Abstract
Redox dysregulation and oxidative stress have been implicated in asthma pathogenesis. Exercise interventions improve symptoms and reduce inflammation in asthma patients, but the underlying mechanisms remain unclear. We hypothesized that a personalised exercise intervention would improve asthma control by reducing lung inflammation through modulation of local and systemic reactive species interactions, thereby increasing antioxidant capacity. We combined deep redox metabolomic profiling with clinical assessment in an exploratory cohort of six female patients with symptomatic asthma and studied their responses to a metabolically targeted exercise intervention over 12 weeks. Plasma antioxidant capacity and circulating nitrite levels increased following the intervention (p = 0.028) and lowered the ratio of reduced to oxidised glutathione (p = 0.029); this was accompanied by improvements in physical fitness (p = 0.046), symptoms scores (p = 0.020), quality of life (p = 0.046), lung function (p = 0.028), airway hyperreactivity (p = 0.043), and eosinophilic inflammation (p = 0.007). Increased physical fitness correlated with improved plasma antioxidant capacity (p = 0.019), peak oxygen uptake and nitrite changes (p = 0.005), the latter also associated with reductions in peripheral blood eosinophil counts (p = 0.038). Thus, increases in “redox resilience” may underpin the clinical benefits of exercise in asthma. An improved understanding of exercise-induced alterations in redox regulation offers opportunities for greater treatment personalisation and identification of new treatment targets.
Highlights
Exercise was long known to be beneficial for health and is increasingly recognised in the prevention and modification of disease processes [1,2]
The group were in the overweight category for body mass index (BMI) at enrolment, and this did not significantly change following the exercise intervention (p = 0.17)
There is growing evidence to support the benefit of exercise in strengthening the resilience of the redox regulation system at the whole-body level
Summary
Exercise was long known to be beneficial for health and is increasingly recognised in the prevention and modification of disease processes [1,2]. Despite appreciation of its widespread benefits, the mechanisms through which these effects are conferred are not well understood. An acute bout of exercise induces oxidative stress in skeletal muscle and triggers an orchestrated molecular response at the whole-body level with thousands of changes in the metabolomic, proteomic and lipidomic profile [3,4]. Much less is known about systems-wide effects of repeated exercise, but improved redox regulation was proposed as a key mechanism through which physical exercise exerts its systemic effects [5]. The observation that antioxidant supplements interfere with the health-promoting effects 4.0/).
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