bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of relationship between eosinophil cationic protein and eosinophil protein X in nasal lavage and urine and the severity of childhood asthma in a 6‐month follow‐up study
Authors: WOJNAROWSKI  , ROITHNER  , KOLLER  , HALMERBAUER  , GARTNER  , TAUBER  , FRISCHER
Published: March 2003

Background

Recent studies suggest that eosinophil cationic protein (ECP) and eosinophil protein X (EPX) may be valuable markers of airway inflammation in various body fluids of asthmatic children. Most of these studies have relied on a single measure of inflammatory markers.

Objective

We measured ECP and EPX in nasal lavage fluids (NALF) and urine samples in children with asthma over a 6‐month period to study the relationship between inflammatory markers and clinical severity.

Methods

Fourteen children with mild persisting asthma (mean age 11.7 years, sd 2.2) were recruited. All patients were on therapy including inhaled steroids. For a 6‐month period asthma severity was monitored by at least monthly physical examination and pulmonary function tests. Daily morning and evening PEF, asthma symptoms and medication were recorded in diaries for the whole study period. Telephone interviews were performed between visits and additional visits were done in case of an increase in asthmatic symptoms or drop of PEF values under 80% of best value. An exacerbation was defined by a fall of FEV1 > 10% and an increase in asthma symptoms and additional need of β2‐agonist. NALF and urine samples were obtained at each visit and analysed for ECP (NALF only) and EPX.

Results

Mean observation time was 186.4 days ( sd 19.8). Thirteen patients completed the study. During the study period 11 exacerbations were observed in six patients. No significant associations between PEF, PEF variability (amplitude % of mean), daily symptoms, additional β2‐agonist, FEV1 and MEF50 and nasal ECP, nasal EPX and urinary EPX were found. However, at exacerbations an average increase of nasal ECP (9.3 vs 50.3 μg/L) and EPX (nasal EPX 36.4 vs 141.7 μg/L, urinary EPX 46.4 vs 74.1 μg/mmol creatinine) was observed.

Conclusion

Serial measurements of ECP and EPX in NALF and urine samples do not provide additional information for the practical management in monitoring childhood asthma.
Role of carbohydrate moieties in IgE binding to allergenic components of Cupressus arizonica pollen extract
Authors: Afferni  , Iacovacci  , Barletta  , Di Felice  , Tinghino  , Mari  , Pini
Published: March 2003

Background

A reduction of IgE immunoreactivity after periodate‐treatment has been previously reported for various glycoprotein allergens.

Objective

The aim of this study was to investigate the role of glycan moiety of a C. arizonica extract in the binding of patients' IgE and to identify the carbohydrates possibly involved.

Methods

The reactivity of IgE with C. arizonica extract, before and after periodate‐treatment, was evaluated by immunoblotting and ELISA inhibition. The specificity of carbohydrate‐reactive IgE was evaluated by ELISA using unrelated glycoproteins with known sugar composition and structure, such as pineapple bromelain, honeybee venom phospholipase A2, and ovalbumin, before and after periodate treatment.

Results

When periodate‐treated C. arizonica extract was probed after SDS‐PAGE and immunoblotting with patients' IgE, no reactivity could be detected. Furthermore, a very poor inhibitory activity of the periodate‐treated C. arizonica extract as compared with the untreated sample could be observed in the ELISA inhibition experiments performed using C. arizonica extract as antigen. When phospholipase A2 and bromelain were used as antigens in ELISA, they were recognized by patients' IgE, whereas ovalbumin was negative. Treatment of phospholipase A2 and bromelain with periodate completely abolishes the IgE reactivity.

Conclusion

A large portion of the IgE reactivity of Cupressaceae‐allergic subjects appears to be associated with sugar moieties of C. arizonica extract which appear to be shared by bromelain and phospholipase A2, thus suggesting that the IgE of patients reacting with such epitopes probably react with β 1 → 2 xylose, α 1 → 3 fucose and/or α 1 → 6 fucose.
T‐cell reaction to local anaesthetics: relationship to angioedema and urticaria after subcutaneous application — patch testing and LTT in patients with adverse reaction to local anaesthetics
Authors: Orasch  , Helbling  , Zanni  , Yawalkar  , Hari  , Pichler
Published: March 2003

Background

Local anaesthetics are known to elicit T‐cell reactions after epicutaneous application, namely contact dermatitis. In addition, adverse reactions like urticaria and angioedema are rather common after submucosal or subcutaneous injection. The pathogenesis of these side‐effects, which appear frequently hours after application, is unknown, but thought to be not immunoglobulin E‐mediated, since immediate skin tests are mostly negative.

Objectives

We investigated whether patients who developed urticaria and angioedema after subcutaneous application have a T‐cell sensitization to local anaesthetics, which might be responsible for the symptoms.

Methods

Twenty patients with generalized and/or local cutaneous reactions after LA were examined with intradermal testing using a standard panel of six LAs and patch testing using between seven and nine LAs in vaseline and four LAs in PBS. In 10 patients, a lymphocyte transformation test (LTT) was performed.

Results

Only 2/20 patients had an immediate skin reaction (positive intradermal test), whereas 6/20 patients had a positive delayed skin reaction (positive patch test). In 6/10 subjects the LTT was positive.

Conclusions

Delayed appearance of urticaria and angioedema after subcutaneous application of local anaesthetics may be related to a T cell‐ mediated sensitization, which might be detected by patch testing or LTT.
Reducing IgE levels as a strategy for the treatment of asthma
Authors: Fahy
Published: March 2003

IgE secretion by B lymphocytes defines the allergic state and nearly all asthmatics have higher than normal IgE levels in serum following adjustment for age and sex. It is thought that allergic mechanisms may be responsible for the increasing prevalence of asthma. In particular, in utero changes may encourage T cells to differentiate into Th2 subtypes. Th2 cells produce cytokines such as IL‐4 and IL‐5, which can act indirectly via B cells, mast cells and eosinophils to mediate the asthma phenotype. Alternatively, IL‐4 and IL‐13 may act directly on the airway. Th2 lymphocyte inflammation in asthma predisposes subjects to B cell and IgE‐mediated airway inflammation. IgE binds to receptors on the surface of a variety of effector cells causing them to release a variety of mediators that promote airway hyperresponsiveness, mucus secretion and increased vascular permeability. Several strategies for decreasing IgE have been developed as a possible treatment for asthma. For example, anti‐IgE monoclonal antibodies such as rhuMAb‐E25 and CGP 56901 block binding of IgE to its high‐affinity receptor and have been shown to reduce IgE levels in humans without causing anaphylaxis. IgE levels must be nearly completely suppressed. Recent clinical studies in subjects with asthma have shown that rhuMAb‐E25 attenuates both the early and late phase responses to inhaled allergen, and reduces the associated increase in eosinophils in induced sputum. rhuMAb‐E25 is well tolerated and has shown promising results in improving symptoms and lung function in patients with moderate to severe asthma. Other strategies for decreasing IgE levels include interferon γ, IL‐4 antibodies, IL‐4 receptor antibodies and soluble IL‐4 receptors.
The role of eosinophils and neutrophils in inflammation
Authors: Sampson
Published: March 2003

The eosinophil is well recognized as a central effector cell in the inflamed asthmatic airway. Eosinophils release toxic basic proteins and lipid mediators such as cysteinyl‐leukotrienes that cause bronchial epithelial damage and airflow obstruction. Eosinophil‐selective cytokines and chemokines including interleukin (IL)‐5, eotaxin and RANTES may represent targets for novel asthma therapies. In contrast, the role of the neutrophil in asthma remains relatively obscure. Recent evidence from the ENFUMOSA project and elsewhere suggests that neutrophils not only contribute to acute asthma exacerbations, but also are present in high numbers in the airways of patients with chronic severe asthma. Production by neutrophils of lipid mediators, reactive oxygen intermediates (ROI) and proteases such as elastase, may contribute to airflow obstruction, epithelial damage and remodelling. Leukotriene B4 and cytokines such as IL‐8, granulocyte‐macrophage colony stimulating factor (GM‐CSF), and tumour necrosis factor (TNF)α chemoattract neutrophils and reduce neutrophil apoptosis, and selective agents directed against these may prevent neutrophil influx and accumulation. Airway neutrophilia remains apparent in severe asthma patients even after treatment with high doses of corticosteroids. In vitro, corticosteroids paradoxically enhance neutrophil survival by reducing apoptosis, so corticosteroid therapy may exacerbate neutrophil activity in vivo. Both corticosteroids and cytokines may suppress neutrophil apoptosis by upregulating endogenous synthesis of leukotriene (LT)B4. Specific blockade of LTB4 synthesis or LTB4 receptors may induce neutrophil apoptosis and combat the unwanted effects of high‐dose steroids on neutrophil survival. Phagocytosis of apoptotic neutrophils stimulates important signals that down‐regulate pro‐inflammatory cytokine production by macrophages, allowing resolution and repair processes to prevail.
The role of co‐stimulation in airway inflammation
Authors: Djukanovic
Published: March 2003

There is considerable evidence to support an important role for co‐stimulatory molecules in regulating the proliferation and activation of T cells in the immune response. Of particular relevance is the interaction between CD28 on T cells and B7 expressed on the surface of antigen presenting cells (APCs). CTLA‐4, another molecule present on activated T cells may downregulate T cell activity, but its role remains uncertain. CTLA4‐Ig, a fusion protein consisting of the extracellular domain of CTLA4 and the Fc portion of human immunoglobulin G1 (IgG1), has been useful for studying the role of CD28/B7 interactions in immune responses. A number of studies have shown that CTLA4‐Ig can switch off T cell activation. In an ovalbumin sensitive murine model of asthma, CTLA4‐Ig treatment suppressed the response to inhaled allergen (increased airway hyperresponsiveness [AHR], IgE production, recruitment of eosinophils into the lungs, production of IL‐4, IL‐5, and IL‐10 and increased IFNγ production from CD3‐TCR‐activated T cells). Anti B7–2 treatment has similar effects suggesting that interaction of B7–2 with CD28 is important in the development of a Th‐2 type inflammatory response in mice. Recent observations have been of relevance to human allergic disease. In vitro studies have shown that CTLA4‐Ig or anti‐B7–2 antibody can inhibit allergen‐induced proliferation and cytokine production by peripheral blood mononuclear cells from atopic subjects. The role of co‐stimulation has been studied in a human bronchial explant model of asthma. CTLA4‐Ig fusion protein effectively blocked allergen‐induced production of IL‐5 and IL‐13 in bronchial explants from atopic asthmatics. These studies confirm the requirement for interaction between co‐stimulatory molecules in cytokine production and allergic inflammation, and point to the CD28‐B7 pathway as being important to the allergen‐induced inflammation in asthma. Studies of organ transplantation in primates suggest that CTLA4‐Ig is extremely effective in preventing organ rejection. While phase 1 clinical trials have shown CTLA‐4‐Ig treatment of patients with psoriasis vulgaris to be well tolerated and to result in clinical improvement, its role in asthma management merits further investigation.
Nasal lavage mediator profile and cellular composition of nasal brushing material during latex challenge tests
Authors: Raulf‐Heimsoth  , Wirtz  , Papenfuss  , Baur
Published: March 2003

Background

Recent studies have shown that airborne latex allergens cause allergic rhinitis and bronchial asthma.

Objective

The aim of this study was to investigate the association between the development of rhinitis reactions during workplace‐related inhalative challenge tests and nasal allergic inflammation.

Methods

Thirty‐two health care workers (HCWs) with suspected respiratory hypersensitivity to latex allergens underwent an inhalative workplace‐related challenge test with powdered latex gloves. Nasal lavage fluid (NALF) and nasal brushing (NAB) material were collected before and after exposure (30 min, 2, 6 and 24 h) to determine mediator and cellular composition. In addition, lung function parameters and nasal flow were recorded. Furthermore, six healthy controls underwent nasal brushing and nasal lavage without latex allergen challenge at the same time intervals.

Results

Twenty‐six HCWs showed acute rhinitis by contact to airborne latex allergen exposure and 10 of them had an additional asthma response. Only in responders, significantly increased eosinophil levels were found 6 h (P < 0.00001) and 24 h (P < 0.0005) post‐challenge when compared with the prechallenge values. The ECP levels measured 2, 6 and 24 h post‐challenge in the responder group were significantly elevated when compared with the prechallenge values as well as with the non‐responders (6 h: P < 0.05, 24 h: P < 0.00001 afterwards). Only in some concentrated NALF samples of responders collected 30 min post‐challenge (seven out of 15) tryptase concentration above the detection limit were found. The NO derivative concentrations in NALF were significantly increased 6 h post‐challenge compared with the prechallenge values (P < 0.05) and were significantly higher in responders than in non‐responders and in controls (P < 0.002). IL‐5 levels increased post‐challenge in the responder group with a pronounced effect 6 h after challenge (P < 0.001). Overall, a variety of parameters was significantly correlated (e.g. ECP with NO derivatives, r = 0.792 P < 0.002).

Conclusions

Our data demonstrate for the first time that nasal and bronchial hyperreactivity to airborne latex allergens are associated with an increase of eosinophils and mediators (e.g. ECP, NO derivatives, IL‐5, tryptase) in nasal mucosa. The combined use of NAB (for cells) and NALF (for mediators) appears to be a useful model to monitor nasal inflammation during workplace‐related challenge tests.
T‐cell cytokine pattern at three time points during specific immunotherapy for mite‐sensitive asthma
Authors: Majori  , Caminati  , Corradi  , Brianti  , Scarpa  , Pesci
Published: March 2003

Backgrounds

Several lines of evidence indicate that specific immunotherapy may act by modifying the patterns of cytokines produced by helper T cells. However, different protocols have been used and different results obtained.

Objectives

To quantify the effect of specific immunotherapy on the TH1/TH2 T‐cell cytokine pattern at the single cell level.

Methods

We examined the interferon‐γ/interleukin‐4 ratio in peripheral blood CD4+ and CD8+ T cells from 12 subjects with house dust mite‐sensitive asthma using a flow cytometric method of intracellular cytokine detection. Cytokine production was determined following stimulation with phorbol myristate acetate/ionomycin, a policlonal activator. Subjects were examined at three occasions: before specific immunotherapy, after the 3‐months dose increase phase and after 1 year of treatment. During the treatment year patients kept a diary in which they recorded: (a) symptoms of asthma according to a 0–3 grading (0 = absent, 1 = mild, 2 = moderate, 3 = severe); (b) number of puffs (100 μg) per day of salbutamol required to control symptoms; and (c) peak expiratory flow.

Results

Specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use during the treatment year, and had a marked effect in increasing the interferon‐γ/interleukin‐4 ratio in peripheral blood CD4+ T cells already after the dose increase phase (5.47 ± 1.5 vs 4.07 ± 1.49%, P = 0.03) with and a further rise after 1 year's treatment (16.12 ± 2.8 vs 4.07 ± 1.49 and 16.12 ± 2.8 vs 5.47 ± 1.5%, P = 0.001 and P = 0.002, respectively). There were no significant changes in the interferon‐γ/interleukin‐4 ratio in peripheral blood CD8+ T cells at the three times of the study.

Conclusions

These data add to view that the efficacy of specific immunotherapy may be attributed to a modified cytokine secretion of CD4+ T cells.
Phleum pratense‐specific T cells of allergic rhinitis patients display a broader recognition pattern than Phleum pratense‐specific serum immunoglobulin E
Authors: Van Neerven  , Arnved  , Ipsen
Published: March 2003

Background

The role of allergen‐specific CD4+ T lymphocytes in the pathophysiology of atopic disease is well established. Previous studies on allergen‐specific T‐cell responses have focused on the recognition of single major allergens to identify T‐cell epitopes.

Objective

However, it is not clear whether immune responses to allergen extracts are exclusively targeted at major allergens or whether additional proteins are recognized.

Methods

Here we describe the Phleum pratense‐specific immunoglobulin E (IgE) and T‐cell responses of six allergic rhinitis patients. Reactivity was measured to size‐separated fractions of a P. pratense extract as well as to the purified major allergens Phl p 1, Phl p 2/3 and Phl p 5.

Results

The specificity of the patients' serum IgE, measured in a fluid phase assay, was restricted to one or two of the major allergens. Even though the majority of the patients had IgE antibodies reactive with a single major allergen, one patient reacted with both Phl p 5 and with Phl p 2/3. Analysis of the T‐cell repertoire with P. pratense‐specific T‐cell lines (TCLs) and CD4+ T‐cell clones (TCCs) revealed that at least six different proteins were recognized, including the three major allergens, most notably Phl p 5. Simultaneous production of IL‐5 and interferon (IFN) ‐γ was detected in supernatants of the TCLs stimulated with P. pratense extract and the major allergens.

Conclusion

These results indicate that allergic rhinitis patients have a large pool of circulating allergen‐specific CD4+ T cells that recognize many different proteins in an allergenic extract, whereas only a small number of these proteins are recognized by serum IgE.
The role of costimulatory molecules (B7‐1 and B7‐2) on allergen‐stimulated B cells in cedar pollinosis subjects
Authors: Morikawa  , Nagashima
Published: March 2003

Background

B7‐1 (CD80) and B7‐2 (CD86), which are costimulatory molecules in T‐cell activation, play important roles in the differentiation of TH1‐ or TH2‐phenotypes. These molecules were also suggested to play important roles in sensitization to a cedar pollen antigen by blocking studies using neutralizing antibodies, but there have been very few studies concerning the effects following induction by antigen.

Objective

In this study, we investigated the roles of B7‐1 and B7‐2 in the differentiation of TH1 and TH2 subsets after stimulation with the antigen in subjects with cedar pollinosis.

Methods

Skin‐prick test was performed in nine subjects with pollinosis and in nine normal controls. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with Japanese cedar pollen extract. After in vitro stimulation, the expression of CD80 and CD86 on CD19+ cells was analysed by two‐colour flow cytometry. Culture supernatants were collected for all subjects and the production of type 1 and type 2 cytokines was measured by ELISA.

Results

After in vitro stimulation, the expression of CD80 (B7‐1) was upregulated in both pollinosis and control subjects, but no significant difference was observed between the two groups. On the other hand, CD86 (B7‐2) was significantly upregulated following stimulation in pollinosis subjects (P = 0.02). A significantly higher level of IL‐5 (P = 0.04) was produced by PBMCs of pollinosis subjects than by those of normal controls. A significantly higher level of interferon (IFN)‐γ (P = 0.03) was produced by PBMCs of normal controls than by those of pollinosis subjects.

Conclusion

These results indicated that TH2 response was predominant in pollinosis subjects, and that CD19+ cells of pollinosis subjects expressed higher levels of B7‐2 than those of control subjects after in vitro stimulation. In pollinosis subjects, B7‐2 rather than B7‐1 may be the costimulatory molecule involved in allergen‐induced activation of PBMCs.
Family patterns of asthma, atopy and airway hyperresponsiveness: an epidemiological study
Authors: Gray  , Peat  , Belousova  , Xuan  , Woolcock
Published: March 2003

Background

The patterns of inheritance of asthma have largely been explored using data of symptom history collected by questionnaires which are subject to bias and which may therefore distort the measured relationship.

Objective

The purpose of this study was to examine family patterns of allergic disease using objective measurements of atopy and of airway hyperresponsiveness (AHR).

Methods

A large random sample of children aged 8–11 years was studied and 3 months later, their parents were also invited for study. Of the sample of 1655 children, both parents of 661 children were studied. In all subjects, respiratory illness history was measured by questionnaire, atopy by skin tests and AHR by responsiveness to histamine.

Results

The odds ratio for a child to have AHR if either parent had the same condition was approximately 2.0, which was the same as the odds ratio for wheeze or diagnosed asthma in the presence of the same condition in either parent. The odds ratio for atopy was smaller (approximately 1.4, NS) but the risk of a nonatopic child having AHR if the parent had AHR was 3.0 (P = 0.01). The correlation between weal size in the child and parent was poor and the severity of AHR in the child was only modestly correlated with the severity of AHR in the parent (R = 0.51, P = 0.04).

Conclusion

The use of objective measurements did not strengthen the association between atopic or asthmatic conditions in the parent and child, but did suggest that atopy and AHR are inherited independently.
Sensitization to oilseed rape is not due to cross‐reactivity with grass pollen
Authors: Welch  , Jones  , Cullinan  , Coates  , Newman Taylor
Published: March 2003

Background

Oilseed rape is an important crop grown in the UK which can cause specific immunological sensitization with clinical symptoms in a relatively small number of the general population. Individuals with immunoglobulin (Ig) E‐mediated allergy to oilseed rape have also been found to be sensitized to other pollen allergens, most frequently being grass pollen. Cross‐reactivity between common grass and oilseed rape would have important implications, especially as their flowering period coincides.

Objective

We have investigated whether the cosensitization found in individuals sensitized to both oilseed rape and grass pollen is due to cross‐reactivity.

Methods

Cross‐reactivity between oilseed rape and grass pollen was determined using RAST, RAST inhibition, Western blotting and inhibition studies with Western blotting.

Results

Competitive RAST inhibition studies between pollen of oilseed rape and grass failed to show any cross‐reactivity between the pollen types. Self‐inhibition with oilseed rape resulted in 90% inhibition, whereas there was less than 10% inhibition with grass pollen. Western blotting revealed allergens of similar molecular weight in both oilseed rape and grass pollen. Despite allergens of similar molecular weights being present in both pollen types, inhibition immunoblot studies confirmed that the allergens in the two allergens were immunologically distinct.

Conclusion

The allergens of oilseed rape and grass pollen, although similar in molecular weights, are immunologically distinct and there is no evidence of cross‐reactivity between them. Individuals allergic to grass pollen will not necessarily develop a specific nasal or airway response to inhaled oilseed rape pollens.
Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life
Authors: Jenmalm  , Björkstén
Published: March 2003

Background

Factors that either protect from or enhance the development of atopic disease appear to be acting early in life. The gestational environment, including maternal immune responses, such as transplacentally transferred immunoglobulin (Ig) G antibodies to allergens, may be of importance in this respect, since allergen‐specific immunity has been demonstrated to develop in utero.

Objective

To evaluate the relation between cord blood IgG subclass antibodies to allergens, maternal atopy and development of atopic disease in the children.

Material and methods

The study group comprised a cohort of 96 children participating in a prospective study up to 8 years of age. Cord blood IgG subclass antibodies to ovalbumin, β‐lactoglobulin, Bet v 1 and cat dander were analysed by ELISA.

Results

The levels of all IgG subclass antibodies to ovalbumin and rBet v 1 were higher in newborn infants with an atopic mother, as compared with babies with nonatopic mothers. IgG1 antibody levels to cat and IgG4 antibody levels to β‐lactoglobulin and cat were also higher in atopic than in nonatopic mothers, whereas the other subclass antibody levels to those allergens were similar. High levels of cord blood IgG antibodies to cat and birch, but not to the food allergens, were associated with less atopic symptoms in the children during the first 8 years of life. Moreover, children who developed IgE antibodies to cat had lower levels of IgG antibodies to that allergen at birth.

Conclusions

High levels of cord blood IgG subclass, especially IgG4, antibodies to food and inhalant allergens are associated with maternal atopy. High levels of IgG antibodies to inhalant, but not food, allergens are associated with less development of atopy in the children.
Characterization of platelet‐activating factor‐induced cytosolic calcium mobilization in human eosinophils
Authors: Oshiro  , Kakuta  , Shimura  , Nara  , Shirato
Published: March 2003

Background

Activated eosinophils play an important role in the pathogenesis of bronchial asthma and other allergic diseases, and platelet‐activating factor (PAF) is a potent activator of eosinophils.

Objective

To characterize the cytosolic Ca2+ ([Ca2+]i) mobilization in human eosinophils in response to PAF.

Methods

[Ca2+]i responses to PAF were examined in human eosinophils using a microscopic fura‐2 fluorescence‐ratio imaging system.

Results

PAF caused a significant and dose‐dependent increase in (Ca2+)i, which consisted of an initial rapid rise followed by a sustained elevation. This PAF‐induced (Ca2+)i rise was inhibited by WEB 2086, a specific PAF receptor antagonist. The addition of 5 m
m EGTA or 1 m
m Ni2+ to a nominally Ca2+‐free solution did not appreciably reduce the initial rise but significantly inhibited the sustained rise. The application of a protein kinase C inhibitor, Ro31‐8220, augmented the sustained increase by PAF. Thapsigargin, a microsomal Ca2+ ATPase inhibitor, induced no appreciable change in a nominally Ca2+‐free solution but induced a marked increase in (Ca2+)i when changed to a Ca2+‐containing solution.

Conclusions

The initial rapid rise and the following sustained rise in (Ca2+)i by PAF depends on Ca2+ release from the intracellular Ca2+ stores and Ca2+ influx, respectively, which are regulated by protein kinase C in human eosinophils. Furthermore, the so called Ca2+‐capacitative entry is possibly involved in the Ca2+ influx from the extracellular solution in human eosinophils.
Ethnicity, childhood environment and atopic disorder
Authors: Hjern  , Haglund  , Hedlin
Published: March 2003

Background

The International Study of Asthma and Allergies in Childhood (ISAAC) has demonstrated large differences in the prevalence of atopic disorders in children between different regions in the world. Populations with a higher standard of living and a more westernized lifestyle tend to have higher rates of atopy and asthma. Many hypotheses regarding environmental causes of atopic disorder focus on the early childhood environment.

Objective

To study the influence of ethnicity and country of birth for the prevalence of atopic disorders.

Methods

The prevalence of atopic disorders in Swedish residents born in Turkey and Chile, who settled in Sweden as adults in the 1980s, was compared with their own Swedish‐born children and a sample of Swedish‐born parents and their children in interview data from the Survey of Living Conditions in 1996. The study group included 1734 adults 27–60 years of age and their 2964 children aged 3–15.

Results

The Chilean‐born parents and their children had the highest risk for allergic asthma; adjusted odds ratios (ORs) 2.2 (1.2–4.0) and 2.7 (1.6–4.5), respectively, and allergic rhino‐conjunctivitis; OR 1.6 (1.1–3) and 1.6 (1.1–2.5) in both groups, when compared with the Swedish‐born parents and their children. The Turkish‐born parents and their children had the lowest risk for allergic rhino‐conjunctivitis; both groups had OR 0.6 (0.4–0.9) and the children in this group also had the lowest risk for eczema; OR; 0.4 (0.3–0.7). The risk for all atopic disorders was lower in the Turkish group compared with the Chileans.

Conclusion

This study demonstrates that ethnicity is an important determinant of atopic disorder independent of the external childhood environment. The value of international comparisons of environment and risk for atopic disorders can be questioned until more is known about factors related to ethnicity, such as genetic susceptibility and diet, for the development of atopy.
Dietary nucleic acids promote a shift in Th1/Th2 balance toward Th1‐dominant immunity
Authors: Sudo  , Aiba  , Takaki  , Tanaka  , Yu  , Oyama  , Koga  , Kubo
Published: March 2003

Background

Dietary sources of nucleic acids and their relative components are known to affect host immune function; however, it has not yet been clarified whether such dietary nucleic acids influence the pathogenesis of allergic reaction.

Objective

The purpose of this study is to elucidate the effect of dietary nucleic acids on Th1/Th2 balance.

Methods

Both human flora‐associated and specific pathogen‐free BALB/c mice were maintained on either nucleic acid‐free, or ‐supplemented diets. The effects of nucleic acids on both in vivo antibody levels and in vitro splenocyte cytokine production were compared using these mice.

Results

Supplementation of nucleic acids caused a reduction in the serum antibody levels of total IgM, IgG, IgG1, and IgE in the human flora‐associated mice without affecting the composition of intestinal flora. In contrast, there was no significant difference of the serum IgG2a levels between nucleic acid‐free and ‐supplemented mice. Such a phenomenon as that, the supplementation of dietary nucleic acids reduces the serum IgE or IgG1 levels, but not the IgG2a level, was also seen in the specific pathogen free mice. Moreover, when the mice were systematically challenged with ovalbumin, the supplementation of nucleic acids also suppressed the serum ovalbumin‐specific IgE and IgG1 antibody levels as well as in vitro IL‐4 and IL‐10 secretion, while enhancing both the serum ovalbumin‐specific IgG2a antibody levels and in vitro IFN γ secretion.

Conclusion

These results suggested that dietary nucleic acids may play an important role in promoting a shift in Th1/Th2 balance toward Th1‐dominant immunity.
Defective tumour necrosis factor‐alpha production in mother's milk is related to cow's milk allergy in suckling infants
Authors: Järvinen  , Laine  , Suomalainen
Published: March 2003

Background

The precise role of leucocytes in human milk is still unresolved.

Objective

To assist in clarifying the immune mechanisms involved in the development of CMA in suckling infants, we studied the role of immunoregulatory leucocytes and their mediators in human breast milk.

Methods

The study population consisted of 43 lactating mothers and their infants, aged 0.25–8.0 months, followed‐up prospectively from birth. Of these mothers, 27 had an infant with challenge‐proven cow's milk allergy manifested with either skin (n = 23), gastrointestinal (n = 2) or skin and gastrointestinal symptoms (n = 3). Sixteen mothers with a healthy infant served as controls. We evaluated the spontaneous and mitogen‐induced tumour necrosis factor‐alpha (TNFα) and interferon‐gamma (IFNγ) production of human milk leucocytes and isolated peripheral blood lymphocytes in vitro with a commercial ELISA kit.

Results

TNFα production of breast milk leucocytes was significantly lower in the mothers with a cow's milk‐allergic infant, whereas IFNγ production of these cells was comparable in the two groups.

Conclusion

Our results suggest that in the breast milk of mothers having an infant with cow's milk allergy, the number and function of TNFα‐producing cells is defective. This might lead to a disturbance in the development of oral tolerance and thereby to the development of CMA in suckling infants. These novel results may help in clarifying the etiopathogenesis of CMA.
Late onset reactions to oral food challenge are linked to low serum interleukin‐10 concentrations in patients with atopic dermatitis and food allergy
Authors: Sütas  , Kekki  , Isolauri
Published: March 2003

Background

Aberrant cytokine production in vitro has been associated with atopic disease. No study has as yet been made of the circulating cytokine profiles in atopic patients with food allergy in response to oral allergen challenge.

Objective

To assess the effect of oral allergen challenge on the serum cytokine concentrations in patients with atopic dermatitis and food allergy.

Methods

Serum concentrations of interleukin (IL)‐10, transforming growth factor beta 1, IL‐1ra, IL‐6, IL‐5, IL‐4 and interferon (IFN)‐γ were measured before and after double‐blind, placebo‐controlled food challenges (DBPCFC) (n = 73). Before DBPCFC, combined skin prick and patch testing was performed for cow milk, egg, soybean and cereals, and production of IFNγ, IL‐4, IL‐10 and tumour necrosis factor alpha (TNFα) was determined in supernatants of cultures of peripheral blood mononuclear cells (PBMCs) stimulated by cow milk.

Results

The oral food challenge triggered immediate onset exanthematous reactions in 22 cases and late onset eczematous reactions in 29. The late‐reacting cases had more positive skin patch test and negative skin prick test reactivities with allergenic food, and they had lower serum IL10 concentrations than immediate‐reacting cases. In challenge‐positive cases, IL‐10 concentrations increased from 2.9 (0.1–5.04) pg/mL to 3.9 (1.2–8.3) pg/mL in response to DBPCFC, P = 0.05, median (interquartile ranges), but not in those tolerant to cow milk. PBMCs of patients with cow milk allergy but not of those tolerant to cow milk generated TNFα in response to cow milk in vitro.

Conclusion

These results indicate that oral allergen challenge in atopic patients with food allergy triggers systemic release of IL‐10. Patients with late onset reactions were found to have lower serum IL‐10 concentrations than their immediate‐reacting counterparts. Considering that IL‐10 is an inhibitory cytokine of delayed‐type hypersensitivity, low IL‐10 in late‐reacting patients may explain the high frequency of their positive skin patch tests combined with negative skin prick tests.
Lung epithelial H292 cells induce differentiation of immature human HMC‐1 mast cells by interleukin‐6 and stem cell factor
Authors: Pompen  , Smids  , Dingemans  , Jansen  , Out  , Lutter
Published: March 2003

Background

Immature mast cells migrate into tissues where they differentiate into mature mast cells under the influence of local factors. In the airways of asthmatics increased numbers of chronically activated mast cells are located nearby the airway epithelium.

Objective

The aim of this study was to evaluate whether and, if so, which products released by epithelial cells may affect mast cell proliferation and differentiation.

Methods

We performed in vitro studies using the human lung mucoepidermoid carcinoma‐derived H292 cell line and the immature human mast cell line, HMC‐1. Proliferation was assessed by 3H‐thymidine incorporation. Differentiation of HMC‐1 cells was inferred from tryptase production.

Results

Exposure of HMC‐1 cells to medium conditioned for 48 h by H292 cells resulted in a reduction of proliferation with 65 ± 4.9% (mean ± sem, n = 9) at day 5. Culturing HMC‐1 cells for 8 days in the presence of H292‐conditioned medium resulted in morphological changes indicative of differentiation, and in a 3.0 ± 0.4‐fold increase of tryptase production (P = 0.0039, n = 9). Conditioned medium from H292 cells that were stimulated by LPS also inhibited HMC‐1 proliferation. Inhibitory antibodies against two mediators from H292 cells, interleukin‐6 (IL‐6) and stem cell factor (SCF), abolished the increase in HMC‐1 tryptase production induced by H292‐conditioned medium. Recombinant human (rh) IL‐6, but not rhSCF, reduced HMC‐1 proliferation with 44% and 13% at day 3 and 5, respectively. Surprisingly, rhIL‐6 did not increase HMC‐1 tryptase production significantly whereas incubation with rhSCF did (1.5 ± 0.1‐fold, P = 0.002, n = 10) although the increase was less than observed for conditioned medium.

Conclusion

Epithelial‐derived IL‐6 and SCF are implicated in differentiation of HMC‐1 cells but additional factors are not excluded. As activated primary bronchial epithelial cells also express IL‐6 and SCF, it should be considered that these cells are involved in mast cell differentiation within the airways, particularly in diseases where epithelial cells are activated, such as asthma.
Endogenous glucocorticoids and antigen‐induced acute and late phase pulmonary responses
Authors: Stokes Peebles  , Togias  , Bickel  , Diemer  , Hubbard  , Schleimer
Published: March 2003

Background

Several studies suggest that endogenous glucocorticoids can dampen the severity of experimental allergic reactions in animals.

Objective

To investigate the influence that endogenous glucocorticoids have on the course of IgE‐mediated pulmonary early and late phase reactions.

Methods

Twenty‐one allergic asthmatic and six healthy control subjects underwent inhaled antigen challenge with measurements of plasma cortisol and cortisone by gas chromatography‐mass spectrometry.

Results

There were no differences between the asthmatic and control groups in the baseline levels of cortisol or cortisone. However, the asthmatic subjects had significantly higher cortisol levels (67.2 ± 8.6 vs 35.1 ± 4.5 ng/mL; P = 0.04) and had higher cortisol/cortisone ratios (4.8 ± 0.6 vs 3.0 ± 0.2; P = 0.01) 8 h after challenge compared to the control subjects. Among the asthmatic subjects, those whose FEV1 recovered rapidly had higher baseline levels of cortisol and those who displayed a late phase reaction had lower levels of cortisol during the late phase period.

Conclusion

The results suggest that endogenous glucocorticoids may play a significant role in the modulation of airway responses to antigen challenge, and that antigen challenge may induce cortisol production in allergic subjects.
Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects
Authors: Cederbrant K. , Marcusson‐StÅhl M. , Hultman P.
Published: March 2003

Background

Antigen‐specific cell lines or clones are often used as models of drug‐specific allergy. However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems.

Objective

Using bacampicillin‐allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy. The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed.

Methods

A total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included. Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls. All subjects were LTT tested. Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR‐Vβ repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures.

Results

LTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms. 69% of the patients with type I allergies were patch test‐positive. Results from LTT and skin test correlated in 87% of the cases. The combined sensitivity of LTT and skin tests was 92%. The specificity of LTT was 90% in healthy controls. Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients. The TCR‐Vβ profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vβ2, Vβ3, Vβ5.1 and/or Vβ14. An increased expression of IFNγ was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients. IL‐5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls. This Th2 environment could also be verified by CD23 and CD134 expression.

Conclusion

LTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects. When the two tests are combined, the sensitivity increases. The patch test is useful not only for detection of type IV but also for the identification of type I allergies. When using primary PBMC cultures, IFNγ is the most suitable cytokine to discriminate between type I and type IV allergy. IL‐5 can possibly be used as a general marker for bacampicillin induced allergy. Thus, primary cell cultures may be considered as an alternative to T‐cell lines or clones for the study of drug induced allergy.
Assessment of latex allergy in a healthcare population: are the available tests valid?
Authors: Pridgeon C. , Wild G. , Ashworth F. , Egner W. , Ward A. M.
Published: March 2003

Background

Latex allergy can cause serious, preventable work‐related health problems in healthcare workers who are a high risk group for this form of allergy. Type I hypersensitivity can produce life‐threatening systemic effects, and involves an allergen‐specific immunoglobulin (IgE) response to proteins found in latex. The estimated prevalence of latex ‘allergy’ in healthcare workers varies widely (2.8% − 18%), and studies do not always distinguish between those who are positive in an assay for latex‐specific IgE and those with clinical allergy.

Objective

To assess the performance of four in‐vitro methods and three skin testing methods for detecting latex‐specific IgE in a group of UK healthcare workers. Test results were compared with reported clinical symptoms defined by questionnaire.

Methods

Skin prick testing was carried out on volunteers using three reagents: (a) stallergenes commercial latex extract (Cedex, France); (b) an in‐house latex glove extract; and (c) a fresh glove piece. Specific IgE levels were determined using Pharmacia AutocapTM (Uppsala, Sweden), Pharmacia UnicapTM (Uppsala, Sweden), DPC Immulite® (Los Angeles, USA) and Hycor HytecTM (Irvine, California, USA) methods. Each volunteer completed a questionnaire detailing latex exposure and allergic history.

Results

In vitro methods for detecting specific IgE to natural rubber latex were positive in 3.6%, to 43.6% of the same population. Skin prick tests positivity varied between 2.9% and 14.3% with different extracts. From the subjects tested 9.1% reported symptoms which could be consistent with type I allergy, although none had been given a pre‐existing diagnosis of latex allergy, and 43.6% of volunteers reported symptoms consistent with type IV hypersensitivity or irritant dermatitis. Contingency tables and chi‐squared analysis revealed no correlation between most methods. No correlation was shown between symptoms consistent with type I allergy and any in vitro or skin testing method for latex‐specific IgE.

Conclusions

A wide variation between testing procedures was found, and no method could be correlated with reported symptoms of type I allergy. At least one in vitro specific IgE assay produced a high percentage of positive results at variance with the clinical symptoms in volunteers. A clinical history is essential in establishing type I hypersensitivity to latex and test results should not be used in isolation. The incidence of clinical sensitization may be seriously over‐estimated if only laboratory parameters are used.
Safety of allergen‐specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side‐effects during induction treatment
Authors: Mellerup M. T. , Hahn G. W. , Poulsen L. K. , Malling H.‐J.
Published: March 2003

Background

Allergen‐specific immunotherapy is a well‐documented treatment for allergic rhinitis, asthma, and allergy to Hymenoptera venoms. The drawbacks of injection immunotherapy are related to the risk of inducing systemic side‐effects (especially during the induction phase), the time used to reach the maintenance dose, and the percentage of patients completing the induction phase).

Objective

To investigate the practicability and safety of three different patient‐friendly induction regimens of clustered immunotherapy (several injections administered during each visit).

Methods

Since 1990, three different clustered induction regimens (regimen 1 = exclusively aqueous extracts; regimen 2 = a combination of aqueous and alum depot extracts; and regimen 3 = induction using exclusively alum depot extracts) have been investigated in 657 patients (10 369 injections).

Results

A total of 454 systemic (immediate and late) reactions were observed in 257 patients corresponding to 4.4% of the injections and 39.1% of the patients. Most of the systemic reactions were of little or no clinical importance (93% grade 1 and grade 2) and < 1% anaphylactic reactions. The 8‐week induction regimen using exclusively alum depot extracts showed a statistical significant lower frequency and severity of systemic side‐effects. Immunotherapy with cat and mite allergen extracts showed the highest frequency of severe side‐effects, which may be related to these extracts being used predominantly in asthmatic patients. The lowest frequency of systemic side‐effects was observed in patients allergic to Hymenoptera venoms and these patients furthermore showed the highest number of patients (97%) completing the induction phase.

Conclusion

An 8‐week clustered induction regimen using alum depot extract seems an acceptable compromise in relation to a reduction in the time used to reach maintenance dose and the risk of inducing clinically relevant systemic side‐effects, and consequently imply a reduction in the costs of the treatment.