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PubMed1989

Association between keratoconus and atopy.

Sixty-seven patients with keratoconus were classified according to atopic status. Keratoconus patients with and without atopy did not differ significantly with regard to sex, age of onset, or rate of keratoplasty, but patients with very high IgE levels were more prone to graft rejection. Atopy was less common in patients with unilateral keratoconus, and keratoconus occurred more frequently on the side of the dominant hand. There was a significantly lower frequency of HLA B7 in the keratoconus group than in the controls. No abnormalities of essential fatty acid metabolism were found in keratoconus patients with or without atopy. There was no social class bias in the group. The study included a brother and sister with keratoconus and atopy, and a non-atopic patient whose identical twin did not have keratoconus.

Asthma↗
PubMed2001

Asthma, atopy and tuberculin responses in Chinese schoolchildren in Hong Kong.

BACKGROUND: The prevalence rates of asthma and other atopic disorders have increased steadily in many developed countries over the past few decades. Recent epidemiological and animal studies have suggested that BCG vaccination might be beneficial in reducing the subsequent development of atopy. This study investigates the relationship between asthma, allergic symptoms, atopy, and tuberculin response in Chinese schoolchildren who received BCG vaccination at birth. METHODS: A total of 3110 schoolchildren aged 10 years were recruited for the Hong Kong arm of the phase II International Study of Asthma and Allergies in Childhood. Of the 2599 children born in Hong Kong and vaccinated with BCG after birth, 2201 had tuberculin testing performed at a mean (SD) age of 8.4 (1.4) years. A random subsample of 980 children was also recruited for skin prick testing. RESULTS: The prevalence rates of asthma ever, wheeze ever, current wheeze, current rhinoconjunctivitis, and current flexural eczema were not significantly different between tuberculin positive and negative subjects. The mean (SE) tuberculin response was 3.4 (0.2) mm in atopic subjects and 3.3 (0.2) mm in non-atopic subjects (difference not significant). Logistic regression analyses did not reveal any significant relationship between asthma ever, current wheeze, atopy, and positive tuberculin responses. CONCLUSIONS: This study did not find any relationship between asthma, allergic symptoms, atopy, and positive tuberculin reactivity in Chinese schoolchildren vaccinated with BCG at birth.

Asthma↗
PubMed2001

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

BACKGROUND: An 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 having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. METHODS: Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. RESULTS: The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. CONCLUSIONS: The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.

Adolescent↗
PubMed2003

Asthma and atopy in overweight children.

BACKGROUND: Obesity may be associated with an increase in asthma and atopy in children. If so, the effect could be due to an effect of obesity on lung volume and thus airway hyperresponsiveness. METHODS: Data from 5993 caucasian children aged 7-12 years from seven epidemiological studies performed in NSW were analysed. Subjects were included if data were available for height, weight, age, skin prick test results to a common panel of aeroallergens, and a measure of airway responsiveness. History of doctor diagnosed asthma, wheeze, cough, and medication use was obtained by questionnaire. Recent asthma was defined as a doctor diagnosis of asthma ever and wheeze in the last 12 months. Body mass index (BMI) percentiles, divided into quintiles per year age, were used as a measure of standardised weight. Dose response ratio (DRR) was used as a measure of airway responsiveness. Airway hyperresponsiveness was defined as a DRR of >/=8.1. Adjusted odds ratios were obtained by logistic regression. RESULTS: After adjusting for atopy, sex, age, smoking and family history, BMI was a significant risk factor for wheeze ever (OR = 1.06, p = 0.007) and cough (OR = 1.08, p = 0.001), but not for recent asthma (OR = 1.02, p = 0.43) or airway hyperresponsiveness (OR = 0.97 p = 0.17). In girls a higher BMI was significantly associated with higher prevalence of atopy (chi(2) trend 7.9, p = 0.005), wheeze ever (chi(2) trend 10.4, p = 0.001), and cough (chi(2) trend 12.3, p<0.001). These were not significant in boys. CONCLUSIONS: Higher BMI is a risk factor for atopy, wheeze ever, and cough in girls only. Higher BMI is not a risk factor for asthma or airway hyperresponsiveness in either boys or girls.

Analysis of Variance↗
PubMed2003

Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study.

BACKGROUND: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. METHOD: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). RESULTS: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). CONCLUSION: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.

Allergens↗
PubMed1997

Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood.

BACKGROUND: There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood. METHOD: In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined. RESULTS: Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity). CONCLUSIONS: Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.

Adolescent↗
PubMed2006

Non classical HLA genes and non-HLA genes in a population of infants at familial risk of atopy.

AIM: We investigated on parental history and IgE serum level in 2588 consecutive newborns to individuate babies "at risk" of atopy at birth and we analysed the polymorphisms of class III region to evaluate the association with immunogenetic markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE receptor (FCERB1) physiologically related gene polymorphisms. RESULT: 791 babies/2588 (30.6%) were considered "at risk" for atopy and followed-up: 400 had familial history of atopy (at least one parent or sibling), 256 had IgE >0.35 kUA/l at birth and during the follow-up and 135 were positive for both conditions. The allele C4B2 was significantly more frequent in the sample of babies at risk (22.1% vs 10%, p< 0.001). Furthermore, the mean value of IgE at birth in babies carrying the allele C4B2 was 2.26 KUA/l versus 0.74 KUA/l in those not carrying this allele (p=0.01). No significant association emerged for RAGE at the centromeric end of class III region and for LTA, TNFA at the telomeric one. TNFRI, TNFRII and FCERB1 gene polymorphisms also seemed not implicated. CONCLUSION: Our study confirms that HLA class III region seems involved in familial predisposition to atopy, and C4B gene probably acts as a marker of a more restricted subregion.

Female↗
PubMedDate not supplied

Is enhanced fetal growth a risk factor for the development of atopy or asthma?

BACKGROUND: The aetiological factors underlying the worldwide increase in the prevalence of asthma and the international patterns of the prevalence of asthma are not well understood. This has led to consideration of factors such as fetomaternal health which may programme the initial susceptibility to allergic sensitisation, or contribute to the development of asthma independently of sensitisation. METHODS: A number of epidemiological studies have examined the relationship between birth anthropometric measures (as a marker of fetomaternal health) and the subsequent development of asthma and atopy in childhood or adult life. RESULTS: Some, but not all of these studies have reported a relationship between enhanced fetal growth and an increased risk of asthma and/or atopy. CONCLUSION: These findings raise the hypothesis that factors responsible for fetal growth may also lead to programming of the developing respiratory or immune systems, predisposing to the subsequent development of asthma and/or atopy. This hypothesis may explain, in part, the increasing prevalence of asthma and atopy over recent decades, which has occurred concurrently with secular trends for improved fetomaternal health, as measured by anthropometric measurements at birth.

Adult↗
PubMed1994

Respiratory symptoms, bronchial responsiveness, and atopy in Fijian and Indian children.

Hospital admission rates for asthma in the 5 to 14 yr age group are three times higher in Fiji Indians than in Melanesian Fijians. Conversely, admission rates for pneumonia are three times higher for Fijians than Indians. To determine the prevalence of respiratory symptoms, bronchial hyperresponsiveness, and atopy, a questionnaire in three languages was distributed to 2,173 Suva City school children (mean age 9.6 yr), half of whom were sampled for histamine inhalation and skin-prick allergen tests. Prevalence of wheeze in the previous 12 mo was identical in both ethnic groups (20.6%). Productive cough was more common in Fijians (29%) than Indians (17%, p < 0.0001). Bronchial hyperresponsiveness was twice as common in Indians (30%) as Fijians (15%), relative risk 2.1 (95% confidence interval [CI]: 1.5 to 2.8), p < 0.0001. The combination of current wheeze and bronchial hyperresponsiveness was found in nearly three times as many Indian children (11.3%) as Fijians (4.0%), and the mean bronchial dose-response slope to histamine was steeper in Indians than Fijians. Prevalence of atopy was similar in Fijians (36%) and Indians (38%). Wheeze was significantly associated with atopy and a steeper dose-response slope to histamine, but productive cough was not. Indians may have more severe asthma than Fijians due to genetic or environmental factors acting independently of atopy. The higher prevalence of productive cough in Fijians is consistent with a greater burden of respiratory infection, and is associated with domestic crowding.

Asthma↗
PubMed1997

Atopy, asthma, and emphysema in patients with severe alpha-1-antitrypysin deficiency.

Bronchial asthma is characterized by episodic airway obstruction and associated with wheezing, a bronchodilator response, an elevation in total serum IgE, and atopy. To determine whether asthma is more common in subjects with severe alpha 1-antitrypsin deficiency (alpha 1-ATD) and airway obstruction, we compared 38 patients who had this condition (Group 1) with 22 control patients with chronic obstructive pulmonary disease (COPD) (Group 2) and with five subjects with alpha 1-ATD and normal spirometry (Group 3). Subjects were evaluated with a symptom questionnaire, pulmonary function testing, intradermal allergen testing, and serum IgE measurement. Self-reported wheezing was a common symptom in all patient groups, but attacks of wheezing with dyspnea were significantly more common in Group 1. Of those patients with airway obstruction, more than 50% showed a bronchodilator response whether suffering from alpha 1-ATD or not. Atopy was more common in Group 1 than in Group 2 (48% versus 27%). Mean serum IgE for all groups was similar but significantly greater in patients with atopy. We estimated the prevalence of asthma in the study groups on the basis of the criteria of attacks of wheezing, reversible airway obstruction, atopy, and that increased IgE. The proportion of patients with asthma in Group 1 was significantly greater than that in Group 2 (22% versus 5%, p < 0.05). Our study shows that with control for the degree of airway obstruction, asthma, as defined, is more common in patients with alpha 1-ATD than in those without it. We suggest that a lack of alpha 1-AT in airways increases the propensity to develop asthma.

Adult↗
PubMed1999

Asthma, wheezy bronchitis, and atopy across two generations.

Although the prevalence of asthma has risen significantly during the last 30 yr, it is not clear whether this has occurred primarily in persons with a strong genetic predisposition to asthma and atopy or in other sections of the population. We have investigated outcomes in children of nuclear families selected through probands previously characterized by studies in 1964 and 1989 as having histories of persistent childhood onset atopic asthma, transient childhood wheezy bronchitis, and no respiratory symptoms or atopy. Children of wheezy bronchitic probands had a significantly better symptomatic outcome in adolescence, irrespective of the atopic status of the parent proband, than do children of either asthmatic or asymptomatic probands, suggesting that this may be a syndrome that shows familial aggregation and is distinct from asthma. Total serum IgE levels were significantly lower in children of nonatopic asymptomatic probands, including those with wheezing symptoms. In contrast children of nonatopic asymptomatic probands had an unexpectedly high prevalence of wheezing (33%), positive skin prick tests (56%), and positive specific serum IgE to common allergens (48%) that was similar to that found in children of atopic asthmatic probands. Our findings support the concept that wheezy bronchitis is a separate syndrome from atopic asthma. High total serum IgE levels within our population appear to be an important marker of genetic predisposition to atopy. Our data also suggest that much of the increase in asthma prevalence is associated with specific IgE sensitization and is occurring in persons previously considered to be at low risk of developing asthma or atopy.

Adolescent↗
PubMed2000

Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma. Increased IFN-gamma-producing CD8(+) T cells in asthma.

Atopy is characterized by an immune system that is biased to T helper cell, type 2 (Th2) activation. This condition predisposes to asthma, a disease in which a Th2 activation was found in blood and lungs. However, most blood studies have considered purified cells, which might give an incomplete view of immune reactions. In this study, we assessed in whole blood cultures the Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asthmatics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control subjects) were included in this study. Interleukin-4 (IL-4), interferon gamma (IFN-gamma), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN-gamma were detected in T cells and CD8(+) T cells by flow cytometry. Atopy was characterized by a higher production of IL-4, which was correlated to total IgE levels, and by an impairment of the T-cell capacity to produce IFN-gamma. This impairment was correlated to the number of positive skin tests. In asthma, the overproduction of IL-4 was still found if atopy was present. Unexpectedly, an overproduction of IFN-gamma was found, which was related to an increased capacity of CD8(+) T cells to produce IFN-gamma. The number of IFN-gamma-producing CD8(+) T cells was related to asthma severity, to bronchial hyperresponsiveness, and to blood eosinophilia. In addition, this number was correlated to IL-12 production. These results show that in addition to the well-known Th2 inflammation in asthma, there are IFN-gamma-producing CD8(+) T cells in the blood, possibly controlled by IL-12.

Adult↗
PubMed2000

Linkage analysis of markers on chromosome 11q13 with asthma and atopy in a United Kingdom population.

Previous studies have suggested that atopy is linked to the beta chain of the high affinity IgE receptor (Fcepsilon R1-beta) on chromosome 11q13. Fcepsilon R1-beta polymorphisms, I181L, V183L, and E237G, are reported to be associated with asthma and atopy. The aim of this study was to investigate linkage to Fcepsilon R1-beta in a UK population and to assess the frequency of the polymorphisms and their association with asthma and atopy. A sample of 131 families was recruited at random with a sample of 109 families ascertained via an asthmatic proband. Each subject completed a written and video-assisted questionnaire and underwent bronchial challenge and skin prick testing. Serum total and specific IgE levels were measured. Quantitative scores were derived for asthma and atopy using principal component analysis. Four microsatellite markers were genotyped, including Fcepsilon R1-beta. The frequency of the I181L and V183L polymorphisms were determined by sequencing, and the E237G polymorphism was determined using the amplification refractory mutation system. We found no evidence for linkage to Fcepsilon R1-beta and only weak evidence for linkage to the less informative marker E237G. We found no examples of the I181L/V183L polymorphism in our population sample. Our study has failed to strengthen the evidence for a candidate gene on chromosome 11q13.

Adult↗
PubMed2001

Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland.

Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.

Adolescent↗
PubMed1985

The relationship of respiratory infections in early childhood to the occurrence of increased levels of bronchial responsiveness and atopy.

We assessed the relationship of antecedent acute respiratory illness to the occurrence of airway responsiveness and atopy in a population-based cohort of 194 children 12 to 16 yr of age from East Boston, Massachusetts. A history of croup or bronchiolitis as reported by their parents was determined at study onset when the children were 5 to 9 yr of age. During the second and third years of the study, acute respiratory illness was assessed. Five years after the prospective respiratory illness assessment, airway responsiveness was evaluated with eucapneic hyperpnea to subfreezing air, and atopy was evaluated with skin tests to 4 environmental antigens. Both a prior history of croup of bronchiolitis (OR = 2.29, p = 0.04) and greater than 2 acute lower respiratory illnesses (OR = 3.72, p = 0.012) were associated with increased levels of airway responsiveness. Neither index of respiratory illness experience was related to the presence of atopy. However, maternal cigarette smoking was significantly associated with atopy in these children (OR = 2.24, p = 0.02). These data suggest that respiratory illness in early life is associated with airway hyperresponsiveness as measured later in childhood. The data further suggest the need for longitudinal studies to better assess the etiologic role of these potential risk factors.

Adolescent↗
PubMed2003

Age-specific relationship between CD14 and atopy in a cohort assessed from age 8 to 25 years.

CD14 influences postnatal switching of T helper cell responses. CD14 C-159T has been associated with altered CD14 and IgE levels in cross-sectional studies. Identifying whether associations vary with age requires data from children of the same age followed longitudinally over many years. In this study, an unselected population with extensive longitudinal data was used to test the hypothesis that CD14 C-159T was associated with early-onset atopy. A total of 305 subjects were assessed on up to seven occasions between ages 8 and 25 years by questionnaire, histamine challenge, and skin prick test. For atopy, airway hyperresponsiveness (AHR), and wheeze, each subject was classified as having early onset, late onset, or no disease onset during follow-up. Compared with subjects with -159CT and -159TT, subjects with -159CC had an odds ratio of 2.2 (p = 0.018) for early-onset atopy and an odds ratio of 2.6 (p = 0.019) for early-onset AHR. Cross-sectional analysis showed increased prevalence of -159CC in subjects with atopy and AHR in childhood but not adulthood. These data suggest that the influence of CD14 -159C on the atopic phenotype may be age specific, exerting an effect during midchildhood, which is no longer apparent by early adulthood.

Adolescent↗
PubMed2001

Symptoms of asthma, bronchial responsiveness and atopy in immigrants and emigrants in Europe. European Community Respiratory Health Survey.

Migration studies on asthma may provide information on its environmental causes. The European Community Respiratory Health Survey has potential advantages due to the number of countries involved, standardized collection of information, assessment of directionality of migration, and availability of physiological data on bronchial responsiveness and atopy. Prevalence rates of symptoms associated with asthma were compared for immigrants, emigrants and nonmigrants living in centres mostly in western Europe. Similar analyses were carried out for bronchial responsiveness (provocative concentration causing a 20% fall in forced expiratory volume in one second and slope) and atopy. Medication and use of health services were also explored. Overall, 1,678 (8.6%) of 19,516 participants were immigrants in the 18 countries participating in the study, of whom 581 were emigrants from one of the participating countries. Rates of asthma symptoms were higher in immigrants (odds ratio (OR): 1.21, 95% confidence interval (CI): 1.00-1.51) and emigrants (OR: 1.31, 95% CI: 0.96-1.51) compared to nonmigrants after controlling for area, sex, age and smoking status. However, bronchial responsiveness and atopy were equally distributed between immigrants, emigrants and nonmigrants. Use of health services was observed to be similar in migrants and nonmigrants with asthma. In the European Community Respiratory Health Survey, migrants reported more asthma symptoms, but had similar bronchial responsiveness, atopy, and use of health services when compared with the nonmigrant population.

Adult↗
PubMed2001

Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence.

There is increasing evidence from epidemiological studies to support the "hygiene hypothesis" with regard to the development of allergic diseases. This review will discuss the epidemiological findings relating to atopy and asthma, separately. The strongest arguments in favour of the "hygiene hypothesis" are the findings relating early life day care attendance to a significantly reduced risk of atopy and asthma, and the strong link between sibship size and the occurrence of atopy as confirmed by numerous studies. Furthermore, data relating serological immune responses to certain infections such as hepatitis A and Toxoplasma gondii suggest a role for such infections, or alternatively the lack of hygiene, to be operative in the inhibition of the development of allergic immune responses. The effects described seem to be stronger for atopy than for asthma. Furthermore, biological plausibility for such a hypothesis can be found from findings of recent in vitro studies and from animal experiments. Epidemiological studies attempting to identify single infections as being harmful or beneficial could fail, because it may be the total burden of microbial stimuli rather than a certain infection that directs the maturing immune system into a Th1-type T-helper cell polarized response. The timing of the exposure seems to be essential for promoting beneficial or harmful effects, and may provide a "window of opportunity".

Agriculture↗