Biological events in systemic and muscle compartments of sarcopenic bronchiectasis patients: implications in pulmonary rehabilitation

We aimed to demonstrate that systemic inflammation and oxidative stress and other molecular events: endoplasmic reticulum (ER) stress and proteolysis are involved in the development of sarcopenia in bronchiectasis. In blood and muscle samples (open muscle biopsy, quadriceps), prooxidants (oxidized and nitrated proteins, ELISA), antioxidants (TEAC, GSH, SOD and catalase, plasma, assays, ELISA), inflammation (MPO, COX-2, TGF-beta1, VEGF, IL-6, plasma, ELISA), ER stress (chaperones and IRE1, PERK and ATF6 pathways), proteolysis (ubiquitin proteasome system) and autophagy markers (muscle, Western blot) of sarcopenic stable patients with mild-to-moderate bronchiectasis (n=20) and controls (n=10). Patients and controls were clinically evaluated: nutritional, respiratory and muscle function (handgrip and quadriceps muscle strength). In sarcopenic patients compared to controls: 1) systemic compartment, levels of MPO, TGF-beta1, VEGF, IL-6, protein oxidation, SOD, and GSH increased, and 2) muscle compartment, levels of ER stress (XBP1, ATF4), proteolysis (MURF1, 20S proteasome) and autophagy (p62) also significantly increased. Inverse correlations were found between molecular markers and both FFMI and QMVC. In bronchiectasis patients, sarcopenia is present in upper and lower limbs. Biological events in systemic and local compartments negatively correlated with muscle mass and strength, suggesting their implications in sarcopenia development. Pulmonary rehabilitation programs should be specifically targeted. Funding: SEPAR-2020, FIS21/00215 (FEDER,ISC-III), BA21/00003, INT19/00002, INT22/00008,2021-SGR-00100, CIBERES (ISC-III), Menarini Labs, SLT028/23/000016