Elastin and Collagen Degradation Products in Urine of Smokers With and Without Chronic Obstructive Pulmonary Disease

Abstract

It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysyl-pyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 ± 5.1 [mean ± SD]; IDES, 11.3 ± 5.0 μg/g creatinine) and in the SM group (DES, 11.0 ± 4.2; IDES, 10.2 ± 2.5 μg/g creatinine) was significantly higher than in the NSM group (DES, 7.5 ± 1.4; IDES, 6.9 ±1.3 μg/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD. Urinary excretion of HP and LP in the COPD group was significantly higher than in the SM and the NSM groups (51.5 ± 24.9, 31.1 ± 8.3, and 24.9 ± 6.1 nmol/mmol creatinine, respectively, for HP and 12.9 ± 5.9, 7.0 ± 1.5, and 4.9 ± 2.0 nmol/mmol creatinine, respectively, for LP). After adjusting for the effect of sex, urinary HP excretion in the SM group was significantly greater than in the NSM group. Because urinary LP is almost exclusively derived from bone collagen degradation, urinary LP can be used to calculate the relative amounts of bone and soft-tissue-derived HP. The excess HP excretion in the SM and the COPD groups was derived from bone collagen turnover. We conclude that COPD and current smoking are independently associated with elevated elastin and collagen degradation. The excess elastin and collagen degradation associated with COPD appears to persist even after the cessation of smoking.