Lars Skadhauge

Intake of Paracetamol and Risk of Asthma in Adults

Intake of paracetamol has been associated with development of asthma. The aim of this study was to address a possible association between intake of paracetamol and risk of adult-onset asthma. Using a multidisciplinary postal questionnaire survey concerning health and lifestyle we prospectively studied 19,349 adult twins enrolled in the nationwide Danish Twin Registry. There was a higher prevalence of new-onset asthma in subjects who reported frequent intake of paracetamol at baseline compared with subjects without this determinant (12.0% vs. 4.3%), OR = 3.03 (1.51–6.11), p = 0.005. The result remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema, and intake of medications other than paracetamol, OR = 2.16 (1.03–4.53), p = 0.041. Frequent intake of paracetamol is an independent risk factor for adult-onset asthma.

Consequences of asthma on job absenteeism and job retention

Aims: Various social and economic effects are associated with asthma. This quantitative study describes the effects of current asthma on work life evaluated from the number of weeks receiving transfer incomes. Methods: The study population comprised 7,241 persons answering the ECRHS II screening questionnaire, which was sent to a random age and gender stratified sample of 10,000 persons aged 20 to 44 years. Participants with current asthma were identified by positive answers to a set of validated questions. Transfer incomes for a five-year period were registered from a study-independent national database, which collects all public administered transfer incomes in Denmark. The numbers of weeks receiving unemployment, welfare, sick-leave and disability benefits were identified for each participant and differences between asthmatics and non-asthmatics were analyzed. Results: Asthmatics had significantly more annual weeks receiving welfare (36.6 vs. 20.7, p=0.00), sick leave (9.2 vs. 6.6, p=0.00) and disability (19.3 vs. 11.4, p=0.00) benefits than non-asthmatics. Adult-onset asthmatics had increased prevalence rate ratios for disability of 2.40 (95% confidence interval 1.70–3.40). Blue collar work significantly increased the probability of all public transfer incomes. Conclusions: Current asthma makes it harder to keep a job. Adult-onset asthmatics and blue collar workers are particularly affected.

Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes

Objective. Glutathione peroxidase 1 (GPX1) is one of the major oxidative enzymes. Our aim was to characterize factors influencing its activity and to determine whether or not the activity is associated with asthma. Material and methods. Serum selenium concentration was measured, GPX1 polymorphisms were genotyped and smoking history was obtained in a Danish population‐derived case‐base cohort of 1,191 subjects designed to evaluate risk factors for asthma. GPX1 activity was measured in 134 male and 164 female subjects equally distributed according to genotype of GPX1. Among these subjects, 82 (28 %) had doctor‐diagnosed asthma. Results. The average serum selenium concentration was too low for optimal enzyme activity (mean (SE), 83.4 (0.76) ng/mL). GPX1 activity in men was lower than in women, 52.6 (0.66) and 56.4 (0.59) U/g protein, respectively (p<0.001). In men, activity was positively associated with serum selenium concentration (p = 0.005) and negatively associated with both active smoking (p = 0.009) and exposure to environmental tobacco smoke (p = 0.02). In women, activity was associated with genotypes with 59.2 (1.4), 56.0 (1.4) and 54.2 (1.4) U/g protein in the homozygote wild‐type, the heterozygote and the homozygote variant type, respectively (p = 0.001). Doctor‐diagnosed asthma was unrelated to GPX1 activity in either sex. Conclusion. Determinants for activity in the oxidative enzyme GPX1 show marked differences between the sexes, but the activity is not associated with asthma. Sex ought to be taken into consideration when analysing the activity of the enzyme.

Differences in associations between markers of antioxidative defense and asthma are sex specific

BACKGROUND Lungs are exposed to high levels of oxygen, air pollutants, and smoke, all of which stimulate the production of reactive oxygen species (ROS). In addition, inflammatory cells produce ROS, and thus there may be increased demand for antioxidants, including antioxidant enzymes, in inflammatory lung diseases such as asthma. Sex-specific differences have been noted for asthma, which in postpubertal subjects is predominantly found in females. These sex-specific differences may be associated with differences on the molecular level as well. OBJECTIVE The aim of this cross-sectional study was to examine associations between markers of antioxidative defense and asthma, and to investigate whether these associations were different between women and men. METHODS Based on the European Community Respiratory Health Survey protocol, subjects were enrolled in a study of asthma risk factors. The multicenter study was conducted in 5 west Danish counties between 2003 and 2006, and the subjects were recruited as a case-enriched random sample of 10,000 Danish inhabitants aged 20 to 44 years selected by their civil registration number. Participants were identified by positive answers to asthma questions on a screening questionnaire, random sampling, or both. Serum selenium concentrations and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase [GPX], glutathione reductase [GR], and glucose-6-phosphate dehydrogenase [G6PD]) in erythrocytes were measured. Asthma was defined as either current asthma symptoms with bronchial hyperresponsiveness (BHR) or a continuous asthma score based on 8 questions. RESULTS A total of 1191 mostly white women and men (mean [SD] age, 34.0 [7.1] and 35.1 [7.1] years, respectively) were enrolled in the study. Current asthma symptoms were present in 29.9% (200/670) of women and 22.5% (117/521) of men, with women reporting more positive answers (51.1% vs 40.9%, respectively; P < 0.01) to asthma questions. Serum selenium concentrations were measured in 1151 subjects (640 women, 511 men), and antioxidant enzyme activities were measured in 295 subjects (161 women, 134 men). Women had higher enzyme activities of most antioxidant enzymes (GPX, P = 0.006; GR, P < 0.001; and G6PD, P = 0.009) than did men. Although the serum selenium concentration was inversely associated with asthma in both sexes, there was a female preponderance, with 3.5% lower serum selenium in subjects with current asthma symptoms with BHR (n = 77) compared with controls (n = 287). GR activity was associated with asthma in men, with 5.7% higher enzyme activity in subjects with current asthma symptoms with BHR (n = 14) compared with controls (n = 77). However, a significant interaction with gender was observed for analyses of GR (P = 0.02), but not for analyses of selenium. CONCLUSIONS In this study of asthma risk factors, women had higher levels of enzyme activities than did men in a randomly selected Danish population, and sex-specific differences were found in the associations between markers of antioxidative defense and asthma.

Regular use of non-steroidal anti-inflammatory drugs increases the risk of adult-onset asthma: a population-based follow-up study

Background:  Little is known about the relation between regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and the risk of asthma at the population level. The aim of this study was to examine a possible association between intake of NSAIDs and risk of adult‐onset asthma.

Genetic polymorphisms in antioxidative enzymes are associated to forced expiratory volume in 1 s (FEV1) in smokers independently of asthma.

Introduction:  In this study, we hypothesised that the genotypes coding for low antioxidative enzyme activity are associated with asthma and reduced lung function.

Are allergen batch differences and the use of double skin prick test important

BackgroundSkin prick tests (SPT) are widely used both in clinical diagnostics and in research. The standardization of allergen extracts is well documented to be crucial for the validity of SPT, whereas less emphasis has been placed on reproducibility and the SPT procedure itself. The objectives of this study are to clarify how the double skin prick test procedure influence the sensitivity and specificity of the test and to analyse the differences in weal size in skin prick tests between two batches of allergen extracts from the same vendor.MethodsThe association between rhinitis and SPT was assessed among 1135 persons from a general population sample. SPT was performed twice with 10 common aeroallergens. In a subsample of 90 persons SPT was performed simultaneously with five of the allergens using different batches.ResultsThirty percent had at least one positive SPT. Among asthmatics this number was 62%. Only minor differences were seen between the sizes of two weals from the same batch. A second SPT with the same batch did not change the association between rhinitis and sensitization. When performing SPT with two different batches disagreement was observed in 2% (Birch) to 11% (Cat) of the subjects.ConclusionsPerforming SPT twice with the same allergen batch does not enhance the validity of the test, and value of double testing can be questioned. Considerable differences in SPT response with different batches from the same manufacturer were observed. Thus inter batch differences in allergen extracts might be a source of variability.

Maternal occupational exposure to asthmogens during pregnancy and risk of asthma in 7-year-old children: a cohort study

Objectives The objective of this study was to examine whether maternal exposure to asthmogens during pregnancy is associated with the development of asthma in 7-year-old Danish children, taking atopic status and sex into consideration. Design The study is a prospective follow-up of a birth cohort. Setting and participants A total of 41 724 women and their children from The Danish National Birth Cohort were categorised according to maternal occupational exposure. Exposure information was obtained by combining job title in pregnancy and 18 months after pregnancy with a commonly used asthma Job Exposure Matrix. Primary and secondary outcome measures Primary outcome was parent-reported asthma among their 7-year-old children in an internet-based questionnaire. Secondary outcome was asthma among the same children with or without atopic dermatitis and among boys and girls, respectively. Results Prenatal exposure to low molecular weight (LMW) agents was borderline associated with asthma in children with OR 1.17 (0.95 to 1.44) for children with atopic dermatitis and 1.10 (0.98 to 1.22) for children without. Maternal postnatal exposure was associated with asthma (OR 1.15 (1.04 to 1.28). After mutual adjustment,postnatal exposure (OR 1.13 (0.99 to 1.29) and the combined effects of prenatal and postnatal exposure (OR 1.34 (1.19 to 1.51)) seem to increase the risk of asthma in children. No significant associations were observed for other prenatal or postnatal exposures. The gender of the child did not modify the aforementioned associations. Conclusions Maternal occupational exposures during pregnancy do not seem to be a substantial risk factor for the development of asthma in 7-year-old children. Maternal prenatal and postnatal exposures to LMW agents may predispose the propensity of the children to develop asthma. Future studies should prioritise the characterisation of the timing of exposure in relation to the birth.

Occupational exposure during pregnancy and the risk of hay fever in 7-year-old children

The prevalence of allergic diseases including hay fever has increased in the last decades, especially in Westernised countries. The aim of this study was to analyse whether occupational exposure during pregnancy is associated with development of hay fever in 7‐year‐old Danish children.

Risk factors for incident asthma and COPD in a cohort of young adults

The aim of the study was to describe potential shared risk factors for incident asthma and COPD in a population‐based, 9‐year follow‐up study.