bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of GABA receptors in the bronchial response: studies in sensitized guinea‐pigs
Authors: Tohda  , Ohkawa  , Kubo  , Muraki  , Fukuoka  , Nakajima
Published: March 2003

Background

γ‐Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the mammalian central nervous system, is also found in peripheral tissues, including the lung. GABA has recently been shown to modulate the contraction of airway smooth muscle.

Objective

We studied the effect of GABA on the contractile properties of tracheal smooth muscle by measuring the tension of the trachea isolated from non‐sensitized and ovalbumin (OA)‐sensitized guinea‐pigs under isometric conditions.

Methods

Guinea‐pigs were sensitized by intraperitoneal doses of OA to prepare a bronchial asthma model. Tracheal spiral rings were prepared from the OA‐sensitized as well as normal, non‐sensitized guinea‐pigs. Using the tracheal preparations, the effects of GABA and GABAa and GABAb receptor agonists (muscimol and baclofen) and antagonists (bicuculline and saclofen) on the basal tone of the trachea and on tracheal contraction induced by electrical field stimulation (EFS) were determined. The effect of GABA on tracheal contraction induced by exogenous acetylcholine was also studied.

Results

GABA and GABA agonists and antagonists had no effect on the basal tone of normal guinea‐pig tracheae. Both GABAa and GABAb receptor agonists, as well as GABA, suppressed EFS‐induced contraction of normal guinea‐pig tracheae in a reversible, dose‐dependent manner. Moreover, this suppression was reserved to the control level by either GABAa and GABAb receptor antagonists. In tracheal spiral ring prepared from OA‐sensitized guinea‐pigs, GABA and baclofen caused a smaller reversible inhibition of EFS‐induced contraction than in normal tracheal spiral ring, while muscimol inhibited EFS‐induced tracheal contraction to a similar extent to that observed in normal tracheae. GABA had no effect on the tracheal contractile response to acetylcholine.

Conclusion

The results suggest that there may be a biological mechanism mediated by prejunctional GABAb receptors which attenuates cholinergic contraction of airway smooth muscle and that dysfunction of the receptors may underlie the airway obstruction in asthmatics.
Epidemiology of insect venom sensitivity in children and its correlation to clinical and atopic features
Authors: Novembre  , Cianferoni  , Bernardini  , Veltroni  , Ingargiola  , Lombardi  , Vierucci
Published: March 2003

The aim of this study was to obtain more accurate figures of the prevalence of cutaneous sensitivity to Hymenoptera venoms (HV) and its correlation with other parameters of atopy in a population of primary schoolchildren. Parents filled out a structured questionnaire and children were tested with a panel of inhalant and food allergens as well as standardized freeze‐dried extracts of HV. Among the 1175 children who completed the study there was a personal history of rhinoconjunctivitis in 242 (20.8%) and a current wheezing in 114 (9.78%). Two‐hundred twenty‐eight (19.40%) children had a history of Hymenoptera sting (HS) reactions (224 or 19.06% of local reactions and 4 or 0.34% of local and systemic reactions). Positive skin‐prick tests (SPT) to any given HV extract were present in 43 children (3.66%). Most subjects had positive SPT to honey bee venom (35/1175; 2.98%); 17/1175 (1.45%) had positive SPT to wasp and only 12 subjects (1.02%) had positive SPT to polistes venom. There was a correlation between a positive SPT to HV and the history of clinical reactions to HS (P = 0.0026). Positive SPT to at least one of the inhalant and food allergens tested were found in 353 subjects (30.04%). Factors such as age, sex, reactions to HV, positive SPT to mite, cat dander, grass, Alternaria, Parietaria, cow's milk, egg white and wheat were significantly associated with a positive SPT to HV using a univariate regression analysis. Only age, reactions to HV, a positive SPT to grass, Parietaria, cow's milk, and egg white were significantly associated with a positive SPT to HV using a multiple regression analysis. In this study, the frequency of immunological sensitization to HV in a population of unselected children is not so high as in adults. There is an association between the presence of positive SPT to HV and an atopy linked humoral IgE response. The presence of a significant and independent association between positive SPT to food of animal origin and positive SPT to HV is surprising and needs further study.
Asthma, rhinitis and eczema in Maltese 13–15 year‐old schoolchildren — prevalence, severity and associated factors [ISAAC]
Authors: Montefort  , Lenicker  , Caruna  , Muscat
Published: March 2003

Background

Allergic conditions, especially asthma, seem to be increasingly common the world over. The International Study of Asthma and Allergies in Childhood [ISAAC] was the first worldwide study carried out with standardized questionnaires in order to create a reliable global map of childhood allergy.

Objectives

The Maltese Islands were one of the centres participating in this study and in this paper the data obtained from 4184 13–15 year olds from 22 state and three private schools [88.7% response rate], and also data obtained from some added ‘local’ questions addressed to the same children, are included. in order to evaluate the problem of allergic conditions in Maltese schoolchildren.

Results

27.9% of the participants were wheezers ‘ever’ while 16% were current wheezers. Of the latter children 15.1% were experiencing nocturnal wheezing at least once a week and 22% had a wheezing episode severe enough to limit speech. Nasal problems were present in 52.7% of these teenagers and 47.4% of all respondents persisted with these symptoms up to the year of answering the questionnaire. Hayfever had been diagnosed in 32.3% of all the children. 12.8% of respondents had a recurring itchy rash suggestive of eczema for at least 6 months of their lives and 10% had it currently. This was slightly lower than the global mean, unlike the case of wheezing, which in Malta was more common than the world average, and rhinitis, for which we had the second highest cumulative prevalence rate in the world. Multiple variables such as gender, smoking, family history of atopy, pets, soft furnishings and living in busy roads affected the prevalence and severity of the allergic conditions studied.

Conclusions

Allergic conditions are very common in Maltese schoolchildren and are causing a lot of hardship to these same youngsters. The results of this study should serve as a stimulus to try and decrease this suffering through better management of these conditions, measures to control possible detrimental factors and further research on asthma, allergic rhinitis and eczema.
Phase‐contrast microscopic studies using cinematographic techniques and scanning electron microscopy on IgE‐mediated degranulation of cultured human mast cells
Authors: Kurosawa  , Inamura  , Kanbe  , Igarashi  , Tomita  , Takeda  , Miyachi
Published: March 2003

Background

Isolating human mast cells is a laborious procedure. Recently, cultured human mast cells raised from umbilical cord blood cells have become available. It is necessary to investigate whether IgE‐mediated activation of these cells is mediated by exocytosis.

Objective

To verify IgE‐mediated activation of these cultured human mast cells morphologically.

Methods

The mast cells were raised from human umbilical cord blood cells in the presence of stem cell factor and interleukin‐6. IgE‐sensitized cultured human mast cells were activated by anti‐IgE, and morphological changes of the cells were examined under phase‐contrast microscopy using cinematographic techniques and scanning electron microscopy. Histamine release from the cells was measured with high‐performance liquid chromatography.

Results

Under the condition in which a significant histamine release was observed from the mast cells, phase‐contrast microscopy showed that the cultured human mast cells became swollen and extruded granules. Scanning electron microscopy disclosed the extrusion of smooth and round bodies from pores formed on the activated mast cell surface.

Conclusion

IgE‐mediated histamine release from cultured human mast cells is accompanied by exocytosis morphologically, indicating that cultured human mast cells will help in studying the functional properties of human mast cells.
Bone mineral density and body composition in patients with airflow obstruction—the role of inhaled steroid therapy, disease and lifestyle
Authors: Lau  , LI  , Woo  , Lai
Published: March 2003

Background

Inhaled steroid therapy has been shown to be associated with low bone mineral density (BMD) in asthmatic patients, but its effect in men has not been specifically studied; and the relative importance of therapy, disease and lifestyle leading to low BMD has not been investigated.

Objectives

The study was designed to compare BMD in women and men who had airflow obstruction (asthma or COAD with or without inhaled steroid therapy) with normal controls. The role of inhaled steroid treatment, disease severity and lifestyle was studied among patients.

Methods

One hundred and fourty‐four patients (106 on inhaled steroids and 38 not on inhaled steroids) and 212 age‐matched controls were studied. Body composition and BMD (at the total body, hip and spine) were measured by dual‐X‐ray densitometry (DEXA). Forced expiratory volume (FEV1) was measured in patients. A validated questionnaire was administered to measure lifestyle factors.

Results

The body mass indices (BMI) (P < 0.001) and percentage of body fat (P < 0.001) were higher among female patients on inhaled steroids than controls. However, the BMD of the total body (P < 0.05) and spine (P < 0.001) were significantly lower in premenopausal and postmenopausal women than controls, respectively (P < 0.005). The BMD at the spine (P < 0.01) and hip (P < 0.01) in male patients were significantly lower than the controls.

By multiple regression, age and use of inhaled steroid was negatively associated with BMD at the hip (P < 0.01), but not at the spine (P > 0.05).

Cigarette smoking was associated with significantly lower BMD at the femoral neck (P < 0.05), and a low dietary calcium intake was associated with lower BMD at the spine (P < 0.05). In women, use of inhaled steroid was not associated with significantly lower BMD.

Conclusion

Men who had asthma and/or COAD had lower BMD, and this was not attributable entirely to steroid use. Cigarette smoking and a low dietary calcium intake may partially account for this difference. The difference in BMD between female patients and controls, even in those taking inhaled steroid, was small.
Primary sequence and molecular model of the variable region of a mouse monoclonal anti‐Der p 1 antibody showing a similar epitope specificity as human IgE
Authors: Mcelveen  , Clark  , Smith  , Sewell  , Shakib
Published: March 2003

Background

Der p 1, a major mite allergen, elicits IgE antibody responses in 80% of patients suffering from dust mite allergy. Given the potent IgE eliciting properties of Der p 1, there is considerable interest in studying the molecular architecture of the variable (Fv) region of IgE antibodies specific for this allergen.

Objectives

IgE is present in human serum at extremely low concentrations, and as such it is practically impossible to purify sufficient quantities for structural studies. We have therefore sought to sequence and model a representative murine monoclonal (MoAb) anti‐Der p 1 antibody, as a surrogate human IgE.

Methods

The cDNA coding for the Fv region of an anti‐Der p 1 MoAb (2C7), that mimics the binding of human IgE to Der p 1, was amplified by PCR, cloned and sequenced. The predicted amino acid sequences were then compared with a directory of human germline V‐gene segments. Modelling of the Fv region of MoAb 2C7 was carried out using the extensive database of existing immunoglobulin structures in the Brookhaven PDB.

Results

The MoAb 2C7 heavy chain showed greater than 70% homology with three members of the VH3 family, DP‐35, DP‐53 and DP‐54. Similarly, the light chain showed greater than 70% homology with 11 VK sequences, including the VKII sequences DPK18, DPK19 and DPK28. A molecular model of the Fv region of MoAb 2C7 was generated and can be accessed from the EMBL databank.

Conclusions

Antibodies similar to MoAb 2C7 could be generated as part of the human repertoire. The availability of 3‐dimensional model of MoAb 2C7, as a surrogate human IgE antibody, combined with further data on its epitope specificity, will facilitate studies into IgE antibody responses to Der p 1.
The effects of anti‐asthma drugs on mediator release from cultured human mast cells
Authors: Shichijo  , Inagaki  , Nakai  , Kimata  , Nakahata  , Serizawa  , Iikura  , Saito  , Nagai
Published: March 2003

Background

A method for generating human mast cells in vitro was recently established. Little is known about the pharmacological profiles of allergic mediator release from cultured mast cells.

Objective

The main objective was to investigate the nature of cultured mast cells from a pharmacological point of view. We examined the effect of anti‐asthma drugs on the release of histamine, sulfidoleukotrienes (LTs) and prostaglandin D2 (PGD2) from the cultured mast cells.

Methods

Using the method established by Saito et al. we cultured cord blood mononuclear cells in the presence of 80 ng/mL stem cell factor (SCF), 50 ng/mL interleukin‐6 (IL‐6) and 300 nmol/L prostaglandin E2 (PGE2), and obtained almost pure (> 99%) mast cells. We sensitized cultured mast cells with immunoglobulin E (IgE)‐rich serum, and then treated them with some anti‐asthma drugs before challenge with anti‐human IgE. Released histamine, LTs and PGD2 were measured by high‐performance liquid chromatography, commercial enzyme‐linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA) systems, respectively.

Results

The cultured mast cells released histamine, LTs and PGD2 following immunological stimulation through IgE. The mast cell stabilizing agents disodium cromoglycate (DSCG, 1 mmol/L) and azelastine (100 μmol/L) significantly inhibited the release of these three mediators. The β‐adrenoceptor agonists isoproterenol, salbutamol, and clenbuterol also inhibited all three mediators' release in a concentration‐dependent manner. The non‐selective and selective phosphodiesterase (PDE) inhibitors theophylline, rolipram, and cilostazol had no significant effect on mediator release at clinically useful concentrations. BAY × 1005 (a 5‐lipoxygenase‐activating protein inhibitor) inhibited the LTs release, whereas indomethacin (a cyclo‐oxygenase I and II inhibitor) and NS‐398 (a cyclo‐oxygenase II inhibitor) inhibited PGD2 release.

Conclusions

The present results indicate that cultured mast cells release histamine, LTs and PGD2 following IgE crosslinking. Anti‐asthma drugs showed a characteristic suppression of the release of each mediator. The suppressive actions of these drugs are similar to their pharmacological actions on human lung mast cells. These results suggest that cultured mast cells are useful for the analysis of function and pharmacological profiles of lung mast cells.
Accumulation of atopic disorders within families: a sibling effect only in the offspring of atopic fathers
Authors: Mattes  , Karmaus  , Moseler  , Frischer  , Kuehr
Published: March 2003

Background

Several studies have reported an association between a child's risk of atopic disorders and family size. However, the inverse association might not be the same in populations with a different genetic disposition for atopic disorders.

Objective

This longitudinal study was designed to assess risk factors of atopy.

Methods

Lifetime prevalence of asthma, hay fever and eczema of 1440 families including 3165 offspring was ascertained by means of standardized questionnaires.

Results

After possible confounders had been controlled for, an inverse association between atopic disorders and the number of older siblings was found only in the offspring of atopic fathers (trend for older siblings: χ2 = 13.38, degrees of freedom [d.f.] = 1, P = 0.0002; odds ratio ‘no older sibling’ = 2.87 (95% confidence interval 2.18–3.78); ‘1 older sibling’ = 2.11 [1.52–2.92], ‘2 older siblings’ = 1.29 [0.74–2.23]; ‘3 or more older siblings’ = 0.15 [0.02–0.98]). No such relationship was found for children without a history of paternal atopy (trend for older siblings: χ2 = 1.51, d.f. = 1, P = 0.22; odds ratio ‘no older sibling’ = 1 [reference]; ‘1 older sibling’ = 0.82 [0.63–1.06]; ‘2 older siblings’ = 0.97 [0.67–1.40]; ‘3 or more older siblings’ = 0.64 [0.31–1.33]). The trend for older siblings in the case of paternal atopy was significantly different from the trend for older siblings without a history of paternal atopy (χ2 = 8.68, d.f. = 1, P = 0.003). The number of younger siblings was not related to child's risk of atopy (trend for younger siblings: χ2 = 0.001, d.f. = 1, P = 0.97).

Conclusions

Data from this study suggest a protective effect of sibship size only in children with a history of paternal atopy and if older siblings are present. The reason for this combined effect remains unclear. Thus, further investigations are needed to interpret the biological cause of the so called ‘sibling effect’.
Cloning, expression and characterization of the major latex allergen prohevein
Authors: Rozynek  , Posch  , Baur
Published: March 2003

Background

About 70–80% of latex allergic health care workers are sensitized to prohevein (Hev b 6.01), a 20 kDa cysteine‐rich chitin‐binding protein of Hevea latex.

Objective

This study reports on the bacterial cloning, expression and immunochemical characterization of rHev b 6.01.

Methods

Prohevein was expressed in the periplasmatic space of Escherichia coli as maltose binding protein (MBP) fusion protein and purified to homogeneity after factor Xa cleavage. The IgE binding capacity of both rHev b 6.01 and prohevein isolated from fresh Hevea latex was compared by immunoblotting experiments using sera of latex‐allergic patients. The diagnostic value of rHev b 6.01 was analysed by enzyme allergosorbent test (EAST).

Results

Two different cDNA clones of rHev b 6.01 were established. The deduced amino acid sequence of both clones revealed two and three amino acid differences in the C‐terminal domain of prohevein compared with the original database entry. Purified rHev b 6.01 bound with high affinity to chitin as its natural counterpart isolated from natural latex. In IgE‐immunblotting using sera of affected subjects binding intensity to both proteins was comparable indicating a very high antigenic similarity. The diagnostic value of MBP‐prohevein was tested in EAST using sera of 33 latex‐allergic subjects. The in vitro test showed high sensitivity and specificity and proved the diagnostic value of uncleaved MBP‐prohevein.

Conclusions

The production of recombinant latex key allergens with defined quality like prohevein is a straightforward strategy for the development of standardized in vitro test systems.
House dust mite allergen exposure in infancy
Authors: Mahmic  , Tovey  , Molloy  , Young
Published: March 2003

Background

Infancy may be a critical time for exposure to house dust mite allergens, when exposure to high levels can increase the risk of allergic sensitization and the development of asthma in later life.

Objective

To measure house dust mite allergen (Der p 1) concentration in the infants' environment and examine lifestyle factors which may influence mite allergen exposure.

Methods

Infants aged between 4 and 12 months (n = 134) from the western region of Sydney, Australia, participated. Reservoir dust samples were collected from four sites within each home: infant's bed, second bed (adult or second child's bed), lounge floor and sheepskins (where available). Settling aeroallergen was collected for 10–14 d in Petri dishes in the infant's room. Der p 1 was measured by ELISA. A questionnaire on types of bedding, sleeping and playing patterns of the infant was completed by the parents at the time of dust collection.

Results

All infants were exposed to at least one site with Der p 1 concentrations greater than 10 μg/g fine dust. The mean settling aeroallergen level in the infants' room was 24 ng Der p 1/m2day and this was weakly related to bed allergen levels (r = 0.21, P < 0.05). Mattress type had a weak effect on Der p 1 levels as measured in the whole bed (P = 0.07), while bed cover and bed type had no effect (P > 0.6). The mean product of time spent at a site and its allergen concentration was highest for beds in 69% of infants.

Conclusion

The high level of allergen exposure in the environment of this group of infants places them at an increased risk of early sensitization and development of asthma. Any strategy to reduce asthma prevalence should address these high and avoidable levels.
Antigenicity of the proteins in soy lecithin and soy oil in soybean allergy
Authors: Awazuhara  , Kawai  , Baba  , Matsui  , Komiyama
Published: March 2003

Background

Soy lecithin and soy oil are usually produced from the hexane extract of soybean. Some of the soybean proteins are included in the extract and are therefore present in small amounts in both soy lecithin and soy oil. The antigenicity of the proteins present in defatted soybean has been studied with respect to soybean allergy, but the antigenicity of those found in the extract is yet to be investigated.

Objective

The antigenicity of soy lecithin and soy oil proteins with regard to soybean allergy were investigated.

Methods

The proteins present in soy lecithin and soy oil were determined according to already established method and analysed by SDS‐PAGE. The IgE‐ and IgG4‐binding abilities of the soy lecithin proteins were investigated by immunoblotting with sera from 30 soybean‐sensitive patients, including seven with a positive challenge test. Immunoblotting of soy oil proteins was performed with the sera from some of these patients.

Results

In 100 g of sample, the soy lecithin and soy oil contained 2.8 mg and 1.4–4.0 μg of proteins, respectively. The results of SDS‐PAGE demonstrated the presence of only three proteins, with molecular weights of about 58–67 kDa in soy oil, and suggested that soy lecithin also contains these proteins. The soy lecithin also contained many proteins besides these. In the soy lecithin, the detection rate of only one protein, with a molecular weight of 31 kDa, by the serum IgE of patients was significantly different compared with controls (detection rate: 40%). The proteins with molecular weights of 58–67 kDa rarely bound to serum IgE. Only one of the patients who presented a positive challenge test had IgE antibodies to soy lecithin proteins. IgG4‐binding proteins were found only rarely in soy lecithin. Neither the IgE nor the IgG4 present in the patients' sera reacted to any soy oil protein.

Conclusion

Proteins present in soy lecithin and soy oil have little antigenicity with regard to soybean allergy.
Is allergy increasing? – early life influences
Authors: Howarth
Published: March 2003

Data from epidemiological studies conducted in several countries worldwide have revealed that the prevalences of allergic conditions, including allergic rhinitis, asthma and eczema, have increased from the 1940s/50s to the 1990s. These allergic conditions involve specific IgE‐mediated responses, and a few studies have demonstrated that IgE levels have increased in some communities over time in a manner similar to the incidences of allergic conditions. The predisposition for atopy appears to be determined in early life, and evidence indicates that events occurring in utero and in infancy can influence the future development of atopy. The intrauterine environment favours TH2 cell development and IgE production and could predispose to atopy. It can be hypothesized that dietary or other factors favouring TH2 proliferation might contribute to the development of atopic disease. Conversely, early infection has been found to have a negative association with the development of atopy, perhaps through promotion of a TH1 response; the reduction in infection in the very young as a consequence of modern healthcare may have contributed to the increase in atopic disease. Thus, it is a plausible hypothesis that changes in the conditions of the intrauterine environment and/or in infancy (for example, in nutrition and in rates of infection) may explain the observed increases in atopy and allergic conditions.
Rhinitis management: the patient’s perspective
Authors: Juniper
Published: March 2003

Seasonal allergic rhinitis causes considerable impairment of health‐related quality of life (HQRL). Generic quality‐of‐life questionnaires enable a comparison to be made between patients with different illnesses, but they often have insufficient depth to measure specific problems that are important to an individual with a particular condition. In order to overcome these shortcomings, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was developed. Eighty‐nine patients, with a wide range of rhinoconjunctivitis severity, scored a list of 91 problems for importance. The highest‐scoring problems were the practical problems: continually having to blow the nose, rub the nose and eyes, and carry tissues. Patients were also bothered by sleep impairments and systemic problems such as tiredness, poor concentration and thirst. Questionnaires have also been developed for adolescents (12–17 years of age) – finding similar results to those for adults – and children (6–12 years of age), who were troubled by their symptoms but did not have the emotional dysfunction experienced by adults and adolescents. All three questionnaires have strong measure‐ment properties and have high reliability and good responsiveness, validity and interpretability. Quality‐of‐life questionnaires can be used in clinical studies to help elucidate which treatments are preferred by patients and the efficacy of treatment regimens. Disease‐specific quality‐of‐life questionnaires can also be used during routine assessments and may reveal problems not spontaneously volunteered by patients, particularly children. Results can also be compared at each clinic visit to determine whether each intervention has been beneficial.
Antihistamines in urticaria
Authors: Ring J. , Brockow K. , Ollert M. , Engst R.
Published: March 2003

Urticaria is one of the most common and, in its chronic course, excruciating dermato‐allergic diseases. Apart from the dermatological diagnosis, the identification and evaluation of causal triggering factors is of utmost importance. Here a ‘three‐step guideline’ (according to Ring and Przybilla) has gained acceptance, ranging from a general basic examination via an intensive investigation until oral provo‐cation tests for food allergy and oral provocation tests for idiosyncrasy (OPTI) against food additives.

 Apart from true IgE‐mediated allergies, pseudo‐allergic reactions against food additives as well as food contents represent a major problem in chronic urticaria. Recently gastric mucosal colonization with Helicobacter pylori as the trigger of chronic urticaria has received attention. New patho‐physiological concepts describe autoantibodies that are directed either against IgE or against the high‐affinity IgE‐receptor on the surface of mast cells and basophil leucocytes. In the intradermal test with autologous serum positive wheal and flare reactions can be observed (Greaves’ test).

 In many patients with chronic urticaria considerable psychosomatic involvement is also observed.

 Histamine is one of the major mediators of most forms of urticaria although in some cases, especially physical urticaria, other mediators seem to play a role. Therefore antihistamines, and mainly H1 antihistamines, are the mainstay of antiurticaria therapy.

 Some studies have shown a benefit of combined H1‐ and H2‐antagonist treatment in special forms of urticaria namely urticaria factitia. Similarily pretreatment with combined H1 and H2 antagonists has been proven to reduce effectively the frequency of pseudo‐allergic reaction to some histamine‐releasing drugs used in radiology or surgery.

 More than 50 years after the first introduction of an antihistamine into allergy therapy, antihistamines still represent modern and exciting agents contributing to the continuous improvement of antiallergic therapy.

 Antihistamine therapy can be performed with either the classical or second generation antihistamines. Classical antihistamines are connected with considerable side‐effects especially sedation and anticholinergic effects. New non‐sedating antihistamines have been developed that do not cross the blood–brain barrier.

 The efficacy of mizolastine, a new non‐sedating H1 antagonist, has been evaluated in several placebo‐controlled and comparative clinical trials. Overall, mizolastine 10 mg/day was found to be significantly more effective than placebo and as effective as other second generation antihistamine drugs in the management of patients with chronic urticaria, with a rapid and sustained action.
Leukotriene pathway inhibitors in asthma and chronic obstructive pulmonary disease
Authors: Busse W. W. , Mcgill K. A. , Horwitz R. J.
Published: March 2003

Leukotrienes can be generated from a wide variety of cells including mast cells and eosinophils. The biological properties of these products include bronchial smooth muscle contraction, stimulation of mucous production, enhancement of vascular permeability, and recruitment of eosinophils. These properties can contribute significantly to the pathobiology of asthma. Recently, zafirlukast and montelukast, and zileuton, leukotriene D4 receptor antagonists and 5‐lipoxygenase inhibitors, respectively, have been developed and are available for treating asthma. Studies have found these compounds modify bronchospasm with exercise, the pulmonary reaction to aspirin in sensitive subjects, and the airway response to inhaled antigen. Furthermore, in patients with chronic asthma, leukotriene modifiers improve airflow obstruction, decrease the need for rescue medication, and diminish symptoms. Moreover, these drugs can prevent asthma exacerbations. However, there is little evidence that these medications have potent anti‐inflammatory activity. Nonetheless, leukotriene modifiers represent new, and effective, therapeutics in the treatment of asthma; at present, the positioning of these products in relationship to inhaled corticosteroids, for example, in the treatment of asthma has not been fully defined but will emerge with further study and use in the clinic setting.
Outcome of double‐blind, placebo‐controlled food challenge tests in 107 children with atopic dermatitis
Authors: NIGGEMANN  , SIELAFF  , BEYER  , BINDER  , WAHN
Published: March 2003

Background and objective

Little is known about late phase clinical reactions during oral food challenges and the value of specific IgE in terms of sensitivity and specificity.

Methods

We therefore analysed retrospectively the clinical outcome of 387 oral provocations during double‐blind, placebo‐controlled food challenge tests in 107 children with atopic dermatitis.

Results

Eighty‐seven (81%) children showed a positive clinical reaction to at least one challenge. The vast majority of children (94%) showed clinical symptoms to one or two allergens. One hundred and thirty‐one of 259 (51%) of verum challenges and 1/128 (0.8%) placebo challenge were assessed as positive. Oral provocations with hen's egg showed the highest percentage of positive reactions (70%). Sensitivity of specific IgE to the four allergens tested was 90%, specificity 30%. Sensitivity of the parental history as a predictive factor was 48%, specificity 72%. Ninety‐two of 131 (70%) children with positive verum provocations showed early reactions, 33 (25%) late and six (5%) combined early and late reactions. In 84/131 (64%) positive provocations one organ system was involved, while in 44 (34%) provocations two and in three (2%) challenges three organ systems were involved. Skin reactions were the most frequent clinical manifestation leading to positive reactions followed by gastro‐intestinal and respiratory symptoms. There was no correlation between titration dose and specific IgE. The subgroup of non‐sensitized children did not differ in terms of sex, age or titration dose from the total study population.

Conclusion

Double‐blind, placebo‐controlled oral food challenges are helpful in distinguishing children with clinically manifested symptoms from those with food sensitization. Accurately identifying children with a clinical relevant food allergy may help to prescribe specific diets on a scientific basis, avoiding dietary limitations which may be unneccessary or even harmful.
Reference values of total serum IgE and their significance in the diagnosis of allergy among the young adult Kuwaiti population
Authors: Ezeamuzie  , Al‐Ali  , Al‐Dowaisan  , Khan  , Hijazi  , Thomson
Published: March 2003

Background

The reference total serum immunoglobulin (IgE) values and the usefulness of total IgE values in the diagnosis of allergy have not been established for the Kuwaiti population. The literature reference values may not be applicable since such values often vary among ethnic nationalities.

Objective

The aim of this study was to establish the reference IgE values for the young adult Kuwaiti population and to determine the usefulness of such values in the diagnosis of allergic diseases in the community.

Methods

A total of 1057 randomly selected young adults were screened for atopy using the Pharmacia CAP‐PhadiatopR method. Atopy was detected in 423 individuals (40.0%). Total serum IgE was then measured in 542 randomly selected Phadiatop‐negative (non‐atopic) cases in the age range 18–50 years (mean 28.9 years) and male:female ratio of 1.3.

Results

Serum total IgE values in non‐atopics covered a very wide range (< 2–1993 kU/L) with a geometric mean (GM) value of 43.7 kU/L. The reference range, calculated as the 95% confidence interval of the log IgE (95% CI) was 3.2–602.5 kU/L. The 90% CI was 11.7–162 kU/L. The GM was significantly higher for males than females, (53.7 vs. 35.5 kU/L, P < 0.001) and for smokers than non‐smokers, (64.6 vs. 40.7 kU/L, P < 0.01), but was independent of age. Although the GM for the non‐atopics (43.7 kU/L) was significantly lower than those of the asymptomatic atopics (213.8 kU/L) and allergic asthmatics (626.6 kU/L), the 95% CI for the three groups showed considerable overlap.

Conclusions

These results show that the normal total IgE values in the young adult Kuwaiti population are generally high and that the distribution of the values is so wide that the diagnostic value of total serum IgE in this community is likely to be very limited.
High prevalence of sensitization to cat allergen among Japanese children with asthma, living without cats
Authors: ICHIKAWA  , IWASAKI  , BABA  , CHAPMAN
Published: March 2003

Background

Cat allergy is common among children with asthma. Many cat‐allergic patients in Japan and elsewhere do not keep cats, but nonetheless become sensitized through environmental exposure to cat allergen.

Objective

To assess the frequency of cat allergy and cat‐specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody responses in young Japanese patients with asthma in relation to self‐reported cat exposure and Fel d 1 levels in dust samples.

Methods

Cat dander‐specific IgE antibody was measured in sera from asthma patients using the CAP system. IgE and IgG antibody to Fel d 1 was measured by antigen binding radioimmunoassay and by chimeric enzyme immunoassay. Fel d 1 levels in dust samples from a subset of patients' homes were measured by monoclonal antibody‐based enzyme immunoassay.

Results

Cat‐specific IgE (CAP class≥2) was found in sera from 70% of 44 patients who kept cats and 34% of 394 patients who had never kept cats. The prevalence of sensitization increased progressively to age 6 years (40%: positive), and then increased gradually to age 16 years (approximately 60%: positive) in patients who had never kept cats. There was an excellent correlation between cat CAP values and IgE levels to Fel d 1. The absolute amount of IgE antibody to Fel d 1 ranged from 0.01 to 15.6% of total IgE. Most patients who did not keep cats were exposed to Fel d 1 levels ranging from 0.07–8 μg/g dust.

Conclusions

Sensitization to cat allergen is common among young asthmatic patients in Japan, even among patients who do not keep cats. Use of CAP and the chimeric enzyme‐linked immunosorbent assay allows accurate diagnosis of cat allergy and quantification of specific IgE antibody levels.
Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical symptoms in atopic asthma
Authors: Ohrui  , Funayama  , Sekizawa  , Yamaya  , Sasaki
Published: March 2003

Background

A high serum immunoglobulin (Ig)E level is considered a potent predictor for the development of asthma and IgE is targeted for treatment of asthma. Although inhaled corticosteroids are well established in the treatment of asthma, the effects of inhaled corticosteroids on serum IgE levels in asthma remain uncertain.

Methods

We therefore examined asthma symptoms, concentrations of total serum IgE and specific IgE antibodies to selected allergens, blood eosinophil counts and lung functions before and 3 months after treatment with either inhaled beclomethasone dipropionate (BDP; 800 μg/day) (n = 7) or inhaled β2‐agonists alone (n = 7) in patients with atopic asthma in a randomized, double‐blind, parallel‐group controlled trial.

Results

Inhaled BDP significantly improved asthma symptom scores and forced expiratory volume in 1 s, and decreased blood eosinophil counts, total serum IgE levels and specific IgE antibodies to house dust mite and cedar. Decreases in total serum IgE significantly correlated with an improvement in asthma symptom scores. In contrast, none of parameters altered in patients with atopic asthma treated with inhaled β2‐agonists alone.

Conclusions

Inhaled corticosteroids may improve the subsequent clinical course of atopic asthma in association with a reduction of serum IgE levels.
Peripheral blood T lymphocytes from asthmatic patients are primed for enhanced expression of interleukin (IL)‐4 and IL‐5 mRNA: associations with lung function and serum IgE
Authors: BORGER  , TEN HACKEN  , VELLENGA  , KAUFFMAN  , POSTMA
Published: March 2003

Background

The TH2‐like cytokines interleukin (IL)‐4 and IL‐5 play a pivotal role in airway wall inflammation in asthma and these cytokines are increased in peripheral blood and bronchoalveolar lavage fluid from asthmatic patients. It is unclear why specifically TH2‐like cytokines are increased in asthmatic patients. A possible explanation may be an impaired adenylyl cyclase activity, which has been observed in peripheral blood mononuclear cells of asthmatics.

Objective

To assess interferon (IFN)‐γ, IL‐4 and IL‐5 mRNA expressions and their control by prostaglandin E2 (PGE2), which activates adenylyl cyclases, of peripheral T lymphocytes from patients with moderately severe asthma and healthy controls.

Methods

Peripheral blood T lymphocytes from asthmatics and healthy controls were isolated and stimulated with antibodies against CD3 plus CD28 in the absence and presence of increasing concentrations of PGE2. IFN‐γ, IL‐4 and IL‐5 mRNA levels were detected by reverse transcription‐polymerase chain reaction.

Results

In contrast to IFN‐γ mRNA, IL‐4 (P = 0.03, n = 8) and IL‐5 (P < 0.05, n = 5) mRNAs in the asthma group were significantly higher than in controls (n = 4). In addition, IL‐5 showed a significant inverse correlation with forced expiratory volume (FEV1) (P < 0.04, n = 5), whereas IL‐4 positively correlated with PC20adenosine‐monophosphate (AMP) (P < 0.02, n = 8). Accumulation of mRNA for IFN‐γ, IL‐4 and IL‐5 mRNA were significantly diminished by 10−5 m PGE2 in both asthmatics and controls. In contrast, 10−6 m PGE2 significantly down‐regulated IFN‐γ and IL‐4 mRNAs (P < 0.05 for both IFN‐γ and IL‐4, n = 4) in the control group, whereas this was not observed for IL‐4 mRNA in the asthma group (n = 7).

Conclusions

Activated peripheral blood T lymphocytes from asthma patients display higher levels of IL‐4 and IL‐5 mRNA in vitro, which may be due to a diminished activity of adenylyl cyclase. A new observation is that higher IL‐4 mRNA levels are associated with less severe AMP responsiveness, which might be due to a negative feedback loop of IL‐4 production by mast cells.
Relationship between allergic status and specificity of IgG antibody to inhaled allergens: the grass pollen model
Authors: MICHILS  , VERVIER  , CHOUFANI  , GOSSART  , DUCHATEAU
Published: March 2003

Background

We have previously reported that IgG antibodies from healthy individuals and patients suffering from non‐seasonal mite allergy bind to different sets of epitopes on Der p 1, allowing almost complete discrimination of the populations.

Objectives

To confirm this observation in a seasonal allergy model where a clear relationship between allergic symptoms and exposure to the offending agent is established. To investigate whether the pattern of modified specificity is related to the differences in IgG subclass hierarchy usually exhibited by nonallergic and allergic populations.

Methods

The capacity of individual sera from patients allergic to grass pollen and healthy individuals, including grass pollen‐sensitized subjects, to prevent the binding of pooled IgG, IgG1, and IgG4 fractions from grass pollen‐allergic patients and healthy individuals to solid‐phase bound grass pollen antigen was evaluated in enzyme‐linked immunosorbent assay (ELISA) using streptavidin‐biotin technology. Specificity controls were performed using sera from patients allergic to cat dander and house dust mite.

Results

The capacity of sera to prevent the antigen binding of allergic IgG averaged 84 ± 5% for allergic sera and 53 ± 6% for healthy sera (P < 0.001 by one‐way
anova). Conversely, using the antigen‐binding capacity of healthy control IgG as reference, percentage inhibitions averaged 46 ± 9% in grass pollen‐allergic subjects compared with 80 ± 4%, 82 ± 2% in healthy individuals, and mite‐ and cat‐allergic patients, respectively, resulting in two well‐separated populations (P < 0.0001 by one‐way
anova). Similar results were found regardless of whether pooled IgG1 or IgG4 were used.

Conclusion

Together with previous data, our results define a new type of humoral signature in the immune response to inhaled allergens. Allergic and healthy status differ not only in the presence or absence of specific IgE antibody but also in the preferential expression of distinct IgG specificities that are better correlated with clinical manifestations and are unrelated to subclass distribution.
Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics — comparison with healthy non‐smokers and smokers and effects of inhaled glucocorticoids
Authors: VAN DER VELDEN  , NABER  , VAN HAL  , OVERBEEK  , HOOGSTEDEN  , VERSNEL
Published: March 2003

Background

Neuropeptides may be involved in the pathogenesis of asthma by evoking neurogenic inflammation. Since the effects of neuropeptides are limited by peptidases, reduced activity of peptidases may contribute to the inflammatory process.

Objective

We hypothesized that soluble peptidase activities are decreased in asthmatics and that inhaled glucocorticoids exert part of their anti‐inflammatory action by increasing soluble peptidase activities.

Methods

Serum and bronchoalveolar lavage (BAL) fluid was obtained from non‐smoking and smoking volunteers and from allergic asthmatics both before and after treatment for 12 weeks with placebo or inhaled fluticasone propionate. Activities of neutral endopeptidase (NEP), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV) were determined using colourometric assays.

Results

Reduced DPP IV activity in serum and reduced NEP activity in BAL fluid were found in healthy smokers compared with non‐smokers. In contrast, no differences in peptidase activities in serum or BAL fluid were observed between allergic asthmatics and healthy non‐smokers. Fluticasone propionate treatment did not affect peptidase activities in the asthmatic patients.

Conclusions

We conclude that reduced peptidase activities in serum or BAL fluid can be found in healthy smokers, but not in allergic asthmatics, and that inhaled glucocorticoids do not affect peptidase activities in BAL fluid or serum of asthmatics. Our results do not support the hypothesized dysfunction of peptidases in the asthmatic airways.
Usefulness of early serial measurement of specific and total immunoglobulin E in the diagnosis of gastro‐allergic anisakiasis
Authors: Daschner  , Alonso‐Gómez  , Caballero  , Suarez‐De‐Parga  , López‐Serrano
Published: March 2003

Background

Sensitization to Anisakis simplex (A. simplex) has been documented to produce severe allergic reactions following ingestion of mainly raw or under‐cooked parasitized fish. False positive skin prick tests (SPT) or specific IgE against this nematode and cross‐reactivity restricts diagnosis. Gastric anisakiasis and gastro‐allergic anisakiasis occur if fish is parasitized by live A. simplex

Objective

To investigate if serial serological analysis could be useful in the diagnosis of acute parasitation by this nematode.

Methods

We included 41 patients who experienced an allergic reaction and/or abdominal symptoms after ingestion of raw or undercooked fish and displayed specific IgE against A. simplex. Total and specific IgE were determined two times: in the 24‐h period after onset of clinical symptoms and after 1 month. SPTs were performed against A. simplex and implicated fish. A fibre optic gastroscopy was performed in 22 patients.

Results

Median total IgE was 80.0 (Interquartile range [IQR] 41.5–186.5) kU/L in the first evaluation and 247.0 (IQR 96.5–649.5) kU/L after 1 month. Median specific IgE against A. simplex was 11.4 (IQR 7.1–33.5) kU/L in the first 24 h and 36.8 (IQR 19.5–79.5) kU/L after 1 month. A rise of total IgE was observed in 35 of 41 patients (P < 0.00001) and a rise in specific IgE against A. simplex in 37 of 41 patients (P < 0.00001). Mean percentage increment was 392% (215–571%; 95% confidence interval [CI]) for total IgE and 339% (177–502%; 95% CI) for specific IgE. In nine of 22 gastroscopic examinations at least one larva, identified as A. simplex, could be detected by our microbiology service. In this group (n = 9) a rise of total and specific IgE was detected in eight patients (89%) (P = 0.02).

Conclusions

We consider a rise of total and specific IgE in the first month after an allergic reaction as a useful tool in the diagnosis of gastro‐allergic anisakiasis (together with patient's history), even if the parasite cannot be seen with fibre optic gastroscopy. The important rise of total and specific IgE against A. simplex can be considered as a reaction induced by the live parasitizing larva in the context of a polyclonal immunological stimulation.