Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency
article
Background: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. Methods: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. Results: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. Conclusions. 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. © 2005 Stolk et al., licensee BioMed Central Ltd. Chemicals / CAS: alpha 1 antitrypsin, 9041-92-3; carbon monoxide, 630-08-0; desmosine, 11003-57-9; elastase, 9004-06-2; fibrinogen, 9001-32-5; heparan sulfate, 9050-30-0; hyaluronic acid, 31799-91-4, 9004-61-9, 9067-32-7; proteinase, 9001-92-7
Topics
Biomedical ResearchAlpha-1-antitrypsinBiomarkersDesmosinesEmphysemaJM403alpha 1 antitrypsinbiological markercarbon monoxidedesmosineelastaseepitopeetx 100fibrinogenheparan sulfatehyaluronic acidproteinasealpha 1 antitrypsin deficiencyblood chemistryclinical articleclinical trialconstants and coefficientscontrolled clinical trialcontrolled studycorrelation analysisdisease associationdrug efficacydrug safetyemphysemafeasibility studyhumanmedical nebulizerphase 1 clinical trialside effectsingle drug doseurinalysisurine level
TNO Identifier
238510
ISSN
1465993X
Source
Respiratory Research, 6
Article nr.
47