Background: The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods: Twenty six outpatients with COPD and eight healthy non-smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results: Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV 1 ), FEV 1 /forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9, and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions: These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema.
Among various biomarkers believed to behave as descriptors of the disease process in chronic obstructive pulmonary disease (COPD), urinary desmosines are commonly used for monitoring elastin degradation. Given the low concentrations of urinary desmosines, their quantitative determination in this biological matrix often requires preconcentration steps. To minimize both solute losses and effects of sample matrix, and to decrease data variability related to the above-mentioned manipulation processes, we have developed a capillary electrophoresis approach combined with laser-induced fluorescence (CE-LIF) detection system using urine samples not submitted to any pretreatment procedure other than filtering the sample. Urines were hydrolyzed, derivatized with fluorescein isothiocyanate (FITC) and endogenous desmosines were identified by addition of standard analytes and submitting to mass spectrometry (MS) analysis the material collected from micropreparative runs. The assay showed good linearity, reproducibility and precision, allowing to detect amounts of desmosines as low as 10(-8) M (equivalent to 0.1 fmol on column). We conclude that CE-LIF technique is a highly sensitive method for detecting urinary desmosines.
Both the urinary and plasma desmosine concentrations indicate that elastin degradation is higher in PXE patients and, to a lesser extent, in healthy carriers than in normal subjects. Data seem to indicate that the amount of elastin breakdown products correlates with the age of patients as well as with the severity of the disease.
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