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Small airway immunoglobulin A profile in emphysema-predominant chronic obstructive pulmonary disease

Chinese Medical Journal 2020年第16期133卷 1915-1921页

作者： Hu Liu Huo-Yan Tang Jian-Ying Xu Zhi-Gang Pang Department of Respiratory Medicine Shanxi Bethune Hospital Affiliated to Shanxi Medical UniversityTaiyuanShanxi 030032China Shanxi Medical University TaiyuanShanxi 030001China

Background:Due to airway remodeling and emphysematous destruction in the lung,the two classical clinical phenotypes of chronic obstructive pulmonary disease(COPD)are emphysema and bronchiolitis.The present study was designed to investigate the levels of small airway immunoglobulin A(IgA)in COPD with“emphysema phenotype.”The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation.Methods:Thirty patients(20 with COPD and ten healthy smokers)undergoing lung resection surgery for a solitary peripheral nodule were included.The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital.The presence of small airway IgA expression was determined in the lung by immunohistochemistry.In vivo,Wistar rats were exposed to silica by intratracheal instillation.Rats were sacrificed at 15 and 30 days after exposure of silica(n=10 for each group).We also evaluated airway IgA from rats.Results:Small airway secretory IgA(sIgA),dimeric IgA(dIgA),and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1–2 COPD patients showed no difference compared with smoking control subjects(5.15±1.53 vs.6.03±0.85;1.94±0.66 vs.1.67±0.04;41.69±21.02 vs.28.44±9.45,all P>0.05).dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema(51.89±24.81 vs.31.49±9.28,P=0.03).The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels(r=0.45,P=0.047),but not associated with the severity of disease by spirometric measurements(forced expiratory volume in the first second%pred,P>0.05).Likewise,in the rat study,significant differences in sIgA,dIgA,dIgA/sIgA,mean linear intercept,mean alveoli number,and mean airwaythickness of bronchioles(VVairway,allP<0.01)were only observed between control rats and those exposed for 30 days.However,in the group exposed for 15 days,although theVVairwaywas higher than th

关键词： Immunoglobulin A B cell emphysema Chronic obstructive pulmonary disease

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Animal models of emphysema

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Chinese Medical Journal 2019年第20期132卷 2465-2475页

作者： Gui-Bin Liang Zhi-Hui He Department of Intensive Care Unit The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

Objective:Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease of human beings characterized by not fully reversible airflow limitation. emphysema is the main pathological feature of COPD which causes high mortality worldwide every year and consumes a large amount of medical expenses. This paper was to review the establishment and evaluation methods of animal models of emphysema or COPD, and put forward some new ideas on animal selection, method of modeling, and model evaluation.Data sources:The author retrieved information from the PubMed database up to July 2019, using various combinations of search terms, including emphysema, model, and animal.Study selection:Original articles, reviews, and other articles were searched and reviewed for animal models of emphysema.Results:This review summarized animal models of emphysema from the perspectives of animal selection, emphysema mechanism, modeling method and model evaluation, and found that passive smoking is the classic method for developing animal model of emphysema, mice are more suitable for experimental study on emphysema. Compared with pulmonary function indicators, airway inflammation indicators and oxidative stress indicators, pathomorphological indicators of lung tissue are the most important parameters for evaluating the establishment of the animal model of emphysema.Conclusions:Mice model induced by passive smoking is the classic animal model of emphysema. Pathomorphological indicators are the most important parameters for evaluating the establishment of the animal model of emphysema.

关键词： Animal Chronic obstructive pulmonary disease emphysema Model

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Cigarette smoking contributes to idiopathic pulmonary fibrosis associated with emphysema

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Chinese Medical Journal 2014年第3期127卷 469-474页

作者： Ye Qiao Huang Kewu Ding Yi Lou Baohui Hou Ziliang Dai Huaping Wang Chen Department of Respiratory and Critical Care Medicine Beijing Chao Yang Hospital Capital Medical University Beijing 100020 China Department of Radiology Beijing Chao Yang Hospital Capital Medical University Beijing 100020 China Institute of Respiratory Medicine Beijing Hospital Ministry of Heath Beijing 100730 China

Background Combined emphysema and pulmonary fibrosis,including idiopathic pulmonary fibrosis （IPF）,is a distinct disorder described with upper-lobe emphysema and lower-lobe fibrosis on chest computed tomography.Smoking appears to be the predominant risk factor for this disorder.We aimed to compare clinical features,smoking history,physiological and radiological findings between IPF with and without emphysema.Methods A sample of 125 IPF patients over a period of 48 months were evaluated.High resolution CT scans were reviewed blinded to clinical data.The IPF patients with or without emphysema were classified accordingly.Results The prevalence of emphysema in this IPF sample was 70/125.IPF with emphysema was significantly associated with smoking status （OR 63; 95％ CI 4.4 to 915; P=0.002） and smoking pack year （OR 1.1; 95％ CI 1.05 to 1.13; P=-0.000）.The patients with IPF and emphysema had a higher decrease in carbon monoxide diffusing capacity adjusted for alveolar volume （（58±19）％ pred vs.（66：±：21）％ pred; P=-0.021） and a higher prevalence of pulmonary hypertension （24/70 vs.7/55; P=0.006）.The two groups of patients had similar forced and residual volumes.No significant differences were found in cell differentials of bronchoalveolar lavage or the scores of fibrosis on chest CT.Survival of the patients with emphysema was significantly less than that of patients with IPF alone.Conclusions Cigarette smoking induces IPF combined with emphysema.emphysema further impairs physiological function and increases the prevalence of pulmonary hypertension that leads to poor prognosis.The inclusion of the patients with combined pulmonary fibrosis and emphysema in IPF clinical trials may lead to under evaluation of the effect of treatment in patients.

关键词： idiopathic pulmonary fibrosis emphysema smoking

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Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema

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Chinese Medical Journal 2012年第17期125卷 3015-3021页

作者： ZHAO Ying CUI Ai WANG Feng WANG Xiao-juan CHEN Xing JIN Mu-lan HUANG Ke-wu Division of Pulmonary and Critical Care Medicine Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Basic Medical Research Center Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Department of Pathology Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Beijing Institute of Respiratory Medicine Beijing 100020 China Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders Beijing 100020 China

Background The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema （CPFE）. CPFE has distinct clinical characteristics compared with emphysema alone （EA） and idiopathic pulmonary fibrosis （IPF） without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF. Methods Fraction exhaled nitric oxide （Fe,NO） and differential cell counts, the concentrations of monokine induced by interferon gamma （MIG/CXCL9）, interferon-inducible protein 10 （IP-10/CXCL10）, and interferon-inducible T cell alpha chemoattractant （I-TAC/CXCL11） were measured in induced sputum obtained from subjects with CPFE （n=22）, EA （n=22）, IPF （n=14）, and healthy volunteers （HV, n=12）. In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects. Results The CPFE group had higher alveolar NO than subjects in the EA and HV groups （P=0.009, P=-0.001, respectively） but not than the IPF group （P 〉0.05）. Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group （P=-0.001, P=-0.008）. In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants （P=0.003, P=0.004）. Immunoreactivity for inducible nitric oxide synthase （iNOS） was higher in the CPFE group than in the EA group （P=-0.018, P=0.006, respectively）. Conclusions The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophi

关键词： pulmonary fibrosis emphysema airway inflammation exhaled nitric oxide

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Oxidative stress and peripheral skeletal muscle dysfunction in rats with emphysema

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Chinese Medical Journal 2010年第1期123卷 40-44页

作者： ZHANG Xiao-lei PANG Bao-sen HOU Xiao-li WANG Jun WANG Chen Department of Respiratory Medicine Beijing Institute ofRespiratory Medicine Beijing Chaoyang Hospital Capital MedicalUniversity Beijing 100020 China Department of Physiology Capital Medical University Beijing100069 China

Background Peripheral skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease （COPD） may be due to the disease per se or as a result of concomitant confounding factors. Although the mechanistic basis for this functional impairment is uncertain, oxidative stress may play a role. The purpose of this study was to investigate whether local oxidative stress is associated with the reduced peripheral skeletal muscle performance in rats with emphysema. Methods In situ mechanical properties of gastrocnemius were measured in Sprague-Dawley rats 5 months after intratracheal instillation of either elastase （EMP, n=-10） or normal saline （CON, n=10）. Lipofuscin inclusions, myocyte apoptosis and antioxidant enzyme activities were examined in the gastrocnemius muscle. Results Lipofuscin inclusions were significantly higher in the gastrocnemius muscle of EMP compared with CON （3.2_--,-0.4 vs. 1.7_＋0.4, P〈0.01 ）. The activities of antioxidant enzymes were significantly increased in muscle homogenates of EMP as compared to CON. No significant differences were found in myocyte apoptosis between EMP and CON （1.2±0.9 vs. 1.0±0.8, P 〉0.05）. EMP decreased the fatigue endurance of gastrocnemius muscle （half-time to fatigue recovery：（150.0±55.4） seconds vs. （55.2±29.3） seconds, P 〈0.01） and had no effect on maximal tetanic force （（467.4±36.6） g vs. （493.2±30.5） g, P 〉0.05）. A significantly positive correlation was found between the level of lipofuscin inclusions and the half-time to fatigue recovery of gastrocnemius muscle in EMP （r=0.664, P 〈0.05）. Conclusion Local oxidative stress may have important functional consequences for peripheral skeletal muscle in rats with EMP.

关键词： emphysema peripheral skeletal muscle dysfunction oxidative stress

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Infliximab protects against pulmonary emphysema in smoking rats

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Chinese Medical Journal 2011年第16期124卷 2502-2506页

作者： ZHANG Xiang-yan ZHANG Cheng SUN Qian-yun LI Dan LUO Rong-rong WAN Zi-fen YE Xian-wei LIU Wei-jia RAO Shan-shan HAN Jing Department of Respiratory Medicine Guizhou Provincial People'sHospital Guiyang Guizhou 550002 China Key Laboratory of Chemistry for Natural Products of GuizhouProvince and Chinese Academy of Sciences Guiyang Guizhou550002 China

Background It is widely accepted that tumor necrosis factor-a （TNF-a） plays an important role in the pathogenesis of emphysema. This study aimed at investigating the protective effects of anti-TNF-a antibody, infliximab, in the development of emphysema induced by passive smoking in rats. Methods Thirty-nine rats were randomly divided into a normal control group （group 1）, an emphysema group （group 2）, and an infliximab-intervention group （group 3）. Rat models of emphysema were established by exposure to cigarette smoking daily for 74 days. After 1 month, the infliximab intervention group was treated with infliximab via subcutaneous injection. The levels of TNF-a, IL-8 and vascular endothelial growth factor （VEGF） in bronchoalveolar lavage fluid （BALF） were measured with enzyme linked immunosorbent assay （ELISA）. The number and classification of cells in the BALF were measured. Lung tissue sections stained by hematoxylin and eosin （HE） were observed, and mean linear intercept （MLI） and mean alveolar numbers （MAN） were measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） methods were used to examine the percentage of positive cells and distribution of apoptotic cells. Results The levels of TNF-a and IL-8 in BALF were higher in group 2 than in group 1 and group 3. The MLI was greater in group 2 than that in group 1 and group 3 while MAN was decreased. The concentration of VEGF in BALF of group 2 was significantly decreased as compared with group 1. The total cells and neutrophils number was significantly increased in group 2 as compared with group 1 and group 3, so was the percentage of neutrophils. The number of TUNEL positive cells in the alveolar septa was significantly increased in group 2 as compared with group 1 and group 3. Conclusion Infliximab protects against cigarette smoking-induced emphysema by reducing airway inflammation, attenuating alveolar septa cell apoptosis and improving pathological changes.

关键词： tumor necrosis factor-a infliximab emphysema rat

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Apoptosis of Alveolar Wall Cells in Chronic Obstructive Pulmonary Disease Patients with Pulmonary emphysema Is Involved in emphysematous Changes

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第4期29卷 466-469页

作者：刘红梅马利军吴纪珍王凯陈献亮 Division of Respiratory Diseases Department of Internal MedicineHe'nan Provincial People's Hospital

This study explored the role of apoptosis of alveolar wall cells of chronic obstructive pulmonary disease （COPD） patients with pulmonary emphysema in the pathogenesis of emphysema. The subjects were divided into three groups： COPD patients with pulmonary emphysema （COPD group）, asymptomatic smokers and non-smokers. Lung tissues were harvested and histologically assessed. TUNEL assay was employed to determine the ap＇optotic cells. The expression of PCNA, Bax and SP-C in the lung alveolar wall cells were immunohistochemically determined. SP-C immunofluorescence staining was used to identify type Ⅱ alveolar cells in the TUNEL-positive cells. The mean linear interval （MLI）, mean alveoli number （MAN） and mean alveoli area （MAA） in COPD group were significantly different as compared with those in asymptomatic smokers and non-smokers, respectively （P〈0.01）. The proliferation index （PI）, apoptosis index （AI） and the percentage of Bax-positive cells in COPD group were significantly greater than those of asymptomatic smokers and non-smokers （P〈0.01）. However, the percentage of SP-C-positive cells was significantly lower in COPD group than in asymptomatic smokers and non-smokers （P〈0.01）. Most of the TUNEL-positive cells expressed SP-C. In COPD group, the apoptosis of alveolar wall cells, especially apoptosis of type- Ⅱ cells, may take part in the pathogenesis of emphysema. Up-regulation of Bax expression may be responsible for the apoptosis of alveolar wall cells in the COPD patients with pulmonary emphysema.

关键词： emphysema apoptosis proliferation

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Interaction of Wnt/β-catenin and Nrf2 pathways in cigarette smoke-induced inflammation and emphysema

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中国药理学与毒理学杂志 2016年第10期30卷 1035-1036页

作者： CUI Wen-hui MO Xiao-ting ZHOU Wen-cheng ZHANG Zhi-hui GAO Jian School of Pharmacy Anhui Medical University The First Affiliated Hospital of Anhui Medical University The Second Affiliated Hospital of Dalian Medical University

OBJECTIVE The present study aimed to investigate the relationship between Wnt/β-catenin and Nrf2 signaling pathways,and understanding the mechanisms underlying the process of inflammatory in chronic obstructive pulmonary disease(COPD),which was a serious disease of respiratory system.METHODS We duplicate the emphysema model with porcine pancreatic elastase(PPE)in Nrf2-/-and WT mouse for 21d,and intraperitoneal injection of Li Cl,the activator of Wnt/β-catenin signaling pathway from 14 d to the end.Hematoxylin and eosin(H&E)staining was performed to assess the histopathologic level,and immunohistochemistry(IHC)for Mac-3(the marker of macrophagocyte)and Ly6G(the marker of neutrophil)was used to observe the inflammatory infiltrate,while the levels of Wnt/β-catenin and Nrf2 signaling pathways related proteins heme oxygenase-1(HO-1),NAD(P)H:quinone oxidoreductase 1(NQO1),and the expression of inflammatory cytokine interleukin-6(IL-6)were detected by Western blotting of lung tissues.In vitro,cigarette smoke extract(CSE)-treated normal human bronchial epithelial(NHBE)cells,cell viability was examined by MTT assay,and then we treated recombinant human Wnt3a,si Nrf2 and si Wnt3a to measure the expression of Wnt3a,β-catenin,Nrf2,HO-1,NQO-1,and IL-6.Cellular immunofluorescence staining was employed to identify the nuclear translocation of Nrf2.RESULTS We found that the Li Cl-treated group has markedly decreased the damage of alveolar structure and inflammatory signs than the model group of WT mice rather than Nrf2-/-group.It also seen that Li Cl not only increasedβ-catenin,but it also led to a comparable increase in Nrf2,HO-1,NQO1,and decrease of IL-6 compared with WT model groups but except to Nrf2-/-group in vivo.And it showed that Wnt3atreatment has significantly increased the nuclear translocation of Nrf2 and the expression of HO-1 and NQO1,reduced the IL-6 release,while there has no significance when Nrf2 was blocked in CSE-induced NHBE cells.CONCLUSION Our results demonstrated that Wnt3a/β-catenin significantly balanc

关键词： chronic obstructive pulmonary disease emphysema interleukin-6 inflammation nuclear factor erythroid-2-related factor-2 Wnt/β-catenin

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Electrocardiographic changes in emphysema

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World Journal of Cardiology 2021年第10期13卷 533-545页

作者： Puneet Gupta Hitangee Jain Misbah Gill Gurpreet Bharaj Nauman Khalid Waseem Chaudhry Lovely Chhabra Department of Interventional Cardiology Northeast Ohio Medical UniversityCantonOH 44272United States BA-MD Brooklyn CollegeBrooklynNY 11210United States Department of Family Medicine Memorial Hospital of CarbondaleCarbondaleIL 62901United States Psychiatry Loretto HospitalChicagoIL 60644United States Department of Interventional Cardiology St.Francis Medical CenterMonroeLA 71201United States Department of Cardiology Westchester Medical Center Network Advanced Physician ServicesPoughkeepsieNY 12601United States

Chronic obstructive lung disease(COPD),predominantly emphysema,causes several thoracic anatomical and hemodynamic changes which may cause changes in various electrocardiographic parameters.A 12-lead electrocardiogram(ECG),which is often a part of routine evaluation in most clinical settings,may serve as a useful screening modality for diagnosis of COPD or emphysema.Our current article aims to provide a comprehensive review of the electrocardiographic changes encountered in COPD/emphysema utilizing published PubMed and Medline literature database.Several important ECG changes are present in COPD/emphysema and may serve as a good diagnostic tool.Verticalization of Pvector,changes in QRS duration,pattern recognition of precordial R-wave progression and axial shifts can be considered some of the most valuable markers among other changes.In conclusion,12-lead surface electrocardiogram can serve as a valuable tool for the diagnosis of COPD and/or emphysema.An appropriate knowledge of these ECG changes can not only help in the diagnosis but can also immensely help in an appropriate clinical management of these patients.

关键词： emphysema Chronic obstructive pulmonary disease Electrocardiogram Pwave axis Sensitivity Specific

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Pulmonary fibrosis and emphysema: Is the emphysema type associated with the pattern of fibrosis?

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World Journal of Radiology 2015年第9期7卷 294-305页

作者： Anastasia Oikonomou Paraskevi Mintzopoulou Argyris Tzouvelekis Petros Zezos George Zacharis Anastasios Koutsopoulos Demosthenes Bouros Panos Prassopoulos Department of Radiology Democritus University of Thrace Department of Medical Imaging Sunnybrook Health Sciences Centre Department of Pneumonology Democritus University of Thrace Yale School of Medicine Department of Internal Medicine Section of Pulmonary Critical Care and Sleep Medicine Department of Endoscopic Unit Democritus University of Thrace Department of Internal Medicine Division of Gastroenterology Sunnybrook Health Sciences Centre Department of Pathology Democritus University of Thrace Department of Pathology University of Herakleion

AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on- HRCT-were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular(CLE), paraseptal(PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia(UIP), probable UIP and nonspecific interstitial pneumonia(NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis(Coarseness), extent of emphysema(emphysema), extent of interstitial lung disease(Tot Ext ILD), extent of reticular pattern not otherwise specified(Ret NOS), extent of ground glass opacity with traction bronchiectasis(extG GOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity(DLCO) and systolic pulmonary arterial pressure were compared among the groups.RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema(P emphysema(P < 0.05), total lung capacity(P < 0.01) and diffusion capacity(DLCO)(P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, e

关键词： emphysema Pulmonary fibrosis High resolution compu

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