bluuebunny/crossref_metadata_2025 huggingface dataset:
Is puberty getting earlier? The views of doctors and teachers
Authors: Finlay F. O. , Jones R. , Coleman J.
Published: March 2003

Aims To determine the views of teachers, general practitioners (GPs) and paediatricians about whether there has been a recent change in the timing of the onset of puberty in children in the UK and in the timing of menarche in girls.

Design Questionnaires were sent to a stratified random sample of each professional group.

Results In relation to girls, almost 80% of teachers believe that the onset of puberty is occurring earlier, and 73% feel that the menarche is occurring earlier. Those who had been working for longer than 10 years were more likely to say that the age of onset of puberty had decreased. GPs feel that both puberty and menarche are starting earlier, whereas paediatricians were evenly divided between those who thought puberty was starting earlier and those who thought that the timing had not changed. In boys, professionals generally believe that the timing of the onset of puberty has not altered significantly.

Conclusion Further study is required to determine whether puberty is really occurring earlier in girls.
Financial effects for families after the death of a disabled or chronically ill child: a neglected dimension of bereavement
Authors: Corden A. , Sloper P. , Sainsbury R.
Published: March 2003

Aim To investigate the financial circumstances of families whose child had died after a long‐term illness and the factors contributing to financial difficulties.

Research methods Qualitative exploration involved semi‐structured interviews with a purposive sample of 16 families whose child had died in the last 2 years and who were in touch with a children’s hospice.

Results All parents were affected by loss of or reduction in social security benefits. This could result in an immediate drop in income of as much as 72%. Paying for funerals and headstones could be hard. Financial problems after the child’s death often had origins in the period of care, when parents had reduced incomes but faced extra costs of care. Some families had got into debt. Re‐engaging with employment could be a slow process, and it was not clear where professional responsibility lay in providing financial advice and support. Insensitive treatment by administrative agencies increased problems for parents.

Discussion Findings provide further evidence of the financial impact for families of caring for severely disabled children. This study shows how this impact can extend far into the period after death. Findings indicate the need for financial advice and support to families both during the period of care and after bereavement.
The meaning of a multimodal approach for children with ADHD: experiences of service professionals
Authors: Hazelwood E. , Bovingdon T. , Tiemens K.
Published: March 2003

Background Attention‐Deficit/Hyperactivity Disorder (ADHD) is a childhood mental disorder characterized by inattention, impulsiveness and overactivity. It is also characterized by heterogeneity and ambiguity. Effective intervention is influenced by these two factors. This pervasive disorder impacts various domains of functioning, including academics, peer relations, familial relationships and self‐esteem. A confounding factor is the high rate of comorbidity with diagnoses such as learning disabilities, oppositional defiant disorder or conduct disorder. No one intervention has emerged as maximally effective across all symptoms and domains. Consequently, a multimodal approach is regarded as the favoured method of intervention. However, no clear definition of ‘multimodal’ exists.

Method This study explored the meaning of multimodal from the perspective of professionals employed in a tertiary care hospital setting in which children with ADHD are assessed and treated. A qualitative design using a phenomenological approach allowed professionals to speak from their practice experiences.

Results and Conclusion Although no clear definition of multimodal emerged, professionals identified issues key to this approach and proposed a model for intervention.
Involving disabled and chronically ill children and young people in health service development
Authors: Sloper P. , Lightfoot J.
Published: March 2003

Aim   To investigate the extent and nature of involvement of physically disabled or chronically ill children and young people in local health service development.

Methods   A postal survey of all health authorities (n = 99) and NHS Trusts (n = 410) in England.

Results   Seventy‐six per cent of health authorities and 59% of Trusts responded. Twenty‐seven initiatives involving chronically ill or disabled children and young people in consultation regarding service development were identified. Over half of these were carried out in partnership between health services and other agencies, usually local authorities and/or voluntary organizations. A variety of methods was used for consultation, including child‐friendly methods such as drawing, drama and making a video. Seventeen initiatives reported that children's involvement had resulted in service changes, but only 11 went beyond consultation to involve children and young people in decision making about service development. Only a third of the organizations had someone with designated responsibility for children's involvement.

Discussion   The involvement of this group of children and young people in service development in the NHS is at an early stage. The failure of policy documents on user involvement to identify children and young people as a group for whom methods of consultation need to be developed, and the lack of people with designated responsibility for developing children's involvement may be a reason for slow progress in this area. The initiatives identified show that such involvement is possible and can have a positive impact on services.
Mechanisms of acute eosinophilic inflammation in a case of acute eosinophilic pneumonia in a 14‐year‐old girl
Authors: Godding  , Bodart  , Delos  , Sibille  , Galanti  , DE Coster  , Jarjour  , Busse
Published: March 2003

Background

Acute eosinophilic pneumonia (AEP) is characterized by respiratory distress, eosinophilic infiltration in the lung, acute onset, resolution of symptoms with corticosteroids and the absence of relapse. Studies to identify the pathophysiology of AEP in adults have demonstrated eosinophil activation in the BAL fluid, and the presence of high levels of interleukin 5 (IL‐5) in the BAL.

Objective

To investigate the pathophysiology of AEP with pleural effusion in a paediatric patient.

Methods

ECP levels in the BALand pleural fluid was determined by radioimmunoassay. IL‐5 and GM‐CSF concentrations in the BAL and pleural fluid were measured by Elisa. Immunohistochemistry studies performed on open lung biopsy included a specific ICAM‐1 immunostaining and a ECP specific immunostaining (EG2+).

Results

High levels of ECP were found in the BAL (5 μg/L) and pleural fluid (750 μg/L) demonstrating eosinophil activation at these sites. Immunohistochemistry illustrated activated (EG2+) eosinophils in the interalveolar septa and alveolar space and detected increased expression of ICAM‐1 on alveolar epithelial cells. High levels of IL‐5 were measured in the BAL (1334 pg/mL) and pleural fluid (7014 pg/mL), while elevated concentrations of GM‐CSF (150 pg/mL) were found in the BAL.

Conclusion

We conclude that in this paediatric patient with AEP activated eosinophils were present in the BAL fluid, in the interalveolar septa and in the pleural space while increased ICAM‐1 expression was detected on alveolar epithelial cells, contributing, at least partly, for their adhesive interactions. IL‐5 and GM‐CSF are likely important to the massive eosinophil recruitment and activation in the lung, while IL‐5 is probably related to eosinophil accumulation and activation in the pleural space. Thus, lung generation of eosinophil‐active cytokines is central to the pathophysiology of AEP in paediatric patients.
Exhaled and nasal nitric oxide is increased in laboratory animal allergy
Authors: Adisesh  , Kharitonov  , Yates  , Snashell  , Newman‐Taylor  , Barnes
Published: March 2003

Background

Allergens from rats, mice, guinea pigs or rabbits cause up to 30% of exposed persons to develop specific immunoglobulin E (IgE) responses. Laboratory animal allergy (LAA) is among the highest occupational risks for asthma in the UK. Elevated levels of nitric oxide (NO) are found in exhaled breath in asthma. In LAA symptoms may progress from conjunctivitis, rhinitis to asthma. Health surveillance aims to detect early sensitization.

Objective

To assess whether an association exists between LAA and exhaled NO.

Methods

A cross‐sectional study was performed in 39 laboratory workers undergoing LAA health surveillance. Volunteers completed two health questionnaires, had skin‐prick tests, spirometry, total IgE and RAST tests. Exhaled and nasal NO was measured by chemiluminescence analyser (LR2000, Logan Research, Rochester, UK).

Results

There were 23 asymptomatic subjects (mean age 29.53 yearss) and 16 symptomatic subjects (29.63 yearss, P = 0.95); 9 early LAA, seven LAA asthma. Exhaled NO was raised in those with LAA symptoms 17.97 ppb ± 1.24 (mean ± SEM) compared with asymptomatics 6.08 ppb ± 1.15, P < 0.05. A trend of increased NO by allergic status was observed; asymptomatic, to early LAA, to asthma. One‐way analysis of variance compared differences between groups (F ratio 13.93, P < 0.001). Symptomatic subjects also had raised nasal NO, vs asymptomatic subjects (mean difference 378 ppb, P < 0.05). A trend was again observed by allergic status (F ratio 5.28, P = 0.01).

Conclusion

Raised NO levels in LAA increasing with symptom severity suggest NO may prove a useful additional tool in monitoring for LAA, and possibly the response to exposure reduction or allergy due to other respiratory sensitizers.
Intranasal salmeterol inhibits allergen‐induced vascular permeability but not mast cell activation or cellular infiltration
Authors: Proud  , Reynolds  , Lichtenstein  , Kagey‐Sobotka  , Togias
Published: March 2003

Background

Salmeterol is a long‐acting β2‐adrenergic agonist that is widely used in the treatment of asthma. It has been suggested that non‐bronchodilator actions of salmeterol may contribute to its efficacy.

Objective

To further evaluate the potential non‐bronchodilator actions of salmeterol in vivo, using a model of nasal challenge with allergen.

Methods

Twelve asymptomatic subjects with seasonal allergic rhinitis participated in a randomized, double‐blind, placebo‐controlled crossover trial of the effects of a single dose of 100 μg of salmeterol on the response to allergen challenge. Sneezing and symptom scores, and levels of histamine and albumin in nasal lavages, were measured throughout the protocol. Concentrations of tryptase, prostaglandin D2 and lysozyme were measured during the acute allergic response, while levels of IL‐3, IL‐5 and IL‐8 were measured at later time points. Numbers of eosinophils and of total white blood cells were also recorded.

Results

Salmeterol did not affect sneezing or symptom scores at any point. During the immediate response to allergen challenge, mast cell activation, reflected by concentrations of histamine, tryptase and prostaglandin D2, and serous glandular secretion, assessed by measurements of lysozyme, were unaffected by salmeterol treatment but vascular permeability, reflected by concentrations of albumin in nasal lavages, was significantly reduced. At later time points, salmeterol had no effect on levels of histamine or albumin and did not affect cellular infiltration. Concentrations of IL‐3, IL‐5 and IL‐8 were not increased by allergen challenge in these subjects, so the effects of salmeterol could not be evaluated.

Conclusions

Treatment with a single dose of salmeterol had no effect on activation of mast cells or cellular infiltration but inhibited vascular permeability. The ability of salmeterol to inhibit antigen‐induced vascular permeability may contribute to its therapeutic efficacy in asthma.
The interleukin‐5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome
Authors: HO  , HO  , Leung  , Lai  , Lai
Published: March 2003

Interleukin‐5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T‐lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL‐5 gene expression by CD4+ T‐lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL‐5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.
Effects of SR 140333 and SR 48968 on antigen and substance P‐induced activation of guinea‐pig alveolar macrophages
Authors: Boichot  , Germain  , Emonds‐Alt  , Advenier  , Lagente
Published: March 2003

Background

Tachykinins, such as substance P, might be involved in the development of airway hyperresponsiveness and airway inflammation.

Objective

This study was designed to investigate the effects of the tachykinin NK1 receptor antagonist SR 140333 (Nolpitantium) and the NK2 receptor antagonist SR 48968 (Saredutant) on the activation of alveolar macrophages in the guinea‐pig.

Methods

Guinea‐pigs sensitized and challenged by ovalbumin administered by aerosol or naive guinea‐pigs were exposed by aerosol to the neutral endopeptidase, phosphoramidon and, 15 min later, to substance P. Twenty‐four hours later, bronchoalveolar lavages were performed and the cell composition of bronchoalveolar lavage fluids and the arachidonate release from alveolar macrophages stimulated in vitro with fMLP were evaluated.

Results

Antigen challenge in sensitized guinea‐pigs induced an increase in the total number of cells and granulocytes in the bronchoalveolar lavage fluids that was not reduced by pre‐treatment of guinea‐pigs with a single dose of SR 140333 or SR 48968 (1 mg/kg). Substance P exposure in phosphoramidon‐pretreated guinea‐pigs did not induce an increase in the total number of cells. In contrast, antigen or substance P exposure induced a significant increase in the in vitro fMLP‐induced arachidonate release from alveolar macrophages. Pre‐treatment of the guinea pigs with SR 140333 or SR 48968 did not reduce the increase in arachidonate release from fMLP‐stimulated alveolar macrophages from sensitized and challenged guinea‐pigs. Pre‐treatment of the animals by SR 140333 and SR 48968 reduced the enhanced arachidonate release induced by fMLP from substance P‐exposed guinea‐pigs.

Conclusion

The present data demonstrate the importance of NK1‐ and NK2‐receptor stimulation in the development of substance P‐induced increased reactivity of alveolar macrophages.
T‐cell‐mediated cytotoxicity against keratinocytes in sulfamethoxazol‐induced skin reaction
Authors: Schnyder  , Frutig  , Mauri‐Hellweg  , Limat  , Yawalkar  , Pichler
Published: March 2003

Background

The incidence of skin rashes or erythema multiforme to sulfamethoxazole in exposed patients is about 3%. Among patients with acquired immunodeficiency syndrome the risk is ≈ 10 times higher. The pathogenesis of these reactions and the reason for the increased frequency in HIV infections are not understood.

Objective

To investigate drug specific T‐cell‐mediated cytotoxicity in sulfamethoxazole‐ induced skin reactions.

Methods

Specific T‐cell lines and T‐cell clones generated from a donor who developed a skin rash to sulfamethoxazole were assessed with a standard 4 h 51Cr cytotoxicity assay in the presence or absence of soluble sulfamethoxazole. B lymphoblasts and keratinocytes with and without interferon gamma pretreatment were used as target cells. Selective blockers of FasL/Fas and perforin‐mediated killing and immunostaining for perforin were used to evaluate the involvement of the different cytolytic pathways.

Results

CD4+ and CD8+ sulfamethoxazole specific T‐cell clones showed a drug‐specific and MHC‐restricted cytotoxicity against autologous B lymphoblasts in the presence of soluble sulfamethoxazole. Keratinocytes, if pretreated with interferon gamma, were specifically killed predominantly by CD4+ T‐cell clones. Specific T‐cell clones of both CD4+ and CD8+ phenotype showed a strong immunoreactivity for perforin and the cytotoxicity was blocked by concanamycin A which suggests a perforin‐mediated killing.

Conclusion

Perforin‐mediated killing of autologous keratinocytes in the presence of soluble sulfamethoxazole by drug‐specific CD4+ lymphocytes may be a pathway for generalized drug‐induced delayed skin reactions. The requirement of interferon gamma pretreatment of keratinocytes for efficient specific killing might explain the increased frequency of drug allergies in generalized viral infections like HIV, when interferon gamma levels are elevated.
Polarized TH1 responses by liposome‐entrapped allergen and its potential in immunotherapy of allergic disorders
Authors: Sehra  , Chugh  , Gangal
Published: March 2003

Background

The conventional immunotherapy used for treating allergic individuals may at times lead to varying degrees of anaphylactic reaction. Liposomes have been proposed as a vehicle for safe and effective allergen‐specific immunotherapy as multiple injections of liposome‐entrapped allergen (LEA) have been shown to reduce specific IgE response and induce specific IgG response in BALB/c mice.

Objective and methods

To elucidate the effect of LEA on polarization of T‐cell responses, its effect on the relative production of TH1/TH2 type cytokines (namely IL‐2, IL‐4 and IFN‐γ by commercially available ELISA kits and immunoglobulin profile as measured by ELISA) were studied. Histamine release on challenge of immunized mice was measured to examine the efficacy of LEA in preventing anaphylactic reactions.

Results

Measurement of cytokine levels in serum and spleen cell culture supernatants of BALB/c mice injected repeatedly with either free allergen (FA) or LEA (three mice per group) indicate that LEA preferentially induces a TH1‐type of response dominated by IFN‐γ and IL‐2 production. Further, it was also shown that immunization of mice with FA or LEA and subsequent challenge with a large dose of the sensitizing allergen leads to fatal systemic reactions in 50–65% of the animals treated with FA, whereas no mortality was observed in mice injected with LEA. Analysis of IgG subclasses in sera of mice immunized with LEA revealed a sixfold higher production of IgG1 antibodies than mice immunized with FA. Serum IgG2a, IgG2b, IgG3 and IgM responses were also enhanced in the group of mice immunized with LEA in comparison with mice injected with FA.

Conclusion

The results indicate that LEA confers protection against anaphylaxis to mice due to their ability to induce a high IFN‐γ:IL‐4 ratio which may lead to decreased synthesis of IgE and reduced histamine release on challenge with FA.
Factors determining the severity of asthma
Authors: Wenzel
Published: March 2003

Asthma typically can range from a disease of very mild and intermittent symptoms to one of debilitating and life‐threatening disease. However, the factors that control these differences remain poorly understood. It is likely that the factors controlling the severity of asthma are many and dependent on each other. Potential factors include: (i) inflammatory; (ii) structural; (iii) hereditary/congenital; (iv) environmental; and (v) psychological/emotional; each potentially interacting and influencing the other. Finally, the question remains as to whether all asthmatics, no matter what their initial severity, potentially can develop severe disease, or whether only a certain subgroup will become severe.
Gene by environment interaction and asthma
Authors: Weiss S. T.
Published: March 2003

The term interaction has two specific meanings in epidemiology. The first definition is purely a statistical one. Interaction is defined as the coefficient of the product term of two or more risk factors. An alternative definition is a more biologically oriented one in which interaction between two risk factors is defined as their coparticipation in the same causal mechanism of disease development. There are at least five different types of biological gene by environment interaction. It is important to recognize that clinical or epidemiological studies alone are unable to distinguish between these five different types of biological interaction. Asthma is a prototypical complex trait in which gene by environment interaction is important in disease causation. Environmental factors important in asthma include cigarette smoking (active/passive), allergen exposure, viral and bacterial respiratory illness, occupation, and possibly diet. There are two primary study designs that have been utilized for the assessment of gene by environment interaction: a traditional case control study or a nested case control study or a case control study nested within the larger longitudinal cohort. There are three important methodological issues in the assessment of gene by environment interaction. The first is the issue of misspecification of either genotype or environmental exposure or, for that matter, disease status. The second is possible confounding, and the third is the confounding of interaction with dose response. The four most critical factors for determining sample size for gene by environment interaction studies are the odds ratio for the interaction, the prevalence for exposure in the population, the prevalence of the genotype in the population, and the case to control ratio. In general, sample sizes have been too small to detect meaningful gene by environment interactions.
Increasing prevalence of asthma over 12 years among dairy farmers on Gotland, Sweden: storage mites remain dominant allergens
Authors: KRONQVIST  , JOHANSSON  , PERSHAGEN  , JOHANSSON  , VAN HAGE‐HAMSTEN
Published: March 2003

Background

Earlier studies from several countries have shown that IgE‐mediated allergy in rural populations is of considerable importance and that storage mites are dominant allergens.

Objective

In an epidemiological follow‐up study among farmers on the island of Gotland, Sweden in 1996 we wished to investigate the prevalence of respiratory allergy and to find out whether storage mites are still important allergens in a farming environment.

Methods

A questionnaire concerning airway symptoms, social and working conditions and smoking habits was distributed to all Gotland farmers aged 15–65 years and was completed by 1577 (86.7%), of whom 1015 were dairy farmers. Based on the answers, 500 dairy farmers were invited to undergo a medical examination which included a skin‐prick test (SPT) and blood sampling for RAST analyses. Prevalence figures (symptoms, RAST and SPT) given for the whole population (n  =  1015) were based on the investigation of the 461 farmers who took part in the examination.

Results

Immediate onset hypersensitivity was present in 41.7% of the 1015 farmers studied, which is almost the same figure as in 1984 (40.0%). The prevalence of asthma had increased significantly during the previous 12 years (5.3% vs 9.8%), as had asthma in combination with rhinoconjunctivitis (3.7% vs 7.0%). Rhinoconjunctivitis, on the other hand, had not changed significantly (36.5% vs 33.1%) and remained one of the most common symptoms. The prevalence of storage mite allergy in the farming population in 1996 was 6.5% and constituted an important cause of allergic symptoms.

Conclusion

Over 12 years, Gotland dairy farmers have developed significantly more respiratory symptoms from the lower airways, although the proportion with atopy is unchanged. Storage mites are still dominant allergens for developing allergic disease.
Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community
Authors: BRAUN‐FAHRLÄNDER  , GASSNER  , GRIZE  , NEU  , SENNHAUSER  , VARONIER  , VUILLE  , WÜTHRICH  ,   THE SCARPOL TEAM
Published: March 2003

Introduction

Lower prevalence rates of allergic diseases in rural as compared with urban populations have been interpreted as indicating an effect of air pollution. However, little is known about other factors of the rural environment which may determine the development of atopic sensitization and related diseases.

Objective

The authors tested the hypothesis that children growing up on a farm were less likely to be sensitized to common aerollergens and to suffer from allergic diseases than children living in the same villages but in nonfarming families.

Materials and methods

Three age groups of schoolchildren (6–7 years, 9–11 years, 13–15 years) living in three rural communities were included in the analyses. An exhaustive questionnaire was filled in by 1620 (86.0%) parents. A blood sample was provided by 404 (69.3%) of the 13–15 year olds to determine specific IgE antibodies against six common aeroallergens.

Results

Farming as parental occupation was reported for 307 children (19.0%). After adjustment for potential covariates such as family history of asthma and allergies, parental education, number of siblings, maternal smoking, pet ownership, indoor humidity and heating fuels, farming as parental occupation was significantly associated with lower rates of sneezing attacks during pollen season (adjusted OR 0.34, 95% CI 0.12–0.89) and atopic sensitization (adjusted OR 0.31, 95% CI 0.13–0.73) whereas the association with wheeze (adjusted OR 0.77 95% CI 0.38–1.58) and itchy skin rash (adjusted OR 0.86, 95% CI 0.49–1.50) was not statistically significant. The risk of atopic sensitization was lower in children from full‐time farmers (adjusted OR 0.24, 95% CI 0.09–0.66) than from part‐time farmers (adjusted OR 0.54, 95% CI 0.15–1.96).

Conclusion

Factors directly or indirectly related to farming as parental occupation decrease the risk of children becoming atopic and developing symptoms of allergic rhintis.
Atopy patch test reactions are associated with T lymphocyte‐mediated allergen‐specific immune responses in atopic dermatitis
Authors: WISTOKAT‐WÜLFING  , SCHMIDT  , DARSOW  , RING  , KAPP  , WERFEL
Published: March 2003

Background

Positive test reactions to epicutaneous application of aeroallergens served as a model of ‘early’ eczema in atopic dermatitis (AD) in a number of dermato‐immunological studies. However, no quantitative evaluation has been performed so far comparing specific T‐cell activation parameters in the peripheral blood of AD patients with positive or negative atopy patch tests (APT).

Objective

The purpose of this study was to investigate specific immunological parameters in patients with atopic dermatitis showing positive or negative atopy patch tests reactions.

Methods

APT results (n = 96) were compared with allergen‐specific IgE, specific lymphocyte proliferation, and the expression of ‘activation’ markers on peripheral blood T‐cells upon in vitro stimulation with house dust mite, cat or grass pollen allergens.

Results

Only a subpopulation (48%) of patients sensitized to aeroallergens (i.e. specific IgE > 0.7 kU/L) developed APT‐reactions to the corresponding allergen. APT reactions were, however, significantly associated with allergen specific lymphocyte proliferation (p < 0.0001), and a higher number of CD54+ or CD30+ T‐cells (p < 0.05) upon in vitro stimulation.

Conclusion

The association of delayed skin reactions with allergen specific T‐cell parameters in the blood points to an immunologically mediated mechanism leading to positive reactions in the APT.
How far can we simplify in vitro diagnostics for Fagales tree pollen allergy? A study with three whole pollen extracts and purified natural and recombinant allergens
Authors: VAN REE  , VAN LEEUWEN  , AKKERDAAS  , AALBERSE R. C.
Published: March 2003

Background

Current diagnostic tests for Fagales tree pollen allergy are often composed of mixtures of pollen of birch, alder and hazel. Their complex composition hampers accurate standardization.

Objective

The aim of this study was to investigate whether mixtures of tree pollen extracts can be replaced by a single pollen species, and whether a single pollen species can be replaced by a limited number of purified natural or recombinant major allergens.

Methods

Sera (n = 1725) were selected on ground of a general suspicion for inhalant allergy, and tested in a RAST for birch, alder and hazel pollen. Sera with > 0.5 RU/mL for any of the three species were tested in a RAST for natural Bet v 1 and Bet v 2 as well as for recombinant versions of both allergens.

Results

Specific IgE antibodies (> 0.3 RU/mL) against birch, alder and hazel were found in 242, 298 and 292 sera, respectively. All sera with a positive RAST for alder and/or hazel and a negative RAST for birch were low‐responder sera on alder and hazel, only five sera having a RAST value > 1.0 (all < 2.0). For all sera with a RAST > 0.5 RU/mL (n = 250), the mean of individual ratio's alder/birch and hazel/birch was 1.02 and 0.54, respectively. Of 223 of these sera, 63.2% had specific IgE against natural Bet v 1 and 63.7% against natural Bet v 2. When responses to both allergens were combined 93.7% were positive. The mean ratios Bet v 1 + 2/extract were 1.00, 1.04 and 2.11 in case of birch, alder and hazel, respectively. For 211 sera the same analysis was performed with recombinant Bet v 1 and Bet v 2. Only six sera with Bet v 1‐specific IgE (all < 0.5 RU/mL) were negative (< 0.3 RU/mL) on recombinant Bet v 1. For Bet v 2, 77/132 sera with specific IgE to the natural allergen did not react to the recombinant version. Twelve false‐negatives had RAST values > 1.0 RU/mL. The mean of the individual recombinant/natural ratios was 0.98 for Bet v 1 and 0.38 for Bet v 2 (P < 0.001). The mean ratio rBet v 1 + 2/birch was 0.75 with 17.5% false‐negatives on the combination of recombinant allergens.

Conclusion

Reliable in vitro diagnosis is possible with a single tree pollen extract (birch or alder). The same is true for purified natural Bet v 1 and Bet v 2. A combination of recombinant molecules is slightly less efficient.
Monitoring allergen immunotherapy of pollen‐allergic patients: the ratio of allergen‐specific IgG4 to IgG1 correlates with clinical outcome
Authors: GEHLHAR  , SCHLAAK  , BECKER  , BUFE
Published: March 2003

Background

Although allergen immunotherapy has been established as a treatment of type I allergy back in 1911, until now the underlying mechanisms have not been fully understood, nor are there any parameters which would allow one to monitor an ongoing treatment or to assess therapeutic success in the meantime.

Objective

We wanted to define allergen‐specific parameters that change due to treatment in correlation with the clinical outcome.

Methods

We conducted a controlled study with grass pollen‐allergic children and compared allergen‐specific antibody titres before and 1 year after the onset of immunotherapy in contrast with untreated allergic and healthy children. Two recombinant forms of the major allergen group V of Phleum pratense (Phl p 5) served as model allergens.

Results

No change in IgE levels and no significant reduction of skin prick test (SPT) reactivity were seen. On the other hand, a significant reduction of symptom scores in the treated group and a significant rise in allergen‐specific IgG1, IgG2 and IgG4 due to the treatment could be observed, but in neither case could we establish a correlation between the increasing amounts of the single antibody classes and the reduction of symptom scores. But most interestingly, when comparing the ratio of IgG4 to IgG1 with the symtom scores, we found significant correlations. Nevertheless, treated allergic patients still differ considerably from healthy controls as nonatopics have hardly any measurable allergen‐specific IgG antibodies and no IgE antibodies at all.

Conclusion

The ratio of IgG4 to IgG1 can serve as a valuable parameter that allows us to assess the success of immunotherapy already 1 year after the onset. The increase of specific IgG1 in relation to IgG4 during treatment reflects a possible influence of this subclass on the induction of tolerance towards allergens.
Risk factors for latex allergy in patients with spina bifida and latex sensitization
Authors: BERNARDINI  , NOVEMBRE  , LOMBARDI  , MEZZETTI  , CIANFERONI  , DANTI  , MERCURELLA  , VIERUCCI
Published: March 2003

Background

Some subjects with spina bifida (SB) and latex sensitization (cutaneous and/or serum IgE) can have clinical reactions, while others may have no symptoms after the exposure to latex products.

Objective

This study was carried out to determine the risk factors associated with latex allergy in patients affected with SB and latex sensitization.

Methods

Fifty‐nine consecutive subjects affected with SB, besides answering a questionnaire, underwent a skin‐prick test (SPT) to latex and the determination of the specific serum IgE (RAST CAP) to latex. The total serum IgE concentration was determined and SPT to common aero‐ and food‐allergens, skin tests (prick + prick) with fresh foods (kiwi, pear, orange, pineapple, tomato, banana) and RAST CAP to the same foods tested by the prick + prick technique, were also performed.

Results

Fifteen out of the 59 subjects (25%) were sensitized to latex according to the presence of IgE to latex detected by SPT (nine patients) and/or RAST CAP (13 patients). Five out of the 15 sensitized patients (33%) suffered from clinical reactions to latex (urticaria, conjunctivitis, angioedema, rhinitis, bronchial asthma) while they were using latex gloves and while inflating latex balloons. In the 15 sensitized patients, the presence of specific latex seric IgE > 3.5 kU/L (≥ class 3), a positive latex SPT, an elevated total serum IgE, and a positive prick + prick and/or a positive RAST CAP to foods, were significant (P < 0.05) risk factors associated with latex symptoms. The other factors tested (age, gender, months of intermittent bladder catheterization, surgical procedures, SPT reactivity and clinical reactions to aero‐allergens and food‐allergens, skin tests for fresh foods, positive RAST CAP to foods) were not significantly different in symptomatic and asymptomatic patients.

Conclusion

Significant risk factors for symptoms to latex in patients with SB and latex sensitization were a presence of specific IgE to latex > 3.5 kU/L, a more frequent positive latex SPT, elevated total IgE, and one or more positive prick + prick and/or RAST CAP to fresh foods.
Allergy to the pine processionary caterpillar (Thaumetopoea pityocampa)
Authors: Vega  , Moneo  , Armentia  , Fernández  , Vega  , De La Fuente  , Sánchez  , Sanchís
Published: March 2003

Background

The contact with the pine processionary caterpillar (Thaumetopoea pityocampa) induces dermatitis and ocular lesions by a mechanic and toxic mechanism. However, IgE‐mediated hypersensitivity to this caterpillar has been demonstrated in two recent studies.

Objective

To find if an IgE‐mediated mechanism was operative among patients with suspected previous reactions to processionary caterpillars, particularly exposed workers.

Methods

Fifty‐five patients were studied by skin prick test (SPT), and specific IgE detection by immunoblotting.

Results

A total of 58.18% patients had a positive SPT for caterpillar extract. Positive SPT patients had more generalized cutaneous reactions (47%) and oedema (50%) as well as a shorter latency period (mean, 36 min) and duration of cutaneous lesions (mean, 26 h) than the patients with negative SPT. A total of 60% of the positive SPT patients had occupational exposure to the processionary caterpillar. The occupationally exposed workers showed significant symptoms from October to December. The anaphylactic reactions only appeared in allergic patients with occupational exposure and were also more frequent from October to December. These patients with anaphylactic reactions had a major size of SPT and the exercise was found in them to be a variable that increased the symptoms. The IgE immunoblot detected in the caterpillar extract several reactive bands with apparent molecular weights from to 35–4 kDa in 72% of the cases with positive SPT.

Conclusions

Allergic reactions to T. pityocampa urticating hairs have different clinical characteristics than those induced by a toxic‐irritative mechanism and are more frequent than suspected. Allergic reactions to this caterpillar among occasional visitors to pine‐wood areas, and particularly in pine‐forest workers, should be taken into consideration by allergists.
Expression of interleukin (IL)‐12 (p40) and IL‐12 (β2) receptors in allergic rhinitis and chronic sinusitis
Authors: Wright  , Christodoulopoulos  , Frenkiel  , Hamid
Published: March 2003

Background

Interleukin (IL)‐12 is a relatively new and structurally distinct TH1‐associated cytokine produced by B cells and macrophages, which may play a suppressive role in the development of allergic sinonasal mucosal responses.

Objective

We investigated the expression of IL‐12 (inducible p40 subunit) and its receptor (IL‐12R β2 subunit) in tissue biopsies of naturally exposed patients with allergy‐associated (ACS) and nonallergy‐associated chronic sinusitis (NCS) and compared it with controls. We also examined IL‐12 and IL‐12R expression in biopsies from a ragweed allergen challenge model. In the allergen challenge model, the effect of pretreatment with topical corticosteroids on IL‐12 and IL‐12R expression was assessed.

Methods

To detect IL‐12 and IL‐12R mRNA, we employed the technique of in situ hybridization using digoxigenin‐labelled riboprobes.

Results

In both ACS and NCS subjects there was decreased expression of IL‐12 as compared with control (P < 0.05). IL‐12R (β2) expression was decreased in ACS subjects as compared with control (P < 0.05), however, there was no significant difference found between NCS subjects and control. In the allergen challenge subjects, there was a significant decrease in IL‐12 expression following challenge (P < 0.05). This effect was abrogated by pretreatment of the subjects with topical corticosteroids. However, IL‐12R (β2) expression showed no change following allergen challenge while pretreatment with topical corticosteroids resulted in increased expression of the (β2) receptor after allergen challenge (P < 0.05).

Conclusion

Our data suggest that IL‐12 plays a role in the in vivo suppression of the allergic inflammatory response and that the control of this suppression may be exerted largely via the IL‐12 (β2) receptor.
Identification of isoform‐specific T‐cell epitopes in the major timothy grass pollen allergen, Phl p 5
Authors: Würtzen P. A. , Bufe A. , Wissenbach M. , Madsen H. O. , Ipsen H. , Arnved J. , Van Neerven R. J. J.
Published: March 2003

Background

The involvement of CD4+ T cells in the pathophysiology of atopic disease is well established.

Objective

To gain further insight into the activation requirements for allergen‐specific T cells, we characterized epitope specificity, HLA restriction and T‐cell receptor (TCR) usage for T cells specific to Phl p 5, the group 5 major allergen of the grass Phleum pratense.

Methods

To identify the T‐cell epitopes of Phl p 5, three Phl p 5‐specific T‐cell lines (TCLs) and 15 T‐cell clones (TCCs) generated from the peripheral blood of three grass‐allergic patients were tested with recombinant truncated Phl p 5a fragments and synthetic Phl p 5b peptides representing these two different recombinant Phl p 5 isoallergens. Additional activation experiments with HLA‐subtyped antigen‐presenting cells and flow cytometry analysis with TCR V‐specific mAb were performed to further characterize the activation requirements for Phl p 5‐specific TCCs.

Results

At least nine distinct T‐cell specificities were identified and the T‐cell epitopes recognized differed considerably among the three patients. Most of the epitopes found were isoform‐specific, whereas three epitopes were shared between Phl p 5a and 5b. Several human leucocyte antigen (HLA) class II molecules were involved in the recognition of Phl p 5. Different HLA restriction specificities were even found among TCCs specific to the same epitope region. All TCCs were TCR‐α/β positive, and an overrepresentation of TCR Vβ 3.1+ clones among TCCs specific to Phl p 5 appear to exists as 31% (4/13) of the TCCs expressed TCR Vβ 3.1 (compared with 5% TCR Vβ 3.1+ T cells in human peripheral blood) with no correlation with epitope specificity or HLA restriction.

Conclusion

The T‐cell reactivity of the three grass‐allergic patients investigated shows that isoallergen‐specific T‐cell epitopes are found throughout the peptide backbone of Phl p 5a and Phl p 5b, and dominant T‐cell epitopes of Phl p 5 were not identified. This indicates that a mixture of at least full‐length rPhl p 5a and rPhl p 5b may be required to target the total Phl p 5‐specific T‐cell response of atopic patients.
Exposure to systemic prednisolone for 4 hours reduces ex vivo synthesis of GM‐CSF by bronchoalveolar lavage cells and blood mononuclear cells of mild allergic asthmatics
Authors: Cotter T. P. , Hood P. P. , Costello J. F. , Sampson A. P.
Published: March 2003

Background

In acute severe asthma, the earliest clinical effects of glucocorticosteroids occur from 4 to 5 h after systemic administration, but the mechanisms are unclear. In persistent asthma, corticosteroids are thought to suppress airway inflammation by modulating the expression of adhesion molecules, enzymes, and leucotactic cytokines, including granulocyte‐macrophage colony stimulating factor (GM‐CSF). GM‐CSF is also overexpressed in the airways of symptomatic asthmatics.

Objectives

To examine the early effects of systemic corticosteroids on cytokine expression, we investigated whether ex vivo synthesis of GM‐CSF is suppressed in the bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) of normal and mild allergic asthmatic subjects obtained 4 h after a single intravenous dose of prednisolone.

Methods

In a randomized, double‐blind, placebo‐controlled study, BAL cells and PBMCs were obtained from mild atopic asthmatic patients (n = 9) and normal subjects (n = 9) 4 h after an intravenous bolus dose of 80 mg prednisolone, and cultured for 0–18 h in the presence or absence of lipopolysaccharide (LPS; 10 μg/mL). Enzyme immunoassay was used to assess GM‐CSF levels in BAL cell and PBMC culture supernatants, and in BAL fluid.

Results

After placebo, GM‐CSF synthesis tended to be higher in BAL cells from asthmatics than in normals. LPS stimulation significantly increased median (interquartile range) GM‐CSF synthesis by BAL cells ex vivo from 16.4 (23 to 74) to 35.8 (3–148) pg/106 cells in normals (P < 0.05), and from 59 (9 to 204) to 134 (24–288) pg/106 cells in asthmatics (P < 0.01). After intravenous prednisolone, the rise in GM‐CSF production induced in BAL cells by LPS was completely abolished in both subject groups. In PBMCs of placebo‐treated asthmatics (but not normals), LPS stimulated median GM‐CSF synthesis from 164 (110 to 300) to 314 (235–485) pg/106 cells (P = 0.02), and this was blocked by intravenous prednisolone.

Conclusions

LPS‐stimulated GM‐CSF synthesis ex vivo is abolished in BAL cells of mild asthmatic and normal subjects, and in PBMCs of asthmatics, obtained 4 h after a single intravenous dose of prednisolone. Suppression of GM‐CSF synthesis in airway and blood leucocytes may contribute to the early clinical efficacy of systemic glucocorticoids in acute allergic asthma.
The use of phage‐peptide libraries to define the epitope specificity of a mouse monoclonal anti‐Der p 1 antibody representative of a major component of the human immunoglobulin E anti‐Der p 1 response
Authors: Furmonaviciene  , Tighe  , Clark  , Sewell  , Shakib
Published: March 2003

Background

More than 80% of individuals who are sensitive to the dust mite Dermatophagoides pteronyssinus produce immunoglobulin (Ig) E antibodies to Der p 1, the most significant domestic allergen. There is therefore considerable interest in elucidating the interaction between human IgE and Der p 1, as a basis for developing strategies for therapeutic intervention.

Objectives

We have therefore sought to determine the Der p 1 epitope recognized by a mouse monoclonal anti‐Der p 1 antibody (mAb 2C7) representative of a major component of the human IgE anti‐Der p 1 response.

Methods

M13 15mer and T7 9mer bacteriophage‐peptide display libraries were screened with mAb 2C7. Mimotope sequences were defined and compared with the native Der p 1 sequence and with those of three homologous molecules, namely chymopapain, papain and actinidin. The sequence of a candidate epitope was then located in the three‐dimensional model of Der p 1 and the corresponding sequences in the homologous molecules were studied for accessibility in the three‐dimensional structure.

Results

We have demonstrated that it is possible to isolate phage clones with peptide inserts specific for mAb 2C7. Examination of the sequences obtained and the location of the corresponding epitope within the three‐dimensional model of Der p 1 has shown that mAb 2C7 recognizes a conformational epitope comprising the sequence Leu147‐Gln160. The relevance of the identified epitope was established by showing that native Der p 1 can block the binding of specific phage clones to mAb 2C7. Similar sequences were identified within the three‐dimensional structures of chymopapain, papain and actinidin, thereby providing a structure‐based explanation for immunological cross‐reactivity.

Conclusion

The identification of the Der p 1 sequence Leu147‐Gln160 as a potential epitope recognized by a major component of the human IgE anti‐Der p 1 response may provide therapeutic opportunities for disrupting the interaction between IgE and this important allergen.
Presentation of new GINA guidelines for paediatrics
Authors: Von Mutius
Published: March 2003

The Global Initiative on Asthma (GINA) has provided guidelines for the management of children with asthma. For a step‐wise approach to therapy, asthma is divided into four categories based on severity of symptoms: intermittent, mild persistent, moderate persistent, and severe persistent asthma. Long‐term preventive therapy is distinguished from quick relief therapy in each group. Although these guidelines are clear and simple there have been few studies on asthma therapy for infants. Moreover, the existence of different wheezing phenotypes with varying pathogenic mechanisms hampers the interpretation of these studies. Transient wheezers have stopped wheezing by the age of 3 years and there is no relationship to atopy or a family history of asthma. In contrast, persistent wheezers continue to wheeze from the first year of life throughout school‐age and have a high risk of atopy. Although they have normal lung function at birth, persistent wheezers develop significant decrements in lung function by the age of 6 years. Whether these impairments are amenable to prevention by early initiation of anti‐inflammatory therapy remains to be seen. At present, there are no disease markers to identify the different wheezing phenotypes in infancy, although eosinophil counts and measurements of eosinophil cationic protein in serum may prove to be helpful in distinguishing these conditions.