الفهرس 
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Abstract
Summary & Conclusion
COPD is a progressive immunological disorder
characterized by three main pathologic phenotypes; chronic
bronchitis associated with mucus hyper secretion, chronic
obstructive bronchiolitis, in which remodeling and
thickening of the airways walls occurs resulting in narrowed or
even obstructed lumens and emphysema resulted from loss of
the elastic recoil of the lung due to inflammation of the alveoli
with destruction of their walls.
COPD is presently the fourth leading cause of death
worldwide, but WHO predicts that it will become the third
leading cause of death by 2030.
Risk factors for COPD are still being studied.
Occupational and environmental exposures, increased airway
responsiveness, exposure to both indoor and outdoor air
pollutants and early life exposure to both infectious and noninfectious
agents are all risk factors that might play an
important role in the development and advancement of COPD
but smoking seems to be the major risk factor and the
predominant cause of COPD; it is implicated in 90 % of
COPD cases. However, only 10–20 % of the smokers develop
COPD, pointing to an additional risk factor, such as genetic
susceptibility, e.g., the polymorphisms in genes coding for
anti-proteases like A1A, MMPs, like MMP-9 or antioxidant
enzymes like SOD.
SNPs in the genes coding for the two counter acting
enzymes; A1A or MMP-9, leading to genetic deficiency of the
former enzyme and up-regulation of the later enzyme,
accompanied by exposure to other risk factors such as tobacco
smoke, facilitate the process of COPD development and
progression.
The current ‘‘measure’’ of COPD is FEV1. It is both the
defining feature of the disease and its measure of severity.
FEV1 is the only accepted marker that meets FDA drug
approval criteria for COPD, however; COPD is a complex
disease with multiple phenotypes that cannot be identified
through measurement of lung function alone. In addition; due
to the fact that COPD onset is relatively asymptomatic,
patients that are at risk or even in the early stages of the
disease are not usually monitored by FEV1 measurements, and
they got diagnosed when the disease has already progressed.
Consequently; there is a considerable need for a reliable
and reproducible biomarker that would be specific for early
stage of the disease, and also informative for the follow-up of
disease progression and development.
The current study had selected the anti-protease A1A and
the protease MMP-9 to test their efficiency as biomarker for
the COPD early detection and staging; by comparing their
mRNA in COPD patient with different grades (e.g. moderate,
severe & very severe) and asymptomatic smoking individuals.
36 subjects were included in this study; 25 COPD
patients divided into three different grades (10 very severe, 7
severe & 8 moderate COPD patients), 6 non - COPD smokers
and 5 non-smoking healthy subjects.
CBC and CRP tests were made for all subjects as
routine laboratory tests to screen for the general health and
inflammatory status of the subjects, then blood was collected
from all of them; for WBCs isolation followed by total RNA
extraction and RNA was reverse-transcribed to cDNA.
cDNA was used as template for conventional PCR, to
make sure of the specificity of the three primer pairs designed
for the genes; MMP-9, A1A & GAPDH, followed by a SYBR
green-based qPCR analysis.
Our results showed similar down-regulation of MMP-9
expression in asymptomatic non - COPD smokers and
moderate COPD group. However, MMP-9 expression could
significantly differentiate between the three COPD grades
(moderate, severe &very severe) involved in this study.
Significant up-regulation of MMP-9 started in severe COPD
group and continued in very severe COPD group, with marked
elevation in the group of very severe COPD patient suffering
from lung cancer too.
In case of A1A expression, it was down-regulated
similarly in all groups and could not differentiate between all
groups of the study, except for the group of very severe COPD
patient suffering from lung cancer as well; A1A expression
was twice its normal expression in this group , however , it
was a statistically non significant increase.
In conclusion, this study could confirm that MMP-9
expression can be used to define COPD stages (moderate,
severe & very severe) but not for early COPD detection; since
the expression of MMP-9 was similar in both non-COPD
smokers and moderate COPD patients.
Unlike MMP-9, A1A expression could not differentiate
between both COPD patients and non - COPD smokers as well
as between moderate, severe, and very severe COPD grades.
Since the studies concerned with A1A as a biomarker for
COPD are few; further studies are required to support this
point of research.