AEROBIC TRAINING MODULATE PULMONARY AND SYSTEMIC INFLAMMATORY AND FIBROTIC RESPONSE IN PATIENTS WITH ASTHMA

Abstract

TOPIC: Pulmonary Rehabilitation TYPE: Original Investigations PURPOSE: Airway remodeling is a hallmark of asthma, characterized by structural changes in the airways, including epithelial metaplasia, subepithelial fibrosis, angiogenesis and thickening of smooth muscle. Airway remodeling promotes irreversible loss of lung function and subside the airway hyperresponsiveness and is associated with severity of the disease. In addition, airway remodeling is caused by an unresolved chronic inflammatory response, involving exacerbated release of profibrotic mediators. Aerobic exercise (AE) is the main component of pulmonary rehabilitation and in pre-clinical studies in models of asthma, AE reduced airway remodeling, by reducing the release of pro-fibrotic mediators and increasing the release of anti-fibrotic mediators. However, no clinical study has tested whether AE could promote any effect on airway remodeling in asthmatic patients. METHODS: Treadmill aerobic exercise (AE) (12 weeks, 3x/week, 40min/session, 60-80%MaxHR) was applied to 17 persistent moderate asthmatic patients (42.11±19.13). Body mass index (BMI), lung function, induced sputum, breath condensate, whole blood analysis and CD4+ cells proliferation, 6MWT, exhaled nitric oxide, was evaluated. RESULTS: AE improved VEF3 (L) (p<0.03) and PEF (L/min) (p<0.005) and PEF (%) (p<0.004), reduced the number of total leukocytes, eosinophils, neutrophils, lymphocytes and macrophages (p<0.01), as well as the levels of IL-1beta, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-23 (p<0.01) in induced sputum. AE also reduced the levels of IL-1beta, IL-5, IL-6, IL-13, VEGF (p<0.01), while increased the levels of anti-inflammatory IL-1ra and IL-10 (p<0.01) and anti-fibrotic Relaxin 3 (p<0.01) in breath condensate. Systemically, AE reduced the number of eosinophils, neutrophils and lymphocytes (p<0.01), as well as the levels of IL-1beta, IL-5, IL-6, IL-13, VEGF (p<0.01), while increased anti-inflammatory IL-1ra, IL-10 (p<0.01) and anti-fibrotic Relaxin 3 (p<0.01) in plasma. AE improved 6MWT (p<0.01) and reduced exhaled nitric oxide (p<0.01) and CD4+ cells proliferation (p<0.01). CONCLUSIONS: In conclusion, AE improves airway and systemic inflammation reducing pro-inflammatory cytokines, while increased anti-inflammatory and anti-fibrotic mediators systemically and into the lungs. CLINICAL IMPLICATIONS: These findings present unprecedented findings on auxiliary treatment and prevention of the health consequences of people with asthma through the practice of physical exercise. From a social point of view, it demonstrates a low-cost and easily accessible intervention, while from a scientific point of view, it will promote research ideas in a promising field. DISCLOSURES: No relevant relationships by thiago alves, source=Web Response no disclosure on file for Helida Aquino-Santos; No relevant relationships by RENILSON FERREIRA, source=Web Response no disclosure on file for Claudio Frison; No relevant relationships by Victor Hugo Palmeira, source=Web Response No relevant relationships by 119 Maysa Alves Rodrigues Rangel, source=Web Response No relevant relationships by Anamei Silva-Reis, source=Web Response No relevant relationships by Rodolfo Vieira, source=Web Response