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. F 2 -isoprostane levels before asthma onset were not different between cases and control subjects. Doubling of a-tocopherol concentrations and PAF-AH activity was associated with 50 and 37% decreased risk of incident asthma (a-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, a-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.

The R213G polymorphism in SOD3 protects against allergic airway inflammation

“…Variability in the effect of MnTE-2-PyP on TSLP and IL-33 levels suggests that it may have different control mechanisms and perhaps work at different stages of asthma sensitization and development. Whether EC-SOD mimetics could be used as novel therapies for allergy-induced asthma remains to be shown, but airway antioxidants (ascorbate, α-tocopherol) have been reported to be low in asthma patients (53).…”

Interaction of vitamin E isoforms on asthma and allergic airway disease

“…First, in the Shanghai Women’s Asthma and Allergy Study, the only known study designed and powered to investigate the association of antioxidant defences on adult incident asthma, we assessed the interaction between α-tocopherol and γ-tocopherol in this population-based asthma incidence cohort on asthma risk. 12 Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. The detailed methods of these studies are included in the online supplementary material.…”

Platelets in the immune response: Revisiting platelet-activating factor in anaphylaxis

“…A study of patients with adult-onset asthma correlated higher PAF-AH activity with decreased development of asthma. 109 The effect of dietary antioxidants on PAF signaling is also being explored. In healthy volunteers healthy dietary patterns and dietary antioxidant intake were inversely correlated with serum PAF and PAF synthetic enzyme levels, suggesting the potential for dietary influences on PAF levels.…”