Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

Abstract

We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

“…The high correlation between urinary and plasma desmosines [45] is consistent with the correlation between urinary and plasma elastin peptides previously reported [9], thus suggesting that plasma and urine generally provide comparable estimates of elastin turnover. The correlation of individual values for plasma and urine levels of desmosines performed by STOLK et al [45] also diminishes the concern, based on previous experimental findings, that the kidney may sequester elastin peptides and release them over an extended period of time [50]: urinary DES excretion would reflect the changes in blood levels of elastin degradation products, although with more variability.…”

“…GOTTLIEB et al [26] found a significant correlation between urinary DES and FEV1 decline in smokers. In a short-term longitudinal study in PI*ZZ individuals with emphysema, STOLK et al [45] could not detect any relationship between plasma or urinary desmosines and FEV1, whereas a significant correlation was found between plasma desmosines (p,0.01) and urinary desmosines (p,0.05) and KCO. In a subsequent investigation of a larger group of patients with emphysema associated with AATD, the lack of significant correlation between urinary desmosines and FEV1 was confirmed, but a significant correlation (r50.57, p50.018) between urinary desmosines and phase III of the single-breath nitrogen test was also demonstrated [52].…”

“…The correlation of individual values for plasma and urine levels of desmosines performed by STOLK et al [45] also diminishes the concern, based on previous experimental findings, that the kidney may sequester elastin peptides and release them over an extended period of time [50]: urinary DES excretion would reflect the changes in blood levels of elastin degradation products, although with more variability. The short-term, longitudinal study of STOLK et al [45] has shown an acceptable variability (intra-individual coefficient of variation ,10%), in spite of some events of mild acute exacerbation not requiring hospitalisation. However, there is a preliminary report showing that after severe, acute exacerbations requiring hospitalisation, the recovery period is characterised by a small but significant decrease in urinary DES excretion [51].…”

“…Plasma (and urine) desmosines content has been determined in a population of 12 patients affected by pulmonary emphysema associated with AATD in a short-term (7-week) longitudinal study during a placebo-controlled trial aimed at evaluating the safety of a single inhalation of hyaluronic acid [45]. This investigation also measured two other biomarkers: elastaseformed fibrinogen fragments (in plasma) and a heparin Determination of desmosines in induced sputum was included in a study that evaluated a series of biomarkers putatively aimed at differentiating COPD subjects with (n511) and without (n515) CT-diagnosed emphysema [46].…”

AZD9668: Pharmacological Characterization of a Novel Oral Inhibitor of Neutrophil Elastase

“…In COPD, the high prevalence of emphysema in patients with ␣ 1 -AT deficiency, particularly in smokers, is believed to be caused by the unchecked action of serine proteases on lung tissue (Laurell and Eriksson, 1963). Lung lavage studies reveal that these patients have an increased number of neutrophils, increased levels of plasma and urinary desmosine (a biomarker of elastin tissue breakdown) correlated to carbon monoxide diffusion capacity (Stolk et al, 2005), and a greater NE burden in the lower airways (Morrison et al, 1987). There is also a positive correlation between the local distribution of NE in contact with alveolar interstitial elastin and the presence of emphysematous changes in COPD lung tissue (Damiano et al, 1986).…”