Physical Training Reduces Chronic Airway Inflammation and Mediators of Remodeling in Asthma

Abstract

Several benefits of aerobic training for asthmatic patients have been demonstrated. However, its effects on systemic inflammation and on airway remodeling mediators and lung mechanics are unknown. This prospective study included 21 intermittent and mild asthma patients, and as primary outcomes, the evaluation of pro- and anti-inflammatory and pro- and antifibrotic mediators in exhaled breath condensate (EBC) and blood were performed, beyond the cell counting in blood and in induced sputum. Aerobic training was performed for 3 months, 3 times per week. Aerobic training increased the levels of anti-inflammatory cytokines and of antifibrotic mediators in the breath condensate: IL-1ra ( $p=0.0488$ ), IL-10 ( $p=0.0048$ ), relaxin-3 ( $p=0.0019$ ), and klotho ( $p<0.0043$ ), respectively. Similarly, in plasma, increased levels of IL-1ra ( $p=0.0147$ ), IL-10 ( $p<0.0001$ ), relaxin-3 ( $p=0.004$ ), and klotho ( $p=0.0023$ ) were found. On contrary, reduced levels of proinflammatory cytokines in the breath condensate, IL-1β ( $p=0.0008$ ), IL-4 ( $p=0.0481$ ), IL-5 ( $p<0.0001$ ), IL-6 ( $p=0.0032$ ), IL-13 ( $p=0.0013$ ), and TNF-α ( $p=0.0001$ ) and profibrotic markers VEGF ( $p=0.0017$ ) and TSLP ( $p=0.0056$ ) were found. Similarly, in plasma, aerobic training significantly reduced the levels of proinflammatory cytokines IL-1β ( $p=0.0008$ ), IL-4 ( $p=0.0104$ ), IL-5 ( $p=0.0001$ ), IL-6 ( $p=0.006$ ), IL-13 ( $p=0.0341$ ), and TNF-α ( $p=0.0003$ ) and of profibrotic markers VEGF ( $p=0.0009$ ) and TSLP ( $p<0.0076$ ). Fractional exhaled nitric oxide (FeNO) was reduced after the intervention ( $p=0.0313$ ). Regarding inflammatory cells in sputum, there was a reduction in total cells ( $p=0.008$ ), eosinophils ( $p=0.009$ ), and macrophages ( $p=0.020$ ), as well as of blood eosinophils ( $p=0.0203$ ) and lymphocytes ( $p=0.0198$ ). Aerobic training positively modulates chronic airway inflammation and remodeling mediators, beyond to improve systemic inflammation in intermittent and mild asthmatic patients.