Objective To investigate the effect of chronic altitude hypoxia exposure on serum lipoprotein levels in healthy subjects and patients with pulmonary hypertension, and whether there is a difference in serum lipoprotein levels between patients with pulmonary hypertension at middle and high altitude. Methods The case data of 245 Han patients with COPD complicated with pulmonary hypertension admitted to the Affiliated Hospital of Qinghai University from January 2018 to September 2022 were retrospectively analyzed. According to the altitude of their long-term residence before onset, the patients were divided into two groups, 119 cases in the middle altitude group (1500 m~2500 m). 126 cases were in the high altitude group of 2500 m~4500 m. In addition, the physical examination data of 50 healthy people in the intermediate and high altitude groups were collected as the control group (the age and gender of the healthy people in the same altitude group were similar to those in the COPD-PH group), a total of 4 groups were collected. The general data, pulmonary artery systolic blood pressure (PASP), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) of the four groups were compared, and the correlation between pulmonary artery systolic blood pressure (PASP) and related variables was analyzed. ResultsThere were no significant differences in age, gender, smoking and drinking between the healthy control group and COPD-PH group (all P>0.05). There were significant differences in body mass index, PASP, TC, TG, HDL-C, LDL-C, TG/HDL-C, HDL-C/LDL-C between the healthy control group and the COPD-PH group (all P<0.05). In the healthy control group, only BMI was significantly different between the high altitude group and the middle altitude group (P<0.05). In the COPD-PH group, PASP, BMI, TC, HDL-C and TG/HDL-C in the high altitude group were significantly different from those in the moderate altitude group (all P<0.05). There were no significant differences in age, gender, smoking, drinking, TG, LDL-C and HDL-C/LDL-C between the two groups (all P>0.05), when gender, age, altitude, body mass index, PASP, smoking and drinking were included in the multi-factor linear regression equation of lipoprotein (TC, TG, HDL-C and LDL-C), it was found that different elevations (middle and higher elevations) only had statistically different effects on HDL-C (b=-0.046, t=-2.209, P=0.028). Correlation analysis showed that PASP was not correlated with age, altitude, body mass index and blood lipids (TC, TG, HDL-C, LDL-C) in the healthy control group (all P>0.05). However, in the COPD-PH group, PASP was negatively correlated with blood lipid indicators (TC, HDL-C and LDL-C). PASP was positively correlated with altitude (a risk factor for hypoxia). ConclusionsHypoxia environment factors characterized by altitude are closely related to the severity of pulmonary artery pressure in patients with COPD-PH, and higher pulmonary artery systolic pressure is closely related to lower levels of TC, HDL-C and LDL-C.
Objective To investigate the intervention effect of 3-phosphoinositede dependent protein kinase-1 (PDK1) inhibitor on prostaglandin E2 (PGE2) in smoking-induced chronic obstructive pulmonary disease (COPD) mice. Methods Fifty C57BL/6 male mice were randomly divided into normal control group, smoking group, smoking +low dose PDK1 inhibitor group, smoking + medium dose PDK1 inhibitor group and high dose PDK1 inhibitor group with 10 mice in each group. The mice in the normal control group inhaled phosphate-buffered saline twice a day for 12 weeks, and the mice in the smoking group were fumigated twice a day, 5 days per week for 12 weeks, and the other three groups were given intraperitoneal injection of low-dose PDK1 inhibitor OSU-03012 (0.25 mg/kg), medium-dose PDK1 inhibitor (0.5 mg/kg) and high-dose PDK1 inhibitor (1.0 mg/kg) respectively before smoking. After smoking, lung function was tested, the bronchoalveolar lavage fluid (BALF) of each mouse was taken for cell count, the PGE2 in serum and BALF of mice was determined by enzyme linked immunosorbent assay, and the lung tissue of mice was sectioned with paraffin and stained by hematoxylin-eosin (HE), and pathological changes were observed under microscope. Results Compared with the control group, FEV100/FVC and FEV200/FVC of the mice in each smoking group were significantly decreased (P<0.05); The number of cells in BALF of smoking group was significantly higher than that of normal control group (P<0.05). There was no significant difference in the total number of BALF cells, the proportion of neutrophils and macrophages between the smoking + low-dose PDK1 inhibitor group and the smoking group. However, the total number of BALF cells and the proportion of neutrophils in the smoking + medium dose PDK1 inhibitor group and the high dose PDK1 inhibitor group gradually decreased, while the proportion of macrophages gradually increased, compared with the normal control group, the PGE2 concentrations of serum and BALF in the smoking group and the smoking + PDK1 inhibitor group were significantly higher than those in the control group. Compared with the smoking group, the PGE2 concentrations of serum and BALF in the middle and high dose PDK1 inhibitor groups were significantly lower than those in the smoking group. HE staining of lung tissue showed that there were a large number of inflammatory cell infiltration, alveolar cavity dilatation, alveolar wall rupture and fusion, alveolar formation, significant decrease in the number of alveoli and other pathological changes in the smoking group, which were consistent with the pathological changes of COPD. The inflammatory cell infiltration, mucus obstruction and alveolar dilatation were slightly alleviated in the smoking + low-dose PDK1 inhibitor group, while the inflammatory cell infiltration, alveolar wall thinning and alveolar dilatation were improved in both the medium-dose inhibitor group and the high-dose inhibitor group, and the improvement was more obvious in the high-dose inhibitor group. Conclusion The lung function of the smoked COPD mouse decreases, the airway inflammation is obvious, and the secretion of PGE2 is also increased, while the use of PDK1 inhibitor could reduce the secretion of PGE2, reduce airway inflammation and pathological changes, and improve lung function in a dose-dependent manner.
Objective To analyze the influence of COPD on the structure and function of left ventricular. Methods Sixty-nine COPD patients ( mean age: 69. 0 ±7. 8 yrs) and forty healthy controls ( mean age: 67. 8 ±7. 6 yrs) were enrolled in this study. Both groups underwent Doppler echocardiography.Heart rate ( HR) were recorded. Left ventricular end-diastolic volume ( LVEDV) , left ventricular enddiastolic diameter ( LVEDD) , interventricular septum( IVS) , stroke volume ( SV) , and cardiac output ( CO)were measured. The changes of left ventricular were compared between the COPD patients and the healthy controls, and also between the COPD patients with or without chronic cor pulmonale. Results Compared with the healthy controls, movement range of IVS, LVEDD, LVEDV, and SV reduced significantly ( P lt;0. 05) , and HR raised significantly in the COPD patients ( P lt; 0. 05) . CO had no significant difference between two groups ( P gt;0. 05) . Sub-group analysis indicated that the thickness and movement range of IVSwere greater in the patients with cor pulmonale secondary to COPD than those without cor pulmonale ( P lt;0. 05) . Conclusions In COPD patients, left ventricular chamber size decreases, and left ventricular systolic function is impaired. Left ventricular function is impaired more severe in cor pulmonale secondary to COPD than COPD without cor pulmonale.
Objective To explore the clinical value of shear wave elastography in the evaluation of quadriceps femoris lesions in patients with chronic obstructive pulmonary disease (COPD). Methods Fifty-eight COPD patients who were admitted to Chengdu First People’s Hospital and 55 healthy controls were included in the study between August 2021 and February 2022. The thickness, circumference, cross-sectional area and Young's modulus of quadriceps femoris in all subjects were measured using shear wave elastography combined with conventional two-dimensional ultrasound. The differences in ultrasound parameters between the two groups were compared, and the correlation between each ultrasound parameter and clinical evaluation indicators (modified British Medical Research Council Scale, COPD Assessment Test, six-minute walk test, and five-time sit-to-stand test) was analyzed. Results Young’s modulus values of the quadriceps femoris muscle were smaller in the COPD group than those in the healthy control group [COPD Group: rectus femoris 6.72 (6.22, 7.36) kPa, vastus medialis 6.25 (5.82, 6.79) kPa, vastus lateralis 6.94 (6.17, 7.48) kPa; healthy control group: rectus femoris 11.40 (10.23, 12.11) kPa, vastus medialis 10.77 (9.62, 11.42) kPa, vastus lateralis 11.14 (10.42, 12.52) kPa]. The differences were statistically significant (all P<0.05). The Young's modulus value of the rectus femoris muscle correlates with the aforementioned clinical evaluation indicators, with positive correlation with six-minute walk distance and negative correlation with COPD Assessment Test, modified British Medical Research Council Scale, five-time sit-to-stand time (P<0.05). Quadriceps thickness, circumference, and cross-sectional area measured by conventional two-dimensional ultrasound were not significantly different between the two groups, nor were there significant correlations between each parameter and clinical parameters (P>0.05). In addition, shear wave elastography has good reproducibility in the measurement of Young's modulus in quadriceps. Conclusions Shear wave elastography can identify quadriceps lesions earlier than conventional two-dimensional ultrasound in COPD patients, and there is a significant correlation between its measurements and the clinical condition of COPD patients. Shear wave elastography may provide a simple and noninvasive method for clinical evaluation of quadriceps femoris lesions in COPD patients.
Objective To analyze the risk factors of treatment failure by noninvasive positive pressure ventilation (NPPV) in patients with acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and explore the best time that NPPV be replaced by invasive ventilation when NPPV failure occurs. Methods The data of patients with ARF due to AECOPD who were treated with NPPV from January 2013 to December 2015 were retrospectively collected. The patients were divided into two groups: the NPPV success group and the NPPV failure group (individuals who required endotracheal intubation or tracheotomy at any time). The Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score was analyzed; the Glasgow Coma Scale score, respiratory rate (RR), pH value, partial pressure of oxygen (PaO2), PaO2/fraction of inspired oxygen (FiO2) ratio, and partial pressure of carbon dioxide were also analyzed at admission, after 2 hours of NPPV, and after 24 hours of NPPV. Results A total of 185 patients with ARF due to AECOPD were included. NPPV failed in 35.1% of the patients (65/185). Multivariate analysis identified the following factors to be independently associated with NPPV failure: APACHEⅡscore≥30 [odds ratio (OR)=20.603, 95% confidence interval (CI) (5.309, 80.525), P<0.001], RR at admission≥35 per minute [OR=3.723, 95%CI (1.197, 11.037), P=0.020], pH value after 2 hours of NPPV<7.25 [OR=2.517, 95%CI (0.905, 7.028), P=0.070], PaO2 after 2 hours of NPPV<60 mm Hg (1 mm Hg=0.133 kPa) [OR=3.915, 95%CI (1.374, 11.508), P=0.010], and PaO2/FiO2 after 2 hours of NPPV<200 mm Hg [OR=4.024, 95%CI (1.542, 11.004), P=0.010]. Conclusion When patients with ARF due to AECOPD have a higher severity score, have a rapid RR at admission, or fail to improve in terms of pH and oxygenation after 2 hours of NPPV, the risk of NPPV failure is higher.
Objective To investigate the risk factors of chronic obstructive pulmonary disease (COPD) combined with obstructive sleep apnea (OSA) and its relationship with apnea-hypopnea index (AHI). Methods Clinical data of 216 COPD patients with OSA were retrospectively chosen in the period from January 2016 to December 2019 in our hospital. All patients were divided into different groups according to with or without OSA and the clinical features of patients with and without OSA were compared. Multivariate analysis was used to analyze the influencing factors of COPD with OSA and the correlation between AHI and COPD with OSA was also evaluated. Results ① The age, body mass index (BMI), neck circumference, smoking index, forced expiratory volume in 1 second (FEV1), FEV1% predicted (FEV1pred), the ratio of FEV1 to the forced vital capacity of the lungs (FEV1/FVC), COPD assessment test (CAT) score, Epworth sleepiness scale (ESS) score, Charlson comorbidity index (CCI) score, sleep apnea clinical score (SACS) score and proportion of patients with essential hypertension in OSA group were significantly higher than non-OSA group (P<0.05). The course of disease and the proportion of severe COPD and GOLD grade 4 in OSA group were significantly less than non-OSA group (P<0.05). ② AHI was positively correlated with age, BMI, neck circumference, smoking index, FEV1%pred, FEV1%pred<50%, CAT score, ESS score, CCI score and SACS score (P<0.05); and negatively correlated with FEV1%pred<50% (P<0.05). ③ Multivariate analysis showed that BMI, FEV1%pred<50%, CAT score and ESS score were the independent factors of COPD patients with OSA (P<0.05). ④ The proportion of AHI<5 times/h in GOLD grade 4 was significantly higher than GOLD grade 1-3 (P<0.05). The proportion of AHI> 30 times/h in GOLD grade 4 was significantly lower than GOLD grade 1-3 (P<0.05). Conclusion The incidence of COPD with OSA was independently correlated with BMI, FEV1%pred, CAT score and ESS score; patients with severe COPD possess lower OSA risk.
Objective To investigate the influence of proteasome inhibitorMG-132 on inflammatory factors in COPD rats and its potential mechanism. Methods The COPD rat model was established by instillation of lipopolysaccharide and exposure to cigarette smoke. Then the rats were randomly divided into 4 groups( n = 12 in each group) , ie. a COPD model group, a COPD + MG-132 low concentration group ( 0. 05 mg·kg- 1·d - 1 ) , a COPD + MG-132 high concentration group( 0. 1 mg· kg- 1 · d - 1 ) , and a normal control group. The rats were injected intraperitoneally with different dose of MG-132 or normal saline. After 1 week and 4 weeks, 6 rats in each group were sarcrificed. Then the following parameters were determined including histopathological changes of lung tissue, and the concentrations of IL-1β, IL-6, IL-8 in serum and diaphragm via ELISA. Results The lung histopathological examination showed obvious emphysema and inflammatory infiltration in the COPD rats. These pathological changes were obviously ameliorated in two MG-132 treatment groups. The IL-1β, IL-6, and IL-8 levels in serumand diaphragmin the COPD model group were all significantly increased from1 week and 4 week than those in the normal control group( P lt;0. 05) .MG-132 down-regulated the expression of these inflammatory factors in a time-and dosedependent manner. The IL-1β, IL-6, and IL-8 levels in serum and diaphragm in the MG-132 low concentration group and high concentration group were all decreased compared with the COPD model group ( P lt; 0. 05) . Conclusion COPD is a systemic inflammatory disease which can be inhibited by the proteasome inhibitor MG-132 through suppressing inflammatory factors.
Objective To investigate the impact of using low limit of normal( LLN) for FEV1 /FVC ratio and fixed ratio ( 70% ) as cut-off point in the qualitative diagnosis on the prevalence of chronic obstructive pulmonary disease( COPD) . Methods An epidemiological study was carried out in preoperative patients who received pulmonary function test in Zhongshan hospital fromNovember 6, 2007 to December 30, 2007. 339 patients were enrolled and diagnosed as COPD by different diagnostic criteria as follows: ①GOLD criteria; ②FEV1 /FVC
ObjectiveTo explore the effects of simvastatin on the expression of matrix metalloproteinase (MMP) and inflammatory factors in rats with smoke-induced chronic obstructive pulmonary disease (COPD). Methods40 male Wistar rats were randomly divided into four groups, including a normal group (group A), a simvastatin group (group B), a COPD model group (group C) and a simvastatin intervention group (group D). The COPD model of the group C and D were induced through exposing to the cigarette smoke repeatedly. At the same time, the rats of group B and D were given by gavage 5 mg/(kg·d) with simvastatin, and the other two groups were given with the same volume saline for 16 weeks. Pulmonary function tests and pathological examination of the lung tissue were performed after the induction of COPD model. Enzyme-linked immunosorbent assay (ELISA) method was used to measure the content of MMP-2, MMP-9, IL-6, IL-8, TNF-α in lung tissue homogenate. ResultsThe airway resistance of group C and group D was significantly higher than the group A and group B (P<0.01), and the airway resistance of group D was significantly lower than group C (P<0.01). The degree of bronchial inflammation and emphysema of group C was more apparent than group D in the pathological section, and there were no bronchial inflammation and emphysema in group A and group B. The ELISA results showed that the contents of MMP-2, MMP-9, IL-6, IL-8, TNF-α in group C were all significantly higher than those in group D. ConclusionSimvastatin has inhibitory effect on pulmonary inflammation of COPD, and can reduce the expression of matrix metalloproteinase and inflammatory factors in the lung.
Objectives To analyze the risk factors for cardiovascular disease (CVD) in patients with chronic obstructive pulmonary disease (COPD) of different severities. Methods The study included 50 patients with mild-to-moderate COPD and 50 with severe-to-very severe COPD admitted between January 2014 and January 2016. Comorbidities were recorded on the basis of data obtained from medical charts and clinical evaluations. The Charlson comorbidity index was calculated, and the Hospital Anxiety and Depression Scale (HADS) score was determined in each subject. Results There were more prevalences of smoking, depression and dyslipidemia in the patients with mild-to-moderate COPD than those with severe-to-very severe COPD (all P<0.001). The prevalences of high blood pressure, diabetes mellitus, alcoholism, and chronic heart failure were not different significantly between the two groups. The Charlson comorbidity index and HADS scores were not different between the two groups. Conclusions Comorbidities are fairly common in COPD regardless of its severity. Certain risk factors for CVD, as smoking, dyslipidemia, and depression, appear to be more prevalent in patients with mild-to-moderate COPD.