Childhood Atopic Disease Research Articles

Animal allergens

Animal allergen exposure in early childhood and its relationship to the development of atopic disease is a subject that has been evolving rapidly. Recently, several well-designed studies have helped elucidate previous, often conflicting findings on this topic. In addition, results from studies on farm-animal exposure have added strength to data on early dog and cat exposure. In this paper, we review several recent studies that have helped clarify the relationship between early animal-allergen exposure and childhood atopic disease.

The relationship between vaccine refusal and self-report of atopic disease in children

In the last 3 decades, there has been an unexplained increase in the prevalence of asthma and hay fever. We sought to determine whether there is an association between childhood vaccination and atopic diseases, and we assessed the self-reported prevalence of atopic diseases in a population that included a large number of families not vaccinating their children. Surveys were mailed to 2964 member households of the National Vaccine Information Center, which represents people concerned about vaccine safety, to ascertain vaccination and atopic disease status. The data included 515 never vaccinated, 423 partially vaccinated, and 239 completely vaccinated children. In multiple regression analyses there were significant ( P < .0005) and dose-dependent negative relationships between vaccination refusal and self-reported asthma or hay fever only in children with no family history of the condition and, for asthma, in children with no exposure to antibiotics during infancy. Vaccination refusal was also significantly ( P < .005) and negatively associated with self-reported eczema and current wheeze. A sensitivity analysis indicated that substantial biases would be required to overturn the observed associations. Parents who refuse vaccinations reported less asthma and allergies in their unvaccinated children. Although this relationship was independent of measured confounders, it could be due to differences in other unmeasured lifestyle factors or systematic bias. Further research is needed to verify these results and investigate which exposures are driving the associations between vaccination refusal and allergic disease. The known benefits of vaccination currently outweigh the unproved risk of allergic disease.

6. Atopic disease in childhood

A child with atopy produces IgE antibodies after exposure to common environmental allergens. The atopic diseases (eczema, asthma and rhinoconjunctivitis) are clinical syndromes each defined by a group of symptoms and signs. Not all children with atopy will have atopic disease or develop symptoms after exposure to an allergen. Both genetic and environmental factors determine the development of atopic disease. The presence of specific IgE antibodies to environmental allergens is determined with skin prick or radioallergosorbent testing in children with atopy. Test results should be interpreted in the context of the clinical history and further investigations (eg, allergen avoidance or challenge). Management of atopic disease is frequently symptomatic, but it is important to avoid identified allergen triggers. Immunotherapy may be considered in selected school-age children with severe rhinoconjunctivitis. Preventing atopic disease in high-risk infants and hindering progression of disease in children with established disease are the areas of active research.

A 17-year study of the prevalence of asthma and allergic diseases among children in Saudi Arabia

RATIONALE: The study aimed to determine the prevalence of asthma and allergic diseases among children in Saudi Arabia. METHODS: A total of 1678 randomly selected schoolchildren comprising of 51.6% males (mean age 11.62 + 3.08 years) and 48.4% females (mean age 11.79 + 3.21) was recruited in a questionnaire-based cross-sectional study during the year 2002 in three regions. Results of the present study were compared with the previously published data from two similar surveys conducted in 1986 and 1995 to establish the prevalence trend for asthma and atopic disorders in the Kingdom over a period of 17 years RESULTS: Significantly higher prevalence rates (p ≤ 0.0001) for asthma, rhinitis and eczema were noted in the eastern region (Hofuf) (33.7%, 48.2% and 43.5%) compared to central region (Riyadh) (17.7%, 29% and 32.6%) and western region (Jeddah) (14.1%, 24.3% and 31.9%), respectively. A comparison of the present cumulative prevalence rates for childhood asthma (21.7%), rhinitis (33.8%) and eczema (36%) with those of the past shows that after an initial sharp rise between 1986 and 1995 asthma has reached a plateau. Allergic rhinitis, on the other hand, shows a steady upward course, however, eczema for the first time, has shown a dramatic increase over a period of 17 years CONCLUSIONS: Prevalence of childhood atopic diseases like asthma, rhinitis and eczema was exceptionally high in the eastern. Although a strong association among allergic diseases is well known, yet long-term prevalence trend for each disorder is variable among atopic children.

Atopy and House Dust Mite Sensitization as Risk Factors for Asthma in Children

Asthma is commonly described as an atopic disease in childhood, but some cases of this disorder do not fit this description. The aim of this study was to evaluate the frequency of atopy, asthma, and sensitization to house dust mites in children with allergic symptoms. This study was performed at the Severance Hospital of Yonsei University with patients who visited the allergy clinic for evaluation of nonspecific upper respiratory symptoms, typical symptoms of asthma, or a general health workup. The patients were divided into three age groups: 0-3 years (group 1), 4-7 years (group 2), and 8-12 years (group 3). Of the 1,244 children examined, 844 (67.8%) were atopic and 400 (32.2%) were non-atopic. The frequency of atopy and asthma increased with age. Asthma was diagnosed in the same proportion (64%) of atopic and non-atopic children. As risk factors for asthma symptoms, the positive values of house dust mite (HDM) sensitivity were significantly increased in groups 1, 2, and 3 to 53.5%, 68.9%, and 80.2%, respectively. A significant difference between the percentage of asthmatics sensitized to HDM and that of asthmatics not sensitized to HDM was found only in group 3. In conclusion, asthma is related to atopy with increasing age, and house dust mite sensitization seems to be an important determinant of asthma in older children in Korea.

Parents' reported preference scores for childhood atopic dermatitis disease states

BackgroundWe sought to elicit preference weights from parents for health states corresponding to children with various levels of severity of atopic dermatitis. We also evaluated the hypothesis that parents with children who had been diagnosed with atopic dermatitis would assign different preferences to the health state scenarios compared with parents who did not have a child with atopic dermatitis.MethodsSubjects were parents of children aged 3 months to 18 years. The sample was derived from the General Panel, Mommies Sub-Panel, and Chronic Illness Sub-Panel of Harris Interactive. Participants rated health scenarios for atopic dermatitis, asthma, and eyeglasses on a visual analog scale, imagining a child was experiencing the described state.ResultsA total of 3539 parents completed the survey. Twenty-nine percent had a child with a history of atopic dermatitis. Mean preference scores for atopic dermatitis were as follows: mild, 91 (95% confidence interval [CI], 90.7 to 91.5); mild/moderate, 84 (95%CI, 83.5 to 84.4); moderate, 73 (95%CI, 72.5 to 73.6); moderate/severe, 61 (95%CI, 60.6 to 61.8); severe, 49 (95% CI, 48.7 to 50.1); asthma, 58 (95%CI, 57.4 to 58.8); and eyeglasses, 87(95%CI, 86.3 to 87.4).ConclusionsParents perceive that atopic dermatitis has a negative effect on quality of life that increases with disease severity. Estimates of parents' preferences can provide physicians with insight into the value that parents place on their children's treatment and can be used to evaluate new medical therapies for atopic dermatitis.

Childhood infections and risk of wheezing and allergic sensitisation at age 7?8 years

Childhood atopic disease has been associated with exposure to infections early in life. There is however considerable controversy on this issue, since evidence exists for both protective and adverse effects of infections. Aim of this study was to investigate the association between childhood infections and the occurrence of wheeze and allergic sensitisation in 7-8-year-old Dutch and German children. A nested case-control study was conducted among German and Dutch children participating in a large longitudinal study on respiratory health. Parents of 510 7-8-year-old children with respiratory complaints and an equal number of children without respiratory complaints were asked to complete a questionnaire. Blood samples were collected for specific serum Immunoglobulin E (IgE) analysis. Data on childhood infections were collected through records of the participating Municipal Health Services. No association was found between recent wheeze and any of the childhood infections investigated. For scarlet fever infection an increased risk of allergic sensitisation (OR: 2.82; 95% CI: 1.40-5.72) and sensitisation against grasses (OR: 3.00; 95% CI: 1.35-6.69) at the age of 7-8 years was found. Varicella infection tended towards increased risk of sensitisation against grasses (OR: 1.88; 95% CI: 0.99-3.58). For allergic sensitisation and sensitisation against grasses the odds ratios increased with increasing number of infections. The results do not lend support to the suggestion that childhood infection protects against wheezing or allergic sensitisation at age 7-8 years. Scarlet fever or varicella infection presented an increased risk of allergic sensitisation.

Asthma prevention: breast is best?

Whilst breastfeeding has been considered to exert a preventative effect on the development of allergic disease, several recent publications have challenged this view, particularly with respect to the long-term outcomes for asthma. There are many other beneficial effects of breastfeeding apart from the possibility of allergy prevention. The suggestion that breastfeeding may increase the development of allergic disease raises concerns about the appropriate steps to take for primary prevention of allergy. It is concluded that breastfeeding can still be recommended for the beneficial effects in reducing atopic disease in childhood in addition to the other demonstrated benefits, and that there are unresolved questions concerning the few studies that suggest the possibility of increased allergic disease in later life.

Atopie maternelle et sensibilisation précoce. Rôle du lait maternel

Fetuses are exposed to allergens during intrauterine period. Neonates T cells are capable of proliferating in vitro in response to both foods and inhalants allergens. This suggest that the initial allergen-specific T cell priming may occur in utero as the result of transplacental transfer of small amounts of the relevant allergens to which mothers are exposed during pregnancy. Response to allergens may appear during the 22nd week of gestation. Recently, mites antigens have been found in the amniotic fluid and in more quantities in both mother’s and neonate’s blood. During allergic sensitization and the establishment of atopic disease in childhood, the cytokine profile as detected at birth gradually shifts to a Th2 cytokine profile which was suggested in utero to be important for a successful pregnancy. Human milk contains numerous components that protect the infant against infections. Probiotics may have also a protective effect, as some other factors which may justify “ the hygienist hypothesis”.

New pregnancies and loss of allergy.

Inverse associations between allergic disease and sibship have been consistently described and are frequently explained by purported lower rates of early infection among children from small families. Alternative explanations include the possibility that pregnancy itself determines maternal atopic status. To test the hypothesis that atopy defined by skin prick test (SPT) declines with increasing numbers of pregnancies. At enrollment to a birth cohort, mothers were skin prick tested to three common allergens. Seven years later these women underwent a second SPT and provided information on their reproductive histories. At both visits, information on allergic disease was also sought. Twenty five (15%) women who were initially atopic were no longer so at the second visit; loss of hayfever symptoms was reported by 33 (29%) women. Women with higher numbers of intervening pregnancies were more likely to 'lose' their atopy (P=0.05) and symptoms of hayfever (P=0.02); this was not true for asthma. The findings could not be accounted for by maternal age. Successive pregnancies may in part determine a mother's atopic state. Since maternal atopy is a risk factor for childhood atopic disease, this process may affect the atopic state of successive children. These findings suggest an alternative explanation for the sibship effect in allergic disease.

Four‐year follow‐up shows continued benefit of perinatal Lactobacillus for childhood atopic disease

Four‐year follow‐up shows continued benefit of perinatal <i>Lactobacillus</i> for childhood atopic disease

THE USE OF DISEASE SUB-GROUP CLASSIFICATION WITHIN THE BROAD SPECTRUM OF CHILDHOOD ASTHMA AND ATOPY WHEN EXAMINING ENVIRONMENTAL DETERMINANTS.

The clinical syndrome of asthma encompasses several subgroups that reflect airway obstruction of differing aetiologies. We discuss epidemiologic approaches that may be used to reduce disease misclassification with regard to allergen-induced airway obstruction and demonstrate these approaches using two recent analyses. First, we examine infant synthetic bedding and subsequent child wheeze. While house dust mite (HDM) sensitisation is only weakly associated with asthma (RR = 1.7), it is strongly associated with frequent wheeze (more than 12 episodes compared to no wheeze over the past year) (RR = 19.6). Thus, a focus on severe symptoms such as frequent wheeze should reduce disease misclassification in studies examining HDM-related airway disease. We examined a 1988 birth cohort in Tasmania (n = 863, 78% traced) with data available on infant bedding at one month of age and respiratory symptoms at age seven. The associations between synthetic bedding and asthma were not strong. However, strong associations emerged when the frequent wheeze was examined. We found synthetic pillow use at one month of age was associated with frequent wheeze at age seven (ARR 2.5 (1.2–5.5)), independent of childhood exposure. Current synthetic pillow and quilt use was strongly associated with frequent wheeze. Among children with asthma, the age of onset of asthma occurred earlier (p = 0.03) if infant synthetic bedding was used. This shift was particularly evident among children with frequent wheeze. Thus in this cohort, synthetic bedding was strongly and consistently associated with frequent wheeze. These associations would not have been evident if only the global outcome of asthma was considered. Second, we examine the use of mutually exclusive allergen-specific classifications within the broad category of atopy. Our aim was to examine the relative importance of family size on sensitisation to two different allergens:- ryegrass and HDM. An eight-year follow-up birth cohort study of children born 1988–1989 was conducted. The follow-up sample consisted of 498 children residing in Northern Tasmania in 1997 (84% of eligible). Outcome measures included skin prick test reaction to nine aeroallergens. Family size was defined as sibling number in 1997. Children with a positive skin prick test to (SPT) either Der p or Der f HDM but not ryegrass were classified as HDM-exclusive (n = 84). Children with a positive SPT to ryegrass but not HDM were classified as ryegrass-exclusive (n = 43). Family size was associated with reduced ryegrass-exclusive sensitisation (AOR 0.57 (0.39, 0.84) per increase in sibling number) but not HDM-exclusive sensitisation (AOR 0.97 (0.77, 1.23)). The difference in the effect of family size on these sensitisation outcomes was significant (p = 0.02). Thus, large family size was strongly associated with reduced sensitisation for ryegrass allergens but not HDM allergens. Further work is required to assess whether these findings reflect differences between these allergens with regard to the level or timing of early life exposure. These two cohort analyses demonstrate that careful sub-group definition within the broad spectrum of asthma or atopy may lead to new insights on the environmental determinants of atopic disease in childhood.

Immunomodulatory treatment strategies for allergic diseases.

Over the last decades the prevalence of allergic disorders, such as hayfever and asthma has increased worldwide, mostly in westernised countries where up to 20 % of the population are affected. The "hygiene hypothesis" suggests that modernised lifestyles such as improved housing conditions, altered dietary habits and smaller family sizes may be responsible for the decrease in infectious and the increase in allergic diseases. Childhood atopic diseases, like eczema, food allergies and recurrent wheezy bronchitis represent a considerable health problem and a major socioeconomic burden due to the chronicity of these disorders. In recent years, a better understanding of the immunopathogenesis of allergic diseases has evolved, which has contributed to the development of novel more targeted forms of therapy. Allergen injection immunotherapy is the only treatment in current use with the potential for modifying the course of allergic disease. In order to better target mucosal allergies, new approaches of administering allergen, via the sublingual or intranasal route, are being developed. The use of modified allergens, allergen peptides, DNA immunization and the use of novel adjuvants represent alternatives to conventional immunotherapy with potential for improved efficacy with less side effects. For atopic asthma, novel treatment strategies aim at locally targeting inflamed airways. Nebulized monoclonal blocking antibodies and soluble interleukin receptors against "Th(2)-type" cytokines have been designed. An alternative approach has been the administration of "Th(1) -type" cytokines. Although, immunomodulatory strategies provide a promising outlook for the treatment of allergic patients, more studies are needed in the future to address issues of efficacy, safety and long-term effects of altered immune responses.

Clinical course of cow's milk protein allergy/intolerance and atopic diseases in childhood

A cohort of 1,749 newborns from the municipality of Odense, born during 1995 at the Odense University Hospital, were followed up prospectively for the development of cow's milk protein allergy/intolerance (CMPA/I) during the first year of life. Once a diagnosis of CMPA/I was confirmed, a milk-free diet was continued until a new milk challenge had shown development of tolerance. All infants with CMPA/I were rechallenged at 12 months of age and, in the event of continued clinical sensitivity to cow's milk protein, controlled rechallenges were performed every 6 months up to 3 years of age; and thereafter every 12 months until the age of 15 years. From the same birth cohort, 276 infants were randomly selected at birth for prospective non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood. Standardized questionnaires on atopic heredity, environmental factors and presence of atopic symptoms were answered at 0, 6, 12 and 18 months and at 5, 10 and 15 years of age. Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months, 5, 10 and 15 years of age. Skin prick test and specific sIgE (Pharmacia CAP) testing were performed at 18 months, 5, 10 and 15 years of age against a panel of inhalant allergens (birch, grass, mugwort, dog, cat, horse, Dermatophagoidespteronyssinus, Dermatophagoides farinae, alternaria and cladosporium herbarum). Furthermore, lung function measurements were performed in children when 10 and 15 years of age. Based on controlled milk elimination and challenge procedures, the diagnosis of CMPA/I was confirmed in 39 out of 117 infants, with symptoms suggestive of CMPA/I, thus resulting in a 1-year incidence of CMPA/I of 2.2%. The overall prognosis of CMPA/I was good, with a total recovery of 56% at 1 year, 77% at 2 years, 87% at 3 years, 92% at 5 and 10 years and 97% at 15 years of age. In children younger than 10 years of age, 41% developed asthma and 31% rhinoconjunctivitis. Children with non-IgE-mediated CMPI had a good prognosis, whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA, development of other food allergies, asthma and rhinoconjunctivitis. During early infancy, recurrent wheezing was the most prevalent disease (20%), followed by atopic dermatitis (14%) and food allergy (7%) at 18 months of age. Physician diagnosed asthma increased from 2% at 1.5 years of age to 9% at 10 years of age. Rhinoconjunctivitis increased from <1% at 1.5 years of age to 9% at 10 years of age. Overall, the current prevalence of any atopic disease was 20% at 1.5 years of age, declining to 14% at 5 years of age and followed by an increase to 25% at 10 years of age. Sensitization to inhalant and/or food allergens (specific IgE of > or = class 2; CAP RAST) showed a low rate of sensitization among asymptomatics (3%, 10% and 12%) compared with higher rates of sensitization of 8%, 39% and 30% among symptomatic atopics at 1.5, 5 and 10 years of age respectively. The highest rate of sensitization (53%) was found among children with current asthma at 10 years of age.

Exposure to birch pollen in infancy and development of atopic disease in childhood.

The relationship between early allergen exposure, sensitization, and development of atopic disease remains controversial. In 1993, extremely high levels of birch pollen were recorded in Stockholm, Sweden, creating the unique opportunity to study children with different exposures during infancy. We sought to assess the influence of early high-dose exposure to an inhalant allergen (birch pollen) on sensitization and development of atopic disease in children. A total of 583 children with atopic heredity born in Stockholm in February through April 1992, 1993, or 1994 were investigated at age 4.5 to 5 years. The children were examined and underwent skin prick testing with inhalant and food allergens. IgE antibodies (RAST) against birch pollen and recombinant birch pollen allergen (rBet v 1) were analyzed in serum. The children born in 1993 (high-dose exposure at 0-3 months) were more often sensitized (ie, positive skin prick test response) to birch pollen than the children born in 1994 (low-dose exposure; 17.8% and 8.8%, respectively; odds ratio [OR], 2.4; 95% CI, 1.2-4.6). A tendency in the same direction was seen for children born in 1992 (high-dose exposure at 12-15 months; OR, 1.7; 95% CI, 0.9-3.2). The results were supported by the RAST analyses. The prevalence of bronchial asthma, allergic rhinoconjunctivitis, and atopic dermatitis did not differ between the birth-year groups. However, the prevalence of pollen- and animal dander-induced allergic asthma was increased in the children born in 1993 (OR, 2.6; 95% CI, 1.2-5.6). An interaction between early high-dose exposure to birch pollen and cat in the household was suggested for sensitization to cat (P =.06). Exposure to high levels of birch pollen in infancy increases the risk of sensitization to the same allergen, as well as the risk of allergic asthma.

Environmental risk factors for allergy and socioeconomic status in a birth cohort (BAMSE).

Associations between parental educational level and possible risk factors for atopic disease during the first months of life were explored in a cohort of 4089 neonate children born 1994-96 in Stockholm, Sweden. Reports concerning a number of life style factors during pregnancy and after the baby was born were obtained by questionnaire. There was a strong negative association between duration of education and maternal smoking during pregnancy, parental smoking after the baby was born and keeping of cat and dog (p-trend < 0.001), respectively. For example, smoking during pregnancy was reported by 6.7% (95% CI 5.5-7.9) of mothers with college or university degree and by 22.2% (95% CI 20.1-24.5) of those with the shortest education. Indicators of dampness and poor ventilation were also more common in homes of those with the shortest education. The results show that the educational level has an influence on risk factors for development of atopic disease in childhood and indicates a need of deeper understanding of life style in different socioeconomic groups. The data also indicate that various possible confounding factors need to be thoroughly investigated when analysing studies of risk factors for allergic disease in childhood.

Environmental factors influencing the development and progression of pediatric asthma.

Recent data underscore the importance of environmental factors in the sensitization of children to certain allergens and the development of asthma. Maternal smoking and family (especially maternal) history of atopy appear to be risk factors for persistent sensitization and development of asthma. Indeed, exposure to tobacco smoke in utero significantly increases asthma risk and influences the timing of sensitization. It must be stated that any smoking at home has consequences for the development of asthma and other respiratory conditions. In addition, reports of possible protective effects of specific environmental conditions suggest that exposure to certain stimuli may reduce or block the development and progression of asthma. Attendance at a day care center early in life appears to offer protective effects against wheezing, as do early episodes of rhinitis, herpes, and measles. Children raised on a farm also have a decreased prevalence of atopic diseases. The protective effect of contact with livestock and poultry is consistent among several studies. Although the pathophysiologic mechanisms involved remain undefined, studies suggest that exposure to endotoxin and other components of bacteria may play an important role in protecting against childhood atopic diseases. Whether in utero exposure is beneficial remains to be determined.

Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease.

Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.

Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III

BACKGROUNDAn increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to...

Immunization and symptoms of atopic disease in children: results from the International Study of Asthma and Allergies in Childhood.

This study tested the hypothesis that immunization is related to the prevalence of atopic disease in childhood. We used data from the International Study of Asthma and Allergies in Childhood to perform an ecologic analysis of national and local immunization rates for tuberculosis, diphtheria and tetanus toxoids and pertussis (DTP), and measles and prevalence of atopic disease symptoms (asthma, allergic rhinoconjunctivitis, and atopic eczema). In 13- to 14-year-old children, there were significant negative associations with local birth-year immunization rates for DTP and measles but none with rates for tuberculosis. No associations were found in 6- to 7-year-old children. No associations with national immunization rates were found. International variations in childhood atopic diseases are unlikely to be explained by variations in immunization.