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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. |