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New Risk Factors for Adult Onset Incident Asthma: A Nested Case Control Study of Host Antioxidant Defense.


AUTHORS

Larkin EK , Gao YT , Gebretsadik T , Hartman TJ , Wu P , Wen W , Yang G , Bai C , Jin M , Roberts Ii LJ , Gross M , Shu XO , Hartert TV , . American journal of respiratory and critical care medicine. 2014 11 19; ().

ABSTRACT

Rationale: Host antioxidant defense, consisting of enzymatic antioxidant activity and non-enzymatic antioxidant micronutrients, is implicated in asthma pathogenesis. Studies of antioxidant defense and adult incident asthma have either used measures of antioxidants estimated from questionnaires or not considered enzymatic aspects of host defense. Objective: We conducted the first study designed and powered to investigate the association of antioxidant defenses on adult incident asthma. Methods: In a nested case-control study, we followed Shanghai women (ages 40-70) without prevalent asthma at baseline, over eight years. Incident asthmatics were ascertained prospectively by gold standard testing of symptomatic women and matched to two asymptomatic controls. Measurements: Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthins, carotenes, and lycopene) and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured from samples collected prior to disease onset. Main Results: Among 65,372 women, 150 (0.24%) developed asthma. F2-isoprostane levels prior to asthma onset were not different between cases and controls. Doubling of α-tocopherol concentrations and PAF-AH activity was associated with 50% and 37% decreased risk of incident asthma (adjusted OR; 95% confidence interval [OR; 95%CI], α-tocopherol OR= 0.52; 95%CI: 0.32-0.84; PAF-AH OR=0.63; 95%CI:0.42-0.93). Conclusions: In this prospective study α-tocopherol, within normal reference ranges, and PAF-AH enzymatic activity, were associated with decreased asthma development. These modifiable risk factors may be an effective strategy to test for primary asthma prevention.


Rationale: Host antioxidant defense, consisting of enzymatic antioxidant activity and non-enzymatic antioxidant micronutrients, is implicated in asthma pathogenesis. Studies of antioxidant defense and adult incident asthma have either used measures of antioxidants estimated from questionnaires or not considered enzymatic aspects of host defense. Objective: We conducted the first study designed and powered to investigate the association of antioxidant defenses on adult incident asthma. Methods: In a nested case-control study, we followed Shanghai women (ages 40-70) without prevalent asthma at baseline, over eight years. Incident asthmatics were ascertained prospectively by gold standard testing of symptomatic women and matched to two asymptomatic controls. Measurements: Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthins, carotenes, and lycopene) and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured from samples collected prior to disease onset. Main Results: Among 65,372 women, 150 (0.24%) developed asthma. F2-isoprostane levels prior to asthma onset were not different between cases and controls. Doubling of α-tocopherol concentrations and PAF-AH activity was associated with 50% and 37% decreased risk of incident asthma (adjusted OR; 95% confidence interval [OR; 95%CI], α-tocopherol OR= 0.52; 95%CI: 0.32-0.84; PAF-AH OR=0.63; 95%CI:0.42-0.93). Conclusions: In this prospective study α-tocopherol, within normal reference ranges, and PAF-AH enzymatic activity, were associated with decreased asthma development. These modifiable risk factors may be an effective strategy to test for primary asthma prevention.


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