Exercise Training Induces a Shift in Extracellular Redox Status with Alterations in the Pulmonary and Systemic Redox Landscape in Asthma

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.

Multimorbidity in Difficult Asthma: The Need for Personalised and Non-Pharmacological Approaches to Address a Difficult Breathing Syndrome

“…There is suggestion of at least two phenotypes of obese asthma with early onset atopic obese asthma and late onset non-atopic asthma [48]. The pathophysiology between early onset atopic obese asthma and late onset non-atopic asthma may vary because the latter resolves after weight loss [65].…”

Individualised Exercise Training Enhances Antioxidant Buffering Capacity in Idiopathic Pulmonary Fibrosis

“…Electro-magnetically braked cycle ergometry combined with an objective assessment of an individual’s physical fitness using cardiopulmonary exercise testing (CPET) enables the prescription of an individualised exercise programme [ 23 ]. Using this approach, we have previously demonstrated that an interval-based, structured responsive exercise training programme (SRETP) is feasible and improves physical fitness in patients with cancer [ 24 , 25 ] as well as quality of life and pulmonary inflammation in asthma [ 26 ]. Here, we utilise this individualised SRETP approach in a prospective study in patients with IPF to test the hypothesis that SRETP can improve exercise capacity, whilst in parallel investigating its effects on extracellular redox status to provide mechanistic insight into its mode of action.…”