatic women, which disappeared after adjusting for BHR.

Conclusion We conclude that atopy was related to a lower lung function, which was only apparent among asthmatics. This relationship was explained by specific sensitization to cat and to house dust mite, the latter being homogeneous across areas.
Evaluation of the CD14 C‐159 T polymorphism in the German Multicenter Allergy Study cohort
Authors: Sengler C. , Haider A. , Sommerfeld C. , Lau S. , Baldini M. , Martinez F. , Wahn U. , Nickel R. ,   the German Multicenter Allergy Study Group
Published: March 2003

Background Multiple genetic studies have shown linkage of atopy‐related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL‐4, IL‐5 and IL‐13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness.

Objective The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort.

Methods Atopy‐related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight‐hundred and seventy‐two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses.

Results CD14‐159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed.

Conclusion The CD14‐159 SNP might not play a major role in the development of atopy in German children.