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.

Introduction:Diabetes mellitus (DM) is characterized by the presence of chronic hyperglycemia and formation of advanced glycation end products (AGEs). Interaction between AGE and its receptor leads to endothelial damage and microangiopathy. This study was undertaken to investigate the possibility of using a postural variation of diffusing capacity as an early marker of lung microangiopathy and its correlation with the level of adhesion molecules, HbA1c, duration of diabetes, and insulin resistance in type 2 DM (T2DM) patients with and without microangiopathy.Materials and Methods:Forty patients having T2DM without any microangiopathy (n = 20) as well as with microangiopathy (n = 20), and 22 age and sex matched healthy controls were enrolled in this cross-sectional study. Measurement of lung volumes and capacities were done. DLco was measured in sitting and supine position. Levels of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, fasting glucose, and insulin were estimated in plasma of the patients and compared with controls.Results:Restrictive type of ventilatory change was observed in DM patients. Diffusing capacity (% predicted) in the supine position (P < 0.0001), postural change in DLco (P < 0.0001), and coefficient of diffusion were significantly less in DM patients as compared to controls. Plasma levels of VCAM-1 were significantly higher in DM patients without microangiopathy and negatively correlated (r = −0.4054, P = 0.0094) with Δ DLco in all diabetic subjects. All patients had significantly higher insulin resistance.Conclusion:Lack of postural increase in diffusing capacity in type 2 diabetic patients along with increased VCAM-1 levels could reflect the presence of an early microangiopathy of the small pulmonary vessels.

The lymphatic vasculature maintains tissue homeostasis via fluid drainage in the form of lymph and immune surveillance due to migration of leukocytes through the lymphatics to the draining lymph nodes. Lymphatic endothelial cells (LECs) form the lymphatic vessels and lymph node sinuses and are key players in shaping immune responses and tolerance. In the healthy lung, the vast majority of lymphatic vessels are found along the bronchovascular structures, in the interlobular septa, and in the subpleural space. Previous studies in both mice and humans have shown that the lymphatics are necessary for lung function from the neonatal period through adulthood. Furthermore, changes in the lymphatic vasculature are observed in nearly all respiratory diseases in which they have been analyzed. Recent work has pointed to a causative role for lymphatic dysfunction in the initiation and progression of lung disease, indicating that these vessels may be active players in pathologic processes in the lung. However, the mechanisms by which defects in lung lymphatic function are pathogenic are understudied, leaving many unanswered questions. A more comprehensive understanding of the mechanistic role of morphological, functional, and molecular changes in the lung lymphatic endothelium in respiratory diseases is a promising area of research that is likely to lead to novel therapeutic targets. In this review, we will discuss our current knowledge of the structure and function of the lung lymphatics and the role of these vessels in lung homeostasis and respiratory disease.

Background & objectives:Chronic obstructive pulmonary disease (COPD) is characterized by slowly progressive airflow limitaion, chronic lung inflammation and associated systemic manifestations. The objective of this preliminary study was to investigate the levels of high sensitivity C reactive protein (hs CRP) and tumour necrosis factor-α (TNF-α) as markers of systemic inflammation and assessment of systemic vascular reactivity that may play an important role in development of cardiovascular disease in COPD patients.Methods:Systemic vascular reactivity was assessed non-invasively by measuring peripheral pulse waveform changes during reactive hyperemia (RH) in 16 COPD patients and 14 controls by photoplethysmography technique (PPG). Parameters measured were pulse wave amplitude (PWA), slope and pulse transit time (PTT). Tumour necrosis factor-α (TNF-α) and hs CRP were measured as markers of inflammation.Results:PWA during the 1st, 2nd and 3rd minutes post release of occlusion were significantly higher than the baseline means in controls, whereas in the patient group there was no significant change in the PWA during any of the observed time periods following release of occlusion, in comparison to the baseline means. Similar results were observed in slope values for patients and controls. Maximum percentage change in PWA during RH with reference to baseline was significantly lower in patients as compared to controls (26.78±20.19 vs 57.20±19.80%, P<0.001). Maximum percentage change in slope during RH with reference to baseline was significantly lower in patients as compared to controls (19.77±10.73 vs 39.25±13.49%, P<0.001). A vascular tone response as represented by PTT was also impaired in the 3rd minute of RH as compared to baseline mean values in COPD patients only.Interpretation & conclusions:Our findings showed raised hs CRP levels and impaired systemic vascular reactivity in COPD patients. Whether these may increase the risk of cardiovascular disease in COPD patients need to be confirmed in future studies with large sample size and appropriate study design.

Rationale: Smoking is the primary cause of chronic obstructive pulmonary disease (COPD); however, only 10-20% of smokers develop the disease suggesting possible genomic association in the causation of the disease. In the present study, we aimed to explore the whole genome transcriptomics of blood monocytes from COPD smokers (COPD-S), COPD Exsmokers (COPD-ExS), Control smokers (CS), and Control Never-smokers (CNS) to understand the differential effects of smoking, COPD and that of smoking cessation. Methods: Exploratory analyses in form of principal component analysis (PCA) and hierarchical component analysis (uHCA) were performed to evaluate the similarity in gene expression patterns, while differential expression analyses of different supervised groups of smokers and never smokers were performed to study the differential effect of smoking, COPD and smoking cessation. Differentially expressed genes among groups were subjected to post-hoc enrichment analysis. Candidate genes were subjected to external validation by quantitative RT-PCR experiments. Results: CNS made a cluster completely segregated from the other three subgroups (CS, COPDS and COPD-ExS). About 550, 8 and 5 genes showed differential expression, respectively, between CNS and CS, between CS and COPD-S, and between COPD-S and COPD-ExS. Apoptosis, immune response, cell adhesion, and inflammation were the top process networks identified in enrichment analysis. Two candidate genes (CASP9 and TNFRSF1A) found to be integral to several pathways in enrichment analysis were validated in an external validation experiment. Conclusion: Control never smokers had formed a cluster distinctively separated from all smokers (COPDS, COPD-ExS, and CS), while amongst all smokers, control smokers had aggregated in a separate cluster. Smoking cessation appeared beneficial if started at an early stage as many genes altered due to smoking started reverting towards the baseline, whereas only a few COPD-related genes showed reversal after smoking cessation.