Objective To investigate the role of vascular endothelial growth factor ( VEGF) in the pathogenesis of emphysema and its relationship with tumor necrosis factor alpha ( TNF-α) . Methods 48 rats were randomly divided into four groups, ie. a normal control group, an emphysema group, a rhTNFR∶Fc intervention group, and a sham intervention group. The rats in the emphysema group, the rhTNFR: Fc intervention group, and the shamintervention group were exposed to cigarette smoking for 80 days. After 30 days of exposure, rhTNFR: Fc hypodermic injection was administered in the rhTNFR: Fc intervention group while placebo was injected in the sham intervention group as control. Lung tissue sections were stained by hematoxylin and eosin. Mean linear intercept ( MLI) and mean alveolar numbers ( MAN) were measured to estimate the extent of emphysema. The level of TNF-αin serumand BALF, and the level of VEGF in BALF were measured with ELISA. Results In the emphysema group, MLI was higher and MAN was lower than those in the normal control group. Moreover, the levels of TNF-αin serum and BALF were higher, and thelevel of VEGF in BALF was lower significantly ( P lt;0. 05) . After the intervention with rhTNFR∶Fc, MAN increased and the serum TNF-αdecreased significantly compared with the emphysema group ( P lt; 0. 05) .However there were no significant differences in MLI, VEGF, and TNF-α in BALF ( P gt; 0. 05 ) . No correlation was found between the level of TNF-αand VEGF in BALF in the emphysema group. Conclusion VEGF and TNF-αare related to the pathogenesis of emphysema of smoking rats, and may contribute to the development of emphysema in different pathways.
Lung volume reduction surgery （LVRS） has been applied generally since it was redeveloped and lucubrated. A recent large, multicenter trial showed LVRS can improve lung function, exercise capacity, quality of life, and even survival in certain highly selected patients. LVRS has been developed as an effective therapy for severe emphysema, which offers a new approach for the victims of emphysema. The development of operative technique and clinical effect about LVRS are reviewed in this article.
Objective To investigate the expression and significance of Fork head /winged helix protein 3 (Foxp3) , retinoic acid-related orphan receptorγt (RORγt) , and interleukin-17 (IL-17) in Guinea pigs with emphysema. Methods Smoking and active immunization with elastin were separately used in guinea pigs to establish emphysema model. Then the destruction of lung tissue was assayed by measurement of the average radius of alveolar. The expressions of Foxp3 , RORγt, and IL-17 in lung tissue of the guinea pigs were detected by immunohistochemical technique. The results were compared with the normal control group by the analysis of variance or kruskal-Wallis test. Spearman rank correlation was used to analyze the correlation between the ratio of Foxp3/RORγt and IL-17, also the correlation between Foxp3/RORγt and the average radius of alveolar. Results In the smoking group and the active immunization group, the average radius of alveolar were significantly longer than the control group (Plt;0.05) . And the expression of Foxp3/RORγt was significantly unbalanced, with the number of Foxp3-positive cells decreased and RORγt-positive cells increased (Plt;0.05) . Meanwhile the level of IL-17 was significantly increased compared with the control group ( Plt;0.05) . The difference between the smoking group and the active immunization group was not significant (Pgt;0.05) . The ratio of Foxp3/RORγt was negatively correlated with the level of IL-17 and the average radius of alveolar. Conclusions Active immunization with elastin can induce emphysema in guinea pigs. The Foxp3/RORγt expression was unbalanced in lung tissue of guinea pigs with emphysema.This imbalance may be an important mechanism attributed to the disordered expression of CD4+ Treg cells and Th17 cells, which may be involved in autoimmune regulation and development of chronic obstructive pulmonary disease.
ObjectiveTo explore the clinical value of Goddard CT grade for comprehensive evaluation of emphysema-type COPD. MethodsA total of 150 patients with emphysema-type COPD were recruited in the study. Chest CT scan was performed with German Siemens Difinition 64-slice spiral CT machine. The Goddard scoring of lung CT manifestations was used to grade lung emphysema. Lung function indexes were measured including FEV1, FVC, FEV1/FVC, RV, TLC, RV/TLC, DLCO, FEV1% pred, FVC% pred and DLCO% pred, etc. The correlation between Goddard scores and pulmonary function indexes were analyzed. The incidence of hospitalizations, length of hospital stay, severity of illness and complications in the previous year were compared between the patients with different Goddard CT grade. ResultsThere were 57 cases of mild emphysema, 53 cases of moderate emphysema, and 40 cases of severe emphysema judged by Goddard scoring. The pulmonary Goddard scores were positive correlated with RV, TLC, and RV/TLC which reflecting pulmonary function (r value was 0.385, 0.349, 0.455, respectively, all P < 0.05), and negatively correlated with DLCO and DLCO% pred which reflecting pulmonary diffusing capacity (r value was-0.771, -0.787, respectively, P < 0.05). Compared with the mild and moderate emphysema-type patients, the incidence of hospitalization more than one time due to acute exacerbation was significantly higher (χ2 value was 44.69, 25.66, respectively, P < 0.05), the average length of hospital stay was significantly longer [(13.5±4.2) d vs. (6.4±3.1) d and (9.0±3.8) d, P < 0.05] in the severe emphysema-type COPD patients. The severe emphysema-type COPD patients suffered from more severe acute exacerbation, and higher incidence of heart failure, ischemic heart disease and respiratory failure than the mild and moderate emphysema-type patients (P < 0.05). ConclusionsGoddard CT grade in complement with pulmonary function evaluation can provide more comprehensive evaluation of emphysema-type COPD. The higher Goddard score is, the more frequently and severe the acute exacerbation occurs, more easily the COPD patients complicated with respiratory failure, heart failure and other complications.
Objective To evaluate the relationship between small airway disease and the progression of chronic obstructive pulmonary disease (COPD), and explore the application value of high resolution computed tomography (HRCT) and impulse oscillometry system (IOS) in assessing small airways in COPD patients. Methods A total of 132 stable COPD patients and 43 healthy controls volunteered to take the IOS and pulmonary function test. The correlations between resonance frequency (Fres), small airway resistance (R5-R20) and spirometry were analyzed. The patients were also examined by HRCT to measure the thickness of the third generation of apical bronchus of the right upper lobe (WT), the adjacent pulmonary artery diameter (BWT) and the degree of emphysema (LAA%). The ratio of WT to BWT (WT/BWT) was calculated to estimate bronchial wall thickening. Relationships between WT/BWT, emphysema and spirometry, IOS were also studied. Results There were negative correlations between Fres and FEV1%pred, FEF25%-75%%pred, FEF50%%pred (r=-0.694, -0.561, -0.619, all P<0.01). R5-R20 was negatively associated with FEV1%pred, FEF25%-75%%pred and FEF50%%pred as well (r=-0.622, -0.537, -0.560, P<0.01). The analysis of receiver operating characteristic curve showed larger areas under the Fres and R5-R20 curves, and the cutoff points to diagnose COPD were 13.93 Hz and 0.055 kPa·L-1·s-1, respectively. LAA% and WT/BWT increased with airflow limitation (F=4.859, 9.792, both P<0.01). WT/BWT was negatively associated with FEV1%pred (r=-0.329, P<0.05), and positively with Fres and R5-R20 (r=0.259, 0.241, P<0.05). LAA% was negatively correlated with FEV1%pred (r=-0.566, P<0.05), and correlations also existed between LAA% and physiological indices of small airways such as FEF25%-75%%pred, FEF50%%pred, Fres and R5-R20 (r=-0.456, -0.474, 0.466, 0.340, all P<0.05). Conclusions The peripheral airway resistance is increased and bronchial wall thickens in patients with COPD, and these changes can reflect the severity of the disease. Small airway disease measured by HRCT and IOS are related to the spirometric indices, and represent the structural and functional changes of small airways. Combinations of these two tests with spirometry will be possible to make early diagnosis and better control the disease.
Emphysema is a chronic progressive disease characterized by abnormal terminal bronchioles. Patients in end-stage have limited treatment. Lung volume reduction surgery(LVRS) is to remove the non-functional emphysematous lung tissue with the aim of palliating symptoms in selected patient with severe emphysema. It provides a new therapeutic method for emphysema. When LVRS is widely accepted after 1990s, a large number of institutions carried out the researches on surgical approaches, perioperative mortality, long-term efficacy and complications. Its targeted beneficial patients and surgical safety had been confirmed too. Bronchoscopic lung volume reduction (BLVR) successfully carried out on the basis of the development of LVRS and bronchoscopy. This article reviews the surgical approaches, safety and efficacy of LVRS and BLVR in patients with emphysema.
Objective To explore the positive rate of emphysema in groups under Low-dose CT screening, then take the regression analysis on related risk factors for emphysema. Methods A total of 1 175 volunteers involved in low-dose CT screening and completing the questionnaire were collected and taken the CT quantitative assessment for emphysema, then the positive rate of emphysema was calculated. Questionnaire data were collected and non-conditional Logistic regression was used to analyze the factors in the questionnaire. Results Ninety-seven cases of emphysema had been detected in 1 175 volunteers, and the positive rate was 8.26%. The positive rate for the males and the females was 9.90% (71/717) and 5.68% (26/458), respectively. Three risk factors (smoking, second-hand smoking, history of chronic bronchitis) were screened out by Logistic regression. Conclusions According to the results of the regression analysis, smoking, second-hand smoking and history of chronic bronchitis are main risk factors for emphysema. Some effective measures could be made against emphysema in high risk population. In that way the morbidity and perniciousness of emphysema could be reduced.
Objective To observe the relationship of serum levels of homocysteine (HCY) and chemokine C-C motifligand 2 (CCL2) with cognitive impairment in COPD patients with different degrees of emphysema. Methods Sixty-twoCOPD patients identified according to emphysema phenotype classification and admitted from January 2016 to March 2017 were recruited in the study. There were 37 cases in emphysema 1-2 grade and 25 cases in emphysema 3-4 grade. Simultaneous 30 healthy subjects undergoing physical examination were recruited as control. Montreal cognitive assessment (MoCA) scale investigation and serum HCY and CCL2 test were completed. Relationship analysis was conducted on serum HCY, CCL2 levels with cognitive impairment in the COPD patients with different degrees of emphysema. Results Compared with the 1-2 grade subgroup, the PaO2 was lower, PaCO2 was higher, the plasma HCY and CCL2 levels increased in the 3-4 grade subgroup with significant differences (all P<0.05). MoCA total score and subscores were relatively low in the COPD group with emphysema than the control group (except visuospatial ability scores in the 1-2 grade subgroup). MoCA scores were statistically lower in the 3-4 grade subgroup than those in the 1-2 grade subgroup (allP<0.05). Correlation analysis showed that HCY and CLL2 levels were negatively correlated with MoCA scores and subscores (P<0.01), and HCY and CLL2 were positively correlated (bothP<0.01). The area under the receiver operating characteristic curve of HCY and CLL2 for evaluating cognitive impairment was 0.79 and 0.97, respectively. Conclusion In patients with different degrees of emphysema phenotype, serum HCY and CCL2 levels are increased in different degree, and the degree of emphysema is closely related with cognitive dysfunction.
Objective To investigate the characteristics on chest high-resolution computed tomography (HRCT) of patients with interstitial pneumonia with positive myeloperoxidase antineutrophil cytoplasmic antibody (MPO-IP). Methods The extent of fibrosis and subtypes of emphysema on HRCT of MPO-IP patients were retrospectively analyzed and compared with idiopathic pulmonary fibrosis (IPF) cases admitted in the same period. Results From July 2014 to March 2016, 10 patients was diagnosed with IPF and 10 patients was diagnosed with MPO-IP. Emphysema was not different between two groups. Among the MPO-IP patients, 8 patients presented with a usual interstitial pneumonia (UIP) pattern. There existed statistical difference in the bronchial bifurcation level, the fibrosis score of lungs in the MPO-IP patients presented with UIP was lower than that in the IPF patients. Conclusions UIP is the predominant radiologic type of MPO-IP patients. Fibrosis in IPF is more serious than that in MPO-IP with UIP. Paraseptal and centrilobular emphysema are main forms in MPO-IP patients.
ObjectiveTo investigate the effects of smoking combined with intermittent hypoxia on the pathophysiology of lung tissue and thoracic aorta, and the endothelial injury.MethodsTwenty-four rats (SPF, female, six weeks old) were divided randomly into 4 groups (n=6). The control group was given false smoking and normal oxygen exposure, the smoking-exposed group was exposed in smoking, the intermittent hypoxia group was exposed in intermittent hypoxia environment, and the overlap group was exposed to smoking and intermittent hypoxia. After 8 weeks, body weight, right ventricular hypertrophy index (RVHI), the pathological changes of lung tissue and thoracic aorta were measured, and the level of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) in serum of rats were evaluated.ResultsRVHI of rats in the smoking-exposed group, intermittent hypoxia group, overlap group were higher than that in the control group. In addition, RVHI in the overlap group was higher than that in the smoking-exposed group, intermittent hypoxia group (all P<0.05). The levels of ET-1, VEGF and SDF-1α in the serum of the smoking-exposed group, intermittent hypoxia group and overlap group were higher than those in the control group, while the level of eNOS was lower than that in the control group, (all P<0.05), the most significant difference was between control group and the overlap group. Pathological observation of lung tissue and thoracic aorta showed obvious emphysema in the smoking-exposed group and overlap group, which was more obvious in the overlap group than that in the smoking-exposed group (all P<0.05). Lung interstitial inflammatory infiltration, bronchial wall lymphocyte hyperplasia and pulmonary fibrosis were shown in different degrees in the smoking-exposed group, intermittent hypoxia group and overlap group, and the pulmonary arteriole wall showed thickening, fibrosis and peripheral inflammatory infiltration also were found in these groups. Thoracic aorta in the smoking-exposed group, intermittent hypoxia group and overlap group showed different degrees of endothelial cell injury, middle membrane thickening, and collagen fiber hyperplasia. The pathological features of the overlap group were most obvious compared to the other two groups.ConclusionsSmoking and intermittent hypoxia exposure can lead to different degrees of lung tissue and vascular endothelial injury and decrease of vascular endothelial protective factors in rats, resulting in dysfunction of vascular endothelial cells, which leads to the structural remodeling of pulmonary arterioles and aorta, such as thickening, fibrosis, etc. Combined smoking and intermittent hypoxia exposure can lead to more serious pathological damage.