DJ Gottlieb, PJ Stone, D Sparrow, ME Gale, ST Weiss, GL Snider and GT O'Connor
Department of Biochemistry, Boston University School of Medicine, Massachusetts, USA.

It is hypothesized that smoking-related chronic obstructive pulmonary disease (COPD) results in part from excess lung elastin degradation. Taking advantage of spirometry performed over a 12-yr period at the Normative Aging Study, we conducted a nested case-control study of elastin and collagen degradation rates in current smokers with (n = 10) and without (n = 8) rapid decline of lung function, using a biochemical assay for urinary desmosine (DES), a specific marker for mature elastin degradation, and hydroxylysylpyridinoline (HP), a specific marker for mature fibrillar collagen degradation. Mean urinary excretion of DES in rapid decliners was 36% greater than in slow decliners (9.8 +/- 0.7 [mean +/- SE] versus 7.2 +/- 0.4 microg/g creatinine, p < 0.01); after adjustment for age and lean body mass (LBM), DES excretion in rapid decliners was 30% greater than in slow decliners (9.6 +/- 0.6 versus 7.4 +/- 0.7 microg/g creatinine, p = 0.06). Among rapid decliners, there was no difference in DES excretion between those with and those without computed tomogaphic evidence of emphysema. There was no significant difference between rapid and slow decliners in mean urinary excretion of HP (24.7 +/- 1.4 versus 21.6 +/- 1.8 nmol/mmol creatinine, p = 0.18). Among all subjects, rate of decline of FEV1 was significantly correlated with DES excretion (r = 0.61, p < 0.01). In a linear regression model adjusting for age and LBM, an increase in DES excretion of 1 microg/g creatinine was associated with an excess decline of FEV1 of 10.6 ml/yr (p = 0.04). This study provides further evidence in support of the elastase-antielastase hypothesis of the pathogenesis of COPD, and it suggests a role for elastin degradation in both emphysema and small airways disease. Moreover, it suggests that urinary DES excretion may be a useful biochemical marker for the study of interventions designed to prevent the development or progression of COPD.

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