Associations of circulating elastin degradation products (iso)desmosine with other blood biomarkers, CT-densitometry, arterial stiffness, lung function parameters, and copper in exhaled breath condensate

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is
defined by the presence of a chronic airway obstruction. Multiple pathological
mechanisms can be responsible for the development of COPD. Pulmonary emphysema
is the COPD phenotype characterized by destruction of lung parenchyma caused by
a protease / antiprotease imbalance resulting in accelerated degradation of
elastin fibers.
The production of elastin fibers in the lungs takes place almost exclusively
around birth [2022748]. The elastin precursor, tropoelastine, is first
synthesized by different cell types and [1] tropoelastine monomers then fuse
into polymers. The tropoelastine polymers are then cross-linked to mature
elastin fibers [1] under the influence of the copper-dependent enzyme lysyl
oxidase. During this crosslinking, desmosin and isodesmosin (jointly
abbreviated as DES) are formed. In the process of elastin degradation, DES is
released into the extracellular matrix, leaks into the bloodstream and is
measurable in the plasma (pDES). The height of pDES reflects the activity of
the elastin degradation process. In disorders characterized by accelerated
elastin degradation, such as COPD, the pDES concentration is increased [2].
Currently, pulmonary lungfunction tests form the basics in diagnostics and
follow up in COPD. Last past years, densitometry measurement using CT scan has
become a reliable method to quantify the degree of destruction of the lung
parenchyma, or the degree of emphysema [4]. The density of the lung tissue is
calculated and compared with the density of healthy lung tissue. We expect that
there is a correlation between the height of the pDES and the degree of lung
destruction measured with densitometry and lung function tests.
Elastin is not only found in the lungs but in all dynamic tissues of the body
and therefore also in the cardiovascular system. The degradation of elastin
leads to damage to the blood vessels and therefore to an increased risk of
cardiovascular morbidity and mortality [3]. Arterial stiffness is increased in
COPD patients and is correlated with the severity of emphysema [5]. The vessel
stiffness can be reflected by the Pulse Wave Velocity (PWV). This is a
measurement method in which the pulse wave of the a.carotis and the pulse wave
of the a.femoralis are measured. The time difference between the two waves
gives information about the elasticity of the aorta. This is a good predictor
for cardiovascular morbidity and mortality. Since elastin degradation leads to
an increase in arterial stiffness, we expect that there is a correlation
between the height of pDES and the PWV.
In addition to correlating pDES with the degree of loss of elasticity in the
pulmonary and vascular compartment, we also want to try to identify biomarkers
that influence the pDES content. The ultimate goal is to investigate whether it
is possible to favorably influence these biomarkers in order to reduce the rate
of elastin degradation. Decreasing the elastin degradation rate could have a
beneficial effect on disease progression in COPD. An earlier study by us showed
that vitamin K is inversely correlated with pDES. It is possible that improving
vitamin K status by vitamin K supplementation would also decrease pDES. In the
present study, we also want to investigate the influence of substances other
than vitamin K, such as phosphate, magnesium and copper, on pDES. We also want
to investigate whether copper, as an essential factor of lysyl oxidase, is
lowered in the lungs, as we suspect, and whether copper in exhalation vapor is
correlated with pDES and CT lung densitometry.

Evaluate whether CT lung densitometry and PWV associate with plasma DES
concentrations. In addition, we want to determine whether certain other
laboratory determinations in the blood and condensed exhalation vapor correlate
with plasma DES.

Descriptive cross sectional study

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