Showing papers in "Allergy in 2001"

A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force.

Abstract: This report has been prepared by an EAACI task force representing the five EAACI Sections and the EAACI Executive Committee composed of specialists that reflect the broad opinion on allergy expressed by various clinical and basic specialties dealing with allergy. The aim of this report is to propose a revised nomenclature for allergic and related reactions that can be used independently of target organ or patient age group. The nomenclature is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. However, the intention has not been to revise the nomenclature of nonallergic hypersensitivity.

Epidemiology of contact allergy in adults.

Abstract: Background: We aimed to determine the prevalence of contact sensitization in the general population and to investigate associations with important sociodemographic and medical characteristics. Methods: Within a population-based nested, case-control study in Germany, we performed patch tests with 25 standard allergens in 1141 adults (50.4% female, age median 50 years). Additional information was obtained by a dermatologic examination, a standardized interview, and blood analysis. Results: At least one positive reaction was exhibited by 40.0% of the subjects, with reactions most frequently observed to fragrance mix (15.9%), nickel (13.1%), thimerosal (4.7%), and balsam of Peru (3.8%). Women were sensitized more often than men (50.2%vs 29.9%, OR 2.36, CI 1.84–3.03), and this was also significant for fragrance mix, nickel, turpentine, cobalt chloride, and thimerosal. Contact sensitization was more frequent in subjects who reported adverse skin reactions (53.8% vs. 32.6%; OR 2.41, CI 1.85–3.14), and this was particularly true for sensitization to nickel (45.5%vs 8.8%, OR 8.64, CI 5.67–13.17) and fragrance mix (29.0%vs 14.0%, OR 2.51, CI 1.60–3.91) and the corresponding intolerance of fashion jewelry and fragrances. Contact sensitization decreased with increasing degree of occupational training (unskilled 45.9%, apprenticeship 40.1%, technical college 40.4%, and school of engineering 12.5%; P=0.023; trend test P=0.042). Significant associations of contact sensitization and presence of allergen-specific IgE antibodies, atopic eczema, or psoriasis were not observed. Frequency estimates for the general adult population based on these findings were 28.0% for overall contact sensitization and 11.4% for fragrance mix, 9.9% for nickel, and 3.2% for thimerosal. Conclusions: It is concluded that contact allergy is influenced by sociodemographic parameters and plays an important role in the general population.

Cross-reactivity of IgE antibodies to allergens.

Abstract: The cross-reactivity of IgE antibodies is of interest for various reasons, three of which are discussed. Firstly, from the clinical view, it is important to know the patterns of cross-reactivity, because they often (but not always) reflect the pattern of clinical sensitivities. We discuss the cross-reactivities associated with sensitization to pollen and vegetable foods: PR-10 (Bet v 1-related), profilin, the cross-reactive carbohydrate determinant (CCD), the recently described isoflavone reductase, and the (still elusive) mugwort allergen that is associated with celery anaphylaxis; cross-reactivities between allergens from invertebrates, particularly tropomyosin, paramyosin, and glutathione S-transferase (GST); and latex-associated cross-reactivities. Clustering cross-reactive allergens may simplify diagnostic procedures and therapeutic regimens. Secondly, IgE cross-reactivity is of interest for its immunologic basis, particularly in relation to the regulation of allergic sensitization: are IgE antibodies to allergens more often cross-reactive than IgG antibodies to "normal" antigens? If so, why? For this discussion, it is relevant to compare not only the structural relation between the two allergens in question, but also the relatedness to the human equivalent (if any) and how the latter influences the immune repertoire. Thirdly, prediction of IgE cross-reactivity is of interest in relation to allergic reactivity to novel foods. Cross-reactivity is a property defined by individual antibodies to individual allergens. Quantitative information (including relative affinity) is required on cross-reactivity in the allergic population and with specific allergens (rather than with whole extracts). Such information is still scarce, but with the increasing availability of purified (usually recombinant) allergens, such quantitative information will soon start to accumulate. It is expected that similarity in short stretches of the linear amino-acid sequence is unlikely to result in relevant cross-reactivity between two proteins unless there is similarity in the protein fold.

A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduces allergic symptoms after only four preseasonal injections.

Abstract: Background: We present data showing that a Th1-inducing adjuvant can reduce the number of injections required for allergy vaccination. Allergy vaccination is the only treatment for type 1 hypersensitivity that can alter the underlying disease process. A switch of specific T-cell activity from Th2>Th1 to Th1>Th2 is believed to be an important change seen after long-term vaccination therapy. An immunologic adjuvant that enhances such a switch could be used to reduce the number of injections required. This would improve compliance with the treatment and provide pharmacoeconomic advantages. Such an adjuvant is 3-deacylated monophosphoryl lipid A (MPL® adjuvant, Corixa). Methods: A multicentre, placebo-controlled, randomized, double-blind clinical study was performed with a new standardized allergy vaccine comprising a tyrosine-adsorbed glutaraldehyde-modified grass pollen extract containing MPL® adjuvant. Four subcutaneous injections of the active product were given preseasonally to 81 grass pollen-sensitive subjects, and 60 received placebo injections (tyrosine alone). Diary cards were used to record symptoms and medication taken during approximately 30 days of the grass pollen season. Results: There was a statistical advantage in favour of the active treatment for nasal (P=0.016) and ocular (P=0.003) symptoms and combined symptom and medication scores (P=0.013). Titrated skin prick testing revealed a significant reduction of skin sensitivity in the active group compared to placebo (P=0.04). Grass-pollen-specific IgG antibody was raised by active treatment (P<0.01). A rise in IgE antibody was seen in the placebo group during the season (P<0.01). The first year's treatment rise of IgE was not seen in the active group, and no rise occurred during the pollen season. More local adverse events were seen in the active group. There was no difference in generalized adverse events. Conclusions: A new, well-tolerated allergy vaccine, incorporating a Th1-inducing adjuvant, MPL®, was efficacious and after only four preseasonal injections produced antibody changes normally associated with long injection schedules. This may encourage wider application of allergy vaccination. The vaccine is now available in a number of countries as Pollinex Quattro®.

Epidemiology, clinical features, and immunology of the "intrinsic" (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis).

Abstract: Departmentof Pharmacology, University of Bern, Bern, SwitzerlandKey words: atopic dermatitis; clinical features;constitutional dermatitis; epidemiology; extrinsictype; immunopathology; intrinsic type.Prof. Dr B. Wu¨thrichAllergy Unit, Department of DermatologyUniversity Hospital8091 ZurichSwitzerlandAccepted for publication 22 March 2001

The prevalence of allergy to egg: a population‐based study in young children

Abstract: Background: The aim of the present study was to estimate the prevalence of adverse reactions to egg, as population-based prevalence estimates based on objective diagnostic procedures are lacking. Methods: The parents of 2721 children in a population-based birth cohort completed questionnaires on the occurrence of any reaction to food at 12, 18, and 24 months of age. Children with parentally reported reactions to eggs at the age of 2 years were selected for further examination. A stepwise diagnostic procedure was developed that included diet trials at home, skin prick tests, and open and double-blind, placebo-controlled food challenges. The mean age of the children at the time of the examination was 2.5 years (CI 2.5–2.6). A sample of children without perceived reactions to egg was also selected for assessment of unrecognized reactions. Results: The estimated point prevalence of allergy to egg in children aged 2½ years was 1.6% (CI 1.3–2.0%), with an upper estimate of the cumulative incidence by this age calculated roughly at 2.6% (CI 1.6–3.6). Almost all reactions were IgE mediated. In general, two-thirds of the parentally perceived reactions were verified. However, the positive predictive value of a parentally perceived reaction depended on the number of times it had been reported, and increased from 50% to 100%, for reactions reported one and three times, respectively. Unrecognized reactions were infrequent. Conclusions: This study confirms that allergy to egg is frequent in a child population.

Epidemiology of food allergy/food intolerance in adults: associations with other manifestations of atopy.

Abstract: Background: Food allergy and food intolerance (FA/FI) are believed to be frequent medical problems; however, information from epidemiologic studies in adults is scarce. The objective was to determine the frequency of FA/FI and allergic sensitization to food in a large adult sample. Furthermore, the associations between FA/FI and other outcomes of atopy were studied. Methods: Within a population-based, nested, case-control study, a standardized interview was performed to obtain detailed information on FA/FI and the history of atopic diseases. In addition, a skin prick test with 10 common food and nine aeroallergens was performed. Results: Overall, 20.8% of the 1537 studied subjects (50.4% female, age median 50 years) reported FA/FI (women 27.5%, men 14.0%; OR 2.35, CI 1.80–3.08). Nuts, fruits, and milk most frequently led to adverse effects, and the sites of manifestation were oral (42.9%), skin (28.7%), gastrointestinal (13.0%), systemic (3.2%), and multiple (12.2%). One-quarter of the subjects (25.1%) were sensitized to at least one food allergen in the prick test, with hazelnut (17.8%), celery (14.6%), and peanut (11.1%) accounting for most of the positive reactions. The corresponding frequency estimates for the representative study base (n=4178) were 15.5% for reported adverse reactions and 16.8% for allergic sensitization. Relevant concomitant sensitization to food and aeroallergens was observed. Food-allergic subjects (positive history and sensitization to corresponding allergen) suffered significantly more often from urticaria, asthma, atopic eczema, and especially hay fever (73.1%) than controls (3.0%). Furthermore, hay fever was treated significantly more often in subjects who suffered from concomitant food allergy. Conclusions: FA/FI in adults is frequently reported and associated with other manifestations of atopy. Hay fever in conjunction with FA/FI tends to be clinically more severe since therapeutic needs are enhanced.

Exposure to pets and atopy‐related diseases in the first 4 years of life

Abstract: Background: It is still unclear how early-life exposure to pets is related to children’s risk of developing atopy-related diseases. We estimated associations between earlylife exposure to pets and atopy-related diseases at 0-4 years of life in a cohort of Norwegian children. Methods: A population-based cohort of 2531 children born in Oslo, Norway, was followed from birth to the age of 4 years. Information on early-life exposure to pets, a number of possible confounders, and atopy-related diseases was mainly collected by questionnaire. Results: In logistic regression analysis adjusting for potential confounders, the odds ratio for being exposed to pets in early life (reference category: not exposed) was, for bronchial obstruction at 0‐2 years of life, 1.2 (95% confidence interval 0.9, 1.8); for asthma at the age of 4 years, 0.7 (0.5, 1.1); for allergic rhinitis at the age of 4 years, 0.6 (0.4, 1.0); and for atopic eczema at 0‐6 months of life, 0.7 (0.5, 0.9). Conclusions: The results indicate that early-life exposure to pets or lifestyle factors associated with exposure to pets reduce the risk of developing atopy-related diseases in early childhood. However, these findings might also be explained by selection for keeping pets.

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.

Abstract: Background: Penicillin is no longer the most commonly prescribed β-lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used β-lactam. Methods: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. Results: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. Conclusions: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

The relation between fungal propagules in indoor air and home characteristics.

Abstract: Results: The number of CFU/m 3 air collected on MEA was significantly higher than on DG-18 (means, respectively, 1033.5 and 846.0 CFU/m 3 )( P<0.0005). However, there was no significant difference between the numbers of CFU/m 3 air collected from the main living area and from the infant bedroom. There was only a very weak relationship between the house characteristics, as described by questionnaire, and the presence of fungal propagules in indoor air. Only the temperature, relative humidity, season, and cats inside homes had a statistically significant impact on the presence of fungal propagules in indoor air. Conclusions: The presence of fungal propagules in indoor air cannot be reliably predicted by home characteristics. Actual measurements are required for fungal exposure assessment, and the use of only one medium to collect samples in one location in a home might be adequate to represent residential levels of fungi in indoor air.

Quantification of major peanut allergens Ara h 1 and Ara h 2 in the peanut varieties Runner, Spanish, Virginia, and Valencia, bred in different parts of the world

Abstract: Background: The serology of peanut allergy seems to be different in various parts of the world. We analyzed the composition of 13 samples of three varieties of peanut in order to compare their allergenic nature. Methods: Peanut cultivars that are commonly processed in the West were analyzed for protein content, protein composition, and Ara h 1 and Ara h 2 content by biochemical methods. IgE-binding properties were analyzed by ELISA using serum from patients with documented peanut allergy. Results: Total protein contents were comparable for all tested samples (24-29%), and proteins were extractable to the same extent. SDS-PAGE patterns differed slightly, but all major bands were visible in all samples (molecular masses of approximately 14-100 kDa under reducing conditions). Ara h 1 and Ara h 2 were quantified by SDS-PAGE densitometry and were expressed as percentage of the total protein content. Ara h 1 was in the range 12-16%, whereas Ara h 2 was 5.9-9.3%. In view of the analytic uncertainty of this determination, the content of both Ara h 1 and Ara h 2 was not significantly different between the tested samples. In an IgE-binding inhibition ELISA, the affinities of the peanut proteins for peanut-specific IgE were measured. Minor differences were observed between the tested samples, with the most potent IgE-binding sample having a two times higher ability to bind IgE than the weakest IgE-binding sample. Conclusions: The results suggest that peanuts of different varieties and from different parts of the world contain similar proteins, including Ara h 1 and Ara h 2. Consequently, the IgE-binding properties are similar to a great extent. This indicates that differences in the serology of peanut allergy may not originate from differences in the allergen composition of the peanut.

Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy.

Abstract: Background: The diagnosis of IgE-mediated immediate reactions to penicillins can be supported by in vivo or in vitro tests using classical benzylpenicillin determinants. The wide variety of β-lactams and the description of new specificities requires a re-evaluation of the different tests available. The objective was to evaluate the diagnostic capacity of Pharmacia CAP System™ RAST FEIA amoxicilloyl c6 (AXO) and benzylpenicilloyl c1 (BPO) in patients with a documented IgE-mediated penicillin allergy. Methods: We studied 129 patients in five groups. Groups 1, 2, and 3 had developed an immediate reaction after penicillin treatment. Group 1 (n=19) were skin test positive to amoxicillin (AX) and/or BPO and/or minor determinant mixture (MDM); group 2 (n=29) were skin test positive to AX but negative to BPO and MDM; and group 3 (n=26) were skin test negative to all determinants, the diagnosis being confirmed by a previous repetitive history or controlled administration. Two control groups, one with nonimmediate reactions – group 4 (n=25) – and one with good tolerance to penicillin – group 5 (n=30) – were included. All samples were analyzed in vitro for AXO and BPO, and the results compared to the in vivo diagnosis. Results: AX was the drug most often involved. In group 1, 53% were in vitro positive for AXO and 68% for BPO, but 74% had at least one positive test result. In group 2, only 10% had a positive in vitro test to BPO compared to 41% to AXO. In group 3, 42% had positive BPO and/or AXO in vitro tests. In the control groups 4 and 5, the negative in vitro results for AXO were 96% and 100%, and for BPO 100% and 97%, respectively. A positive correlation between specific IgE levels and the time interval from the reaction to the evaluation was found only for group 3. Conclusions: This in vitro assay is beneficial for evaluating subjects allergic to β-lactams. It is necessary to test for specific IgE to AXO in addition to BPO in patients with immediate allergic reactions after AX. The combination of in vivo and in vitro tests for estimating IgE antibodies to penicillins is important because of the existence of patients with a positive history but negative skin test.

In vitro T-cell responses to beta-lactam drugs in immediate and nonimmediate allergic reactions.

Abstract: Background:β-Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. Methods: Fifty patients with a well-documented history of allergic reactions to β-lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty-eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. Results: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. Conclusions: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.

Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome.

Abstract: Background: Chicken serum albumin (α-livetin) has been implicated as the causative allergen of the bird-egg syndrome However, the clinical relevance of sensitization to this allergen has not been confirmed by specific challenge tests and environmental sampling We investigated whether chicken albumin can be detected in air samples collected in a home with birds, and whether sensitization to this protein may cause respiratory and food allergy symptoms The heat resistance of chicken albumin and the possible cross-reactivity with conalbumin were also investigated Methods: We studied eight patients with food allergy to egg yolk who also suffered from respiratory symptoms (rhinitis and/or asthma) caused by exposure to birds Sensitization to egg yolk and bird antigens was investigated by skin and serologic tests Hypersensitivity to chicken albumin was confirmed by specific bronchial, conjunctival, and oral provocation tests Results: All patients had positive skin tests and serum IgE against egg yolk, chicken serum, chicken meat, bird feathers, and chicken albumin The presence of airborne chicken albumin in the domestic environment was confirmed Specific bronchial challenge to chicken albumin elicited early asthmatic responses in six patients with asthma An oral challenge with chicken albumin provoked digestive and systemic allergic symptoms in the two patients challenged IgE reactivity to chicken albumin was reduced by 88% after heating at 90°C for 30 min ELISA inhibition demonstrated only partial cross-reactivity between chicken albumin and conalbumin Conclusions: Chicken albumin (Gal d 5) is a partially heat-labile allergen that may cause both respiratory and food-allergy symptoms in patients with the bird-egg syndrome

Validation of a new questionnaire on asthma, allergic rhinitis, and conjunctivitis in young adults.

Abstract: Background: Epidemiologic data on asthma and allergies among adults are mainly based on questionnaires: this study validates the questions on asthma, allergic rhinitis, and conjunctivitis of a new Finnish questionnaire. Methods: To validate questions used in a country-wide study among university students aged 18–25 years, we examined 150 subjects who had ever reported asthma or wheezing, and 140 without asthma symptoms. Questions were validated in relation to current diseases including 1) symptoms detected during the preceding year at the physician's interview 2) objective measurements, such as methacholine challenge, skin prick tests, and specific IgE. Data were adjusted for original proportions of “asthmatics” and “nonasthmatics” in the questionnaire study. Results: Questions on “reported asthma” and “doctor-diagnosed asthma” had good positive predictive value (PPV) and specificity in diagnosing current asthma. The question on “attacks of shortness of breath with wheezing”, and especially the question on “cough with wheezing” were most sensitive. Questions on “allergic nasal symptoms” and “allergic eye symptoms” that were “related to pollen or animals” were sensitive, but a further question on doctor's diagnosis yielded higher specificity and PPV. Conclusions: Diagnosis-based questions were found suitable for risk-factor studies, because of their good specificity and PPV, and symptom-based questions for screening, because they were highest in sensitivity.

How can thermal processing modify the antigenicity of proteins

Abstract: This paper is a brief review of thermally induced covalent modifications to proteins in foods, focussing mainly on the advanced glycation end-products (AGE) of the Maillard reaction. Most foods are subjected to thermal processing, either in the home or during their production/manufacture. Thermal processing provides many beneficial effects, but also brings about major changes in allergenicity. Far from being a general way to decrease allergenic risk, thermal processing is as likely to increase allergenicity as to reduce it, through the introduction of neoantigens. These changes are highly complex and not easily predictable, but there are a number of major chemical pathways that lead to distinct patterns of modification. Perhaps the most important of these is through the reaction of protein amino groups with sugars, leading to an impressive cocktail of AGE-modified protein derivatives. These are antigenic and many of the important neoantigens found in cooked or stored foods are probably such Maillard reaction products. A deeper understanding of thermally induced chemical changes is essential for more advanced risk assessments, more effective QC protocols, production of more relevant diagnostic allergen extracts and the development of novel protein engineering and therapeutic approaches to minimise allergenic risk.

Is obesity a risk factor for childhood asthma

Abstract: Background: In adolescents and adults, an association between obesity and asthma was found in females. Does this sex-specific association already exist in young children? Methods: Questionnaire data on 9357 5- and 6-year-old German children were collected in 1997 in two rural regions in Bavaria. The diagnosis of asthma, hay fever, and eczema was ascertained with the ISAAC core and other validated questions. Overweight was defined by a BMI of >90th and ≤97th percentile and obesity by a BMI of >97th percentile. Results: The lifetime prevalence of doctor's diagnosed asthma in girls was 3.5% (95% CI 2.9–4.1%) for normal weight, 5.8% (95% CI 3.2–8.4%) for overweight, and 10.3% (95% CI 5.3–15.2%) for obesity, whereas no relation to weight was found in boys. Hay fever and eczema were unrelated to weight in girls and boys. The adjusted odds ratio for asthma in girls was 2.12 (95% CI 1.22–3.68) for overweight and 2.33 (95% CI 1.13–4.82) for obesity. Conclusions: A sex-specific association with doctor's diagnosed asthma was also observed in girls at school entry. Since this association was confined to doctor's diagnosed asthma in the absence of other atopic conditions, and no association with other atopic manifestations was found, we hypothesize that this association is related to factors other than atopic sensitization.

Diet, serum fatty acids, and atopic diseases in childhood

Abstract: Background: The reasons behind the reported increase in the occurrence of childhood atopic sensitization rates are unclear. We wanted to evaluate the association between dietary fats, serum fatty acids, and the occurrence and development of atopic diseases. Methods: From a longitudinal database of a population-based sample, 231 sex- and age-matched pairs in 1980 and 154 pairs in 1986 were chosen, between whom we compared the dietary data, serum fatty acid composition, and occurrence of atopic diseases. The same variables were also compared between those who developed atopic disease later and those who did not during the 9-year follow-up. Results: Examination of the dietary data in 1980 for those who had developed atopic disease compared with those who had remained healthy showed that the atopic children had used less butter before the expression of atopy. According to the cross-sectional data, the children with atopic disease consumed more margarine (mean 8.6 vs 7.3 [P=0.04]), and less butter (mean 9.4 vs 11.6 g/1000 kcal [P=0.002]), than the nonatopic children in 1980. Differences supporting these dietary findings were similarly found in the serum fatty acid data. Conclusions: The diet of the atopic children differed from that of the nonatopic children in the consumption of polyunsaturated fat.

Local side-effects of inhaled corticosteroids in asthmatic children: influence of drug, dose, age, and device

Abstract: Background: The objective was to investigate the local side-effects of inhaled corticosteroids (ICS) in daily life in asthmatic children, particularly the younger ones, by an observational prospective cross-sectional cohort study. Methods: Asthmatic children (n=639, 75.9±48.9 months, 61.3% boys), treated with beclomethasone dipropionate (BDP) (721.0±287.3 µg per day) or budesonide (BUD) (835.5±684.9 µg per day) for at least 1 month, were recruited at the time of a scheduled visit. Local side-effects were researched by questionnaire (cough during inhalation, hoarseness, dysphonia, and thirsty feeling) and clinical examination (perioral dermatitis, oral candidiasis, and tongue hypertrophy). Results: Exactly 63.3% of the children aged under 6 years and 59.5% of the older ones reported one local side-effect. Cough (39.7%) was dependent on young age, use of BDP, and mainly use of spacer device, with an OR of 4.7 (95% CI: 2.7–8.2). Thirsty feeling (21.9%) and hoarseness (14.1%) occurred in children using ICS and long-acting β2-agonists. Dysphonia (11.1%) was favored by high doses of BDP and BUD, and by inhalation from spacer devices or nebulizers. No factor favored oral candidiasis (10.7%). Perioral dermatitis (2.9%) and tongue hypertrophy (0.1%) were associated with nebulization. Conclusions: Local side-effects of ICS are common in asthmatic children of all_ ages, and the device used constitutes the most influential factor.

Structure and function of milk allergens

Abstract: Proteins (CMP) involved in milk allergy are numerous and heterogeneous, with very few structural or functional common features. This heterogeneity is complicated by their genetic polymorphism, resulting in several variants for each protein. These variants are characterized by point substitutions of amino acids or by deletions of peptide fragments of varying size or by post-translational modifications such as phosphorylation or glycosylation. All of these modifications may affect allergenicity. No common molecular structure can be associated with allergenicity, although some homologous regions such as casein phospho-peptides can explain an IgE cross-reactivity. Three-dimensional structure is an important feature in CMP allergenicity but denatured and linear epitopes are also involved. Epitopes are numerous and widely spread along the CMP molecule. They may be located in hydrophobic parts of the molecule where they are inaccessible for IgE antibodies in the native conformation of the protein but become bioavailable after digestive processes. Peptides as short as ca. 12-14 amino acid residues may account for a significant part of the allergenicity of the whole molecule, which justifies the need to be careful before proposing any CMP hydrolysate for highly allergenic children.

Asthma and sex hormones

Abstract: A chronic in ammatory state of the airways is considered the hallmark of asthma (1). However, the incidence, severity, and prognosis of asthma can be affected by a number of factors, including the patient's sex and age. The sex of the fetus seems to in uence the development of the respiratory apparatus. In fact, between weeks 28 and 40 of gestation, the lungs are in a more advanced state in females than in males (2), a fact which could explain, at least in part, the higher incidence of respiratory distress in male infants (3). Clinical observations and epidemiologic studies agree that childhood asthma is more frequent in boys than in girls (4). Moreover, in some children, usually boys, asthmatic symptoms that started in infancy disappear around puberty (5), while many girls have the disease only during adolescence (6). Age has been implicated in the severity of asthma. Asthma beginning during adulthood is generally more severe than childhood-onset asthma (7). Asthma that starts around the menopause or in old age is generally quite severe (5). According to two recent epidemiologic investigations, the patient's sex and age affect the hospitalization rate for asthma (8, 9), which is a marker of severity. In the ®rst study (a retrospective study of 33 269 patients), the admission rate of boys in the 0±10-year age group was almost twice that of girls. In the next decade, sex differences in the hospitalization rate were irrelevant, although there was a small, but signi®cant prevalence of females. At all ages above 20 years, hospital admission rates were higher in women than men, with a female/ male ratio ranging from 3:1 in subjects aged 20±50 years to 2.5:1 in those over 50 years of age (8). Similar data were reported by Elliasson (9). Both studies found a relationship between the age and sex of the patient and the severity of the asthma attack as indicated by duration of hospitalization. In fact, the duration of hospitalization increased with age in both sexes; moreover, hospital stays were longer in women over 30 years of age than in men of the same age (8, 9). Abbreviations. FSH: follicle-stimulating hormone; LH: luteinizing hormone; NK cell: natural killer cell; IL-1, -4, -5, -6: interleukin-1, -4, -5, -6; TGF-b: tumor growth factor-beta; PEFR: peak expiratory ow rate. Allergy 2001: 56: 13±20 Printed in UK. All rights reserved Copyright # Munksgaard 2001

A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers

Abstract: Background: Cetirizine is a highly efficacious and long-acting second-generation H1-receptor antagonist for the treatment of allergic diseases, such as allergic rhinitis and chronic idiopathic urticaria, in adults and children. Pharmacologic studies have demonstrated that cetirizine, a racemate mixture composed of equal amounts of two enantiomers, does not undergo hepatic metabolism to any significant level. The enantiomers are excreted mainly unchanged, predominantly in the urine and to a lesser extent in the faeces. Methods: The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles. Results: Both cetirizine and levocetirizine caused a marked inhibition of histamine-induced wheal and flare, whereas ucb 28557 was inactive in this model. Inhibition of the wheal response observed for cetirizine and levocetirizine was apparent by 1 h after dosage and lasted for mean durations of 24.4 and 28.4 h, respectively. In addition, the response for cetirizine and levocetirizine became maximal by 6 h after treatment, rising to 79.5% and 83.8%. Similarly, cetirizine and levocetirizine also markedly inhibited the histamine-induced flare response. This effect was evident for both drugs by 1 h after dosage and lasted over a mean period of 28.4 and 26.0 h, respectively, for cetirizine and levocetirizine. The inhibitory effect of these compounds on histamine-induced flare response was also maximal by approximately 6 h after dosage, peaking at 88.5% and 83.6%, respectively. Statistical evaluation showed that cetirizine and levocetirizine were equivalent for maximum inhibition of histamine-induced wheal and flare. However, levocetirizine was found to be superior to cetirizine when area under the curve was compared. In contrast, ucb 28557 was not found to inhibit histamine-induced wheal and flare responses at any time during the study period. Plasma concentrations of levocetirizine were found to be approximately double those of ucb 28557 at 4 and 8 h after dosing, and 50–60% of the drugs were excreted unchanged in urine over a period of 32 h. Conclusions: The finding that, in this model, levocetirizine 2.5 mg has comparable antihistaminic activity to cetirizine 5 mg, whereas its other enantiomer ucb 28557 has no pharmacodynamic effect, suggests that the antihistaminic properties of cetirizine observed in the management of allergic skin conditions are likely to be attributable to levocetirizine.

Adult-onset asthma is associated with self-reported mold or environmental tobacco smoke exposures in the home.

Abstract: Background: In recent years, we have gained better knowledge about the influence of indoor environments on respiratory symptoms and asthma. The purpose of this study was to examine certain exposures in the home environment and the risk of adult-onset asthma. Methods: A nested case-referent study of adult-onset asthma was performed in a random population sample (n=15 813), aged 20–50 years. Cases for the study included subjects reporting “physician-diagnosed” asthma (n=174). The referents (n=870) were randomly selected from the whole population sample. The case-referent sample was investigated with a comprehensive mailed questionnaire about exposures in the home environment, asthma, respiratory symptoms, smoking habits, and atopy. Odds ratios (OR) with 95% confidence intervals (CI) were calculated while controlling for age, sex, smoking, and atopy. Results: Increased adjusted OR for asthma were associated with exposure to molds (OR 2.2, 95% CI 1.4–3.5), environmental tobacco smoke (OR 2.4, 95% CI 1.4–4.1), and the presence of a wood stove (OR 1.7, 95% CI 1.2–2.5). Conclusions: This population-based case-referent study indicates that self-reported domestic exposures to molds or environmental tobacco smoke can be associated with adult-onset asthma.

Natural history of “intrinsic” atopic dermatitis

Abstract: . IT is well known that allergy plays a pathogenic role in the development of atopic dermatitis (AD) (1). However, approximately 20% of AD patients suffer from a skin disease that clinically resembles the skin lesions and the distribution pattern of AD, but is not associated with atopic status. This kind of ‘‘intrinsic’’ AD (iAD) seems to differ from the classical or ‘‘extrinsic’’ form (eAD) both in the T-cell cytokine production and in the immunohistology (2, 3), but no data are available about its natural history. In this study, we investigated the persistence of AD and the development of respiratory allergic diseases in a group of children seen at the ages of 2 and 11 years according to the skin prick test (SPT) reactivity to allergens at those ages. The parents of 111 children with AD evaluated at our allergy unit in 1989–90 were asked for re-evaluation of the children about 9 years later. Seventy percent of the children (77/111) underwent clinical history, and SPTs to food (egg white, wheat, milk, tomato, codfish, and soy [Lofarma, Milan, Italy]) and inhalant allergens (dust mite, cat, dog, Alternaria, grass pollen, Parietaria, mugwort, olive pollen, and Cupressus sempervires [Lofarma]). AD was diagnosed according to Hanifin & Rajka (4). The presence of asthma and SPT reactivity was studied as previously described (5, 6). According to the SPT results, we defined the following groups: 1) ‘‘early atopic’’, i.e., those children who were already SPT positive at age 2 and were still SPT positive at age 11 2) ‘‘late-onset atopic’’, i.e., those who were negative at age 2 but became SPT positive by the age of 11 3) ‘‘nonatopic’’, i.e., those who were SPT negative at the ages of both 2 and 11. We considered patients SPT negative at age 2 as having iAD. The data were analyzed by the statistical program SPSS 6.0 for Windows with the chi-square and chi-square for trend tests. A two-sided type 1 error lower than 0.05 was considered statistically significant. Seventy-seven AD patients, with a mean age (uSE) of 24.1u2.28 months at the first evaluation, and 132u3.24 months at the second evaluation, were identified. At diagnosis, all of them had AD (77/77), 22% (17/77) had asthma, and 64% (49/77) had at least one positive SPT. At 11 years of age, 46% of them had AD (36/77), 43% (33/77) had asthma, and 84% had (65/77) at least one positive SPT. Forty-nine out of the 77 (64%) studied children had early atopy, 16/77 (21%) had late-onset atopy, and 12/77 (15%) were nonatopic. None of the nonatopic children developed asthma by age 11 (0/12), compared with the 25% (4/16) and the 59% (29/49) of the late-onset and early atopic children, respectively (chi square for trend, P,0.0002). AD was still present by age 11 in 67% (8/12) of nonatopic AD as compared with 44% (7/16) and 43% (21/49) of the late-onset and early atopic children (Fig. 1). Altogether, the 28 AD children ALLERGY 2001: 56 :452^463 . COPYRIGHT G MUNKSGAARD 2001 . ISSN 0105-4538 . ALL RIGHTS RESERVED . CONTRIBUTIONS TO THIS SECTION WILL NOT UNDERGO PEER REVIEW, BUT WILL BE REVIEWED BY THE ASSOCIATE EDITORS .

In utero and perinatal complications preceding asthma.

Abstract: Background: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases. Methods: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data. Results: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence=14.3%; adjusted odds ratio [ORadj]=2.01; 95% confidence interval, 1.52–2.67), labor, or delivery (19.3%, ORadj=1.35, 1.01–1.81); child illness or health complications during the first week of life (22.6%, ORadj=1.35, 1.01–1.82); and birth weight of <2.5 kg (7.0%, ORadj=1.57, 1.10–2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor (ICD: 644) (4.8%, ORadj=1.58, 1.03–2.40) and the malposition or malpresentation of the fetus (ICD: 652) (1.6%, ORadj=3.63, 1.47–8.91). Conclusions: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.

Bacterial infections and atopic dermatitis.

Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease which often begins in infancy and runs a course of remission and exacerbation. The acute eczematous lesions of AD are characterized by erythema, oozing, and crusting, whereas the chronic lesions show thickened skin and papules. Furthermore, pruritus and sleeplessness are characteristics of AD (1). There is increasing evidence that environmental allergens and food allergens are major provocation factors for the flare-ups of AD (2). Specific IgE antibodies to food or environmental allergens can be detected in the serum of 80% of patients with AD. A subgroup of patients with specific IgE and positive skin prick tests to inhalant or food allergens exhibit positive cutaneous late-phase reactions after epicutaneous application of allergens (3–5). The mononuclear infiltrate in the eczematous reactions to patch testing and in the lesional skin of AD is similar to that of allergic contact dermatitis when stained with immunohistochemical techniques. Mononuclear cells and eosinophil granulocytes can be found mainly in the dermis (4, 6, 7), and Langerhans cells with specific IgE bound to FceRI on their surface in the epidermis (8, 9). CD4-positive T-helper cells predominate in the cellular infiltrate.

Dog allergen in indoor air and dust during dog shows

Abstract: Background and methods: Dog dander is one of the most important indoor allergens in Nordic countries. Due to the population flow into cities, the number of dogs in urban areas has increased. Dog allergens can be found practically everywhere indoors. We measured allergen content in indoor air and dust during dog shows. Results: In facilities used for dog shows, the dog allergen content was exceptionally high, up to 2 100 000 ng Can f 1/g dust, but it can be reduced by proper cleaning. The efficiency of cleaning will remain poor if furniture and textiles are not cleaned or the distribution of airborne allergen cannot be prevented. Conclusions: Dog shows should not be held in public facilities, such as schools, where a significant proportion of occupants are hypersensitive to dog allergens and may therefore suffer symptoms due to the exposure to dog dander.

The prevalence of CMA/CMPI in young children: the validity of parentally perceived reactions in a population‐based study

Abstract: Background: The present study aimed to estimate the prevalence of adverse reactions to milk, as population-based prevalence estimates based on objective diagnostic procedures are rare. Methods: Children with parentally reported reactions to milk were selected for further examination from a population-based cohort of 2721 children. At the age of 2½ years, they underwent a stepwise diagnostic procedure that included diet trials at home, skin prick tests, and open and double-blind, placebo-controlled food challenges. A sample of children with symptoms not attributed to milk was selected for assessment of unrecognized reactions. Results: The estimated point prevalence of cow's milk allergy and cow's milk protein intolerance (CMA/CMPI) in children with parentally perceived reactions at the age of 2½ years was estimated to be 1.1% (CI 0.8–1.6). However, this was an underestimate, as unrecognized reactions were detected. Most reactions were not IgE-mediated. The positive predictive value of a parentally perceived reaction depended on the number of times it had been reported and was good for reactions reported three times (at 12, 18, and 24 months of age). Conclusions: The present study confirms previous findings that parents overestimate milk as a cause of symptoms in their children; however, it also indicates that unrecognized reactions may be a problem as well.

Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity

Abstract: Background: Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects. Methods: A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined. Results: No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups. Conclusions: In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/ antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.