Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 (CXCR2) would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.

Background: Chronic Obstructive Pulmonary Disease (COPD) development may be associated with CNV in susceptible genomic regions. CNV also contributes to COPD heritability.CNVs in COPD smokers (CS) and COPD former smokers (CFS) have not been deciphered so far. Objective: To study the genome wide CNV to identify the vulnerable candidate genes for genetic susceptibility by performing array based comparative genomic hybridization (aCGH).Methods:COPD smokers (n=6) and COPD former smokers (n=9) were recruited from the Pulmonary Critical Care and Sleep Medicine OPD donated blood samples with prior informed consents. DNA was isolated from each sample using Qiagen DNeasy kit. aCGH was performed using Agilent two-colour microarray protocol to evaluate CNV. Agilent Cytogenomics software was used for analysis. Thresholds for gain, loss, amplification and deletion were set at log-ratios of 0.3, -0.3, 0.8 and -0.8, respectively. Results: Copy loss and deletion of 15q11.1-q11.2 was only detected in COPD smokers but not in COPD former smokers. Copy gain and deletion of 1q31.3 was only detected in COPD smokers, but not in COPD former smokers.Copy loss of four genes (CHECKP2, HERC2P3, GOLGA6L6 and GOLGA8CP) in all the samples of CS. Copy loss and gain of Xq28 and 22q11.21 was observed only in CFS. LICAM, LCA10, AVPR2 and GD11 were found to be associated with copy gain in all samples of COPD former smokers. Conclusion: The CNV located in 15q11.1-q11.2 region of CS might be associated with both smoking and COPD, while the CNVs located in Xq28 and 22q11.21 were observed only in samples from CFS suggesting their association in reversal to baseline after quitting smoking.