Tine Halsen Malling

CD4dimCD25bright Treg cell frequencies above a standardized gating threshold are similar in asthmatics and controls

Thymus selected CD4+CD25bright natural regulatory Treg cells expressing FOXP3 may contribute to control of immune responses. No unique markers have been available to identify and characterize Treg. We present a gating strategy that allows enumeration of Treg on the basis of CD4 and CD25 and investigate whether asthmatics have fewer Treg than controls.

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.

Occupational COPD among Danish never-smokers: a population-based study

Occupational exposures have been shown to be risk factors for chronic obstructive pulmonary disease (COPD) among never-smokers. In a Danish population-based cohort, we analysed this association and the population attributable fraction. The study population (N=1575) was aged 45–84, COPD was defined by lung function measurements and the method of lower limit of normal (LLN), and occupational exposure was assessed by questionnaire and expert judgement. Furthermore, the estimates additionally were provided according to the Global Initiative for Chronic Obstructive Lung Diseases. More than a threefold increased risk (LLN OR=3.69 (95% CI 1.36 to 10.04) was found for occupational exposure to vapour, gas, dust and fumes (predominantly organic dust) in this never-smoking population, with a corresponding 48% (95% CI 30% to 65%) population attributable fraction among never-smokers.

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.

Occupational Chronic Obstructive Pulmonary Disease in a Danish Population-Based Study

Abstract The aim was to explore the impact of occupation on chronic obstructive pulmonary disease (COPD) in a cross-sectional population-based study among subjects aged 45 to 84 years. In a stratified sampling 89 general practitioners practices (GPP) in Denmark recruited 3106 males and 1636 females through the Danish Civil Registration System. COPD was defined by spirometry by the 2.5th-centile Lower Limit of Normal of FEV1 and FEV1/FVC. Information about smoking, occupational exposure and the respective occupations were obtained from questionnaires. Occupations followed the Danish adaptation of The International Standard Classification of Occupations, revision 1988 (DISCO-88). Exposure to vapour, gas, dust (organic and inorganic), and fume (VGDF) in each occupation (yes/no) was evaluated by two independent specialist in occupational medicine. Exposures were divided in no, low, medium, and high exposure as 0, <5, 5–14, and ≥ 15 years in the job, respectively. Data was analysed by a mixed random effect logistic regression model. The age-standardised COPD study prevalence was 5.0%. Of 372 DISCO-88 codes 72 were identified with relevant exposure to VGDF. 46% of the participants reported at least one occupation with VGDF exposure. Adjusted for smoking, age, sex, and GPP a dose-dependent association of COPD was found among workers in jobs with high organic dust exposure, with OR 1.56 (95% CI 1.09–2.24). Restricted to agriculture the OR was 1.59 (95% CI: 1.08–2.33). No association was observed for workers in jobs with inorganic dust, fume/gas, or vapour exposures. In summary, occupational organic dust exposure was associated to the prevalence of COPD.

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.

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.

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

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

Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes, Scand. J. Clin. Lab. Invest. (2009) (1)

Gender difference in GPX1-activity was fi rst reported among the 295 subjects to be 3.7 (95% CI: 2.0–5.5) U/g protein. In subjects recruited as random sample the difference in activity was 3.6 (95% CI: 1.2–6.0) U/g protein. Association between GPX1 activity and selenium in males was still signifi cant when restricted to subjects recruited as random sample The difference in GPX1 activity per Δ 10 μg/L serum selenium was 2.5 U/g protein (95% CI: 1.1–3.9). Adjusted for smoking the corresponding difference was 2.3 U/g protein (95% CI: 0.8–3.7). Figure 1 presents the combined effects of sex, genotype, and smoking status (current smokers vs. former or never smokers) on GPX1 activity in subjects recruited as random sample as it should have been presented. Discussion