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.
Malling
Tine Halsen
TH
Department of Occupational Medicine, Aalborg Hospital, Denmark. t.malling@rn.dk <t.malling@rn.dk>
Sigsgaard
Torben
T
Andersen
Helle R
HR
Deguchi
Yoji
Y
Brandslund
Ivan
I
Skadhauge
Lars
L
Thomsen
Gert
G
Baelum
Jesper
J
Sherson
David
D
Omland
Oyvind
O
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000276:immunology / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000276:immunology / Q000378:metabolism; D005980:Glutathione Reductase / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D012307:Risk Factors; D012643:Selenium / Q000097:blood / Q000276:immunology; D012727:Sex Characteristics; D013482:Superoxide Dismutase / Q000276:immunology / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D012643:Selenium