Development Of Chronic Obstructive Pulmonary Disease Research Articles

Endothelium-related and neuro-mediated mechanisms of emphysema development in chronic obstructive pulmonary disease

Emphysema is one of the main manifestations of chronic obstructive pulmonary disease (COPD), and smoking is one of the most significant risk factors. The results of studies in humans and animals show the vascular endothelium initiates and modulates the main pathological processes in COPD and smoking is an important factor initiating, developing and persisting inflammation and remodeling of blood vessels and tissues, including the destruction of small respiratory tracts with the development of lung tissue destruction and emphysema. The latest studies describe mechanisms not just associated with the endothelium, but specific neuro-mediated mechanisms. There is reason to believe that neuro-mediated and neuro-similar mechanisms associated and not related to endothelial dysfunction may play the significant role in the pathogenesis of COPD and emphysema formation. Information about components and mechanisms of neurogenic inflammation in emphysema development is fragmentary and not systematized in the literature. It is described that long-term tobacco smoking can initiate processes not only of cells and tissues damage, but also become a trigger for excessive release of neurotransmitters, which entails whole cascades of adverse reactions that have an effect on emphysema formation. With prolonged and/or intensive stimulation of sensor fibers, excessive release of neuropeptides is accompanied by a number of plastic and destructive processes due to a cascade of pathological reactions of neurogenic inflammation, the main participants of which are classical neuropeptides and their receptors. The most important consequences can be the maintenance and stagnation of chronic inflammation, activation of the mechanisms of destruction and remodeling, inadequate repair processes in response to damage, resulting in irreversible loss of lung tissue. For future research, there is interest to evaluate the possibilities of therapeutic and prophylactic effects on neuro-mediated mechanisms of endothelial dysfunction and damage emphysema in COPD and smoking development.

Rat bone mesenchymal stem cells exert antiproliferative effects on nicotine‑exposed T cells via iNOS production.

Adoptive transfer of bone marrow‑derived mesenchymal stem cells (BMSCs) significantly alleviates smoking‑induced chronic obstructive pulmonary disease (COPD) in rats. Considering the critical roles of T cells during COPD development, the present study aimed to further identify the molecular mechanisms underlying the antiproliferative effect of BMSCs on splenic T cells isolated from rats following chronic exposure to nicotine. Splenic T cells were co‑cultured with rat BMSCs at various ratios and subsequently, T‑cell proliferation was measured using the Cell Counting Kit‑8 assay. The effects of the inducible nitric oxide synthase (iNOS) inhibitor N‑nitro‑L‑arginine methylester (L‑NAME) and short hairpin (sh)RNA‑lentivirus‑mediated knockdown of iNOS in BMSCs on T‑cell proliferation were evaluated. The expression levels of iNOS and STAT5 phosphorylation in BMSCs and T cells, respectively, were assessed by reverse transcription‑quantitative PCR and western blotting. A higher ratio of BMSCs to T cells resulted in increased inhibition of T‑cell proliferation; therefore, the ratio of 1:20 was selected for further invitro experiments. At a dose of 5µM, L‑NAME displayed the strongest ability to reverse the antiproliferative effects of BMSCs in the co‑culture system. Both L‑NAME treatment and shRNA‑mediated knockdown of iNOS expression significantly decreased the suppressive effects of BMSCs, downregulated iNOS expression at the mRNA and protein levels in BMSCs, and enhanced STAT5 phosphorylation in Tcells. BMSCs inhibited the proliferation of nicotine‑exposed Tcells, which was associated with iNOS expression in BMSCs and decreased STAT5 phosphorylation in T cells. The present study indicated the potential mechanisms underlying the beneficial effects of BMSC infusion in patients with chronic smoking‑induced COPD and emphysema.

LncRNA SNHG5 regulates cell apoptosis and inflammation by miR-132/PTEN axis in COPD

Long non-coding RNAs small nucleolar RNA host gene 5 (lncRNA SNHG5) plays well-defined roles in the malignant progression. However, the roles of SNHG5 in chronic obstructive pulmonary disease (COPD) progression remain unclear. In the present study, SNHG5 expression was low expressed in COPD tissues and positively correlated with low forced expiratory volume in one second (FEV1)% in patients. Subsequently, cigarette smoke extract (CSE) decreased SNHG5 expression in 16HBE cells, and SNHG5 overexpression in 16HBE cells mitigated the effects of CSE on the proliferation, apoptosis and inflammation (IL-1β, IL-6 and TNF-a). Mechanistically, SNHG5 functioned as a competing endogenous RNA (ceRNA) for miR-132 in COPD, thereby increasing the expression of the miR-132 target PTEN. Moreover, rescue assays demonstrated that PTEN suppression (or miR-132 overexpression) attenuated the effects of SNHG5 upregulation on COPD progression. In conclusion, the SNHG5-miR-132-PTEN axis might play critical roles in COPD development, providing an effective target for the treatment of COPD.

Pulmonary hypertension in chronic obstructive pulmonary disease.

Even mild pulmonary hypertension (PH) is associated with increased mortality and morbidity in patients with chronic obstructive pulmonary disease (COPD). However, the underlying mechanisms remain elusive; therefore, specific and efficient treatment options are not available. Therapeutic approaches tested in the clinical setting, including long-term oxygen administration and systemic vasodilators, gave disappointing results and might be only beneficial for specific subgroups of patients. Preclinical studies identified several therapeutic approaches for the treatment of PH in COPD. Further research should provide deeper insight into the complex pathophysiological mechanisms driving vascular alterations in COPD, especially as such vascular (molecular) alterations have been previously suggested to affect COPD development. This review summarizes the current understanding of the pathophysiology of PH in COPD and gives an overview of the available treatment options and recent advances in preclinical studies. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

Family determinants as a risk factor for chronic obstructive pulmonary disease: a systematic review

Introduction: Chronic obstructive pulmonary disease (COPD) is a preventable respiratory disease, with repercussion in quality of life. Worldwide COPD is a leading cause of mortality. Cigarette smoking is the most debated risk factor, but it’s important to identify other determinants at stake. Family context and behaviors have an impact in the individual’s health. Objective: This systematic review aims to characterize family determinants as possible risk factors for the development of COPD. Methods: A systematic search was conducted in PubMed, followed by a three-step selection process. Data was processed by two independent reviewers and studies were gathered based in pre-defined variables. English written, articles about risk factors for COPD related to the familiar context, meta-analysis, case control, cohort and cross-sectional studies were included. The family determinants considered were childhood maltreatment, education level of the patient, socioeconomic status and family history of tobacco. Results: From 196 references retrieved, inclusion and exclusion criteria were applied, and 8 studies were included. This review found six articles about education, one about socioeconomic status, one about family history of tobacco and one about childhood maltreatment as possible risk factors. One of the studies was a meta-analysis that did not contain any of the other studies included. Conclusions: Little evidence is available on the effect of family determinants in the development of COPD. The studies reported an association between COPD and low socioeconomic status and low education and an interaction with childhood maltreatment. Keywords: chronic obstructive pulmonary disease, family, risk factors

Assessment of CYP1A1 (MspI) Gene Polymorphism in Patients with Chronic Obstructive Pulmonary Disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is one of the most important causes of morbidity and mortality worldwide, characterized by persistent and progressive airflow limitations. The etiology seems to be an interaction between genetic and environmental factors. Objectives We aim in this present study to evaluate the role of Cytochrome P450 1A1 (CYP1A1 MspI) (3801 T/C) gene polymorphism in the development of Chronic Obstructive Pulmonary Disease ( COPD) by PCR-RFLP. Subjects and Methods Our study was performed on 50 subjects ( 35 COPD patients & 15 control ). Pulmonary function test was performed for patient group,DNA extraction was done and polymorphism was assayed for all participants by polymerase chain reaction-restriction fraction length polymorphism ( PCR-RFLP). Results We found that smoking rate among COPD patients was significantly higher than the control group ( P value = 0.003). The genotypic distribution of the single nucleotide polymorphisms (SNP) 3801 T/C did not differ significantly between patients and healthy controls (P value = 0.78).As regards disease severity , the genotype distribution was found to be significantly different between GOLD 1&2 and Gold 3&4 groups. Combined TC +CC alleles was found in 6 patients ( 100%) of Gold 3&4 ( P value<0.001) Conclusion Our study demonstrated that there is no relation between CYP1A1 gene polymorphism and development of COPD.It shows significant relation between COPD development and smoking, it also shows significant relation between MSPI gene polymorphism and disease severity regarding Gold staging and decline in lung function.

Role of Pneumocystis jirovecii infection in chronic obstructive pulmonary disease progression in an immunosuppressed rat Pneumocystis pneumonia model.

Pneumocystis jirovecii (P. jirovecii), an opportunistic fungal pathogen, is the primary cause of Pneumocystis pneumonia (PCP), which affects immunocompromised individuals and leads to high morbidity and mortality. P. jirovecii colonization is associated with development of chronic obstructive pulmonary disease (COPD) in patients with HIV infection, and also non-sufferers, and in primate models of HIV infection. However, the mechanisms underlying P. jirovecii infection in the pathogenesis of COPD have yet to be fully elucidated. To investigate the pathogenicity of P. jirovecii infection and its role in COPD development, the present study established a PCP rat model induced by dexamethasone sodium phosphate injection. Expression of COPD-related biomarkers, including matrix metalloproteinases (MMPs) MMP-2, MMP-8, MMP-9, and MMP-12, and heat shock protein-27 (HSP-27), were quantified in the rat PCP model using reverse transcription-quantitative polymerase chain reaction, ELISA, western blot analysis, immunohistochemistry and gelatin zymography. Body weight, COPD symptoms, and pulmonary histopathology were assessed. Inflammatory cell counts in splenic tissues were measured using flow cytometry. It was identified that MMP and HSP-27 expression increased in the PCP rats, which was in agreement with previous literature. Therefore, it was hypothesized that P. jirovecii infection may have an important role in COPD development.

Neutrophil-to-Lymphocyte Ratio, Lung Function, COPD, and <i>AHRR</i> Hypomethylation in Older Adults: A 30-Year Longitudinal Study of US Veterans

Background: Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil-to-lymphocyte ratio (NLR) is an inflammation biomarker and predictor for COPD morbidity and mortality; however, its associations with lung function decline and COPD development are incompletely understood. Methods: We performed a longitudinal study of US veterans with >30 years of follow-up to investigate the associations of NLR with lung function, COPD, and the hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 white males each examined up to 13 times during 1982-2018. NLR was estimated based on automated whole blood cell counts, and cg05575921 profile was measured in blood DNA using Illumina 450K BeadChip from a subset of 1228 visits. Findings: A one-unit increase in NLR was associated with a 0∙021-liter, 0∙016-liter, 0∙29%, and 3∙7-liters/min lower FEV1, FVC, FEV1/FVC, and MMEF, respectively (p-values <0∙001). NLR changes up to ~10 years were robustly associated with corresponding longitudinal changes in lung function. Further, this increase in NLR was associated with 9% higher odds of COPD (95% CI: 1∙03-1∙15) and 27% higher risk of incident COPD (95% CI: 1∙07-1∙51). NLR was associated with cg05575921 hypomethylation, which may mediate the adverse effect of NLR-related inflammation on lung function. Applying NLR and cg05575921 in combination could classify the extent of lung function impairment and COPD risk. Interpretation: NLR may be a valuable biomarker to promote the primary prevention of lung function decline and COPD in the general population. Funding Statement: This work was supported by the National Institute of Environmental Health Sciences (grants P30ES009089, R01ES021733, R01ES025225, and R01ES027747). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The NAS was approved by the Department of Veterans Affairs Boston Healthcare System, and each subject provided written informed consent before participation.

Chronic obstructive pulmonary disease: A review about gender differences

The major risk factor for chronic obstructive pulmonary disease (COPD) is smoking. COPD is thought to be traditionally a male illness, but its prevalence in women is increasing because they are adopting lifestyle habits similar to men. A literature review of publications indexed in MEDLINE, Latindex, SciELO, and DOAJ databases was carried out. Were considered 44 articles with relevance to the topic addressed. The literature review aim was to characterize the gender susceptibility differences in COPD development as well as the changes that this disease may induce in the lung function. Through the present literature review, it was verified that there are multiple aspects that contribute to gender inequalities in COPD development. Among them are genetic predisposition, hormonal factors, tobacco smoke components metabolization, anatomical and physiological characteristics, bronchial hyperreactivity, and noxious agent's exposure. Gender differences in deleterious effects of tobacco smoke on lung function do not hold consensus, as there are authors reporting a greater lung functional decline in women even when less exposed to harmful substances, while others have found no differences in many of lung functional parameters. The studies analyzed were different regarding methodology and sample characteristics, which may contribute to results discrepancy obtained by the researchers. COPD affects men and women in increasingly similar proportions, so it is important to identify and characterize the particularities of tobacco smoke effects in both genders to improve the knowledge about the disease.

Combined Antioxidant, Anti-inflammaging and Mesenchymal Stem Cell Treatment: A Possible Therapeutic Direction in Elderly Patients with Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide health problem associated with high morbidity and mortality, especially in elderly patients. Aging functions include mitochondrial dysfunction, cell-to-cell information exchange, protein homeostasis and extracellular matrix dysregulation, which are closely related to chronic inflammatory response and oxidation-antioxidant imbalance in the pathogenesis of COPD. COPD displays distinct inflammaging features, including increased cellular senescence and oxidative stress, stem cell exhaustion, alterations in the extracellular matrix, reduced levels of endogenous anti-inflammaging molecules, and reduced autophagy. Given that COPD and inflammaging share similar general features, it is very important to identify the specific mechanisms of inflammaging, which involve oxidative stress, inflammation and lung mesenchymal stem cell function in the development of COPD, especially in elderly COPD patients. In this review, we highlight the studies relevant to COPD progression, and focus on mechanisms associated with inflammaging.

Early COPD: current evidence for diagnosis and management.

Chronic obstructive pulmonary disease (COPD) affects one-tenth of the world’s population and has been identified as a major global unmet health need by the World Health Organisation, which predicts that within 10 years, COPD will become the third leading cause of death. Despite active research, there have been no recent major strides in terms of disease modifying treatment for COPD; smoking cessation remains the only intervention known to alter disease progression and improve mortality. As established COPD is a key driver of disease burden, earlier diagnosis coupled with disease-modifying intervention carries promise as a route to address this global health priority. The concept of early COPD is emerging as an area of focus for research and consideration of new treatment modalities, as it has been hypothesised that intervention at this stage may potentially halt or reverse the disease process. However, at present, a globally accepted criteria for defining early COPD does not exist. Several studies propose small airways disease as the earliest stage in the development of COPD, and this has been demonstrated to be a precursor to development of emphysema and to correlate with subsequent development of airflow obstruction. However, treatment strategies for early disease, which pre-date the development of airflow obstruction, remain uncertain. This review addresses the rationale and current evidence base for the diagnosis and treatment of early COPD and highlights the challenges of implementing trials and clinical pathways to address COPD earlier in the life course, particularly in the absence of a universally accepted definition of COPD. The reviews of this paper are available via the supplemental material section.

Regional differences in airway susceptibility to cigarette smoke: An investigational case study of epithelial function and gene alterations inin vitroairway epithelial three-dimensional cultures

Cigarette smoke (CS) is a risk factor contributing to lung remodeling in chronic obstructive pulmonary disease (COPD). COPD is a heterogeneous disease because many factors contribute in varying degrees to the resulting airflow limitations in different regions of the respiratory tract. This heterogeneity makes it difficult to understand mechanisms behind COPD development. In the current study, we investigate the regional heterogeneity of the acute response to CS exposure between large and small airways using in vitro three-dimensional (3D) cultures. We used two in vitro 3D human airway epithelial tissues from large and small airway epithelial cells, namely, MucilAir™ and SmallAir™, respectively, which were derived from the same single healthy donor to eliminate donor differences. Impaired epithelial functions and altered gene expression were observed in SmallAir™ exposed to CS at the lower dose and earlier period following the last exposure compared with MucilAir™. In addition, severe damage in SmallAir™ was retained for a longer duration than MucilAir™. Transcriptomic analysis showed that although well-known CS-inducible biological processes (i.e. inflammation, cell fate, and metabolism) were disturbed with consistent activity in both tissues exposed to CS, we elucidated distinctively regulated genes in only MucilAir™ and SmallAir™, which were mostly related to catalytic and transporter activities. Our findings suggest that CS exposure elicited epithelial dysfunction through almost the same perturbed pathways in both airways; however, they expressed different genes related to metabolic and transporter activities in response to CS exposure which may contribute to cytotoxic heterogeneity to the response to CS in the respiratory tract.

Some morphological factors of resistance of the bronchial wall to the development of chronic obstructive lung disease in smoking individuals

According to current epidemiological studies, chronic obstructive pulmonary disease (COPD) develops in only 15-20 % of smokers. This suggests that exposure to tobacco smoke is just a trigger of the pathological process, and other pathophysiological factors play a key role in the development of COPD. The aim of the study was to perform morphological analysis of bronchial mucosa features in smokers with and without chronic obstructive pulmonary disease. Material and research methods . Morphological and electron-microscopic analysis of biopsy samples of the bronchial mucosa of smoking patients with (n = 40) and without (n = 30) chronic obstructive pulmonary disease was carried out. The study involved men (80.2 % of men) and women aged 42 to 67 years (62.3 ± 2.24 years) with smoking experience of more than 20 years and smoking intensity of 20-45 pack-years. In the main group was a verified diagnosis of COPD. All patients of the studied groups underwent morphological, morphometric counting of bulk densities of various types of epithelial cells and structures of their lamina propria of the bronchial mucosa, as well as the density of inflammatory infiltrate and various cell populations, immunohistochemical (typing of CD4- and CD8positive lymphocytes, expression of transforming growth factor β 1 receptors) and electron microscopic analysis of bronchobioptates. Results and discussion . Smokers without chronic obstructive pulmonary disease develop exudative inflammation, which does not violate the structural architectonics of the epithelial layer, but causes activation of proteinsynthetic and energy processes in the epithelial cells of the bronchial wall. With prolonged exposure to tobacco smoke associated with the development of chronic obstructive pulmonary disease, chronic neutrophilic inflammation forms in the bronchial mucosa, leading to a violation of the functional morphology of the vessels and epithelial cells of the bronchial mucosa, followed by remodeling of the bronchial wall.

ВЗАИМОСВЯЗЬ СОСТОЯНИЯ БИОМЕМБРАН С ПОКАЗАТЕЛЯМИ ДИСФУНКЦИИ ЭНДОТЕЛИЯ У БОЛЬНЫХ С ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЁГКИХ

Objective: Examination the relationship between the state of biomembranes and indicators of endothelial dysfunction in patients with chronic obstructive pulmonary disease (COPD). Methods: 40 patients with COPD at the age of 27-64 years were treated at the City Health Center № 2 named after academician K.T. Tadzhiev. There were 21 men (52.5%), and 19 women (47.5%). The control group is represented by 30 healthy persons, comparable by sex and age. The content of inflammatory markers of vascular endothelium – CRP, fibrinogen and von Willebrand factor (VWF) – was studied. The functional state of erythrocyte membranes was studied by determining of permeability of erythrocyte membranes (PEM) and sorption ability of erythrocytes (SAE). Results: Study of endothelial dysfunction in patients with COPD showed an increase in fibrinogen content by 71.15% (2.6±0.08 and 4.45±0.16 g/L), VWF by 35.4% (95.7±2.3 and 129.6±2.3%) and an increase in serum CRP by 15 times (2.09±0.1 and 32.2±0.1 mg/L). There was a change in PEM and an increase in SAE by 27.8% (39.5±0.5 and 50.5±0.6%, respectively) compared with the control group, that reflects damage of erythrocytes and is considered as a factor of endogenous intoxication. A significant direct relationship was established between SAE and indicators of vascular dysfunction: with VWF (r=0.34; p&lt;0.05) and fibrinogen (r=0.47; p&lt;0.05). Conclusions: The development and progression of COPD are accompanied by dysfunction of the vascular endothelium, the criteria for which are an increase in the level of CRP, fibrinogen and VWF. On the background of COPD, erythrocytes are involved in the pathological process, which is confirmed by an increase in PEM and SAE and with a significant relationship between SAE and endothelial dysfunction. Laboratory manifestations of endothelial dysfunction accompanied by functional impairment of biomembranes (increased PEM and increased SAE), can be considered as a factor of the poor prognosis of COPD. Keywords: COPD , biomembrane, endothelial dysfunction, CRP, fibrinogen, von Willebrand factor, permeability of erythrocyte membranes, sorption ability of erythrocytes.

Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential.

There are rising evidences of the human microbiome as a potentially influential player that is actively engaged in shaping the pathogenetic processes and other unresolved issues both in asthma and other chronic respiratory diseases, particularly of the airways. The biological components such as microbiome in inhaled air can induce immune dysfunction and inflammation, leading to inflammatory pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Microbe-derived extracellular vesicles (EVs) with biologically active information or functions can reprogram their respective target cells and EV may have a role for the development of asthma and COPD. To evaluate the role of microbe-derived EV in the pathogenesis of asthma and COPD and its role in diagnosis, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement method was used for the study. An electronic search was performed using PubMed, PubMed Central, and Embase up to 2020. EVs serve as an intercellular transporter of miRNAs for cell-to-cell communication in the lungs. Bacteria-derived EVs have distinctive characteristics in the lungs of patients with asthma and COPD compared to healthy controls. Furthermore, bacterial EV IgG antibody titers in serum were significantly higher in patients with asthma and COPD than in healthy controls, suggesting that antibacterial EV antibodies titers can be used as a diagnostic tool for lung disease. Taken together, microbial EVs and miRNAs have important roles in the pathogenesis of asthma and COPD and they can provide novel diagnostic biomarkers for asthma and COPD.

Influence of smoking on forced expiratory volume in first second: A case-control study

Background: Smoking is one of the significant contributing risk factors for chronic obstructive pulmonary disease (COPD) and increases risk of death in cardiovascular and respiratory disorders. Aims and Objectives: This study was planned to see the influence of cigarette smoking on forced expiratory volume in first second (FEV1). Materials and Methods: FEV1 of 50 male moderate smokers (asymptomatic) and 50 healthy male non-smokers of age and height matched was recorded using RMS Helios 401 Spirometer. Results: The reduction of FEV1 in smokers was statistically significant. Conclusion: Smoking is preventable cause of COPD. Reduced FEV1 value in smokers is an indicator of risk factor for the development of COPD which can be prevented by early identification and proper counseling in asymptomatic smokers. This is important to prevent future complications.

Immunomodulatory Effects of Hydrolyzed Seawater Pearl Tablet (HSPT) on Th1/Th2 Functionality in a Mice Model of Chronic Obstructive Pulmonary Disease (COPD) Induced by Cigarette Smoke.

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death around the world. The present study is designed to investigate whether hydrolyzed seawater pearl tablet (HSPT) has immunoregulatory effects on the Th1/Th2 functionality in cigarette smoke-induced COPD model mice. The determination of the amino acid composition of HSPT was carried out by high-performance liquid chromatography (HPLC) with precolumn phenylisothiocyanate (PITC) derivatization. COPD model mice were constructed by cigarette smoking (CS) treatment and HSPT was administered. HSPT inhibited the infiltration of inflammation in the airway of the lung, reduced influx of eosinophils (EOSs), lymphocytes (LYMs), neutrophils (NEUs), and macrophages (MACs) in the bronchoalveolar lavage fluid (BALF), decreased the levels of IFN-γ, IL-2, IL-4, and IL-10 in the serum and lung, and decreased the expression of aforementioned cytokines in the spleen and lung in CS-treated mice. Besides, HSPT also had the ability to reduce the amount of CD3+CD4+ T cells and modulate the Th1/Th2 balance. Taken together, this study supports the consensus that CS is a critical factor to induce and aggravate COPD. HSPT could regulate the balance of Th1/Th2 in CS-induced COPD model mice, indicating its effects on inhibiting the development of COPD.

Metabolic profiling of chronic obstructive pulmonary disease model rats and the interventional effects of HuaTanJiangQi decoction using UHPLC-Q-TOF/MSE

The occurrence of chronic obstructive pulmonary disease (COPD) will lead to physiological and pathological variations and endogenous metabolic disorders. A traditional Chinese medicine formula, HuaTanJiangQi decoction (HTJQ), exhibits an unambiguous therapeutic effect on COPD in China. Nevertheless, the mechanism of its therapeutic effect on COPD is not clear. With this purpose, pulmonary function, histopathological and the inflammatory factors in bronchoalveolar lavage fluid (BALF) in rats model of COPD were investigated. Then, ultra high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) analysis and multivariate statistical analysis were used to further reveal the mechanism of HTJQ therapeutic effect on COPD via metabolomics study. The results showed that the characteristics of lung tissues were significantly reversed, the concentration of LTB4 and LTC4 were gradually decreased, and the lung function began to recover after HTJQ treatment. These typical indicators of COPD in HTJQ intervention group were reversed similar to the control group, suggested that HTJQ has a therapeutic effect on COPD. Moreover, 32 dysregulated metabolites, including Thromboxane a2, Sphingosine 1-phosphate, PC(18:2(9Z,12Z)/18:1(11Z)), Leukotriene B4, Glutathione, Arachidonic acid, Sphingosylphosphocholine acid, N-Acetyl-leukotriene e4, Lysopc(18:1(11Z)), L-Cysteine, and Guanosine diphosphate. All the altered metabolites were associated with the onset and development of COPD, and involved in glycerophospholipid metabolism, sphingolipid metabolism, glutathione metabolism, and arachidonic acid metabolism, which were significantly changed in rats model with COPD. Generally, these findings provide a systematic view of metabolic changes linked to the onset and development of COPD, also indicated that HTJQ could provide satisfactory therapeutic effects on COPD and metabolomics study can be utilized to further understand the molecular mechanisms.

Distinct Chronic Post-Viral Lung Diseases upon Infection with Influenza or Parainfluenza Viruses Differentially Impact Superinfection Outcome

Chronic obstructive pulmonary disease (COPD) and asthma remain prevalent human lung diseases. Variability in epithelial and inflammatory components that results in pathologic heterogeneity complicates the development of treatments for these diseases. Early childhood infection with parainfluenza virus or respiratory syncytial virus is strongly associated with the development of asthma and COPD later in life, and exacerbations of these diseases correlate with the presence of viral RNA in the lung. Well-characterized animal models of postviral chronic lung diseases are necessary to study the underlying mechanisms of viral-related COPD and asthma and to develop appropriate therapies. In this study, we cross-analyzed chronic lung disease caused by infection with Sendai virus (SeV) or influenza A virus in mice. Differences were observed in lesion composition and inflammatory profiles between SeV- and influenza A virus-induced long-term lung disease. In addition, a primary SeV infection led to worsened pathologic findings on secondary heterologous viral challenge, whereas the reversed infection scheme protected against disease in response to a secondary viral challenge >1 month after the primary infection. These data demonstrate the differential effect of primary viral infections in the susceptibility to disease exacerbation in response to a different secondary viral infection and highlight the usefulness of these viral models as tools to understand the underlying mechanisms that mediate distinct chronic postviral lung diseases.

Acute air pollution exposure alters neutrophils in never-smokers and at-risk humans.

Outdoor air pollution exposure increases chronic obstructive pulmonary disease (COPD) hospitalisations, and may contribute to COPD development. The mechanisms of harm, and the extent to which at-risk populations are more susceptible are not fully understood. Neutrophils are recruited to the lung following diesel exhaust exposure, a model of traffic-related air pollution (TRAP), but their functional role in this response is unknown. The purpose of this controlled human-exposure crossover study was to assess the effects of acute diesel exhaust exposure on neutrophil function in never-smokers and at-risk populations, with support from additional in vitro studies.18 participants, including never-smokers (n=7), ex-smokers (n=4) and mild-moderate COPD patients (n=7), were exposed to diesel exhaust and filtered air for 2 h on separate occasions, and neutrophil function in blood (0 h and 24 h post-exposure) and bronchoalveolar lavage (24 h post-exposure) was assessed.Compared to filtered air, diesel exhaust exposure reduced the proportion of circulating band cells at 0 h, which was exaggerated in COPD patients. Diesel exhaust exposure increased the amount of neutrophil extracellular traps (NETs) in the lung across participants. COPD patients had increased peripheral neutrophil activation following diesel exhaust exposure. In vitro, suspended diesel exhaust particles increased the amount of NETs measured in isolated neutrophils. We propose NET formation as a possible mechanism through which TRAP exposure affects airway pathophysiology. In addition, COPD patients may be more prone to an activated inflammatory state following exposure.This is the first controlled human TRAP exposure study directly comparing at-risk phenotypes (COPD and ex-smokers) with lower-risk (never-smokers) participants, elucidating the human susceptibility spectrum.