Formaldehyde exposure enhances inhalative allergic sensitization in the guinea pig

Formaldehyde (FA), a common indoor air pollutant, has been associated with increased prevalence rates of asthmatic symptoms among exposed individuals in epidemiologic surveys. We studied the influence of FA exposure on inhalative allergic sensitization in the guinea pig. Three groups of guinea pigs ( n = 12 each) were exposed to clean air or two different FA concentrations (0.13 and 0.25 ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5% ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial provocation with OA was performed with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgG1 (reaginic) antibodies were determined in serum. In a further six animals, the respiratory tract was examined histologically for signs of inflammation directly after the end of FA or clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found to be sensitized to OA (positive reaction on specific provocation) vs. 3/12 animals in the control group ( P < 0.01). Furthermore, CA measurements of specific bronchial provocation and serum anti-OA-antibodies were significantly higher in the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P < 0.01; anti-OA-IgG1 13 vs. < 10 EU median, P < 0.05), indicating enhanced sensitization. In the group exposed to 0.13 ppm FA, no significant difference was found compared to the control group. There was no sign of inflammation of the lower airways in FA-exposed guinea pigs other than mucosal edema, which was discovered by morphometry. We conclude that short-term exposure to a low concentration of FA (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the guinea pig.     

Cat sensitization according to cat window of exposure in adult asthmatics

Background In adults, there is limited information on tolerance to cat, which may be reflected by high IgG₄ without IgE sensitization. Early exposure to cat may play a critical role.
Objective The aim was to assess among adults the association of Fel d 1 IgG₄, Fel d 1 IgE, skin prick test (SPT) response to cat and pet-related symptoms in relation to exposure to cat considering the period of exposure.
Methods SPT response to cat, specific IgE and IgG₄ to Fel d 1 were assessed in 167 asthmatics recruited in chest clinics (40 years of age in average) from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Childhood and/or current exposure to cat were studied retrospectively.
Results IgG₄ was higher in relation to current cat exposure (0.53 vs. 0.09 ng/mL; P <0.001) and higher in women than in men. The period of cat exposure was significantly related to Fel d 1 IgE, the IgE/IgG₄ pattern and cat weal size. The lowest values of Fel d 1 IgE, cat weal size, pet-related nasal or respiratory symptoms were observed in those with both childhood and current exposure as well as the highest proportion of the IgE⁻/IgG₄⁺ pattern observed in 1.4%, 4.0%, 38.1% and 12.5% of those with −/−, +/−, +/+, −/+ childhood/current exposure, respectively.
Conclusions Adult asthmatics exposed to cats since childhood present an immunologic pattern with high IgG₄ and low IgE. Continuous exposure may maintain a state of immunological tolerance to cat.     

Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins

BACKGROUND: Previous twin studies of asthma and allergy implicate both genetic and environmental factors in disease risk, but few have related the occurrence of clinical disease to objective markers of allergic sensitization in twins. OBJECTIVE: We sought to investigate the concordance and interrelationships of self-reported allergic disease and total and aeroallergen-specific IgE levels within pairs of British adult female twins. METHODS: Three hundred forty monozygotic and 533 dizygotic pairs, aged 18 to 72 years, completed questionnaires about allergic disease. Of these, 282 monozygotic and 270 dizygotic pairs were tested for total IgE and specific IgE to Der p 1, mixed grass pollen, and cat dander by means of fluoroimmunoassay. RESULTS: Concordance rates for all variables were higher for monozygotic than for dizygotic twins, significantly (P < .05) so for hay fever, eczema, and specific IgE positivity but not (P > .05) for self-reported asthma or allergies. Within-pair correlations of log-transformed IgE were 0.59 for monozygotic twins and 0.29 for dizygotic twins, implying heritability of 60%. Within both monozygotic and dizygotic pairs discordant for hay fever or reported allergies, the affected twin had significantly higher total and specific IgE levels. Within pairs who were doubly discordant for 3 allergic diseases, associations between diseases were of similar strength for monozygotic and dizygotic pairs. CONCLUSIONS: These results confirm that genetic factors influence susceptibility to aeroallergen sensitization and clinical allergic disease. However, genetically identical twins are often discordant in their expression of atopy, suggesting a substantial modifying role for environmental factors.     

Sputum cytopathological findings in pig farmers

The purpose of this study is to compare the cytological changes in the respiratory tracts of pig farmers exposed to an environment of swine confinement buildings with control, non-exposed subjects living in the same geographical area. Spontaneously produced sputum specimens were obtained from 133 pig farmers and 120 control subjects, all clinically healthy, and grouped according to smoking habits and sex. The findings of siderophages, eosinophils, abnormal columnar cells and respiratory spirals were significantly more frequent in the pig farmers. Siderophages were noted in 25.6% of pig farmers and in 5% of control subjects. By logistic regression analysis, pig farming is the single predictive factor for siderophages and eosinophils. For other cytological abnormalities, except Creola bodies and granular debris, smoking is the most significant predictive variable, but pig farming, age and male sex also correlate with smoking. Atypical squamous metaplasia was observed in 11.3% of pig farmers and in 5.8% of control subjects. These findings are in concordance with previous epidemiological and clinical studies and also reveal a new aspect of the harmful effect of pig farming exposure to the vascular and epithelial structures of the respiratory tract. It also demonstrates the usefulness of the simple method of sputum cytological analysis.     

Environmental determinants of atopic eczema phenotypes in relation to asthma and atopic sensitization

BACKGROUND: There is still uncertainty about the determinants of atopic eczema (AE). To explain the heterogeneity of the disease, different phenotypes of AE have been suggested. METHODS: The cross-sectional PARSIFAL study included 14 893 school-age children of farmers or children attending Steiner schools and their respective reference groups. A detailed questionnaire was completed, and house dust was collected for the measurement of endotoxin and glucans. Atopic sensitization was defined by allergen-specific IgE levels in the serum. RESULTS: In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor's diagnosis of AE [aOR = 0.65 (95% CI: 0.46-0.93) and 0.73 (0.51-1.05)], respectively. Severe lower respiratory tract infections (LRTI) in the first 2 years of life and usage of antibiotics ever were found to be positively related only to asthma-associated AE, whereas the effect of LRTI on AE without asthma had an opposite effect. Levels of beta(1-->3)-glucans in mattress dust were inversely related to a doctor's diagnosis of asthma-associated AE [aOR = 0.75 (0.57-0.98)], and endotoxin levels to current symptoms of asthma-associated AE [aOR = 0.73 (0.57-0.94)]. CONCLUSIONS: The analyses of the PARSIFAL study revealed two different phenotypes of AE, depending on the association with asthma and wheezing ever. With regard to the hygiene hypothesis, help with haying, exposure to beta(1-->3)-glucans and endotoxin were found to be inversely associated with the AE phenotype associated with asthma and wheezing.     

Atopic sensitization and atopic dermatitis in Estonian and Swedish infants

BACKGROUND: Early life events seem to have a major impact on the development of tolerance or sensitization. OBJECTIVE: The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden. METHODS: Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months. RESULTS: The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%; P = 0.06 and 13% vs. 24%; P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%; P = 0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1-2.5), but not in the Swedish infants. This may be explained by the use of broad-spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed. CONCLUSIONS: The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad-spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor.     

Role of current and childhood exposure to cat and atopic sensitization. European Community Respiratory Health Survey.

BACKGROUND: Clinical and population studies have shown that exposure and sensitization to allergens derived from furred pets, particularly cats, represent an important risk factor of allergic respiratory disease and also a significant risk factor for asthma. OBJECTIVE: In the framework of the multicenter European Community Respiratory Health Survey an analysis of the association of current and childhood exposure to cat with atopic sensitization to cat was conducted. METHODS: This study included cross-sectional data from 35 centers representing 16 countries. Altogether, 18,097 subjects were included, of whom 13,509 (75%) provided a blood sample for the measurement of specific IgE. Exposure data and data for potential confounders were extracted from an interviewer-led questionnaire. RESULTS: The prevalence of sensitization to cat (serum specific IgE >0.35 kU/L) was 9%. Among those who did not report allergic symptoms in the presence of pets or house dust, those who owned cats were significantly more likely to be sensitized to cats than were those who did not (odds ratio [95% confidence interval] 1.57 [1.20-2.06]. Childhood exposure to pets including cats was associated with lower sensitization to cats in adulthood, particularly among those with a positive family history of atopy (odds ratio [95% confidence interval] 0.68 [0.51-0.93]. Positive correlations were found between the community prevalence of cat and the prevalences of sensitization to cat, respiratory symptoms, physician-diagnosed asthma, and current asthma medication. CONCLUSIONS: Current cat ownership represents a significant risk for sensitization to cat if cats are allowed indoors. Our results support the hypothesis that childhood exposure to pets, including cats, might modulate immunologic mechanisms and reduce sensitization to cat in adulthood. The significant correlation found between the community prevalence of cat ownership and community prevalence of specific sensitization to cat represents the first documentation of such a relationship.     

Food sensitization in infants and young children with atopic dermatitis

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. Children with AD tend to have a higher prevalence of food allergies. This study investigated the clinical significance of food sensitization in AD patients. A total of 266 AD patients participated in this study. The prevalence of food sensitization and clinically relevant sensitization were compared in the subjects according to their age and AD severity. Sera from all patients were analyzed for food-specific IgE levels using the Pharmacia CAP System FEIA. The serum specific IgE levels for egg, milk, peanut and soybean were measured. Patients were regarded as sensitized to the food if their food-specific IgE levels were above 0.35 kUA/L. Also the food-specific IgE levels, the so-called diagnostic decision point, which is recommended as the clinically relevant level, for clinical food allergy, as suggested by Sampson et al, was used as an alternative method. From the measurement of food-specific IgE antibodies of the four foods, egg was the most highly sensitized and the main causative allergenic food in children with AD. The positive rates of specific IgE to the four major food allergens, and the prevalences of clinically relevant food sensitization, were higher for all foods tested in the group less than 1 year of age, and were significantly higher in moderate to severe AD compared to mild AD in infants and young children. In summary, presence of food specific IgE is prevalent in infants and young children with AD, and clinically relevant food sensitization is important in Korean infants and children with moderate to severe AD.     

Possible modes of allergen-specific sensitization and boosting in an atopic child

Several studies document that allergen-specific IgE levels are boosted by allergen contact via the respiratory tract in allergic patients. Only few data are available on whether other routes of allergen contact have an influence on systemic IgE responses. We report the case of a boy who developed egg allergy after heavy consumption of eggs by the mother during pregnancy and breast feeding. In contrast to other children who outgrow egg allergy during the first years of life, the boy experienced further dramatic increases in hen egg-specific IgE antibodies after prolonged consumption of ostrich eggs containing cross-reactive allergens. IgE antibodies to most of the important respiratory allergens remained either low or not detectable. The dramatic increases in hen egg-specific IgE antibody levels after oral intake of allergens demonstrate that systemic IgE responses in allergic patients can be strongly boosted by allergen contact via routes other than the respiratory tract.     

Hypersensitivity pneumonitis in grain farmers due to sensitization to Erwinia herbicola

Two cases of hypersensitivity pneumonitis in grain workers are described. Both cases had evidence of sensitization to the gram-negative bacteria Erwinia herbicola as judged by skin tests, detection of serum precipitins, and inhalation challenge. E. herbicola is frequently found in the microflora of grains.     

Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children

BACKGROUND: There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. OBJECTIVE: We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. METHODS: In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. RESULTS: Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively. CONCLUSION: Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation. CLINICAL IMPLICATIONS: When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.     

Allergen sensitization and exposure to irritants in infancy

We investigated the relationship between residence in the neighbourhood of an aluminium smelter and the prevalence of atopy in schoolchildren (7–13 years of age). Atopy was assessed in 556 of the 620 participants by a skin prick test with eight common aeroallergens. The median exposures to sulphur dioxide and fluoride during the pollen season in the age interval 19–36 months were 24 and 3.1 μg/m³ in the spring and 20 and 3.3 μg/m³ in the summer, respectively. The odds ratio (OR) of having atopy was 2.0 (95% CI: 1.2–3.3) in those children who had lived in the index area for 7 years or more compared with those who had lived there less than 7 years (cumulative effect). The OR of atopy was 2.5 (1.44.4) in those who had lived in the index area during the age interval of 19–36 months compared with rural residence during this age-interval (age-specific effect). When the age-specific effect and the cumulative effect were compared in the same logistic model, the former decreased to 1.1 (0.43.0), whereas the latter was 2.2 (0.7–6.6). The results indicate that exposure to these low levels of irritants during early childhood increases allergen sensitization in children.