Thomas A.E. Platts-Mills

Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study.

BACKGROUND AND METHODS Children with asthma commonly have positive skin tests for inhaled allergens, and in the United Kingdom the majority of older children with asthma are sensitized to the house-dust mite. In a cohort of British children at risk for allergic disease because of family history, we investigated prospectively from 1978 to 1989 the relation between exposure to the house-dust mite allergen (Der p I) and the development of sensitization and asthma. RESULTS Of the 67 children studied in 1989, 35 were atopic (positive skin tests), and 32 were nonatopic. Of the 17 with active asthma, 16 were atopic (P less than 0.005), all of whom were sensitized to the house-dust mite, as judged by positive skin tests and levels of specific IgE antibodies (P less than 0.001). For house-dust samples collected from the homes of 59 of the children in 1979 and from 65 homes in 1989, the geometric means for the highest Der p I exposure were, respectively, 16.1 and 16.8 micrograms per gram of sieved dust. There was a trend toward an increasing degree of sensitization at the age of 11 with greater exposure at the age of 1 (P = 0.062). All but one of the children with asthma at the age of 11 had been exposed at 1 year of age to more than 10 micrograms of Der p I per gram of dust; for this exposure, the relative risk of asthma was 4.8 (P = 0.05). The age at which the first episode of wheezing occurred was inversely related to the level of exposure at the age of 1 for all children (P = 0.015), but especially for the atopic children (r = -0.66, P = 0.001). CONCLUSIONS In addition to genetic factors, exposure in early childhood to house-dust mite allergens is an important determinant of the subsequent development of asthma.

Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

BACKGROUND Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, is approved for use in colorectal cancer and squamous-cell carcinoma of the head and neck. A high prevalence of hypersensitivity reactions to cetuximab has been reported in some areas of the United States. METHODS We analyzed serum samples from four groups of subjects for IgE antibodies against cetuximab: pretreatment samples from 76 case subjects who had been treated with cetuximab at multiple centers, predominantly in Tennessee, Arkansas, and North Carolina; samples from 72 control subjects in Tennessee; samples from 49 control subjects with cancer in northern California; and samples from 341 female control subjects in Boston. RESULTS Among 76 cetuximab-treated subjects, 25 had a hypersensitivity reaction to the drug. IgE antibodies against cetuximab were found in pretreatment samples from 17 of these subjects; only 1 of 51 subjects who did not have a hypersensitivity reaction had such antibodies (P<0.001). IgE antibodies against cetuximab were found in 15 of 72 samples (20.8%) from control subjects in Tennessee, in 3 of 49 samples (6.1%) from northern California, and in 2 of 341 samples (0.6%) from Boston. The IgE antibodies were shown to be specific for an oligosaccharide, galactose-alpha-1,3-galactose, which is present on the Fab portion of the cetuximab heavy chain. CONCLUSIONS In most subjects who had a hypersensitivity reaction to cetuximab, IgE antibodies against cetuximab were present in serum before therapy. The antibodies were specific for galactose-alpha-1,3-galactose.

Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study

BACKGROUND Although asthma is strongly associated with immediate hypersensitivity to indoor allergens, several studies have suggested that a cat in the house can decrease the risk of asthma. We investigated the immune response to cat and mite allergens, and asthma among children with a wide range of allergen exposure. METHODS We did a population-based cross-sectional study of children (aged 12-14 years), some of whom had symptoms of asthma and bronchial hyper-reactivity. Antibodies to mite (Der f 1) and cat (Fel d 1) allergens measured by isotype (IgG and IgG4) specific radioimmunoprecipitation assays were compared with sensitisation and allergen concentrations in house dust. FINDINGS 226 children were recruited, 47 of whom had symptoms of asthma and bronchial hyper-reactivity. Increasing exposure to mite was associated with increased prevalence of sensitisation and IgG antibody to Der f 1. By contrast, the highest exposure to cat was associated with decreased sensitisation, but a higher prevalence of IgG antibody to Fel d 1. Thus, among children with high exposure, the odds of sensitisation to mite rather than cat was 4.0 (99% CI 1.49-10.00). Furthermore, 31 of 76 children with 23 microg Fel d 1 at home, who were not sensitised to cat allergen had >125 units of IgG antibody to Fel d 1. Antibodies to Fel d 1 of the IgG4 isotype were strongly correlated with IgG antibody in both allergic and non-allergic children (r=0.84 and r=0.66, respectively). Sensitisation to mite or cat allergens was the strongest independent risk factor for asthma (p<0.001). INTERPRETATION Exposure to cat allergen can produce an IgG and IgG4 antibody response without sensitisation or risk of asthma. This modified T-helper-2 cell response should be regarded as a form of tolerance and may be the correct objective of immunotherapy. The results may also explain the observation that animals in the house can decrease the risk of asthma.

Indoor allergens and asthma:Report of the Third International Workshop

In parallel with changes in lifestyle over the last 50 years (sedentary living in warm houses with extensive furnishing and low ventilation rates), there has been a progressive increase in the prevalence and morbidity of asthma in many parts of the world. The increase has been in perennial rather than seasonal asthma, and a large proportion of the patients are sensitized to one or more of the allergens found predominantly inside houses, that is, indoor allergens. The Third International Workshop on Indoor Allergens and Asthma was designed to discuss recent progress in basic and clinical research in this area, to formulate recommendations for allergen-specific management of asthma, and to consider future research directions. As with the two previous workshops, discussion topics included biology; allergen immunochemistry; molecular biology and immune response; epidemiology of asthma; and the role of allergen avoidance, a, 2 Because of dramatic progress in recent years, the Third International Workshop was expanded to cover not only house dust mite allergens but also allergens from cat, dog, and cockroach, for which immunochemical and epidemiologic data are available. Over the past 5 years there have been significant advances in several areas of research on indoor allergens, including: (1) cloning and expression of recombinant allergens, 3-7 (2) analysis of T-cell responses to indoor allergens, derivation of T-cell clones, and analysis of T-cell epitope specificity and cytokine profiles, s, 9 (3) investigation of the dose-response relationship between exposure to mite, cat, and cockroach allergens and sensitization, 1°-13 and (4) epidemiologic studies on indoor allergens as risk factors for the symptoms of asthma and bronchial hyperreactivity (BHR)? 4-17 Better definition of the allergens has made it possible to analyze their structure and biologic function and to define epitopes recognized by antibodies or T cells. Information obtained from those studies has provided exciting possibilities for developing new vaccines for safe and effective immunotherapy. 9, 18. 19 Studies of T-cell responses to dust mites have confirmed the dominance of T-helper cell (Tin) responses in allergic individuals.

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative ** , which is endorsed by both academies.

A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p I and Der f I

A two-site monoclonal antibody (Mab) ELISA was developed to measure the Group I allergens from Dermatophagoides spp., Der p I from D. pteronyssinus and Der f I from D. farinae. Species-specific Mabs were used to coat microtiter plates which were then incubated with allergen or house dust extracts. Bound allergen was detected using a biotinylated Mab which recognized a common epitope on both Der p I and Der f I, followed by the addition of streptavidin-peroxidase and ABTS/H2O2 substrate. The assay had low non-specific binding (approximately 0.08 absorbance units) and had a sensitivity of 5 ng/nl for aqueous allergen extracts (equivalent to 0.1 microgram allergen/g dust). 53 dust samples were assayed using the Mab ELISA and an RIA previously described using 125I-labelled Mab. The results showed a very good quantitative correlation between the assays (r = 0.96, p less than 0.001 for Der p I; r = 0.92, P less than 0.001 for Der f I). A further 132 dust samples from a different geographical areas were also assayed by both methods and gave correlation coefficients of 0.90 (P less than 0.001) and 0.86 (P less than 0.001) for Der p I and Der f I, respectively. The Mab ELISA will be useful in epidemiological studies of allergic asthma, both in the assessment of levels of dust mite allergen present in houses and the efficacy of allergen avoidance regimes.

Risk factors for asthma in inner city children

Inner city children have the highest prevalence and the highest mortality rates for asthma in the United States. The purpose of this study was to evaluate sensitization and exposure to common indoor allergens among children aged 3 years to 15 years seen for treatment of asthma at Grady Memorial Hospital, Atlanta, Ga. Eighty children in this study were enrolled in the emergency department and 64 in hospital clinics. Dust from 57 homes, assayed for three indoor allergens (dust mite, cat, and cockroach), revealed similar exposure for asthma and control groups. Sixty-nine percent of the children with asthma had IgE antibodies to dust mite, cockroach, or cat; only 27% of the control subjects were similarly sensitized (p < 0.001). Of 35 children with asthma 21 had both sensitization and significant exposure to the relevant allergen; this was true for only 3 of 22 control subjects (odds ratio, 9.5; p < 0.001). Neither sensitization nor exposure to cat allergen was common in this population. The results show that black children in inner city Atlanta are exposed to high levels of mite and cockroach allergens and that a high proportion of the children with asthma are sensitized to these allergens; the combination of sensitization and exposure is a major risk factor for asthma in this population.

Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose

BACKGROUND Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. OBJECTIVE We sought to determine whether IgE antibodies to alpha-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. METHODS Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. RESULTS Twenty-four patients with IgE antibodies to alpha-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cows milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for alpha-gal. CONCLUSION We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope alpha-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.

Epidemiology of acute asthma: IgE antibodies to common inhalant allergens as a risk factor for emergency room visits

In recent years the morbidity and mortality of asthma has increased, although the etiology is still poorly understood. Most patients with asthma suffer acute attacks that are commonly treated in hospital emergency rooms (ER). In the present study, asthma in adults was studied with acute attacks as a marker for the disease; 102 patients first observed at a university hospital ER with acute airway obstruction were compared to 118 patients observed at the same ER with any diagnosis other than shortness of breath to evaluate allergy as a risk factor for asthma in adults. Sera were assayed for IgE antibody (Ab) to dust mites, cockroach, cat dander, and grass and ragweed pollen. The results demonstrate that in adults younger than 50 years of age, the prevalence of IgE Abs was fourfold greater among subjects with asthma than among control subjects (46/67 versus 12/81; odds ratio, 10.1; 95% confidence interval, 4.9 to 20.7). The population attributable risk for the presence of IgE Ab to one of the five allergens was greater than 50%. Among individuals older than 50 years of age, the prevalence of serum IgE Abs was not significantly increased among patients with acute airway obstruction. In the whole group, the prevalence of IgE Abs to different allergens demonstrated significant seasonal and socioeconomic differences, suggesting that the associated risk is related to exposure to those allergens. The results establish that, with acute attacks of asthma as a marker for adult asthma, the presence of serum IgE Abs to common inhalant allergens is a major risk factor.(ABSTRACT TRUNCATED AT 250 WORDS)