Association between markers of emphysema and more severe chronic obstructive pulmonary disease.

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.

High levels of desmosines in urine and plasma of patients with pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE), a rare heritable disorder caused by mutations of the ABCC6 gene, is characterized by fragmentation and mineralization of elastic fibres. We determined the extent of degradation of elastin by measuring and comparing the amount of desmosines in plasma and urine of PXE patients, healthy carriers and normal subjects. METHODS: Using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) we measured the amount of desmosines in the urine of 46 individuals (14 PXE patients, 17 healthy carriers and 15 controls) and in the plasma of 56 subjects (18 PXE patients, 23 healthy carriers and 15 controls). Pseudoxanthoma elasticum patients and carriers were identified by clinical, structural and molecular biology analyses. RESULTS: The urinary excretion of desmosines was two-fold higher in PXE patients than in controls (P < 0.01); the values for healthy carriers were intermediate between those of PXE patients and controls. A very similar trend between patients and their relatives was observed for plasma desmosines. There was a significant correlation between the amount of the desmosines in plasma and urine. Moreover, a positive correlation was observed between urinary desmosine content and age of the patients as well as between urinary desmosine content and severity of clinical manifestations. CONCLUSIONS: 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.

Therapeutic apheresis exchange in two patients with prolidase deficiency.

BACKGROUND: Prolidase deficiency is a rare genetic disorder for which a cure has not yet been found. OBJECTIVES: To assess the effectiveness of apheresis exchange as a new therapeutic approach. METHODS: Apheresis exchanges were repeated monthly for four consecutive months, in parallel, on two patients, replacing prolidase-deficient red blood cells with normal filtered cells. Prolidase activity and urinary dipeptides were determined at regular intervals. RESULTS: The constant presence of active prolidase inside cells allowed a continuous, although partial, degradation of imidodipeptides, with a concomitant improvement of skin ulceration. CONCLUSIONS: Apheresis exchange could be a reasonable way of obtaining a clinical improvement in these patients.