MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients

Degradation of extracellular matrix components is central to many pathologi cal features of chronic destructive lung disorders. Desmosine and isodesmos ine are elastin-derived cross-linked amino acids whose urine levels are con sidered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-perfo rmance capillary electrophoresis, to the quantification of desmosine and is odesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha(1)-antitrypsin de ficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in co mparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels w ere higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p less than or equal to 0.05). The highest desmosine level s were found in subjects with alpha(1)-antitrypsin deficiency, bronchiectas is and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longit udinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determinat ion of elastin-derived cross-linked amino acid excretion in urine, giving r esults similar to those obtained using other separation methods. In additio n, evidence is presented that urinary desmosine excretion is increased in c onditions characterized by airway inflammation, such as exacerbations of ch ronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Re sults obtained in subjects with alpha(1)-antitrypsin deficiency suggest tha t this method might be used to evaluate the putative efficacy of replacemen t therapy.