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.

Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process.

Background: Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of previously treated TB, with frequent symptomatic presentation. This pilot study was aimed to investigate the pulmonary functions and systemic inflammatory markers in patients with post-TB sequelae (PTBS) and to compare them with post-TB without sequelae (PTBWS) participants and healthy controls.Methods: A total of 30 participants were enrolled, PTBS (n=10), PTBWS (n=10), and healthy controls (n=10). Pulmonary function tests included spirometry and measurement of airway impedance by impulse oscillometry. Serum levels of matrix metalloproteinase (MMP)-1, transforming growth factor-β, and interferon-γ were estimated.Results: Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, and peak expiratory flow were significantly lower in PTBS as compared to controls. SVC and FEV1 were significantly less in PTBS as compared to PTBWS. Total airway impedance (Z5), total airway resistance (R5), central airway resistance (R20), area of reactance (Ax), and resonant frequency (Fres) were significantly higher and respiratory reactance at 5 and 20 Hz (X5, X20) were significantly lower in PTBS as compared to PTBWS. Spirometry parameters correlated with impulse oscillometry parameters in PTBS. Serum MMP-1 level was significantly higher in PTBS as compared to other groups.Conclusion: Significant pulmonary function impairment was observed in PTBS, and raised serum MMP-1 levels compared with PTBWS and healthy controls. Follow-up pulmonary function testing is recommended after treatment of TB for early diagnosis and treatment of PTBS.

The risk of coronary artery disease (CAD) increases in women after menopause. [1,5] In addition, recent evidence Effect of menopause on lipid profile in relation to body mass indexAbstract Background: Menopause is a natural event in the ageing process and signifies the end of reproductive years with cessation of cyclic ovarian function as manifested by cyclic menstruation. Lipid profile is altered in menopause because of various reasons. Objectives: The study was aimed to compare the lipid profile in women with normal body mass index (BMI) = 18.9-24.9 and women with BMI = 25-29.9 in both pre-and post-menopausal group. Materials and Methods: Estimation of total cholesterol (TC) by CHOD-PAP Cholesterol Oxidase -Peroxidase + Aminophenazone + Phenol method, triglyceride (TG) by enzymatic calorimetric method, high density lipoproteincholesterol (HDL-C) phosphotungstic acid method, low density lipoprotein-cholesterol (LDL-C) by using Friedewald formula and very low density lipoprotein (VLDL) was done by using the formula -VLDL = TG/5 in 30 women selected in each group. Results: Our study revealed that serum levels of TC, TG and LDL-C were significantly higher in postmenopausal women in comparison to their pre-menopausal counterparts, irrespective of BMI (P < 0.05). Similarly, HDL-C levels were significantly lower in post-menopausal women as compared with pre-menopausal women of similar BMI (P < 0.05). Conclusions: We found that serum levels of TC, TG and LDL-C were significantly higher in post-menopausal women in comparison to their pre-menopausal counterparts, irrespective of BMI. Similarly, HDL-C levels were significantly lower in post-menopausal women as compared to pre-menopausal women of similar BMI. Since we found similar changes in women of different BMIs, the difference in hormonal status is the probable cause of altered lipid profile. Hence, all post-menopausal women irrespective of body weight and BMI should be strongly counseled to have proper physical exercise and dietary habits to avoid the possible cardiovascular complications.

N95 masks filter 95% of the small particles and respiratory droplets (>0.3 µm diameter). Therefore, they are widely used both by general public and health workers during pandemic.When physical activity or exercise is performed wearing N95 mask, it induces hypercapnic environment. The heat burden is also increased leading to discomfort and reduced compliance.This study was done to compare physiological effects and subjective perceptions while wearing N95 mask and powered air-purifying respirator (PAPR) (2 fans, N95 filter) during incremental exercise. ECG, respiratory movement, SpO2, temperature inside the mask were recorded and perception of discomfort was also assessed. Heart rate variability (HRV) values during baseline were within normal limits in both the mask conditions signifying that cardiac autonomic tone is comparable. During incremental exercise, fall in SpO2 was significantly lesser in PAPR as compared to N95 mask at 60-70% and 70-80% of maximum achievable heart rate. The temperatures inside both the mask conditions were significantly higher than ambient temperature. The scores of humid, hot, breath resistance and fatigue were significantly lower in PAPR than N95 mask. In conditions where prolonged use of mask is required with strenuous physical exertion or exercise, PAPR could be preferred over N95 mask.

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.

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.

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