Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma

Abstract

Dietary antioxidants are important in protecting against oxidative stress. We have previously demonstrated that circulating dietary antioxidant levels are reduced in asthma. The present study examined the variation in dietary antioxidant levels in asthma, according to airway responsiveness, asthma control and clinical asthma pattern. Peripheral blood was collected from forty-one subjects with stable, persistent asthma. Airway responsiveness was assessed by hypertonic saline challenge. Asthma control was assessed using the Asthma Control Questionnaire. Clinical asthma pattern was determined using Global Initiative for Asthma (GINA) criteria. Whole-blood carotenoids (β-carotene, lycopene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin) and tocopherols (α-, δ-, γ-tocopherol) were measured by HPLC. Plasma antioxidant potential (AOP) was determined by colorimetric assay (OxisResearch, Portland, OR, USA). Asthmatic subjects with airway hyper-responsiveness (AHR) had reduced levels of β-carotene and α-tocopherol compared with those without AHR. Subjects with uncontrolled asthma had low levels of AOP compared with those with controlled or partly controlled asthma. Subjects with a severe persistent clinical asthma pattern had reduced levels of α-tocopherol compared with those with a mild to moderate asthma pattern. We conclude that asthmatic subjects with AHR, uncontrolled asthma and a severe asthma pattern have impaired antioxidant defences and are thus most susceptible to the damaging effects of oxidative stress. This highlights the potential role for antioxidant supplementation in these subjects.

Anti-malarial drug artesunate ameliorates oxidative lung damage in experimental allergic asthma

“…Oxidative stress is associated with airway inflammation, mucus secretion, airway hyperresponsiveness, and even insensitivity to steroids in asthma [6,[27][28][29]. Normally, low levels of oxidative stress are well tolerated under the protection of antioxidants present in the lungs, including SOD, catalase, and GPx [18,30].…”

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

“…In prevalent asthma, supplementation with a-tocopherol has also been shown to decrease measures of oxidative stress and decrease inflammation (47). The lack of association observed with other micronutrients on incident disease in this study may reflect an association of these other micronutrients only with prevalent asthma or may reflect limitations in how to interpret the protective effect of these micronutrients from these prior studies' cross-sectional study designs (5,18,39,48,49). This is the first incidence study to assess the role of antioxidant enzyme activity in asthma inception and report of decreased PAF-AH activity predating asthma onset.…”

“…Both enzymatic and nonenzymatic antioxidants are implicated in the pathogenesis of asthma through mediation of oxidative stress and airway inflammation (4). Moreover, associations of nonenzymatic antioxidants with prevalent disease support the need for additional studies of incident asthma (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Enzymatic and nonenzymatic antioxidant host defense pathways have the potential to be modified, likely contribute to host defense to causal environmental asthma risk factors, and, thus, provide the rationale to investigate their role in asthma inception.…”

Antioxidant Strategies in the Treatment of Bronchial Asthma

“…They supported epidemiologic studies that linked antioxidant intake with decreased risk of asthma severity 30,31 , and reinvigorated a search for antioxidant therapeutics to treat asthma despite the fact that single antioxidant agents were largely ineffective in clinical trials. In adition, studies using a mouse model of impaired glutathione metabolism together with those using glutathione precursors to manipulate glutathione homeostasis raised the possibility that antioxidants from separate intracellular or extracellular pools may be relevant for different cell types during asthma pathogenesis, such as immune cells during sensitization and epithelial cells in response to inflammation 12,14 .…”