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PubMed1997

Neonates at risk of atopy show impaired production of interferon-gamma after stimulation with bacterial products (LPS and SEE)

Recent studies demonstrate reduced interferon-gamma (IFN-gamma) secretion in neonates who became atopic later in life. The underlying pathomechanism is still unknown. We therefore examined the effects of bacterial products on neonatal IFN-gamma production acting through different T-cell- or antigen-presenting-cell (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a combination of both and restimulated with PMA and ionomycin. LPS and SEE as single stimuli induced IFN-gamma production to the same extent in CBMC of neonates with high and low risk of atopy. In contrast, a combination of LPS and SEE had a multiplying effect on IFN-gamma secretion only in CBMC of neonates with low risk of atopy. Phenotype analysis revealed that only memory T cells showed impaired IFN-gamma synthesis (median 3.6% IFN-gamma-producing cells vs 14.2% in controls: P < 0.01), whereas IFN-gamma production by naive T cells did not differ in either group. Taken together, these results point to the existence of a disturbed function of costimulatory mechanisms in neonates at high risk of atopy, provoking reduced memory T-cell IFN-gamma production.

Antigen Presentation↗
PubMed1998

Atopy and intolerance of antimicrobial drugs increase the risk of reactions to acetaminophen and nimesulide in patients allergic to nonsteroidal anti-inflammatory drugs.

This study evaluated the risk factors for developing allergic reactions to alternative drugs such as acetaminophen and nimesulide in 367 patients intolerant of nonsteroidal anti-inflammatory drugs (NSAID) compared to 243 healthy controls. All subjects were given test doses (TD) of acetaminophen and nimesulide, and age, sex, atopy, and history of reactions also to unrelated drugs were compared in those who reacted and those who were tolerant of the challenge. TD was positive in 49 of 367 (14%) NSAID-allergic patients and in one (0.4%) of the controls (P<0.001). No difference was found in age and sex between the TD-positive and TD-negative subjects, although a significantly larger number of females were NSAID allergic (P<0.01). Of the 367 patients, 208 had a history of reactions only to NSAID, and 148 to NSAID and antimicrobial drugs (AMD). TD with acetaminophen or nimesulide was positive in 6% of patients intolerant only of NSAID and in 24% of those intolerant of both NSAID and AMD, with an odds ratio of 4.82. Atopy was more frequent among patients (36%) than controls (23%) (P=0.004), among TD-positive (51%) than TD-negative patients (33.5%) (P<0.02), and among patients intolerant of NSAID and AMD (48%) than those intolerant only of NSAID (P=0.006). The odds ratios were, respectively, 1.87, 2.57, and 3.16. This study provides evidence that atopy and history of allergic reactions to AMD increase the likelihood of intolerance of usually well-tolerated alternative drugs such as acetaminophen and nimesulide in subjects allergic to NSAID.

Acetaminophen↗
PubMed1994

Immunoglobulin E and G responses to pertussis toxin after booster immunization in relation to atopy, local reactions and aluminium content of the vaccines.

The role of aluminium for IgG and IgE responses to pertussis toxin (PT), as well as for side effects, was investigated in 49 children with known atopy status. Primary immunization had been given with an adsorbed monocomponent or an adsorbed two-component acellular pertussis vaccine. The children were then randomized to receive a booster immunization with either aluminium-adsorbed or non-adsorbed, whole cell, pertussis vaccine. Both vaccines induced good IgG responses with the adsorbed vaccine giving higher post-booster levels (p < 0.05). The adsorbed vaccine was, however, associated with more local side effects (p < 0.05) and tended to induce higher PT-IgE responses than the non-adsorbed vaccine. Furthermore, individuals who had received the two-component vaccine as primary immunization had higher PT-IgE responses after the booster, compared with individuals initially receiving the monocomponent vaccine (p = 0.041). No correlation between PT-IgE and PT-IgG levels was seen in any of the groups. Total serum IgE levels correlated to PT IgE levels, particularly in children with atopy (r = 0.950, p < 0.001). The addition of aluminium to the pertussis vaccine, was, thus, associated with a stronger IgG antibody response, but tended also to induce a stronger IgE antibody response. The correlation between total IgE and PT-IgE, which was most prominent in children with atopy, indicates that the role of immunization for the development of allergy merits further studies.

Adjuvants, Immunologic↗
PubMed1997

Inflammation markers and symptom activity in children with bronchial asthma. Influence of atopy and eczema.

BACKGROUND: Eosinophil cationic protein (ECP) has been reported to reflect the eosinophil inflammatory activity in asthma. However, the relative impact of asthma symptoms and atopic eczema upon serum (s)-ECP in asthmatic children has not been established. OBJECTIVES: To examine s-ECP levels and s-myeloperoxidase (MPO) in relation to asthma symptoms and atopic eczema in asthmatic children. METHODS: S-ECP and s-MPO were assessed in relation to symptom activity, lung function, exercise-induced bronchoconstriction and bronchial responsiveness in 101 children; median age 9 years, range 1-16 years; with moderate to severe asthma, admitted to Voksentoppen Center. RESULTS: S-ECP was significantly higher in children with persistent compared to episodic or no asthma symptoms in the past four weeks. S-ECP was also higher in children with atopic compared to non-atopic asthma, as well as in those with active compared to past history or no history of atopic eczema. S-MPO was higher in children with persistent asthma symptoms, but did not differ in relation to atopy or eczema state. Persistent asthma symptoms had the greatest impact upon s-ECP levels, followed by atopy and active eczema. CONCLUSION: S-ECP may be used in assessing symptom activity in asthmatic children, but with the realisation that active eczema and the presence of atopy may also influence levels.

Adolescent↗
PubMed1997

Genetic factors in lung disease: atopy and bronchial asthma.

Atopy defined as high IgE responsiveness has now been subject to genetic studies at the molecular level owing to the development of a great number of DNA markers over the human genome. Either by linkage analysis or by association study strong candidate genes of atopy have been proposed to be located on chromosome 11q13 and 5q31 where high-affinity IgE Fc receptor beta subunit and allergy-associated cytokines, respectively, have been mapped. Meanwhile, we found a novel association between one of alleles of D11S97, an anonymous DNA marker on 11q13, and high total serum IgE in a large number of Japanese general population and atopic family members. However, failure to replicate linkage or association studies by different investigators suggest polygenic nature of atopy. In addition to the genes regulating IgE synthesis, the requirement of local (pulmonary) genetic factors in the development of bronchial asthma have been speculated. Linkage analysis suggested possible existence of gene(s) regulating susceptibility and/or clinical characteristics of bronchial asthma also on chromosome 5q. One of the candidate is beta 2-adrenergic receptor gene polymorphism. Mutated gene transfection studies suggested functional significance of some polymorphisms and clinical evaluations have revealed their contribution to airway responsiveness and severity of asthma.

Asthma↗
PubMed1994

Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies.

Traits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provides no evidence of imprinting, maternal effect, or a major role of environment shared by sibs. Commingling analysis favours more than one distribution, the upper one being common for asthma and very common for atopy. Segregation analysis of rank-transformed variables provides only equivocal evidence of major genes against a polygenic background but suggests that such genes (if present) are individually common and not of large effect. Segregation analysis under a two-locus model gives consistent results with minimal distributional assumptions. To enter combined segregation analysis we favour a restricted model in which the major locus is additive on the liability scale and the pseudopolygenic modifier locus accounts for at least half the genetic variance. Total IgE and bronchial reactivity are proposed for meta-analysis of atopy and asthma respectively. Genetic analysis of complex inheritance is discussed and it is shown that allelic association with random loci is not a feasible approach.

Adolescent↗
PubMed1998

Atopy and other risk factors for UK dentists reporting an adverse reaction to latex gloves.

A study was conducted to assess the significance of a personal history of atopy and other risk factors for UK dentists reporting an adverse reaction to natural rubber latex (NRL) gloves. 2535 dentists completed a self-administered questionnaire and, of these, 1034 (group 1) reported an adverse reaction to NRL gloves and 1501 (group 2) did not. Risk factors investigated were: sex, years in clinical practice, exposure to gloves and a history of atopy or food allergy. The signs and symptoms reported by group 1 dentists were recorded. Logistic regression analysis was used to identify a set of risk factors that produced the most discrete model for a dentist reporting an adverse reaction to NRL gloves. A personal history of atopy was a significant risk factor. Dentists with a history of eczema and hand eczema in childhood were most likely to report an adverse reaction to NRL gloves.

Adult↗
PubMed1975

Prevalence of atopy and exercise-induced bronchial lability in relatives of patients with cystic fibrosis.

Skin tests and exercise tests were performed on children with cystic fibrosis (CF) and first-degree relatives of CF children. Positive skin tests were found in 56% of patients and 19% of relatives, but the prevalence of atopy in CF patients bore no relationship to its prevalence in their relatives. Increased 0ronchial lability, mainly due to bronchoconstriction, was present in 54% of patients and 27% of relatives. The results showed that increased prevalence of bronchial lability, but not atopy, is found in first-degree relatives of CF children, and that the abnormal lability and atopy found in CF children does not indicate a familial allergic background.

Adolescent↗
PubMed1978

Cystic fibrosis, atopy, and airways lability.

In a survey of cystic fibrosis (CF) in the Avon area, 48 children with CF from 40 families together with 71 of their parents were studied by spirometry, exercise tests, and pinch tests. A control group of 42 young adults was similarly tested; control data for children were taken from previously published work. The prevalence of atopy (any positive prick test) in children with CF was 48%. Sensitivity to grass pollens and house dust mite was no more common in these children (29%) than in a normal population (34%). Hypersensitivity to Aspergillus fumigatus was found in 35% of children with CF and was associated with severe lung disease. The parents had a normal pattern and prevalence of atopy. Exercise-induced airways obstruction was present in only 22% of children with CF; its association with severe lung disease rendered interpretation difficult. The parents had a normal response to exercise. Both hypersensitivity to A. fumigatus and exercise-induced airways lability had the features of acquired characteristics. There was nothing in the present study to support the hypothesis that the possession of a CF gene predisposed to atopy.

Adult↗
PubMed1987

Symptoms, atopy, and bronchial response to methacholine in parents with asthma and their children.

We have studied 50 children with one parent with asthma at a mean age of 6.4 years by symptom questionnaire and performed allergy skin testing and measurement of bronchial responsiveness to methacholine in both parent and child in 29-32 cases. Ninety eight per cent of the parents were receiving medication for asthma. Fifty one per cent had visited their doctor and 20% had taken more than five days off work in the previous 12 months; 12% had been admitted to hospital during the preceding 10 years. In the children the prevalences of wheeze, shortness of breath, and cough were all about double that found in a general population survey of children of similar age. Atopy was present in 90% of parents, but the prevalence of atopy among the children was not significantly different from the children in the general population. Eczema and hay fever, however, had high prevalences of 40% and 24%, respectively. Responsiveness to methacholine (provocation dose achieving 20% fall in forced expiratory volume in one second less than 6.4 mumol) was found in 93% of parents and 45% of children, which is compatible with a large increase compared with the general population. All atopic but only 50% of non-atopic children with symptoms of asthma responded to methacholine. These findings indicate that children who have one parent with asthma have roughly double the chance of developing clinical features of asthma compared with the general population and suggests that, in these children, a causal interaction occurs between atopy and bronchial hyper-responsiveness.

Asthma↗
PubMed2004

Decreased prevalence of atopy in paediatric patients with familial Mediterranean fever.

BACKGROUND: A number of inflammatory diseases, including familial Mediterranean fever (FMF), have been shown to be driven by a strongly dominated Th1 response, whereas the pathogenesis of atopic diseases is associated with a Th2 response. OBJECTIVE: Because dominance of interferon gamma has the potential of inhibiting Th2 type responses-that is, development of allergic disorders, to investigate whether FMF, or mutations of the MEFV gene, have an effect on allergic diseases and atopy that are associated with an increased Th2 activity. METHOD: Sixty children with FMF were questioned about allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis, as were first degree relatives, using the ISAAC Study phase II questionnaire. The ISAAC Study phase II was performed in a similar ethnic group recruited from central Anatolia among 3041 children. The same skin prick test panel used for the ISAAC Study was used to investigate the presence of atopy in patients with FMF and included common allergens. RESULTS: The prevalences of doctor diagnosed asthma, allergic rhinitis, and eczema were 3.3, 1.7, and 3.3%, respectively, in children with FMF, whereas the corresponding prevalences in the ISAAC study were 6.9, 8.2, and 2.2%, respectively. Only the prevalence of allergic rhinitis was significantly different between the two groups (p<0.001). The prevalence of atopy in these patients with FMF (4/60 (7%)) was significantly lower than in the children of the population based study (20.6%) (p<0.001). CONCLUSION: Family Mediterranean fever seems to be protective against development of atopic sensitisation and allergic rhinitis.

Asthma↗
PubMed1998

Occurrence of exercise induced bronchospasm in elite runners: dependence on atopy and exposure to cold air and pollen.

OBJECTIVES: To study factors affecting the occurrence of exercise induced bronchospasm (EIB) in elite runners. METHODS: Fifty eight elite runners, 79% of them belonging to Finnish national teams, volunteered. The athletes answered a questionnaire on respiratory symptoms. Skin prick tests were used to investigate atopy, and spirometry to examine lung function at rest and after an exercise challenge test (ECT) at subzero temperature in the winter and after a similar ECT in the summer at the end of the birch pollen season. RESULTS: Definitive EIB (a post-exercise reduction of 10% or more in forced expiratory volume in one second (FEV1) was observed in five (9%) of the 58 runners. A subgroup consisting of 19 non-atopic symptom-free runners with no family history of asthma was used to establish a normal range for post-exercise reduction in FEV1. When this group's mean exercise induced change in FEV1 minus 2 SDs (a reduction of 6.5% or more in FEV1) was taken as the lower limit of the reference range, 15 (26%) of the runners had probable EIB in either the winter or the pollen season. The occurrence of probable EIB depended on atopy (odds ratio increased with number of positive skin prick test reactions, p < 0.05). Nine (22%) of the 41 runners, challenged in both the winter and the pollen season, had probable EIB only in the winter, and three (7%) had it only in the pollen season. Only one runner (2%) had EIB in both tests. CONCLUSIONS: Mild EIB is common in Finnish elite runners and is strongly associated with atopy. Seasonal variability affects the occurrence of EIB, and thus exercise testing should be performed in both cold winter air and the pollen season to detect EIB in elite runners.

Adult↗
PubMed1985

Interaction of smoking and atopy in producing specific IgE antibody against a hapten protein conjugate.

A survey was carried out of a population of workers exposed to tetrachlorophthalic anhydride, an acid anhydride epoxy resin curing agent known to cause asthma. Using a radioallergosorbent test with a tetrachlorophthalic anhydride human serum albumin conjugate, specific IgE antibody was detected in serum from 24 out of 300 factory floor workers exposed to tetrachlorophthalic anhydride. Of these 24, 20 (83.3%) were current smokers compared with 133 (48.2%) of 276 without antibody (p less than 0.01), and there was a weaker association with atopy, defined by skin tests with common allergens. Smoking and atopy interacted, the prevalence of antibody being 16.1% in atopic smokers, 11.7% in non-atopic smokers, 8.3% in atopic non-smokers, and nil in non-atopic non-smokers (p less than 0.025). Smoking may predispose to, and interact with atopy in, the production of specific IgE antibody to this hapten protein conjugate.

Adult↗
PubMed1995

Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample.

OBJECTIVE: To establish the prevalence of Fc epsilon RI-beta polymorphisms Leu181 and Leu181/Leu183 on chromosome 11q13 in the general population and to examine whether when maternally inherited they confer a risk of atopy. DESIGN: A population based survey for measures of atopy (skin prick test reactions, specific IgE titres, total serum IgE concentration), bronchial hyperresponsiveness, and carriage of Fc epsilon RI-beta Leu181 and Leu181/Leu183. SETTING: The rural coastal town of Busselton, Western Australia. SUBJECTS: 1004 members of 230 two generation families identified through adults aged under 55. RESULTS: Fc epsilon RI-beta Leu181/Leu183 was identified in 45 subjects (4.5%). All 13 children who had inherited the variant maternally were atopic. Six had asthma and nine rhinitis. The odds ratio of a positive skin prick test reaction to house dust mite or grass pollen in these children compared with the other 523 children was 7.37 (95% confidence interval 1.62 to 33.60). The 95% confidence interval for the odds ratio of a positive specific IgE response (radio-allergosorbent test) was 3.00 to infinity, and the odds ratio for bronchial hyperresponsiveness was 3.70 (1.21 to 11.60). By contrast, the eight children who had derived the variant paternally had negative skin prick and radioallergosorbent test results and did not have increased bronchial responsiveness. CONCLUSION: Fc epsilon RI"' beta Leu181/Leu183 when inherited maternally identifies a genetic risk factor for atopy and bronchial hyperresponsiveness.

Adolescent↗
PubMed2000

Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study.

OBJECTIVE: To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. DESIGN: Retrospective case-control study. PARTICIPANTS: 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. SETTING: Air force school in Caserta, Italy. MAIN OUTCOME MEASURES: Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis. RESULTS: Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18% v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0. 70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). CONCLUSION: Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.

Adolescent↗
PubMed1980

Interaction of atopy and exposure to cotton dust in the bronchoconstrictor response.

A survey of 255 workers in four cottonseed crushing mills included a respiratory health questionnaire, allergy skin testing, and measurements of lung function over the Monday working shift. Atopy was defined as having two or more positive weal reactions to common inhalant antigens. Categories of exposure to dust were based on the stage of milling, and one category contained workers with continuous exposure to cotton dust derived from linters, the cotton fibres adherent to cottonseed. Atopy and exposure to dust were found to have significant interaction: large mean declines in FEV1 and FEF 25-75 occurred only in the workers exposed to linter dust who were also atopic. Skin-testing surveys in cotton textile mills have concentrated on specific cotton antigen reactivity and its first-order relations to symptoms. Our results indicate a need to identify atopic workers, and to search for interactions between atopy and other variables that may influence acute changes in expiratory flow rates.

Adult↗
PubMed2005

Maternal age of menarche is not associated with asthma or atopy in prepubertal children.

BACKGROUND: Maternal sex hormones in pregnancy can theoretically influence the developing fetal immune system and modulate the subsequent development of atopic disorders. Early onset of menarche has been linked to increased oestrogen levels in adult women. A study was undertaken to examine the association between early onset menarche in pregnant women and asthma and atopic status of their children at 7 years of age. METHODS: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal birth cohort study in which pregnant women, resident in Avon (UK), were recruited on the basis of an expected date of delivery between 1 April 1991 and 31 December 1992. Maternal age at menarche was assessed from prenatal questionnaires administered to the women. Clinical outcomes in the children were based on mothers' responses to self-completion questionnaires and included asthma, eczema, and hay fever. The atopic status of the child was objectively assessed by skin prick tests to a panel of common aeroallergens at the age of 7 years. Analyses used multivariable logistic regression with a diverse range of possible confounders. RESULTS: Complete data were available on 5765 woman and child pairs. The prevalence of ever reported asthma to 7 years was 20.4%, eczema 58.6%, hay fever 12.1%, and atopy (defined as any positive (>2 mm weal) response) was present in 20.6%. There were no significant differences in mean age of menarche between mothers of children with and without each of the primary outcomes. Adjusted odds ratios (95% CI) for the latest age of menarche (16+ years) compared with the lowest (<12 years) reference group were 1.41 (1.00 to 1.99) for asthma, 0.98 (0.73 to 1.91) for eczema, 0.95 (0.62 to 1.44) for hay fever, and 0.98 (0.68 to 1.42) for atopy. CONCLUSION: No consistent association was found between maternal age at menarche and asthma, eczema, hay fever or atopy in their children during early childhood.

Adolescent↗
PubMed1984

Atopy, immunological changes, and respiratory function in bronchiectasis.

Cystic fibrosis has been reported to be associated with an increased prevalence of atopy and reversible airways obstruction. To determine whether such features can also result from other chronic suppurative lung infections, we studied 23 patients with proved bronchiectasis, and 23 age and sex matched normal controls. A personal or family history of atopy was reported with equal frequency in the two groups. Although the groups displayed a similar prevalence of positive immediate hypersensitivity skinprick test responses, the positive patients reacted to more antigens (p less than 0.05) and had larger weal diameters (p less than 0.01) than the positive controls. Other indices, such as blood eosinophil counts and serum IgE, did not differ significantly. Serum concentrations of immunoglobulins G, A, and M and of the four IgG subclasses tended to be higher in patients than controls, but only in the case of IgA (p less than 0.01) was this difference significant. No case of IgG subclass deficiency was noted. The patients displayed significant airflow obstruction, the mean basal one second forced expiratory volume (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) being 67%, 77%, and 67% of their predicted values. There was evidence of a significant reversible obstructive component in that FEV1 or PEFR or both increased by 15% or more in nine of the 23 patients after inhalation of fenoterol, the mean increases in FEV1, FVC, and PEFR for the whole group being 9.5%, 11%, and 16.9%. These results indicate that while bronchiectasis provokes a hyperimmune response it differs from cystic fibrosis in that there is no significant increase in the prevalence of atopy. The finding of reversible airways obstruction, however, suggests that bronchodilators may be useful adjuncts to treatment.

Adolescent↗