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PubMed1990

Atopy in infancy predicts the severity of bronchial hyperresponsiveness in later childhood.

We have prospectively followed 52 children of atopic parents from birth to age 7 years, documenting clinical atopic disease and allergen skin test reactions. We found bronchial hyperresponsiveness (BHR) to histamine in 13 (25%) of the children at 7 years of age with 25 (48%) being atopic on skin testing and 15 (29%) having current wheeze, whereas 30 children (58%) had wheezed at some time during this period. BHR was significantly associated with wheeze and atopy at 5 and 7 years of age, but not during infancy. The six children with moderate to severe BHR (provocative dose causing a 20% fall in FEV1 less than 0.8 mumol) formed a distinct subgroup with significantly more wheeze and atopy both during infancy and at 5 years of age when these children were compared to children with milder degrees of BHR. The group with moderate to severe BHR also differed significantly from the nonhistamine-reactive group, whereas children with milder degrees of BHR were not significantly different. We conclude that subjects most likely to develop the more severe degrees of BHR during later childhood are children who manifest atopy in infancy.

Aging↗
PubMed1990

Atopy and IgE in patients with leprosy.

The atopic status of patients with leprosy was assessed by medical history, physical examination, serum total IgE, and specific IgE antibodies to common allergens (by skin testing and RAST). Tests for specific IgE antibody to Mycobacterium leprae were performed by RAST and immunoblotting technique. We studied 28 patients with leprosy and 49 control subjects. The two groups did not differ significantly in the prevalence of atopic disease. The IgE level was significantly higher in the patients, however, than in the control subjects, whether there was atopy (296.1 versus 96.3 IU/ml) or not atopy (72.9 versus 18.9 IU/ml). Neither RAST nor immunoblotting technique detected significant levels of IgE antibodies to M. leprae. Our data indicate that leprosy was associated with increased total IgE level, but clinical atopy in patients with leprosy was similar to that in control subjects. The observed IgE increase in patients with leprosy appears to be generally nonspecific.

Adolescent↗
PubMed1994

Total serum IgE and eosinophil count in children with and without a history of asthma, wheezing, or atopy in an urban community in Indonesia. The Respiratory Disease Working Group.

AIM: The objectives of the study were to assess total serum IgE and eosinophil count in a random sample of 20% of the children between 12 and 54 months old in a suburban community of Bandung, Indonesia, and to investigate a possible relationship between these values and atopy, asthma or wheezing and parasite infestation. METHODS: Two hundred sixty-nine children were examined at the Integrated Primary Health Care Unit, and the parents or guardians were interviewed with the use of a standardized questionnaire. RESULTS: The overall median value of IgE was 436 IU/ml (range, 18 to 9707 IU/ml); almost 94% of the children showed an IgE value of more than 100 IU/ml, and 29% showed a value of more than 1000 IU/ml. The median value for eosinophils was 580/mm3 (range, 70 to 5090/mm3); only 31% of the children had less than 400 eosinophils/mm3. IgE levels and eosinophilia were not related to age but showed a significant, although not high, correlation with each other (p < 0.05). In about 36% of the children parasites were demonstrated in a single stool sample; in those subjects eosinophilia and IgE values tended to be greater, but the difference was not significant. About 7% of the children had asthma, and in those subjects the eosinophil counts and IgE levels were much more increased (p < 0.001 and p approximately 0.01, respectively). No difference was found in IgE or eosinophil count in relation to other forms of atopy in the child (milk-induced dermatitis, urticaria, eczema, rhinitis) or in relation to a history of asthma or atopy in other family members. Yet, the occurrence of asthma in the child was significantly related to a history of asthma in other family members. CONCLUSIONS: IgE values and eosinophilia are markedly increased in these children under 5 years of age in Bandung, Indonesia, and the highest values are found in the 7% with asthma.

Asthma↗
PubMed1993

Chromosome 11q13 and atopy underlying atopic eczema.

Genetic linkage has been reported between atopic respiratory disease and chromosome site 11q13. We recruited 95 multiplex families through probands with active atopic eczema. Linkage analyses between atopy and markers on 11q13 excluded a major susceptibility locus for atopy in this region. Nor was there significant deviation from the expected proportions of alleles shared by affected sib-pairs. When we analysed families according to parental atopic phenotype, we observed a positive lod score (0.8) in 19 families with unaffected fathers, in contrast to markedly negative scores for other combinations of affected parental phenotype. The possibility of a maternal influence on the inheritance of atopy cannot, therefore, be excluded.

Adult↗
PubMed2004

Immunization and atopy: possible implications of ethnicity.

The possible effects of immunization on subsequent development of asthma and atopy remains a matter of controversy. Although some studies have suggested that immunization might increase the risk for atopic disease, a number of studies have found no association or have even reported a protective effect for immunization against atopy. Recent studies have provided evidence that ethnicity might affect the susceptibility to the immunomodulatory effects of vaccination. In this review the association between immunization and atopy and the effect of ethnicity on this association are briefly outlined. The focus will be particularly on BCG vaccination.

Adjuvants, Immunologic↗
PubMed2004

Can bacterial endotoxin exposure reverse atopy and atopic disease?

Studies have shown that endotoxin exposure in childhood is associated with a reduced risk of atopy and atopic asthma. It is commonly assumed that these effects only occur in early life. However, recent epidemiologic studies suggest that immune deviation might take place throughout life. Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of atopic sensitization and disease at any time throughout life but might also reverse this process. This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone. In addition, some animal studies demonstrated the potential of endotoxin to downregulate pre-existing airway eosinophilia and hyperreactivity. However, there is currently little direct evidence that endotoxin might reverse atopy and allergic diseases. Observational studies and randomized trials to test this hypothesis could ultimately lead to the development of novel treatments for atopic diseases, such as allergic asthma, hay fever, and eczema.

Bronchial Hyperreactivity↗
PubMed2004

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.

Adult↗
PubMed2005

Duration of postviral airway hyperresponsiveness in children with asthma: effect of atopy.

BACKGROUND: Respiratory viruses induce asthma exacerbations and airway hyperresponsiveness (AHR). Atopy is an important risk factor for asthma persistence. OBJECTIVE: We sought to evaluate whether atopy is a risk factor for prolonged AHR after upper respiratory tract infections (URIs). METHODS: Twenty-five children (13 atopic and 12 nonatopic children) with intermittent virus-induced asthma were studied. Clinical evaluation, skin prick tests, methacholine bronchoprovocation, questionnaires, and a nasal wash specimen were obtained at baseline. For 9 months, subjects completed diary cards with respiratory symptoms. During their first reported cold, a nasal wash specimen was obtained. Methacholine provocation was performed 10 days and 5, 7, 9, and 11 weeks later. In case a new cold developed, the provocation schedule was followed from the beginning. RESULTS: Viruses were detected in 17 (68%) of 25 patients during their first cold, with rhinovirus being most commonly identified (82%). AHR increased significantly 10 days after the URI, equally in both groups (P = .67), and remained so up to the fifth week. Duration of AHR in subjects experiencing a single URI ranged from 5 to 11 weeks, without a significant difference between groups. In the duration of the study, atopic children experienced more colds and asthma exacerbations than nonatopic children. Thus for duration of AHR, significant prolongation was noted in the atopic group when assessed cumulatively. CONCLUSION: In asthmatic children the duration of AHR after a single natural cold is 5 to 11 weeks. However, an increased rate of symptomatic cold and asthma episodes in atopic children is associated with considerable cumulative prolongation of AHR, which might help explain the role of atopy as a risk factor for asthma persistence.

Asthma↗
PubMed2005

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

BACKGROUND: A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma. OBJECTIVES: To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk. METHODS: We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif). RESULTS: ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027). CONCLUSION: Variation in arginase genes may contribute to asthma and atopy in children.

Adolescent↗
PubMed2006

Influence of dog ownership and high endotoxin on wheezing and atopy during infancy.

BACKGROUND: Increased exposure to microbial products early in life may protect from development of atopic disorders in childhood. Few studies have examined the relationship of endotoxin exposure and pet ownership on atopy and wheezing during infancy. OBJECTIVE: Evaluate relationships among high endotoxin exposure, pet ownership, atopy, and wheezing in high-risk infants. METHODS: Infants (n = 532; mean age, 12.5 +/- 0.8 months) with at least 1 parent with confirmed atopy were recruited. A complete medical history and skin prick testing to foods and aeroallergens were performed at age 1 year. House dust samples were analyzed for endotoxin. RESULTS: Prevalences of wheezing were not independently associated with dog or cat ownership or endotoxin levels. Percutaneous reactivity to at least 1 allergen was observed in 28.6% of infants. Univariate analyses showed significant associations of any wheezing, recurrent wheezing, and recurrent wheezing with an event with daycare attendance, number of siblings, respiratory infections, maternal smoking, and history of parental asthma. Logistic regression adjusting for the latter variables showed that recurrent wheezing (odds ratio, 0.4; 95% CI, 0.1-0.9) as well as 2 other wheeze outcomes were significantly reduced in homes with high endotoxin exposure in the presence of 2 or more dogs. CONCLUSION: Pet ownership or endotoxin did not independently modify aeroallergen sensitization or wheezing during infancy. However, high endotoxin exposure in the presence of multiple dogs was associated with reduced wheezing in infants. CLINICAL IMPLICATIONS: A home environment with many dogs and high levels of endotoxin may be conducive to reduced wheezing in infancy.

Allergens↗
PubMed2005

Prevalence of allergic bronchopulmonary aspergillosis in cystic fibrosis in an area with a high frequency of atopy.

BACKGROUND: Lower airway colonisation with Aspergillus fumigatus and the complicating hypersensitivity reaction allergic bronchopulmonary aspergillosis (ABPA) is well recognised in patients with cystic fibrosis (CF). There is a wide range in reported prevalence of ABPA in CF. Differences in predisposing factors such as atopy and climatic humidity, but also differences in reporting may in part explain this observation. In the Australian population there is a high frequency of atopy and the climate is relatively humid. PATIENTS AND METHODS: Children and adolescents with CF (n = 277) from the CF Clinic, Children's Hospital at Westmead, Sydney, Australia were included in a retrospectively conducted study of Aspergillus colonisation and ABPA (1998-2003). RESULTS: The prevalence of Aspergillus colonised patients increased significantly from 7.4% in 1998 to 18.8% in 2002. No seasonal variation in initial positive Aspergillus culture or in humidity was observed. A total of 13 patients (4.7%) were diagnosed with ABPA over the study period, with a significant increase in prevalence from 0.3% in 1998 to 4.0% in 2002. In addition, the criteria used for reporting ABPA in the study population were in agreement with the recently published diagnostic criteria for ABPA in CF. CONCLUSIONS: In spite of a high frequency of atopy and a relatively humid climate in the Sydney area, Aspergillus colonisation and ABPA in CF patients was not disproportionate. Moreover, criteria for reporting of ABPA in this setting was not different from that in the Northern Hemisphere.

Adolescent↗
PubMed1999

Atopy, the use of condoms, and a history of cesarean delivery: potential predisposing factors for latex sensitization in pregnant women.

OBJECTIVE: Our purpose was to assess the prevalence of latex sensitization among women admitted for delivery and the relevant risk factors. STUDY DESIGN: In a prospective study 333 consecutive patients admitted for delivery were screened for specific immunoglobulin E antibodies to latex and for atopic status. A questionnaire was filled in and included questions about the obstetric and surgical history, known contact with latex, and previous use of condoms. RESULTS: Nine of 333 (2.7%) women showed latex-specific immunoglobulin E. All 9 women had atopy (100% vs 26. 2% in the latex-negative group; P <.00001). Of 8 patients with specific immunoglobulin E who gave details about the use of condoms, 6 had had frequent contact with latex condoms (75% vs 51%). Previous cesarean delivery was more frequent in latex-sensitized patients (33% vs 8.4%; P <.05), whereas previous pregnancies, previous deliveries, and total number of operations had no influence. CONCLUSION: Given a prevalence of 2.7% of latex sensitization, all obstetric patients should be questioned about known immediate allergic reaction to latex, a predisposition to atopy, previous intra-abdominal operations, and the regular use of condoms in the past. Patients with atopy and additive risk factors should be treated in a latex-free environment.

Adolescent↗
PubMed1999

Reduced expression of hemopoietic cytokine receptors on cord blood progenitor cells in neonates at risk for atopy.

BACKGROUND: Recent findings point to an association between allergic asthma in adults and increased responsiveness of myeloid progenitor cells to certain hemopoietic growth factors. However, it is not clear at what age these changes in progenitor cells first become manifest, although increasing evidence suggests that the allergic phenotype may begin to emerge in very early life. OBJECTIVE: We sought to compare expression of hemopoietic cytokine receptors on CD34(+) progenitor cells in cord blood from normal infants ("low risk" for subsequent atopy) and infants with at least one atopic first degree relative ("at risk" for subsequent atopy). METHODS: Cord blood was obtained from 21 neonates. Nonadherent mononuclear cells were stained with mAbs directed against CD45, CD34, and the alpha-chains of the GM-CSF, IL-3, and IL-5 receptors and analyzed by flow cytometry. RESULTS: No differences in absolute CD34(+) numbers were observed between the 2 groups. However, expression of GM-CSF receptor on CD34(+) cells was reduced in the "at-risk" compared with the "low- risk" group (P =.021), although no significant differences were noted between the 2 groups with respect to IL-3 and IL-5 receptor expression. CONCLUSION: The functional sequelae of reduced GM-CSF receptor expression on CD34(+) cells remain to be determined. Nonetheless, these findings show an association between genetic risk for atopy and changes in the expression of hemopoietic cytokine receptors on cord blood progenitor cells and support the notion that the allergic phenotype may begin to evolve in the perinatal period.

Adult↗
PubMed2000

Delta 32 deletion of CCR5 gene and association with asthma or atopy.

The CCR5-delta32 deletion polymorphism (CCR5-delta32) was investigated for linkage and association to asthma and atopy using two panels of nuclear families containing 1284 individuals. No statistically significant linkage to asthma/wheeze or atopy was observed in either of the two panels of families. Multiallelic transmission disequilibrium tests (TDT) of the combined data found no significant association for atopy (52 independent alleles transmitted, 51 non-transmitted) or asthma/wheeze (39 transmitted, 44 non-transmitted). Although functional evidence might suggest that CCR5 is a good candidate gene for atopic asthma, this study provides no genetic evidence from CCR5-delta32 polymorphism to support this hypothesis.

Alleles↗
PubMed2002

Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study.

BACKGROUND: Breastfeeding is widely advocated to reduce risk of atopy and asthma, but the evidence for such an effect is conflicting. We aimed to assess long-term outcomes of asthma and atopy related to breastfeeding in a New Zealand birth cohort. METHODS: Our cohort consisted of 1037 of 1139 children born in Dunedin, New Zealand, between April, 1972, and March, 1973, and residing in Otago province at age 3 years. Children were assessed every 2-5 years from ages 9 to 26 years with respiratory questionnaires, pulmonary function, bronchial challenge, and allergy skin tests. History of breastfeeding had been independently recorded in early childhood. FINDINGS: 504 (49%) of 1037 eligible children were breastfed (4 weeks or longer) and 533 (51%) were not. More children who were breastfed were atopic at all ages from 13 to 21 years to cats (p=0.0001), house dust mites (p=0.0010), and grass pollen (p<0.0001) than those who were not. More children who were breastfed reported current asthma at each assessment between age 9 (p=0.0008) and 26 years (p=0.0008) than those who were not. Breastfeeding effects were not affected by parental history of hayfever or asthma. Multifactor analysis controlling for socioeconomic status, parental smoking, birth order, and use of sheepskin bedding in infancy, showed odds ratios of 1.94 (95% CI 1.42-2.65, p<0.0001) for any allergen positive at age 13 years, 2.40 (1.36-4.26, p=0.0003) for current asthma at 9 years, and 1.83 (1.35-2.47, p<0.0001) for current asthma at 9-26 years by repeated-measures analysis. INTERPRETATION: Breastfeeding does not protect children against atopy and asthma and may even increase the risk.

Adult↗
PubMed1996

Measles and atopy in Guinea-Bissau.

BACKGROUND: Epidemiological studies have led to speculation that infections in early childhood may prevent allergic sensitisation but evidence to support this hypothesis is lacking. We investigated whether measles infection protects against the development of atopy in children of Guinea-Bissau, West Africa. METHODS: We conducted a historical cohort study in Bandim, a semi-rural district of Bissau, the capital of Guinea-Bissau. 395 young adults, first surveyed in 1978-80 aged 0-6 years, were followed up in 1994. Our analyses were restricted to 262 individuals still living in Bandim for whom a measles history, documented in childhood, was judged to be reliable. We defined atopy as skin-prick test positivity (> or = 3 mm weal) to one or more of seven allergens. FINDINGS: 17 (12.8 percent) of 133 participants who had had measles infection were atopic compared with 33 (25.6 percent) of 129 of those who had been vaccinated and not had measles (odds ratio, adjusted for potential confounding variables 0.36 [95 percent CI 0.17-0.78], p=O.O1). Participants who had been breastfed for more than a year were less likely to have a positive skin test to housedust mite. After adjustment for breastfeeding and other variables, measles infection was associated with a large reduction in the risk of skin-prick test positivity to housedust mite (odds ratio for Dermatophagoides pteronyssinus 0.20 [0.05-0.81], p=0.02; D farinae 0.20 [0.06-0.71], p=0.01). INTERPRETATION: Measles infection may prevent the development of atopy in African children.

Allergens↗
PubMed1999

Definition of human interleukin-4 receptor alpha chain haplotypes and allelic association with atopy markers.

Cumulative evidence indicates that the human interleukin-4 receptor alpha chain gene (IL-4Ralpha, CD124) is highly polymorphic in contrast to other cytokine receptor genes. Our group recently identified the IL-4Ralpha variant R551 as being strongly associated with decreased kidney allograft survival. Due to the key immunoregulatory role of IL-4 and controversial reports on the association of IL-4Ralpha variants with atopy, we present here the development of polymerase chain reaction-primer sets for sequence-specific amplification of all seven hitherto described amino acid polymorphisms, and we investigated 158 blood donors prospectively. By using an Expectation-Maximization algorithm, we calculated the presence of 11 putative human IL-4Ralpha haplotypes and identified 4 putative IL-4Ralpha haplotypes with a cumulative frequency of >90%. None of the polymorphisms showed a significant association with the phenotype atopy. All mutant alleles showed a trend toward decreased total IgE levels. This association was only significant (p < 0.05; Mann-Whitney U-test) for the A375, R406, and P478 variants in non-atopic blood-donors (n = 90), presumably due to the high variance of IgE levels among the smaller group of atopic individuals. We postulate that IL-4Ralpha mutations are associated to different extents with a decrease in function of the receptor but do not present a major atopy locus.

Adult↗
PubMed1997

[Relation between asthma and atopy markers in children and young adults].

The aim of this study was to assess whether atopy, measured as total IgE level (IgEt) and/or skin test (ST) reactivity is related to bronchial asthma in the same way in children and young adults. Three hundred fifty-three children between 11 and 15 years of age (mean 12.6 years) and 208 adults between 20 and 44 years old (mean 32.1 years) were selected randomly as representative of persons living in the city of Huelva (Spain). All subjects filled out a questionnaire on respiratory symptoms (The European Community Respiratory Health Survey--[ECRHS]) and were given a methacholine challenge test (MT) with results expressed as PD20 as well as IgEt and ST assessments of atopy. We defined bronchial asthma as the association of having experienced wheezing within the last 12 months and having a positive ST. Among children, 4.5% suffered bronchial asthma. Among adults the proportion was 5.3%. The IgEt value that best discriminated between asthmatics and non asthmatics was 145.5 U/ml in children (sensitivity 75% and specificity 69.1%) and 96.6 U/ml in adults (sensitivity 90.9% and specificity 73.6%). A logarithmic transformation (log IgEt) was used to study the relation between bronchial asthma and IgEt. By simple analysis, IgEt and ST were related to bronchial asthma in children (p = 0.002 and p < 0.0001, respectively), while only IgEt (p < 0.001) was related in adults. By multiple regression analysis, controlling for both factors simultaneously as well as for smoking in adults, we found that ST (p = 0.023) but not IgEt was related in children, whereas IgEt (p = 0.0005) but not ST was related in adults. We conclude that the two markers of atopy studied are related to bronchial asthma differently and have different manifestations at different stages of life. ST is more useful in children, whereas IgE determination is of more use in adults.

Adolescent↗