Skin advanced glycation end-products do not predict pulmonary function trajectories in adults from the ILERVAS cohort

Abstract

Advanced glycation end-products (AGEs) activate specific receptors (RAGE) promoting inflammation and oxidative stress. The lungs, with high RAGE expression, may be particularly susceptible to AGE-related injury. This study assessed whether baseline skin AGE levels, measured by skin autofluorescence (SAF), predict pulmonary function decline in middle-aged adults with cardiovascular risk factors. This ancillary analysis of the ILERVAS cohort included adults aged 45-70 years with cardiovascular risk factors but without diabetes or chronic kidney disease. Baseline data included demographics, lifestyle, and fasting blood tests. SAF was measured using AGE Reader™, and spirometry performed at baseline and after a median follow-up of 4 years. Associations between baseline SAF and annual declines in FEV, FVC, and FEV/FVC were analysed using adjusted models and generalized additive models, stratified by smoking status. Among 658 participants (median age 56 years, 48% female), median baseline SAF was 1.90 AU [1.60; 2.20]. Baseline lung function was preserved, with median FEV, FVC and FEV/FVC of 2795 mL [2270; 3,341], 3,525 mL [2870; 4300], and 78.6% [74.4; 82.8]. Annual declines were - 81.9 mL [- 120.6; - 43.3] for FEV, - 99.6 mL [- 159.3; - 37.9] for FVC, and - 0.04% [- 0.85; 0.70] for FEV/FVC. No significant associations were found between SAF and spirometry changes. Results were consistent across smoking subgroups. Baseline skin AGE levels did not predict pulmonary function decline over four years in middle-aged adults with cardiovascular risk factors. While SAF reflects cumulative AGE exposure, it has limited prognostic value for lung function in this population.

This work was supported by Instituto de Salud Carlos III (ISCIII) through the Project PI23/00237, and The Ministerio de Ciencia, Innovación y Universidades (MCIN) through the project IJC2018-037792-I, co-funded by the European Union. This research was also funded by the Spanish Ministry of Science, Innovation, and Universities (grant PID2023-152233OB-I00) and by the “European Regional Development Fund, A way of making Europe”. Further funded by Programa de donaciones “estar preparados” UNESPA (Madrid, Spain), and Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES) CB07/06/2008 an initiative of the Instituto de Salud Carlos III. With the support of the Generalitat of Catalonia (AGAUR—2021SGR00990) and with the support of the Diputació de Lleida. MHB is supported by Instituto de Salud Carlos III through a predoctoral fellowship (FI23/00253), co-funded by European Union; and from the 2023 “Grants for Research Staff in Training” (11th Edition, Modality E) of the IREP Program “amb la col·laboració de: Diputació de Lleida” and IRBLleida. ADST is supported by Instituto de Salud Carlos III (ISCIII) through the project CP23/00095 (Miguel Servet 2023), co-funded by the European Union. FB is supported by the ICREA Academia programme.