Showing papers by "Allan Linneberg published in 2008"

Prevalence of self-reported symptoms and consequences related to inhalation of airborne chemicals in a Danish general population

Abstract: To estimate the prevalence and consequences of self-reported symptoms related to inhalation of airborne chemicals in a Danish general population. A random sample of 18–69-year-old individuals (n = 6,000) was drawn from the Danish Civil Registration System. A questionnaire on self-reported symptoms related to inhalation of 11 categories of airborne chemicals was mailed to the population. Respondents who reported symptoms received an additional questionnaire to verify the reported symptoms and to characterise factors related to the initial onset of symptoms. The response rate to the primary questionnaire was 71%. A total of 1,134 individuals (27%, 95% CI 25–28) reported symptoms related to inhalation of airborne chemicals, 141 individuals (3.3%, 95% CI 2.8–3.9) reported adjustments of social life or occupational conditions due to symptoms, whereas 20 individuals (0.5%, 95% CI 0.3–0.7) had made adjustments of both social life and occupational conditions. Women reported more exposures as annoying than men and had more symptoms related to inhalation of airborne chemicals (P < 0.001). However, sex had no effect on the reporting of adjustments of social life or occupational conditions (P = 0.54). Symptoms related to inhalation of airborne chemicals were common in this general population, and a minority reported that these symptoms affected social life or occupational conditions. Women as compared to men reported more symptoms but not adjustments of social life or occupational conditions.

Association of obesity and insulin resistance with asthma and aeroallergen sensitization.

Abstract: Background: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization. Methods: Cross-sectional population-based study of 3609 Danish men and women aged 30–60 years. Aeroallergen sensitization was defined as positive levels of specific IgE against a panel of inhalant allergens. Asthma was defined as self-reported physician diagnosed asthma. Allergic asthma was defined as the presence of both asthma and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses. Results: Obesity was associated with increased risk of aeroallergen sensitization as well as allergic and nonallergic asthma. Insulin resistance was asssociated with aeroallergen sensitization and allergic asthma, but not nonallergic asthma. The associations of obesity with aeroallegen sensitization and allergic asthma became nonsignificant after adjustment for insulin resistance, whereas the association of obesity with nonallergic asthma was unaffected. No sex-differences were observed. Conclusion: Obesity may be related to an increased risk of aeroallergen sensitization and allergic asthma through mechanisms also involved in the development of insulin resistance.

Sero-epidemiology as a tool to study the incidence of Salmonella infections in humans.

Abstract: Although most foodborne infections are undiagnosed, the incidence of these infections is usually calculated from reported cases. We present a novel population-based method to estimate the incidence of non-typhoid Salmonella infections. From 154 patients with confirmed Salmonella serotype Enteritidis infection, we determined the kinetics of the antibody response. The estimated mean responses for the three classes of serum antibodies were combined such that the time from infection could be estimated from antibody measurements. Next, serum samples collected in 1983, 1986, 1992, and 1999 from the general population were analysed for antibodies. We demonstrated how these measurements can be translated into an estimate of the general incidence. Based on serology markers there were 13 exposures leading to seroresponse of Salmonella Enteritidis/1000 person-years in 1983; the similar number in 1999 was 217. This trend confirms the increase in the number of culture-confirmed cases reported to the national surveillance system.

The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors.

Abstract: Background: Genetic variation in ethanol metabolism may have an influence on both alcohol drinking habits and the susceptibility to health effects of alcohol drinking. Such influences are likely to bias exposure-disease associations in epidemiologic studies of health effects of alcohol drinking. In a Caucasian population, we examined the association of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genetic variants with alcohol drinking habits, biomarkers of alcohol exposure, and risk factors for cardiovascular disease. Methods: The study population consisted of 1,216 Danish men and women aged 15–77 years participating in a health examination in 1998. The health examination included a self-administered questionnaire (alcohol drinking habits), a physical examination (blood pressure), and various blood tests [alanine aminotransferase (ALAT), erythrocyte mean corpuscular volume (E-MCV), and lipids]. ADH and ALDH gene variants were determined by standard techniques. Data were analyzed by regression analyses adjusted for relevant confounders. Results: Self-reported alcohol drinking was significantly associated with increasing levels of ALAT, E-MCV, high-density lipoprotein cholesterol, and blood pressure. The ALDH1b ala69val variant was associated with nondrinking and total alcohol intake. The ALDH2 promoter variant was associated with binge-drinking, and the ALDH1b1 ala69val polymorphism was associated with diastolic blood pressure. We did not find any statistically significant interactions between any of the gene variants and alcohol consumption in relation to the various outcomes. Conclusions: In this Caucasian population sample, we found evidence to support that genetic variation in ethanol metabolism may influence drinking habits, but no statistically significant gene-environment interactions. More large-scale epidemiologic studies are needed to confirm theses results and to further investigate genetic susceptibility to the effects of alcohol drinking.

Alcohol consumption and the risk of self‐reported perennial and seasonal allergic rhinitis in young adult women in a population‐based cohort study

Abstract: BACKGROUND: Alcohol consumption has been suggested to be associated with the development of allergic rhinitis (AR), but there is limited data on the topic. OBJECTIVES: The objective of this study was to investigate the association between alcohol consumption and the risk of developing AR among young women. METHODS: Five thousand eight hundred and seventy Danish women aged 20-29 years participated in a prospective cohort study, and were free of seasonal and perennial AR at baseline (1991-1993). Alcohol consumption was assessed by a food frequency questionnaire. The main outcome measures were self-reported information on seasonal and perennial AR debuting during a mean follow-up period of 7.8 years. RESULTS: During follow-up, 831 women developed seasonal AR and 523 women developed perennial AR, corresponding to 14% and 9%. Alcohol consumption was positively associated with the risk of developing perennial AR. The adjusted odds ratio (OR) for perennial AR was 1.78 (95% CI, 1.13-2.80) among women drinking more than 14 drinks/week compared with women drinking <1 drink/week. There was no association between alcohol consumption and seasonal AR. Having one or two parents with asthma was, after adjustment, significantly associated with the risk of developing seasonal (OR, 2.01; 95% CI, 1.65-2.45) and perennial AR (OR, 2.28; 95% CI, 1.70-2.74). Smoking was not associated with an increased risk of developing AR. CONCLUSION: In this population of young adult women, alcohol consumption was associated with an increased risk of developing perennial AR.

Are we getting enough allergens

Abstract: This paper proposes that reduced allergen exposure is one of the factors underlying the higher risk of IgE-mediated allergic disease in populations with an urbanized, westernized, and affluent lifestyle. This lower allergen exposure results in the failure to induce and maintain immune tolerance to common environmental allergens. The paper summarizes different lines of evidence that may support or contradict this hypothesis and points to areas where more knowledge is needed.

Interference of cross-reactive carbohydrates in the determination of specific IgE in alcohol drinkers and strategies to minimize it: the example of latex.

Abstract: Background: Cross-reactive carbohydrate determinants (CCDs) are N-glycans in plant and invertebrate proteins that interfere with specific IgE determinations. The prevalence of IgE to Man2XylFucGlcNAc2 (MUXF), the CCD from bromelain, may be increased in heavy drinkers. Objective: To further investigate the relationship of alcohol consumption to CCD specific IgE. Latex was used as an example for investigating CCD interference with in vitro allergy testing and how to minimize the interference by using nonglycosylated recombinant allergens and inhibition assays. Methods: We determined the levels of IgE to CCD markers (MUXF and ascorbate oxidase) and natural rubber latex in 270 adults without a history of latex allergy (73 abstainers or occasional drinkers, 76 light drinkers, 47 moderate drinkers, and 74 heavy drinkers). In cases with latex reactivity, we performed inhibition assays with MUXF and screened for IgE to a panel of recombinant latex allergens. Fourteen-day serologic follow-up was available for a subset of individuals. Results: Moderate to heavy drinkers displayed an increased prevalence of IgE to CCD markers. The presence of CCD specific IgE was closely associated with latex IgE reactivity. Inhibition studies and the absence of reactivity to nonglycosylated recombinant latex allergens indicated CCD interference in latex IgE determinations. Serum levels of specific IgE decreased with alcohol abstention. Conclusions: In this population, alcohol consumption is associated with an increased prevalence of IgE reactivity to natural rubber latex due to CCD interference. The use of nonglycosylated recombinant allergens and inhibition assays may help to minimize CCD interference in populations in which IgE to CCDs is common. Ann Allergy Asthma Immunol. 2008;101:394–401.

The allergic march in early childhood and beyond

Abstract: Atopy is defined as a personal and/or a familial tendency to become sensitized and produce IgE antibodies in response to ordinary exposures to allergens, usually proteins [1]. As a consequence, these persons can develop typical symptoms of asthma, rhinoconjunctivitis, eczema and food allergy. Atopy may thus be viewed as a risk factor or an intermediate phenotype of these atopic (or allergic) diseases. The prevalence of allergic diseases has increased in developed countries and this trend is supported by documented increases in objectively measured atopy [2]. The incidence of atopic eczema and food allergy seems to peak already within the first 2 years of life, and these infants are at increased risk of later manifestations of allergic disease such as asthma and allergic rhinitis. This phenomenon of switching from one clinical manifestation of allergy to another is often referred to as ‘The allergic march’. Knowledge about the natural (or spontaneous) course of atopy and its relation to the manifestations of allergic disease is important in risk stratification of patients and may further provide clues to the causes of the allergy epidemic as well as increased insights into the mechanisms underlying the development of disease. This knowledge is best obtained by longitudinal studies of general populations. In this issue of Clinical and Experimental Allergy, Asarnoj et al. present important data on the development of sensitization (serum allergen-specific IgE) during early childhood (from 4 to 8 years of age) from a population-based birth cohort study: the BAMSE birth cohort [3]. They report a remarkably high incidence of IgE sensitization to inhalant allergens during this period of life, adding fuel to the continuation of the allergic march beyond early childhood. The high incidence and the persistence of sensitization resulted in a marked increase in the prevalence of sensitization to inhalant allergens from 15% to 25% over this 4-year period. The persistence of sensitization was generally high for all inhalant allergens [3]. For example, 97% of children sensitized to birch pollen at 4 years of age were still sensitized to birch pollen at 8 years, i.e. a remission rate of 3%. This is a remarkably low remission rate emphasizing the persistent nature of IgE sensitization to inhalant allergens in this period of life. From a biological point of view, the ‘true’ remission rate may be even lower, because measurement error and seasonal variation in levels of serum-specific IgE are likely to decrease the reproducibility of test results. There is evidence that the persistent nature of IgE sensitization to inhalant allergens goes beyond early childhood. Thus, Rhodes et al. performed repeated follow-ups including measurement of sensitization from birth to 22 years of age in a high-risk birth cohort [4]. The prevalence of IgE sensitization to inhalants continued to increase over the whole time span, supporting both the high incidence and the chronic nature of inhalant sensitization up to the age of 22 years. Even in much older populations, the remission of sensitization to inhalant allergens appears to be low. In a prospective study of a general population of 18–69 year olds, the 8-year remission rates of serumspecific IgE sensitization to pollen allergens and dust mite/ pet allergens were 6% and 11%, respectively [5]. The rates of remission for specific allergens are shown in Table 1. The 8-year remission rate for grass pollen sensitization in this adult population was 12%, which was remarkably similar to the 4-year remission rate for grass pollen sensitization observed in the much younger BAMSE cohort (13%). Hence, although we need more data on the natural course of atopy and its clinical manifestations, it is becoming clear that inhalant sensitization is more persistent than previously recognized. In contrast to the persistent nature of sensitization to inhalant allergens, food allergen sensitization tends to be more transient. The incidence of food sensitization peaks during infancy, while the incidence of inhalant sensitization peaks later in childhood. In the German Multicenter Correspondence: Allan Linneberg, Research Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark, 57 Nordre Ringvej, Building 84/85, DK-2600 Glostrup, Denmark. E-mail: alli@glo.regionh.dk Cite this as: A. Linneberg, Clinical and Experimental Allergy, 2008 (38) 1419–1421. Clinical and Experimental Allergy, 38, 1419–1421 doi: 10.1111/j.1365-2222.2008.03063.x

The association between alcohol consumption and biomarkers of alcohol exposure with total serum immunoglobulin E levels.

Abstract: Background: A number of studies have shown that self-reported alcohol intake is positively associated with total serum immunoglobin E (IgE) levels. The purpose of the present study was to investigate the association of self-reported alcohol consumption and different biomarkers of alcohol exposure to total serum IgE levels in a general adult population. Methods: A total of 3,443 subjects aged 20 to 79 years from the population-based cross-sectional Study of Health in Pomerania (SHIP) were included in the analyses. Information on alcohol consumption and serum carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), aspartate-amino transferase (ASAT), andalanine-amino transferase (ALAT) levels were measured. Multivariable linear regression models were performed separately in atopic and nonatopic subjects. Results: In nonatopic subjects positive associations between self-reported alcohol consumption as well as all considered biomarkers of alcohol exposure and total serum IgE levels were found. Further the results also suggested positive associations between alcohol consumption as well as alcohol biomarkers and total serum IgE level in atopic subjects, even though not all tests for linear trend reached statistical significance. Conclusions: In conclusion, biomarkers of alcohol exposure were positively associated with total serum IgE levels supporting that the positive association between self-reported alcohol intake and IgE levels observed in previous studies is real and not due to misclassification of alcohol intake or confounding by other factors that may be linked to both alcohol intake and total serum IgE levels.

Effects of alcohol consumption on the allergen-specific immune response in mice.

Abstract: Background: There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization. Objective: To investigate the effects of alcohol consumption on the allergen-specific immune response in mice. Methods: BALB/cJBomTac mice were immunized intraperitoneally with ovalbumin (OVA) using a low dose sensitization protocol. Throughout the experiment, mice were kept on isocalorical liquid diets containing 0 to 6.2% ethanol. Evaluation of immunomodulatory effects of ethanol was based on measurements of total serum IgE, as well as OVA-specific IgE, IgG1, and IgG2a. Furthermore, levels of OVA-induced interleukin (IL)-4 and interferon-γ were determined in ex vivo splenocyte cultures. Results: Alcohol intake decreased the level of OVA-specific IgG2a in a dose-dependent manner, whereas high levels of alcohol markedly increased the level of total IgE, but not OVA-specific IgE. Th1 suppression was supported by the cytokine profile. Conclusions: Alcohol consumption induced a marked decrease in markers of the Th1-type allergen-specific immune response and an increase in total serum IgE. In this model, there was no effect of alcohol on OVA-specific IgE. Studies using other routes of immunization may be warranted.

Analysis of heterogeneity and epistasis in physiological mixed populations by combined structural equation modelling and latent class analysis.

Abstract: Biological systems are interacting, molecular networks in which genetic variation contributes to phenotypic heterogeneity. This heterogeneity is traditionally modelled as a dichotomous trait (e.g. affected vs. non-affected). This is far too simplistic considering the complexity and genetic variations of such networks. In this study on type 2 diabetes mellitus, heterogeneity was resolved in a latent class framework combined with structural equation modelling using phenotypic indicators of distinct physiological processes. We modelled the clinical condition "the metabolic syndrome", which is known to be a heterogeneous and polygenic condition with a clinical endpoint (type 2 diabetes mellitus). In the model presented here, genetic factors were not included and no genetic model is assumed except that genes operate in networks. The impact of stratification of the study population on genetic interaction was demonstrated by analysis of several genes previously associated with the metabolic syndrome and type 2 diabetes mellitus. The analysis revealed the existence of 19 distinct subpopulations with a different propensity to develop diabetes mellitus within a large healthy study population. The allocation of subjects into subpopulations was highly accurate with an entropy measure of nearly 0.9. Although very few gene variants were directly associated with metabolic syndrome in the total study sample, almost one third of all possible epistatic interactions were highly significant. In particular, the number of interactions increased after stratifying the study population, suggesting that interactions are masked in heterogenous populations. In addition, the genetic variance increased by an average of 35-fold when analysed in the subpopulations. The major conclusions from this study are that the likelihood of detecting true association between genetic variants and complex traits increases tremendously when studied in physiological homogenous subpopulations and on inclusion of epistasis in the analysis, whereas epistasis (i.e. genetic networks) is ubiquitous and should be the basis in modelling any biological process.

Maternal employment in child-care institutions and the risk of infant wheeze and atopic dermatitis in the offspring

Abstract: It has been proposed that exposure to infections and microbes protects against atopic diseases, but epidemiological data has so far been conflicting. We hypothesized that maternal exposure to infections and microbes before or during pregnancy would be of particular importance. To test this hypothesis, we studied the incidence of wheezing and atopic dermatitis (AD) in infants of mothers employed in child-care institutions - and thus presumably being highly exposed to infections and microbes - compared with infants of mothers not so employed. A total of 31471 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, maternal employment, and other variables were collected by interview at 12 and 30 wk of gestation, and 6 and 18 months of age, and by linkage to the Danish Medical Birth Register and the Child-care Database. The relative risk was estimated in Cox proportional hazard models. Analyses were stratified by sibling status (first born or not), as older siblings are likely to be a significant source of infectious agents. The adjusted relative risks of wheeze, recurrent wheeze and AD was 1.14 (95% CI: 0.96-1.37), 1.37 (95% CI: 1.05-1.77), and 1.03 (95% CI: 0.81-1.31), respectively, for first-born infants of mothers employed in child-care institutions compared with infants of mothers not so employed. There was no effect of maternal employment in child-care institutions among infants with older siblings. In conclusion, the results did not support the hypothesis that maternal microbial exposure before or during pregnancy as reflected by maternal employment in child-care institutions protects the offspring against infant wheeze and AD.

[Methods of first-choice for clinical temperature measurement in Danish hospital wards].

Abstract: Introduction The aim was to investigate the methods of first-choice for clinical temperature measurement in Danish hospital wards. Materials and methods A questionnaire study involving 444 Danish hospital wards specialised in internal medicine, orthopaedic surgery, abdominal surgery or paediatrics. Results 348 hospital wards (78%) responded to the questionnaire. Ear and rectal temperature measurement were the most frequent methods of first-choice in Danish hospital wards (44% and 50%, respectively). There was a statistically significant difference in the method of first-choice between specialties and between the regions of Denmark. Regardless of specialty and region both methods were frequently used as first-choice. Conclusion Our results reflect a lack of consensus on the method of first-choice in daily clinical assessment of temperature in Danish hospital wards.