New risk factors for adult-onset incident asthma. A nested case-control study of host antioxidant defense

Abstract

Rationale: Host antioxidant defense, consisting of enzymatic antioxidant activity and nonenzymatic 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.

Objectives: 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 (aged 40-70 years) without prevalent asthma at baseline, over 8 years. Subjects with incident asthma were ascertained prospectively by gold standard testing of symptomatic women and matched to two asymptomatic control subjects.

Measurements and main results: Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthines, carotenes, and lycopene), and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured from samples collected before disease onset. Among 65,372 women, 150 (0.24%) developed asthma. F2-isoprostane levels before asthma onset were not different between cases and control subjects. Doubling of α-tocopherol concentrations and PAF-AH activity was associated with 50 and 37% decreased risk of incident asthma (α-tocopherol: adjusted odds ratio = 0.52; 95% confidence interval, 0.32-0.84; PAF-AH: adjusted odds ratio = 0.63; 95% confidence interval, 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.

Keywords: antioxidants; asthma; incidence study; platelet-activating factor acetylhydrolase; α-tocopherol.

Figure 1.

Flow diagram of participants through enrollment, screening, and asthma identification phases of the Shanghai Women’s Asthma and Allergy Study (SWAAS), 2003 to 2009, Shanghai, China.

Figure 2.

Adjusted odds ratios (ORs) for association between asthma and antioxidant concentrations and antioxidant enzyme activity in the Shanghai Women’s Asthma and Allergy Study (2003–2009), matched case–control study. Conditional multivariable logistic regression was used including covariates: any exercise in past 5 years, workplace smoking exposure (yes/no), and vitamin supplement use (yes/no). *Zeaxanthin demonstrates a nonlinear association that is presented in the online supplement (Figure E8). ORs are based on a twofold biomarker increase. PAF-AH = platelet-activating factor acetylhydrolase; SOD = superoxide dismutase.