Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy

Background: The increased consumption of n-6 polyunsaturated fatty acids (PUFA) has been shown to coincide with the increased prevalence of atopic diseases. We aimed to investigate whether maternal diet and atopic status influence the PUFA composition of breast milk and the serum lipid fatty acids of infants.
Methods: Maternal diet was assessed by a food questionnaire. The PUFA composition of breast milk obtained at 3 months from 20 allergic and 20 healthy mothers and of their infants' (10 atopic and 10 nonatopic/group of mothers) serum lipids was analyzed.
Results: Although no differences in maternal PUFA intake were observed, the breast milk of allergic mothers contained less γ-linolenic acid (18:3 n-6) than that of healthy mothers. Similarly, atopic infants had less γ-linolenic acid in phospholipids than healthy infants, although n-6 PUFA were elevated in other serum lipid fractions in atopic infants. The serum lipid fatty acids in atopic infants did not correlate with those in maternal breast milk.
Conclusions: Our results suggest that dietary n-6 PUFA are not as readily transferred into breast milk or incorporated into serum phospholipids, but may be utilized for other purposes, such as eicosanoid precursors, in allergic/atopic individuals. Subsequently, high dietary proportions of n-6 PUFA, or reduced proportions of regulatory PUFA, such as γ-linolenic acid and n-3 PUFA, may be a risk factor for the development of atopic disease.     

Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life

BACKGROUND: Factors that either protect from or enhance the development of atopic disease appear to be acting early in life. The gestational environment, including maternal immune responses, such as transplacentally transferred immunoglobulin (Ig) G antibodies to allergens, may be of importance in this respect, since allergen-specific immunity has been demonstrated to develop in utero. OBJECTIVE: To evaluate the relation between cord blood IgG subclass antibodies to allergens, maternal atopy and development of atopic disease in the children. MATERIAL AND METHODS: The study group comprised a cohort of 96 children participating in a prospective study up to 8 years of age. Cord blood IgG subclass antibodies to ovalbumin, beta-lactoglobulin, Bet v 1 and cat dander were analysed by ELISA. RESULTS: The levels of all IgG subclass antibodies to ovalbumin and rBet v 1 were higher in newborn infants with an atopic mother, as compared with babies with nonatopic mothers. IgG1 antibody levels to cat and IgG4 antibody levels to beta-lactoglobulin and cat were also higher in atopic than in nonatopic mothers, whereas the other subclass antibody levels to those allergens were similar. High levels of cord blood IgG antibodies to cat and birch, but not to the food allergens, were associated with less atopic symptoms in the children during the first 8 years of life. Moreover, children who developed IgE antibodies to cat had lower levels of IgG antibodies to that allergen at birth. CONCLUSIONS: High levels of cord blood IgG subclass, especially IgG4, antibodies to food and inhalant allergens are associated with maternal atopy. High levels of IgG antibodies to inhalant, but not food, allergens are associated with less development of atopy in the children.     

Urinary eosinophil protein X in children with atopic dermatitis: relation to atopy and disease activity

BACKGROUND: Parameters of eosinophil inflammation have been suggested as markers of disease activity in atopic dermatitis (AD), but the value of urinary eosinophil protein X (U-EPX) in children with AD, as well as the influence of allergic sensitization, is not known. METHODS: We measured U-EPX in 59 atopic and 29 nonatopic children with mild (n = 32), moderate (n = 34), and severe (n = 22) AD, as well as in 64 controls. RESULTS: U-EPX was increased in children with AD (110; 67-164 microg/mmol creatinine, median; quartiles) compared to controls (62; 41-95, P<0.001). Children with mild (97; 63-164, P < 0.01), moderate (108; 67-157, P < 0.01), and severe disease (152; 99-202, P < 0.001) had levels of U-EPX higher than controls. U-EPX was significantly higher in children with severe AD than in mild and moderate disease (P < 0.05 for both). Children with AD and a positive skin prick test (120; 81-176) had higher levels of U-EPX than children with a negative skin prick test (87; 56-155, P<0.05). CONCLUSIONS: U-EPX is significantly increased in children with AD and may reflect disease activity. U-EPX may also reflect differences in eosinophil activation between those sensitized and those not sensitized to common allergens.     

Cultures of human cord blood metachromatic cells in relation to family history of atopy, development of atopic disease, nasal metachromatic cells and perinatal factors

The appearance of basophilic cells by maturation from progenitors was studied in cultures of cord blood mononuclear cells (CB-MNC) from 83 newborns. In unstimulated cultures, the numbers of basophilic cells increased 5-fold after 14 days of cultivation. This increase and the cell numbers were similar in cultures from atopic individuals and controls. Other cultures were stimulated with conditioned medium (CM) prepared from 3-day cultures of blood cells from atopic individuals activated with allergen or with CM from the Mo leukemic cell line. The addition of such CM resulted in an increase in the number of basophilic cells, as compared to the cultures which were unstimulated (p less than 0.01). No correlation was found between the maturation of basophils and heredity for atopy, development of atopic disease, appearance of metachromatic cells in the nasal mucosa and perinatal factors, such as maternal infections, perinatal stress, birth weight, month of birth and IgE levels. The study confirmed that basophilic cells can be driven to mature in cultures of CB-MNC, although the maturation did not seem to depend on atopic predisposition as indicated by family history of allergy and CB IgE levels nor on symptoms and signs of atopic disease during the first 18 months of life. Therefore, the predictive value of elevated basophilic cell numbers in CB or CB-MNC cultures with regard to allergic disease seemed to be limited.     

The severity of atopic dermatitis and the relation to the level of total IgE,onset of atopic dermatitis and family history about atopy

The aim of this study is the evaluation, if the level of total IgE, onset of atopic dermatitis (AD) and the family history are in the significant dependence to the severity of AD. The statistical evaluation of the dependence between the severity of AD and the the level of total IgE, family history and onset of AD was performed. 296 patients were examined. The level of total IgE above 200 IU/ml is recorded in 93 % of patients suffering from severe form and the positive data about atopy in family history are recorded in 66 % of patients with severe form of AD. The significant dependence was recorded between the severity of AD and parameters such as the level of total IgE, and family history about atopy. No dependence was recorded between the severity of AD and the onset of AD.     

Relationship of diet in the development of atopy in infancy

We examined the relationship of diet to the development of atopic manifestations in a group of infants with an immediate family history of atopy, followed prospectively from birth for up to 20 months of age. There was no relationship between the development of atopic dermatitis, rhinitis and wheeze and either 2 or 4 months exclusive breast feeding, or the introduction of cow's milk or solids in the first 4 months of life. In addition there was no relationship between the introduction of milk, egg or wheat into the diet and the development of skin-test positivity to these foods. In fact, five infants developed positive skin tests to the food prior to its introduction into the diet, suggesting exposure via maternal breast milk. Thus we have been unable to show a protective effect of either breast feeding or cow's milk or solid avoidance on the development of atopic disease in infancy.     

The association of family size with atopy and atopic disease

Background Studies in children have shown that family size is negatively associated with atopy and atopic disease. Objective To describe the association of family size with atopy and atopic disease in young adults. Methods A randomly selected sample of 1159 men and women aged 20–44 years provided information on respiratory symptoms, hay fever and eczema. Blood samples were taken for assessment of total IgE and specific IgE to house dust mite, grass, cat, Cladosporium and birch. The association of family size and birth order with respiratory symptoms, atopy and total IgE was assessed by multiple logistic and linear regression. Results There was a negative association between family size and the reporting of ‘wheeze with breathlessness’ (adjusted odds ratio for an increase of one sibling 0.85; 95% confidence interval 0.75–0.98), ‘wheeze without a cold’ (adjusted odds ratio for an increase of one sibling 0.85; 95% confidence interva l0.75–0.98) and ‘asthma attacks’ in the last 12 months (adjusted odds ratio for an increase of one sibling 0.77; 95% confidence interval 0.61–0.97), current ‘hayfever and nasal allergies’ (adjusted odds ratio for an increase of one sibling 0.84; 95% confidence interval 0.75–0.94) and sensitization to grass (adjusted odds ratio for an increase of one sibling 0.87; 95% confidence interval 0.76–0.99). Birth order was negatively associated with ‘hayfever and nasal allergies’ only. A decreased risk of sensitization to grass in those from large families did not fully explain the negative association between family size and hayfever. No statistically significant (P > 0.05) association of family size or birth order with the reporting of other respiratory symptoms, eczema, sensitization to the other allergens or total IgE was observed. Conclusion There is a negative association between family size and some symptoms suggestive of asthma, ‘hayfever and nasal allergies’ and sensitization to grass in young adults. There is no consistent, significant association between family size and eczema, total IgE or sensitization to other allergens.     

Survey of gastrointestinal reactions to foods in adults in relation to atopy, presence of mucus in the stools, swelling of joints and arthralgia in patients with gastrointestinal reactions to foods

Background Food intolerance in adults is mostly associated with vague symptoms and not clearly related to atopy and food allergy. A combination of different pathogenetic mechanisms may be responsible for the symptoms. Objective The aim of this study was to describe patients with a history of food-related gastrointestinal symptoms in relation to the presence of mucus in the stools, joint swelling and arthralgia and to determine whether or not there is an association between the presence of these parameters, atopic disease and the presence of immune complexes in serum. Methods Fifty-eight patients consecutively referred to our clinic with food-related gastrointestinal symptoms were investigated. Results Thirty-five patients (60%) had mucus in their stools, 24 patients (41%) complained about joint swelling and 41 patients (71%) had arthralgia. There were no correlations between these parameters and atopy according to Phadiatope test or skin prick test (SPT). No correlations were found between the occurrence of mucus in the stools, arthralgia and joint swelling. There were significantly higher levels of circulating immune complexes in patients with a history of arthralgia compared with patients with no such history (P < 0.03) and the number of individuals with the presence of such immune complexes was higher among the patients with arthralgia than among the patients without. In general the patients did not relate the exposure to certain foods to symptoms like joint swelling, arthralgia and presence of mucus in the stools. However, there were significant positive correlations between food-related gastrointestinal symptoms in the following instances: chocolate-induced gastrointestinal symptoms and mucus in the stools (P= 0.006), vegetable-induced gastrointestinal symptoms and mucus in the stools (P= 0.002) and meat-induced gastrointestinal symptoms and mucus in the stools (P= 0.003). In a group of individuals without foodrelated symptoms investigated separately, a very low frequency of mucus in the stools, joint swelling and arthralgia was seen (none, two and three individuals of the 20 subjects, respectively). Of 41 patients with immediate onset of gastrointestinal symptoms, 20 were atopic according to Phadiatope and SPT, Of 11 patients with late onset of symptoms 10 were negative in Phadiatope and SPT (P < 0.05). The most frequently involved foods were fruits, vegetables, milk, fish and meat. Conclusion The results suggest the involvement of different inflammatogenic mechan isms in food-related gastrointestinal symptoms.     

IgE-mediated allergy to peanut, cow's milk, and egg in children with special reference to maternal diet

Nineteen children with IgE-mediated allergy associated with strongly positive prick skin tests and RASTs to peanut or cow's milk and/or egg were studied. Seventeen of the children had been breast fed, ten had been exclusively breast fed for a minimum of 5 months. Reactions to these foods occurred on first exposure to the food in all but one instance, suggesting that in 18 instances sensitization had occurred antenatally or via the breast. A retrospective inquiry indicated that most of the mothers had had a generous intake of the food(s) to which their children were sensitized, but mothers of sensitized children did not consume more of these foods than the mothers of non-sensitized children; moreover, avoidance of the foods (peanut in two instances and egg in one) did not ensure freedom from sensitization to peanut and/or egg. Breast feeding by itself cannot be guaranteed to protect against the development of food allergy.     

Parental history of atopic disease: disease pattern and risk of pediatric atopy in offspring

BACKGROUND: Family history is an important risk factor for atopic disease. However, most studies assess only limited information on family history. Because atopic disease can exhibit transient or persistent patterns, it may be useful to assess information on patterns of disease within families. This approach has been applied in other diseases, such as cancer, to discriminate between predominantly inherited versus environmentally caused (sporadic) cases. OBJECTIVE: In a cohort of children who were followed from birth until age 6 to 7 years, we examined the relationship between parental onset (ie, childhood and adulthood) and duration of atopic disease (ie, persistent disease) and the risk of pediatric atopic disease. Our hypothesis was that different parental disease patterns would be important to pediatric risk of disease. METHODS: Data from 476 families in the ongoing Childhood Allergy Study in Detroit, Mich, were analyzed by using logistic regression. We examined the association between parental patterns of disease and disease onset in their children. Results Father's disease history, particularly asthma history, was more strongly related to pediatric outcomes than mother's history. Asthma status in the fathers, whether it was childhood-only, adulthood-only, or persistent, was associated with current asthma in the children. Childhood-only and persistent asthma in fathers conferred a higher risk of atopy in the study children, whereas adulthood-only disease did not. There was also a significant relationship between persistent allergy in the father and atopy in the study children. CONCLUSION: Our data support the hypothesis that there are complex inheritance patterns for allergy and asthma. Therefore, a detailed family history of atopy, including childhood and adulthood experiences, is critical to identifying and classifying risk and disease phenotypes.     

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study

BACKGROUND: Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. OBJECTIVE: To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow's milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1-year-old children. METHODS: All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut-off value. RESULTS: Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow's milk. CONCLUSION: An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.     

Antibodies IgG, IgA, and IgM to food antigens during the first 18 months of life in relation to feeding and development of atopic disease

Serum levels of IgG, IgA, and IgM antibodies against ovalbumin, beta-lactoglobulin, and gliadin were measured in a series of 210 "allergy-risk" infants and their mothers. The antibody levels were determined with ELISA in sera obtained from mothers at delivery, and from their babies at birth, 6 weeks, 6 months, and 18 months. High levels of maternal IgG, IgA, or IgM antibodies to food at delivery did not appear to protect the baby against development of atopic disease. Maternal avoidance of cow's milk and egg during pregnancy had no significant influence on the level of food antibodies in cord blood, but the mother's intake of these foods during lactation affected the immunologic response of the baby, not only to these antigens but also to gliadin as well. Babies with minimal cow's milk exposure before 6 months had significantly lower levels of IgG to beta-lactoglobulin than babies regularly exposed to cow's milk. We conclude that maternal elimination diet during lactation influences the immunologic response of the baby, but if this prevents the development of atopic disease or just delays the immunologic maturation remains to be evaluated.     

Soy versus cow's milk in infants with a biparental history of atopic disease: development of atopic disease and immunoglobulins from birth to 4 years of age

Forty-eight children with a biparental history of atopic disease were followed from birth to 4 years of age. One group was fed soy and the other cow's milk from weaning to 9 months of age. Two-thirds of the children developed symptoms of atopic disease with no significant difference between the groups. No difference was found in the serum immunoglobulins (IgE antibodies, IgA, IgG and IgM) during the observation period. The soy fed children showed transiently lower levels of IgG antibodies to cow's milk but higher levels of IgG antibodies to soy protein. Six children showed cow's milk intolerance and a further five had symptoms possibly related to the use of cow's milk. Withholding cow's milk during the first 9 months did not reduce the incidence of symptoms of cow's milk intolerance from birth to 4 years of age. Thus, no benefit was found from replacing cows' milk with soy. A prolonged breast feeding seems most rational for infants at risk of developing atopic disease, even if the present study did not show evidence of a prophylactic effect of breast milk against the development of atopic disease.     

Specific IgE antibodies in the diagnosis of atopic disease

A new immunoassay system utilizing new automatic instrumentation, new software for evaluation of data, and reagents updated for increased speed and accuracy was evaluated. Six clinical studies included 894 consecutive patients. Major symptoms were rhinoconjunctivitis, asthma, atopic dermatitis, and urticaria. The prevalence of inhalant allergy was 54–69%. Phadiatop®, detecting atopic sensitization to common inhalant allergens, agreed with clinical diagnosis in 764/836 cases (91.4%). TTie clinical sensitivity and specificity were 93% and 89%, respectively The clinical sensitivity and specificity of UniCAP specific IgE derived from 5170 comparisons with clinical diagnosis were 89% and 91 %, respectively Specific IgE measurements in UniCAP and in the Pharmacia CAP System agreed in 266/274 cases (97%). A comparison of the sensitivity and specificity of Pharmacia CAP System RAST in 1987 and with UniCAP specific IgE in 1995 showed equivalent performance without change of efficacy or degradation of IgE antibodies after 8 years. The systems were equivalent also in terms of measured values (r=0.96, slope=1.12), confirming the standardization of allergens and of assay calibration. UniCAP is an efficient laboratory system for routine diagnostic testing of allergy and a valuable tool for basic studies on allergens and antibodies.     

Lymphocyte subsets in infants: relationships to feeding, atopy, atopic heredity and infections

Numbers of T and B lymphocytes and T cell subsets were measured longitudinally in blood samples of 68 healthy infants from 1 month to 28 months of age. Monoclonal antibodies against cell surface antigens (OKT3, OKT4, OKT8, and OKIal) and antibodies to immunoglobulin heavy chains (gamma, mu, alpha and delta) were used for immunofluorescent staining. The absolute number of T lymphocytes (OKT3) was found to be highest at the age of 6-7 months, reflecting the greater numbers of both helper (OKT4) and suppressor (OKT8) cells. The percentages of OKT4 and OKT8 positive cells and hence the ratios of these cells were very stable throughout the study period. Relatively, breast-fed infants had more suppressor (OKT8) cells than infants on formula, but the difference was not apparent in absolute counts. Change to formula feeding caused an increase in B cells. The heredity for atopy did not influence the total numbers of T cells or cell numbers in the different subgroups. At the age of 4 months an altered helper/suppressor ratio was noted in infants who later developed a severe atopy. At the age of 28 months the relative number of T cells was lower in atopic than nonatopic infants. The rate of respiratory infections did not affect these numbers.     

Asthma, atopy and Chlamydia pneumoniae antibodies in adults

BACKGROUND: Factors involved in the development of inflammation and asthma in nonatopic subjects have remained largely obscure, although there is some evidence to suggest that certain infections may play a role. OBJECTIVE: We investigated the association between serological evidence of Chlamydia pneumoniae infection and asthma in adults, and the possible modifying effect of the patients' atopic status on this association. METHODS: Four hundred and thirty consecutive patients who attended the hospital between 1992 and 1993 with symptoms suggestive of asthma, rhinitis or allergy were enrolled. Diagnostic procedures including lung function measurements and skin-prick tests were performed in all patients. The patients with established asthma (n = 332) were divided into those with recent asthma (n = 224, onset 1985 onward) and longstanding asthma (n = 108, onset before 1985). The controls (n = 98) comprised all subjects who did not meet the criteria of asthma. Serum immunoglobulin (Ig)G, IgA and IgM antibodies to C. pneumoniae were measured by the microimmunofluorescence test. RESULTS: In women, the prevalences of elevated IgG (a titre of >/= 128) and IgA (>/= 32) antibody levels and the age-adjusted geometric mean titres (GMT) of IgG and IgA antibodies were invariably highest among subjects with nonatopic longstanding asthma. Elevated IgG titres in women occurred in 11% of controls, in 28% of nonatopic recent onset asthmatics, and in 43% of asthmatics with nonatopic longstanding disease; for men the respective figures were 33, 50 and 64%. Logistic regression analysis controlling for age, sex and smoking showed that asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae (odds ratio 3.3, 1.6-6.8 for longstanding asthma, 2.3, 1. 2-4.4 for recent asthma, and among women only 4.2, 1.6-10.9 for longstanding asthma, and 3.0, 1.3-7.2 for recent asthma). When the atopics and nonatopics were analysed separately, an even stronger relationship in the nonatopics was obtained for longstanding asthma (6.0,2.1-17.1). In contrast, the relationship between atopic asthma, either recent or longstanding, and elevated IgG titres was not significant, indicating that asthma per se does not predispose to C. pneumoniae infection. CONCLUSIONS: Asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae, and this association was strongest for nonatopic longstanding asthma.     

Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants

Background The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections.
Objective To investigate the relation between early intestinal viral infections in relation to the development of atopic symptoms (eczema, wheeze and atopic sensitization) in the first and second year(s) of life.
Methods In the KOALA Birth Cohort Study, we assessed IgG seropositivity for rota- and norovirus (GGI.1 and GGII.4) at 1 year of age. This was related to allergic sensitization [specific immunoglobulin E (IgE)] at 1 and 2 years, and parent reported eczema and wheeze in the first 2 years, using logistic regression analysis adjusted for confounders.
Results Rotavirus seropositivity (39%) was associated with an unexpected higher risk of recurrent wheeze in the first and second year of life [adjusted odds ratio (OR) 3.1 and 95% confidence intervals (CI) 1.1–9.1] and persistent and new recurrent wheeze (adjusted OR 2.7 and 95% CI 1.1–6.2). No further associations were found between intestinal viral seropositivity and atopic manifestations.
Conclusion Our data did not show a clear protection by enteric viral infections in young children on development of IgE response to allergens, but rotavirus infection in the first year was a risk factor for wheeze. However, this needs to be followed up to older ages in order to establish the true importance of intestinal viral infections and especially cumulative effects in AD aetiology. Exposure to rotavirus may offer a new and interesting focus on infant wheeze and later asthma development.