Macrophages are highly plastic and can be polarized into classical activated macrophages (M1) and alternative activated macrophages (M2) under the induction of inflammatory factors and regulation of a variety of information molecules. Chronic pulmonary inflammation and pulmonary parenchyma injury are the main pathological manifestations of chronic obstructive pulmonary disease (COPD). M1 promotes pulmonary inflammation, whereas M2 inhibits inflammatory response, participates in lung tissue injury and repair, and swallows and removes pathogenic microorganisms and apoptotic cells. Target intervention in the polarization direction of macrophages may be a new strategy for COPD treatment.
Humans ; Lung ; Macrophages ; cytology ; Pulmonary Disease, Chronic Obstructive ; pathology

Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease, featured by airflow obstruction. Recently, a comprehensive analysis of the transcriptome in lung tissue of COPD patients was performed, but the heterogeneity of the sample was not seriously considered in characterizing the mechanistic dysregulation of COPD. Here, we established a new transcriptome analysis pipeline using a deconvolution process to reduce the heterogeneity and clearly identified that these transcriptome data originated from the mild or moderate stage of COPD patients. Differentially expressed or co-expressed genes in the protein interaction subnetworks were linked with mitochondrial dysfunction and the immune response, as expected. Computational protein localization prediction revealed that 19 proteins showing changes in subcellular localization were mostly related to mitochondria, suggesting that mislocalization of mitochondria-targeting proteins plays an important role in COPD pathology. Our extensive evaluation of COPD transcriptome data could provide guidelines for analyzing heterogeneous gene expression profiles and classifying potential candidate genes that are responsible for the pathogenesis of COPD.
Gene Expression Profiling ; Humans ; Lung ; Lung Diseases ; Mitochondria ; Pathology ; Population Characteristics ; Pulmonary Disease, Chronic Obstructive ; Transcriptome

OBJECTIVEAsthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases.

DATA SOURCESArticles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of "asthma" or "pulmonary disease, chronic obstructive", "neutrophils" and "extracellular traps."

STUDY SELECTIONArticles were obtained and reviewed to analyze the role of NETs in asthma and COPD.

RESULTSNETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease.

CONCLUSIONSExcessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

Animals ; Asthma ; metabolism ; pathology ; Extracellular Traps ; metabolism ; physiology ; Humans ; Neutrophils ; metabolism ; pathology ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology

AIMTo elucidate the location and effects of transcription factor-nuclear factor-kappaB (NF-kappaB) in lung tissues of rats with chronic obstructive pulmonary disease (COPD).

METHODSFourteen male Wistar rats were randomly divided into COPD model and control groups equally. The COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposure to cigarette smoke daily. We detected the NF-kappaB p65 protein in lung by immunohistochemical method, and the expression of NF-kappaB p65 mRNA in lung by in situ hybridization.

RESULTSImmunohistochemistry, the expression of NF-kappaB p65 protein in alveolar, bronchiolar epithelium and arteriolar endothelium was significantly higher in the COPD group (0.426 +/- 0.007, 0.434 +/- 0.012 and 0.313 +/- 0.007, respectively) than those of the control group (0.115 +/- 0.006, 0.116 +/- 0.005 and 0.095 +/- 0.007, respectively, all P < 0.01). In situ hybridization showed that the expressions of NF-kappaB p65 mRNA in alveolar epithelium (0.203 +/- 0.008), bronchiolar and arteriolar smooth muscle cell (0.208 + 0. 010 and 0.206 + 0.007) of rats in the COPD group were stronger than those in the control group (0.100 +/- 0.006, 0.102 +/- 0.002 and 0.103 +/- 0.003 respectively) by semiquantitative analysis (all P < 0.01).

CONCLUSIONThe expression and nuclear translocation of NF-kappaB may be the basis event of gene expression of many cytokines and inflammatory mediators, which may positively regulate gene expression of many cytokines and inflammatory mediators in various cell lines.

Animals ; Lung ; metabolism ; pathology ; Male ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Rats ; Rats, Wistar ; Transcription Factor RelA ; metabolism

Bone marrow mesenchymal stem cells (MSCs) transplantation could repair injury tissue, but no study confirms whether MSCs can promote the proliferation of endogenous lung stem cells to repair alveolar epithelial cells of mice with chronic obstructive pulmonary disease (COPD). This study was designed to investigate the effect of MSCs on the proliferation of endogenous lung stem cells in COPD mice to confirm the repair mechanism of MSCs. The mice were divided into control group, COPD group, and COPD+MSCs group. The following indexes were detected: HE staining of lung tissue, the mean linear intercept (MLI) and alveolar destructive index (DI), the total cell number in bronchoalveolar lavage fluid (BALF), pulmonary function, alveolar wall apoptosis index (AI) and proliferation index (PI), the number of CD45(-)/CD31(-)/Sca-1(+) cells by flow cytometry (FCM), and the number of bronchoalveolar stem cells (BASCs) in bronchoalveolar duct junction (BADJ) by immunofluorescence. As compared with control group, the number of inflammatory cells in lung tissue was increased, alveolar septa was destroyed and the emphysema-like changes were seen, and the changes of lung function were in line with COPD in COPD group; AI of alveolar wall was significantly increased and PI significantly decreased in COPD group. There was no significant difference in the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs between control group and COPD group. As compared with COPD group, the number of inflammatory cells in BALF was decreased, the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs was increased, AI of alveolar wall was decreased and PI was increased, and emphysema-like changes were relieved in COPD+MSCs group. These findings suggested that MSCs transplantation can relieve lung injury by promoting proliferation of endogenous lung stem cells in the cigarette smoke-induced COPD mice.
Animals ; Cell Proliferation ; Lung ; pathology ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive ; pathology ; therapy

BACKGROUND: The effect of PEEP(ed note: Define PEEP.) on the lung volume in patients with auto-PEEP during mechanical ventilation is not even. In patients with an expiratory limitation such as COPD, a PEEP of 85% from an auto-PEEP can be used with minimal increase in the lung volume. However, the application of PEEP to patients without an expiratory flow limitation can result in progressive lung. This study was carried out to evaluate the different PEEP effects on the lung volume according to the different pulmonary diseases. METHODS: Sixteen patients who presented with auto-PEEP during mechanical ventilation were enrolled in this study. These patients were divided into 3 groups: asthma, COPD and tuberculosis sequela (patients with severe cicatrical fibrosis as a result of previous tuberculosis and compensatory emphysema). A PEEP of 25, 50, 75 and 100% of the auto-PEEP was applied, and the lung volume increments were estimated using the trapped lung volume. RESULTS: In the asthma group, the trapped lung volume was not increased at a PEEP of 25 and 50% of the auto-PEEP. This group showed a significant lung volume increment from a 75% PEEP. In the COPD group, the lung volume was increased only at 100% PEEP. In the tuberculosis sequela group, the lung volume was increased progressively from low PEEP levels. However, a significant increment of the lung volume was noted only at 100% PEEP. CONCLUSION: The effects of the applied PEEP on the lung volume were different depending on the underlying lung pathology. The level of the applied PEEP >50% of the auto-PEEP might increase the trapped lung volume in patients with asthma.
Asthma ; Fibrosis ; Humans ; Lung Diseases* ; Lung* ; Pathology ; Positive-Pressure Respiration, Intrinsic* ; Pulmonary Disease, Chronic Obstructive ; Respiration, Artificial ; Tuberculosis

BACKGROUNDAnxiety and depression are two of the commonest and most modifiable comorbidities of chronic obstructive pulmonary disease (COPD) and have an independent effect on health and prognosis. FEV1% has been shown to be a poor predictor of anxiety and depression. The body mass index, degree of airflow obstruction, dyspnea, and exercise capacity (BODE) index is a multidimensional assessment system which may predict health outcome in COPD patients. The purpose of this study was to investigate the predictive validity of the BODE index for anxious and depressive symptoms in COPD patients.

METHODSThis was a multicenter prospective cross-sectional study in 256 patients with stable COPD. Anxious and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). The relationships between anxiety, depression and potential predictors (including the BODE index) were analyzed by a binary Logistic regression model.

RESULTSSubjects who were anxious and depressive walked a shorter six-minute walking distance (6MWD), had more dyspnea, a higher BODE index, and lower health-related quality of life (P < 0.01). Anxiety and depression score was significantly correlated with BODE index, respectively (r = 0.335, P < 0.001; r = 0.306, P < 0.001). The prevalence of anxiety and depression increased with BODE stage increasing (P < 0.05). On the basis of binary Logistic regression, the BODE index was a good and independent predictor of anxiety and depression because it comprised dyspnea and 6MWD, which were shown to be the main determinants.

CONCLUSIONSThe predictive validity of the BODE index for anxiety and depression was demonstrated. We propose that the BODE index should be included in assessment of COPD severity.

Anxiety ; diagnosis ; Cross-Sectional Studies ; Depression ; diagnosis ; Humans ; Multivariate Analysis ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; pathology ; psychology

BACKGROUNDCritically ill chronic obstructive pulmonary disease (COPD) patients admitted to an intensive care unit (ICU) due to respiratory failure are at particularly high risk of Aspergillus infection. The serum galactomannan index (GMI) has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis (IPA) in classical immunocompromised patients. However, the prognostic value of serum GMI in critically ill COPD patients needs evaluation. The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.

METHODSIn this single-center prospective cohort study, serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients' discharge or death. Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission. Univariate analysis and survival analysis were tested in these two groups.

RESULTSOne hundred and fifty-three critically ill COPD patients were included and were divided into survival group (106 cases) and non-survival group (47 cases) according to their outcome. Univariate analysis showed that the highest GMI level during the first week after admission (GMI-high 1st week) was statistically different between the two groups. Independent prognostic factors for poor outcome in severe COPD patients were: GMI-high 1st week >0.5 (RR: 4.04, 95% CI: 2.17-7.51) combined with accumulative dosage of corticosteroids >216 mg before the RICU admission (RR: 2.25, 95% CI: 1.11-4.56) and clearance of creatinine (Ccr) ≤ 64.31 ml/min (RR: 2.48, 95% CI: 1.22 ± 5.07).

CONCLUSIONSThe positive GMI-high 1st week (>0.5) combined with an accumulative dosage of corticosteroids >216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.

Aged ; Aged, 80 and over ; Critical Illness ; Female ; Humans ; Invasive Pulmonary Aspergillosis ; blood ; complications ; pathology ; Male ; Mannans ; blood ; Middle Aged ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; blood ; etiology ; pathology

Adrenal Cortex Hormones ; metabolism ; Adrenergic beta-2 Receptor Agonists ; metabolism ; Humans ; Multiple Pulmonary Nodules ; diagnosis ; metabolism ; pathology ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; metabolism ; pathology ; World Health Organization

Aged ; Bronchiectasis ; etiology ; pathology ; Comorbidity ; Dyspnea ; etiology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; complications ; pathology ; Smoking ; adverse effects