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Risk factors for respiratory symptoms and atopic sensitisation in the Baltic area.

Recent studies have indicated that atopic sensitisation is uncommon while respiratory symptoms are common among schoolchildren in Eastern Europe. Risk factors for respiratory symptoms and atopic sensitisation were evaluated in a cross sectional study involving 2594 schoolchildren (10-12 years) from Sweden (n = 665), Poland (n = 410), and Estonia (n = 1519). The measurements included parental questionnaires and skin prick tests with eight standardised allergens. Multiple logistic analyses demonstrated that atopic heredity was a significant independent risk factor for respiratory symptoms and atopic sensitisation in all the countries. Current dampness and maternal smoking were related to respiratory symptoms whereas domestic crowding, male gender, and passive smoking during infancy were related to atopic sensitisation. Current maternal smoking had a strong dose response association with current coughing attacks (nocturnal cough > 4 weeks or exercise induced coughing attacks) but only in Eastern Europe. A strong inverse relationship was recorded between domestic crowding and sensitisation as the risk for sensitisation increased with decreasing number of persons per room in the household (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.43 to 0.77). Exposure to tobacco smoke at home during infancy was a risk factor for atopic sensitisation but only to animal dander and only in Eastern Europe (OR 1.41, 95% CI 1.03 to 1.93). In conclusion, there were small differences in the pattern of risk factors between Eastern and Western Europe. The only exception was environmental tobacco smoke being a risk factor only in Eastern Europe. The study also suggests that factors related to domestic crowding protect against atopic sensitisation in Estonia and Poland. A higher standard of living with less crowding may give rise to an increasing prevalence of atopic sensitisation also in Eastern Europe.

Analysis of Variance↗

Season of birth as predictor of atopic manifestations.

The relation between month of birth, sensitisation, and manifestations of atopy was assessed in 209 children who were followed from birth to 12-15 years. Children born during the tree pollen season were less likely to develop allergic rhinoconjunctivitis, IgE antibodies to pollen, or a positive screening test for IgE antibodies (odds ratio 0.28, 0.41, 0.35, respectively) than children born during the rest of the year. The prevalence of IgE antibodies to food and animal dander at 9 months and to atopic disease was higher in children born in the autumn and winter, that is, September to February, compared to the spring and summer (egg 20% v 6%; milk 10% v 2%). Thus sensitisation to pollen and allergic rhinoconjunctivitis is least common in children born in the spring, while birth in September to February is associated with an increased incidence of sensitisation to food and of atopic disease.

Dermatitis, Allergic Contact↗

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

OBJECTIVE: To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. DESIGN: Double blind randomised placebo controlled parallel group study. SETTING: Hospital in Hampshire. PARTICIPANTS: 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. INTERVENTIONS: Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. MAIN OUTCOME MEASURES: Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. RESULTS: The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. CONCLUSIONS: Enzyme potentiated desensitisation showed no treatment effect in this study.

Adult↗

Effect of farming environment on sensitisation to allergens continues after childhood.

AIMS: The farming environment in childhood has been reported to decrease the risk of sensitisation to allergens. The purpose of the present study was to explore whether later exposure to a farming environment also could affect this sensitisation. METHODS: A population based sample of 202 women who did not live on a farm and 231 who did. The subjects filled in a questionnaire and underwent skin prick tests for several common and farming related allergens. RESULTS: The prevalence of sensitisation to any of the allergens was similar in the two groups (37.1 v 34.6% (p = NS). However, compared with women who did not live on a farm, the women who lived on a dairy farm showed a low prevalence of sensitisation to pollens (4.4 v 17.3%, p = 0.01) and cats (3.5 v 10.4%, p = 0.047). The risk of sensitisation to pollens and pets was lowest among women with both a childhood and adulthood farming environment and was dose dependently associated with current contact with farm animals. However, this contact increased the risk of sensitisation to bovine dander. CONCLUSION: The farming environment may reduce sensitisation to common allergens also after early childhood. However, it may also increase sensitisation to farm allergens.

Adolescent↗

Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthma.

BACKGROUND: Increased fractional exhaled NO concentrations (FENO) and blood/tissue eosinophilia are frequently reported in allergic children with mild asthma and are thought to reflect the intensity of the inflammation characterising the disease. The aim of this study was to investigate possible differences in FENO levels or in the intensity of the blood eosinophilia in allergic and non-allergic asthmatic children. METHODS: 112 children with stable, mild, intermittent asthma with a positive bronchial challenge to methacholine were consecutively enrolled in the study; 56 were skin prick test and RAST negative (non-sensitised) while 56 were sensitised to house dust mites (23 only to house dust mites (monosensitised) and 33 were sensitised to mites and at least another class of allergens (pollens, pet danders, or moulds)). Nineteen sex and age matched healthy children formed a control group. RESULTS: Compared with non-allergic patients, allergic children had a significantly higher rate of blood eosinophilia (p=0.0001) with no differences between mono- and polysensitised individuals. Forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of vital capacity (FEF(25-75%)), and the degree of bronchial reactivity to methacholine were similar in non-atopic and atopic children, with no differences between mono- and polysensitised individuals. FENO levels measured by chemiluminescence analyser were higher in asthmatic children (15.9 (14.3) ppb) than in the control group (7.6 (1.6) ppb, p=0.04) and higher in allergic patients (23.9 (2.1) ppb) than in non-allergic patients (7.9 (0.8) ppb, p=0.0001), but there were no differences between mono- and polysensitised individuals (p>0.1). Significant correlations between blood eosinophilia and FENO levels were seen only in allergic (r=0.35, p<0.01) and in polysensitised individuals (r=0.45, p<0.05). CONCLUSIONS: In children with mild asthma, a similar degree of functional disease severity may be associated with a higher inflammatory component in allergic than in non-allergic subjects.

Adolescent↗

An analysis of skin prick test reactions in 656 asthmatic patients.

Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied.

Adrenal Cortex Hormones↗

Effect of the 5-lipoxygenase inhibitor ZD2138 on allergen-induced early and late asthmatic responses.

BACKGROUND: Leukotrienes are lipid mediators generated from arachidonic acid by the 5-lipoxygenase pathway which may play an important part in the pathophysiology of asthma. Previous studies have demonstrated attenuation of the allergen-induced early and late asthmatic responses by leukotriene receptor antagonists. The effect of the 5-lipoxygenase inhibitor ZD2138, a non-redox lipoxygenase inhibitor which inhibits leukotriene synthesis for 24 hours after single doses of 350 mg, on allergen-induced early and late asthmatic responses has been assessed. METHODS: Eight asthmatic subjects with baseline FEV1 > 70% were studied. On screening, all subjects developed an allergen-induced biphasic asthmatic response to grass pollen, cat dander, or house dust mite. ZD2138 (350 mg) or placebo was given on two occasions separated by two weeks in a randomised double blind fashion. Allergen inhalation challenge was performed four hours after dosing and FEV1 was measured for eight hours. The inhibitory activity of ZD2138 on the 5-lipoxygenase pathway was assessed by measurements of calcium ionophore-stimulated generation of LTB4 in whole blood ex vivo and by analysis of urinary LTE4 levels before administration of drug or placebo and at regular intervals after oral drug dosing and allergen challenge. RESULTS: ZD2138 produced no significant bronchodilatation or attenuation of the early or late asthmatic response, although there was 82% inhibition of whole blood generation of LTB4 in response to calcium ionophore stimulation and 52% reduction in urinary excretion of LTE4. CONCLUSIONS: In asthmatic subjects the 5-lipoxygenase inhibitor ZD2138 did not protect against allergen-induced asthmatic responses, despite substantial inhibition of 5-lipoxygenase.

Adult↗

Identification of a novel cat allergen--cystatin.

BACKGROUND: Cat allergen is an important cause of sensitization among children with asthma in Japan. Although there is good evidence that cats produce other allergens, only one major allergen, Fel d 1, has been studied in detail. AIMS: To identify and define the molecular structure of the other potential cat allergens. METHODS: A cat skin cDNA library was screened using IgE antibodies to cat dander and selected clones were sequenced and expressed. RESULTS: One cDNA clone contained an open reading frame encoding a 98-amino acid residue protein. Sequence homology searches revealed a high degree of identity with bovine and human cystatin A, 79 and 75%, respectively. This cat cystatin clone contained the conserved cysteine protease motif and two of three lipocalin motifs. By plaque immunoassay, 60-90% of cat allergic sera had IgE Ab to cat cystatin. This cysteine protease inhibitor motif was partially conserved in dog allergens, Can f 1 and Can f 2, which are lipocalins. Recombinant cystatin was produced in Escherichia coli cells and purified as an 11-kD protein, corresponding to the predicted MW of cystatin. The structure of cat cystatin was modeled on human cystatin B using the SWISS-MODEL. CONCLUSION: A newly identified allergen, cystatin, has been cloned from cat skin and is a member of the cysteine protease inhibitor family.

Allergens↗

Contact urticaria to giraffe hair.

BACKGROUND: Immediate-type hypersensitivity to animal proteins is a common problem in people occupationally exposed to animals. METHODS: A 19-year-old female working as a voluntary zookeeper in her off-time suffered from hives on her forearms following contact to the fur of a giraffe. For diagnostic evaluation, skin prick tests, assessment of specific serum IgE antibodies, and basophil activation tests were performed. RESULTS: Skin prick tests with a standard series of common aeroallergens were positive for various pollens. Prick testing with native materials was positive for extracts of hair from two different giraffe subspecies in the patient, but not in control subjects. By CAP-FEIA, no specific serum IgE antibodies to dander of a large variety of animals were found in the patient. In the basophil activation test, expression of the activation marker CD63 was induced by extract of giraffe hair on the cells from the patient, but not on those from unaffected controls. CONCLUSIONS: This patient suffers from an 'exotic' immediate-type contact allergy to giraffe hair.

Adult↗

Modulation of atopy patch test and skin prick test by pretreatment with 1% pimecrolimus cream.

BACKGROUND: In a subgroup of patients with atopic eczema (AE), aeroallergens are relevant eliciting factors. The atopy patch test (APT) was proposed as inflammation model for AE. OBJECTIVE: It was the aim of this study to investigate the effect of pretreatment with 1% pimecrolimus cream (Elidel) on the APT and skin prick test (SPT). METHODS: In a randomized, controlled, double-blind study, 20 patients with AE and positive SPT and APT screening reaction to house dust mite Dermatophagoides pteronyssinus, cat dander, grass or birch pollen were enrolled (age 20 +/- 11 years, 55% males). For 2 weeks, patients twice daily applied pimecrolimus and vehicle control to marked fields on their backs and forearms. Then, APT was performed (200 index of reactivity/g extracts in petrolatum; Stallergènes, France) on both fields on the back and SPT was performed on the pretreated forearms. RESULTS: Including only patients with different readings (n = 13), stronger APT suppression of at least 1 ETFAD (European Task Force on Atopic Dermatitis) grade in the pimecrolimus area versus intraindividual control was observed in 10 of these patients after 48 and 72 h (p < 0.05; 90% CI 50.5-93.4). Including all 20 subjects, the analysis still showed a borderline significance compared with the vehicle (p = 0.0564). SPT with histamine and aeroallergens showed a median 7.5-10% reduction in actively pretreated areas (p = 0.086). Immunohistochemical analysis in 2 patients revealed an induction of interferon-gamma in primecrolimus-pretreated skin. CONCLUSION: APT can be used as a model for AE skin inflammation. It was shown for the first time that pimecrolimus pretreatment has a potential to suppress the development of lesions induced by aeroallergen exposure in patients with AE.

Adult↗

Sensitization to rabbit allergens in Italy--a multicentre study in atopic subjects without occupational exposure.

BACKGROUND: Rabbits as pets are becoming popular in Italy, but few data are available on sensitization to rabbits in patients without occupational exposure. In a multicentre study, we assessed the prevalence of rabbit sensitization in atopic subjects and their modality of exposure. METHODS: Allergists from the whole country were required to assess the presence of skin prick test positivity to rabbits in about 100 consecutive patients with allergic rhinitis and/or asthma. In the rabbit-positive patients, clinical history, pet ownership and modality of exposure were assessed. RESULTS: Skin tests were performed on 2,329 outpatients, of whom 1,602 had at least one positivity. Among them, 39 (2.43%) were sensitized to rabbit dander (4 monosensitized). The prevalence of sensitization ranged between 0.65 and 4.72%. Nineteen patients reported direct rabbit contact (10 for ownership and 9 for occasional contact) and 5 patients only indirect exposure through the contact with rabbit owners. Fifteen subjects denied any direct or indirect exposure. All the monosensitized patients were rabbit owners and had persistent (moderate-severe) respiratory symptoms. CONCLUSIONS: Sensitization to rabbit in Italy is not to be neglected. In atopic subjects without occupational exposure, contact and indirect exposure to rabbits may induce sensitization. A progressive increase in rabbit sensitization is expected in the future as consequence of the increased rabbit ownership.

Adolescent↗

Human antibodies to bovine alpha-globulin.

Antibodies to bovine gamma-globulin (anti-BGG antibodies) were detectable by a radio-immunoassay in 70% of healthy blood donors but, generally, the titres were low. Significantly increased concentrations of anti-BGG antibodies were found in patients lacking IgA but not in patients with allergic disorders. The anti-BGG antibodies were shown to give rise to falsely high IgE values in the radio-immunosorbent test for IgE determination (RIST) when a sheep anti-IgE antiserum was used. Furthermore, falsely positive results can sometimes be caused by such antibodies in the determination of cow-dander- or cow's-milk-specific IgE by the radio-allergosorbent test (RAST). When a rabbit anti-IgE antiserum was used instead of the sheep anti-IgE, normal IgE levels and negative RAST results were obtained. The difference is explained by the higher degree of cross-reactivity between the anti-BGG antibodies and sheep alpha-globulin than between anti-BGG antibodies and rabbit alpha-globulin.

Absorption↗

Possible role of IgG4 in discordant correlations between intracutaneous skin tests and RAST.

Comparison of intracutaneous skin tests and RAST in 2 groups of patients, one consisting of 16 individuals having multiple allergies to pollen, mold and animal dander and the other of 10 patients allergic to mold only, revealed that skin tests were more sensitive than RAST. Skin reactions of 3+ to 4+ were frequently associated with negative RAST results. This was observed more so in mold-allergic patients. In a few cases (6%) RAST showed 2+ reactions while the skin tests were negative. Leukocytes from allergic individuals who had positive skin tests and negative RAST released a significant amount of histamine upon challenge with specific allergen as well as antihuman IgG4, suggesting that this immunoglobulin is a functional component of some immediate hypersensitivity reactions.

Adult↗

A sandwich enzyme immunoassay for the detection of human IgG antibodies to dog allergens.

A double-sandwich enzyme immunoassay (DSEIA) was developed for the detection of human IgG antibodies to dog dander and hair (DH) allergens. Since DH allergens are immunogenic in rabbits, the gamma-globulin fraction of rabbit antiserum to DH (RGG-a-DH; 10 micrograms/ml) was used for coating of polystyrene microtiter plates. Dog allergens (1 microgram/ml of DH extract) were bound to RGG-a-DH. Binding of human IgG Ab to nonimmune RGG (10 micrograms/ml)--used as a background control--was substracted from the DH specific one and nonspecific binding was further eliminated by using 0.5% of normal rabbit serum in the dilution buffer. Sera were diluted 1:10 in this buffer. Specificity of the assay was shown by absorption experiments: protein A, anti-IgE discs (Phadebas PRIST) and dog or birch (e5, t3; Phadebas RAST) allergen discs were used to remove total and allergen specific IgG and IgE, respectively. The results were expressed as net absorbances or as a percentage of a reference serum. A significant correlation (r = 0.65, p less than 0.001) between IgG (DSEIA) and IgE (RAST) antibodies to dog allergens was observed in 40 untreated dog allergic subjects. The DSEIA was found to be more sensitive than conventional ELISA in detecting IgG Ab in 15 asthmatic children during hyposensitization: a significant rise was observed in 14 compared to 12 with ELISA, while no significant increases were observed in the placebo-treated group.

Adolescent↗

Mechanism of allergic cross-reactions. V. High incidence of unanticipated cross-stimulation by natural allergens of rat basophilic leukemia cells sensitized with monoclonal IgE antibodies.

The incidence of cross-stimulations by natural allergens was investigated using RBL-2H3 cells sensitized with five different mouse monoclonal anti-DNP IgEs and four mercury-induced rat monoclonal IgEs. Cells sensitized with 3 of the 5 monoclonal anti-DNP IgEs (clones SPE-7, SRT-1, LB4) responded by serotonin release upon stimulation by natural allergens such as Dermatophagoides pteronyssinus, horse dander and mugwort extracts. Serotonin release could be inhibited by monovalent DNP-lysine, indicating the involvement of DNP-binding sites of IgEs. Two of the clones (LO-DNP-30 and LA2) were negative on all tests with allergens. All but one (Hg32) of the mercury-induced rat IgE monoclonal antibodies tested positive with DNP-BSA, and with at least one of the six allergen extracts. IgE clone Hg12 mediated serotonin release with 5 of the 6 allergens tested.

Allergens↗

Mite and cat allergen levels in homes and severity of asthma.

The relationships between mite and cat allergen levels in the home, skin test reactivity, and severity of asthma were explored in 120 asthmatic subjects, 57 in Vancouver and 63 in Winnipeg. Patients in the two cities were similar in age, gender distribution, and severity of asthma. Skin tests were performed using 13 common allergens, including D. pteronyssinus, D. farinae, and cat dander, as well as control subjects. Patients recorded their asthma symptoms, medication requirement, and twice daily peak expiratory flow rate for 1 yr. Dust samples were collected every 3 mo during each season of 1992 through 1993 in both cities. Mite and cat allergen levels were determined with an ELISA using monoclonal antibodies against Der p I, Der f I, and Fel d I. There was no relationship between skin test reactivity and levels of mite and cat allergens. In children with positive skin tests to either mite allergen, total mite (sum of Der p I and Der f I) allergen level was positively related to the mean daily symptom score and negatively related to the daily mean PEF (% of predicted). There was no such relationship among adult asthmatic patients with positive skin tests to either mite allergen. No relationship was found between cat allergen level and the severity of asthma.

Adult↗

Treatment of cat allergy with T-cell reactive peptides.

We induced in allergic humans the counterpart of murine experimental T-cell tolerance. T-cell lines from cat-allergic humans were used to map T-cell epitopes for the principal allergen of cat dander, Fel d 1. Two peptides of 27 amino acids each were synthesized to contain the dominant epitopes (ALLERVAX CAT). After a safety trial, we carried out a blinded study of the dose required for efficacy. We randomly divided 95 cat-sensitive patients into placebo, 7.5 micrograms, 75 micrograms, and 750 micrograms groups. Patients received a subcutaneous injection weekly for 4 wk. Before and after treatment, patients were exposed in a room inhabited by live cats and scored by nose and lung symptoms. Baseline nasal and lung scores (+/-SEM) were 6.2 +/- 0.56 and 5.4 +/- 0.73 in the 750 micrograms group; 7.8 +/- 0.53 and 4.7 +/- 0.68 in the placebo group. Six weeks after treatment, scores adjusted for baseline differences were reduced in the 750 micrograms group: -2.3 +/- 4.9 and -2.3 +/- 0.59 compared with -0.84 +/- 0.50 and -0.85 +/- 0.62 in the placebo group. The 75 micrograms group showed intermediate effects and the 7.5 micrograms group no effect. Linear trend analysis indicated a significant dose response effect: p = 0.05 for nose and 0.03 for lung symptoms. Allergic side effects occurred an hour or more after the first 750 micrograms dose in 16 of 24 patients but required little or no treatment with one exception. T-cell reactive treatment peptides safely improved allergic responses to cats.

Allergens↗

Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital.

To investigate the role of indoor allergens in adult patients with acute asthma, we conducted a case-controlled study on patients presenting to an emergency room. One hundred and fourteen patients and 114 control subjects were enrolled over a 1-yr period in Wilmington, Delaware. Sera were assayed for total IgE, and for IgE antibodies to dust mites, cat dander, cockroach, grass pollen, and ragweed pollen. Dust was obtained from 186 homes and assayed for dust mite, cat, and cockroach allergens. IgE antibodies to mite, cat, and cockroach were each significantly associated with asthma, and this association was very strong among participants without medical insurance and among African Americans. Among 99 uninsured participants, sensitization to one of the indoor allergens (> 200 RAST units) was present in 28 of 57 asthmatics and in one of 42 control subjects (odds ratio, 39; confidence interval, 9.4 to 166). For cat and cockroach the combination of sensitization and presence of allergen in the house was significantly associated with asthma. Furthermore, there was a strong inverse relationship between IgE antibodies to cat and to cockroach, and the risk of this sensitization was in large part restricted to homes or areas with high levels of allergen. Thirty-eight percent of the asthmatics, but only 8% of the control subjects, were allergic to one of the three indoor allergens, and had high levels of the relevant allergen in their houses (odds ratio, 7.4; confidence interval, 3.3 to 16.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗