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Atopy in children with and without a family history of atopy. I. Clinical manifestations, with special reference to diet in infancy.

The influence of a family history of atopy on atopic morbidity, and relationships between diet in infancy and allergic manifestations at the ages of one and five years were prospectively studied in 91 children. A control group consisted of 72 children with no family history of atopy. At the age of one year, atopic manifestations were found in 19% of 163 children, in 23% of those with a family history of atopy and in 14% of those with no such history. Skin problems were more common in children with a family history of atopy (43%) than in the control children (19%). Of the children with a family history of atopy, 23% had prolonged rhinorrhoea during infancy. The corresponding figure in children with no family history of atopy was 10%. Prolonged rhinorrhoea during infancy correlated with parental smoking only in children with a family history of atopy (47% vs. 18%). At the age of five years, atopic disease was found in 17% of 128 children, 24% of those with a family history of atopy and 9% of those with no such history. Atopic eczema was more common in children with a family history of atopy, irrespective of the diet consumed during infancy. Atopic signs were found in about half of all the children with a family history of atopy. If atopy had been present in the family, the child usually exhibited the same manifestation. Onset of atopic manifestations was not prevented or delayed.

Breast Feeding

Does atopy have any predictive value for laboratory animal allergy? A comparison of different concepts of atopy.

Atopy is widely used as a discriminant in selection for employment involving exposure to allergenic substances. The validity of this has been tested in a population with a known burden of what is largely considered to be an IgE mediated disease, laboratory animal allergy. The findings suggest that atopy is insufficiently sensitive and specific for this purpose and that this is probably true for other occupational allergic diseases. The relation between different concepts of atopy--namely, atopy defined by family history, by personal history, and by skin prick tests with common allergens--has also been examined. The subpopulations identified by these criteria differed appreciably. Different concepts of atopy should not be used synonymously as they often are at present.

Animals

Higher risk of infantile atopic dermatitis from maternal atopy than from paternal atopy.

The risk of infantile atopic dermatitis (AD) posed by maternal atopy and paternal atopy, respectively, were compared in the infants from a birth cohort in whom one of the parents had been designated atopic by skin prick testing. Nineteen with atopic mothers were compared with 20 with atopic fathers. AD, other atopic manifestations and potentially influential factors such as breast-feeding were documented prospectively during the first year in all infants. At 3, 6 and 12 month assessments skin prick sensitivity and total serum IgE concentration were determined. Nine of 19 infants with atopic mothers and two of 20 with atopic fathers had AD (P = 0.023) giving a relative risk of 4.7 (95% confidence interval 2.5 to 9.0). Seven of 19 with atopic mothers and none with atopic fathers had AD with onset before 6 months (P = 0.007). When all types of disease evidence (AD, recurrent wheeze and food reactions) were analysed together no significant difference was apparent between the groups. The two groups were found to be well matched with regard to breast-feeding, time of starting cow's milk, solids and egg, sex, month of birth, parental AD and smoking, race, household pets and neonatal IgE concentration. IgE concentrations at each age and the prevalence of skin prick positivity were similar between the groups. Maternal atopy poses a higher risk for infantile AD and paternal atopy. Whether this may be due to genetic or congenital factors or both is uncertain, but clearly the finding is of relevance in the prediction of allergy in childhood.

Adult

Atopy in children with and without a family history of atopy. II. Skin reactivity.

The influence of prolongation of breast feeding and postponement of introduction of solid food during infancy on skin reactivity at the age of five years was studied. At least one positive skin prick test result was observed in 23% of the 70 children with a family history of atopy and in 17% of the 58 children with no such history. Of the 26 skin-test-positive children, 54% exhibited positive reactions to cat dander and 42% to birch pollen. Of the 6 children with asthma, 6 with rhinitis and 17 with eczema, skin reactivity was observed in 66%, 66% and 35%, respectively. Contact with a cat during the first three to four months of life did not correlate with skin test positivity at the age of five years. Skin test positivity to birch pollen was more common in children born in January to February, probably because they were at a vulnerable age in their first birch pollen season in May. No preventive effect by the diet consumed during infancy was seen on subsequent skin test results in relation to common allergens.

Breast Feeding

[The concept of cryptic cutaneous atopy in contact reactions. Considerations on the clinical control over the subgroup of patients with frustrated cutaneous atopy].

Contact dermatitis, allergic or irritative, is not distributed by chance among the general population, but appears in a determined group of patients. The clinical and anamnestic picture of this group of patients (and that of their close blood relatives) is described. Clinical facts lead us to consider that group of patients as a subgroup of cutaneous atopy. The medical-legal importance which the acceptance of this type of patient could have on occupational contact dermatitis is pointed out. In contact dermatitis the factors of the person suffering the contact rather than those of the contact agents seem to be of decisive power in the response, although at the present moment, the possibility of carrying out analytical studies on the allergens and irritants is easier than on the patients who react to them.

Dermatitis, Atopic

The human dander atopy. I. The prototype of auto-atopy.

Human dander is shown to be a true allergen giving skin reactions most frequently in atopic patients. The clinical importance of human dander is discussed and data of a group of patients atopic only to human dander are given. It seems probable that human dander is an auto allergen and that there are many more auto allergens to which the atopic organism produces IgE-type antibodies.

Adolescent

Prolonged exclusive breast feeding and heredity as determinants in infantile atopy.

We followed 183 infants for two years, 31 of whom were breast fed less than three and a half months (median 70 days; short breast feeding group) and a further 31 of whom were exclusively breast fed for more than nine months (long breast feeding group). We assessed heredity for atopy, number of infections, and duration of breast feeding as determinants of atopy. During the first year of life 14 infants has signs of atopy. During the second year parents reported signs of atopy in a further 31. Heredity was the only significant predictor of atopy. Atopy was seen in 33% of infants with a positive heredity and in 16% without family history for atopy. The duration of breast feeding affected the incidence of atopy only among the infants without family history for atopy: fewer in the short breast feeding group (1/18) had atopy than in the long breast feeding group (5/13). Duration of breast feeding did not associate with incidence of respiratory infections. Diarrhoea was more common in the short breast feeding group than in the long breast feeding group during the first year of life. We conclude that prolonging exclusive breast feeding from the median of 70 days to nine months did not contribute to the prevention of infantile atopy and respiratory tract infections.

Breast Feeding

The relationship between atopy and non-specific bronchial responsiveness.

Atopy is often regarded as a risk factor for the development of asthma, particularly childhood asthma and occupational asthma. This could reflect an association with non-specific bronchial responsiveness (NSBR), though atopy could influence asthma independently. We have evaluated the possible relationship between atopy and NSBR (PD20FEV1 to methacholine) in the siblings of 59 probands with atopic asthma. Thirty-four (58%) were atopic (greater than or equal to 1 prick test with weal diameter greater than or equal to that of a 0.1% histamine control) and 28 (47%) showed NSBR. Atopy and NSBR occurred together more frequently than would be expected by chance (P less than 0.05); both variables being observed in 20 subjects, neither in 17, and only one in 22. A significant association was also noted when atopy was defined by a serum total IgE greater than 150 IU (or greater than 50 IU), but when atopy was defined by other commonly used criteria (greater than or equal to 2 prick tests with weal diameter greater than or equal to histamine control; or weal diameter 2 mm or more greater than a saline control), no significant association was demonstrated. Furthermore, linear logistic regression and multiple regression analyses showed that both the presence and the degree of NSBR were influenced much more by the baseline level of FEV1 than by atopic status. At best, atopy accounted for 10% of the variance of the PD20 measurements. We conclude that atopy is associated with NSBR but not strongly; that the relationship may be readily obscured according to the defining criteria used for atopy; and that atopy should not be used as a marker for NSBR.

Adolescent

Longitudinal changes in atopy during a 4-year period: relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren.

A total of 380 schoolchildren living in Belmont, New South Wales, a coastal town where the predominant aeroallergens are house dust mites, were studied on three occasions at 2-year intervals. At each study, atopy was measured by skin prick tests to 13 allergens, bronchial responsiveness was measured by histamine inhalation test, and respiratory illness history was assessed by a self-administered questionnaire to parents. The age of the group was 8 to 10 years at enrollment. We found that skin wheals less than 4 mm were not associated with respiratory or allergic illness, and therefore, we defined atopy as the presence of a skin wheal of greater than or equal to 4 mm. In the sample, 24% of the children were atopic at 8 to 10 years (early-onset atopy), and an additional 15% became atopic during the study (late-onset atopy). Both early- and late-onset atopy had a close association with hay fever. Late-onset atopy was strongly associated with inconsistent reporting of symptoms. Early-onset atopy was an important risk factor for bronchial hyperresponsiveness (BHR), diagnosed asthma, and continuing symptoms of wheeze, and was a particularly important risk factor for BHR with current wheeze in late childhood years. We conclude that atopy acquired at an early age is an important predictive factor for respiratory symptoms occurring with BHR and continuing into late childhood.

Bronchi

Atopy, smoking, and chronic bronchitis.

The aim was to test the hypothesis that atopy increases the occurrence of chronic bronchitis. Relations between atopy, smoking, and chronic bronchitis were studied in farmers. The data were from two successive postal surveys and a skin prick tested subsample. The cross-sectional study consisted of 9017 farmers. Those 6899 farmers who did not have chronic bronchitis at the beginning and who continued farming were followed for three years. A sample of 150 farmers was skin-tested with 36 allergens. The prevalence of chronic bronchitis (rate per 1000), standardised for age and sex, was 41 in non-atopic non-smokers, 101 in atopic non-smokers, 106 in non-atopic smokers, and 257 in atopic smokers (effect of atopy: p less than 0.001; effect of smoking: p less than 0.001). The standardised incidence rates of chronic bronchitis (per 1000 farming years) were 14, 34, 36, and 50, respectively (atopy: p less than 0.001; smoking p less than 0.001). The relative risk of chronic bronchitis, calculated from the incidence data adjusting for the effects of age, sex, smoking or atopy by logistic regression analysis was 2.2 for atopy (95% confidence interval 1.8-2.7) and 2.3 for smoking (1.8-2.9). Only 20 farmers had chronic bronchitis in the skin-tested subjects; the results were consistent with the findings in the surveys but did not reach statistical significance for atopy. In conclusion, atopy and smoking have independent and additive effects on the occurrence of chronic bronchitis at least in dusty farming work.

Adult

Lack of linkage between atopy and locus 11q13.

Atopy as defined in terms of IgE responsiveness was reported to be controlled by a single gene in British families, and this concept was further supported by a significant linkage between atopy and restriction fragment length polymorphism (RFLP) detected by a DNA probe specific to chromosome 11q13. To confirm this observation in a Japanese population, segregation and linkage analyses were done in four large families. Although segregation patterns of atopy were in agreement with the pattern of autosomal dominant inheritance, there was no significant linkage between atopy and locus 11q13. Alterations in the definitions of atopy did not affect the results. These findings suggested the presence of heterogeneity in genetic elements of atopy, even though atopy may be determined mainly by a single dominant gene.

Adolescent

The relationships between atopy, bronchial hyperresponsiveness, and a family history of asthma: a cross-sectional study of migrant Tokelauan children in New Zealand.

We have examined age-related changes in the association between nonspecific bronchial hyperresponsiveness (BHR) and atopy in 494 second-generation Polynesian migrant children, aged 5 to 15 years. BHR (provocative dose of methacholine, less than or equal to 7.8 mumol, causing a 20% fall in FEV1) was present in 125 children (25.3%). Atopy (skin wheal, greater than or equal to 4 mm diameter) was present in 157 children (32%). BHR associated with atopy demonstrated a constant age-related frequency in the 7- to 15-year-old children that was influenced by a family history (FH) of asthma (FH, 50%; no FH, 34%; p = 0.051). BHR not associated with atopy demonstrated a marked decreasing frequency with age from 25% in 5- to 7-year-old children to 3% in 13- to 15-year-old children and was uninfluenced by an FH of asthma. We conclude that the differences in the frequency of BHR with age, together with the genetic influence on BHR associated with atopy, compared with the findings in nonatopic children, indicate distinct heterogeneity in the pathogenesis of BHR in these Tokelauan children. These differences may be important for understanding the relationships between nonspecific BHR, atopy, and asthma in children.

Adolescent

Genetic analysis using DNA polymorphism of the linkage between chromosome 11q13 and atopy and bronchial hyperresponsiveness to methacholine.

Previous studies have suggested that there is a genetic predisposition for the development of asthma and atopy. A recent study has also demonstrated that there is a striking link between chromosome 11q and the IgE response underlying asthma and rhinitis. To assess the linkage between chromosome 11q (region D11S97) and atopy or bronchial hyperresponsiveness (BH), we have studied nine families of two and, in many instances, three generations with the index case having asthma and/or atopy. With variable number of tandem repeat analysis with the probe, p lambda-MS.51, we have been unable to confirm a significant link between region D11S97 of chromosome 11q and either atopy or BH to methacholine. We have demonstrated that atopy and BH produce similar log of odds scores with linkage analysis at each recombination fraction from 0.001 to 0.5 with both Hinf1 and Taq1 restriction digests and that the use of either a positive skin prick test or positive RAST as a definition of atopy does not significantly alter the log of odds score.

Adolescent

Factors confounding genetic linkage between atopy and chromosome 11q.

The results of testing for linkage between atopy and the chromosome 11 marker D11S97 is shown for all the 723 subjects genotyped by us up to January 1992. Lod score estimations were confounded by the high population prevalence of atopy, maternal inheritance of atopy at the 11q locus, genetic heterogeneity, and excess of atopy in families not ascertained through a single proband. Affected sib-pair analysis shows evidence for linkage which is not dependent on the definition of atopy or model specification. We suggest that presentation of sib-pair data will be suitable for meta-analysis of the different studies of genetic linkage and atopy.

Alleles

Atopy and bronchial hyperresponsiveness: exclusion of linkage to markers on chromosomes 11q and 6p.

Previous studies have reported a familial predisposition for the development of atopy, bronchial hyperresponsiveness and clinical asthma, and therefore have suggested the presence of a heritable component to these disorders. The specific contributions of genetic and environmental factors in the pathogenesis of allergic disease and asthma have not been determined although Cookson et al. [1] have postulated linkage between atopy and chromosome 11q. We have studied 20 families (two and three generations) ascertained through a proband identified as having asthma (90% were also allergic) during the period of time between 1962 and 1970. Of those who were originally skin test positive, 82% remained positive. All probands whose pulmonary function allowed retesting (FEV1 > 1.2 l) remained hyperresponsive to histamine. The children of these probands are now in the same age range as their parents when they were originally evaluated; 66% are atopic using criteria described by Cookson et al. (one or more positive skin tests > or = 2 mm, an elevated total serum IgE or a positive specific IgE) and 22% demonstrate bronchial hyperresponsiveness (PC20 FEV1) to histamine. Using the highly polymorphic marker INT2 (which maps 2 cM from p lambda MS.5 l on chromosome 11q) and atopy, we obtained a lod score of -2.00 at a recombination fraction of 0.12. In addition, because many studies have suggested an association between atopy and certain HLA antigens, we investigated the possibility of linkage between atopy and bronchial hyperresponsiveness and D6S105, a polymorphic marker on chromosome 6p, located 7 cM from HLA-DR. For this marker and atopy, we observed a lod score of -2.00 with a recombination fraction of 0.07.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Associations between respiratory symptoms, bronchial response to methacholine, and atopy in two age groups of schoolchildren.

Data on respiratory symptoms were obtained on 2503 schoolchildren aged 7 and 11 in Southampton by means of a self administered parental questionnaire. Children were classified into seven symptom groups from which 330 were tested for bronchial responsiveness to less than or equal to 6.4 mumol methacholine and skin tested for the presence of atopy. The symptoms of wheeze, cough, and shortness of breath were all significantly associated both with each other and bronchial responsiveness to methacholine but only wheeze was associated with atopy. The association of wheeze with both bronchial responsiveness to methacholine and atopy remained highly significant when controlling for the symptoms of cough and shortness of breath. Neither cough nor shortness of breath, however, were significantly related to bronchial responsiveness to methacholine when controlling for the symptom of wheeze. This study therefore calls into question the epidemiological relevance of these two symptoms as diagnostic features of asthma, particularly in the absence of wheeze, although they may be useful indicators of morbidity. Wheeze was not related to bronchial responsiveness to methacholine in the absence of atopy or to atopy in the absence of bronchial responsiveness to methacholine but was strongly related to the combination of the two phenomena. The presence of these three characteristics could therefore indicate a discrete disease entity. The decrease in the prevalence of cough between 7 and 11 years appeared to be mirrored by a similar decrease in the prevalence of wheeze when the symptom was not associated with the combination of bronchial responsiveness to methacholine and atopy. On the basis of these findings and those of others we suggest that the latter group may represent children with a separate disease entity(ies) or with residual symptoms secondary to acute viral or other infections of the lower respiratory tract.

Asthma

Atopy in childhood and diet in infancy. A nine-year follow-up study. I. Clinical manifestations.

A national program for the prevention of atopy in children has been in progress in Finland since 1979. Its aim is to prevent or at least to reduce atopic symptoms in childhood. Since the start of the program we have followed a group of 119 children with and without a family history of atopy. Half the atopy-prone children kept to the diet intended to prevent atopy, i.e., breast-feeding prolonged up to age 3 months and introduction of solid food and formulae based on cow's milk after age 3 months. All children were examined at ages 5 and 10 years. In addition to clinical examination and interview, skin-prick tests using eight common inhalant allergens were performed. At age 9 to 10 years, 38 of the 119 children (32%) exhibited at least one atopic illness (bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic eczema or food allergy). Forty percent of children with family histories of atopy had atopic illness, independent of diet in infancy. The occurrence of atopic manifestations in the children of nonatopic families was 21%. Only half the children who had atopic symptoms at age 12 months had symptoms 9 years later. Asthma, allergic rhinitis, and positive skin-prick test results at age 5 years, however, correlated well with the subsequent occurrence of respiratory allergy. Our observations indicate that the preventive measures in early infancy intended to reduce the risk of atopy had no influence on atopic manifestations 9 years later.

Child