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

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 FEV₁, FVC, and FEV₁/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 FEV₁, FVC and FEV₁/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 FEV₁, - 99.6 mL [- 159.3; - 37.9] for FVC, and - 0.04% [- 0.85; 0.70] for FEV₁/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.