This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.
Animals ; Rats ; Caspase 8 ; Pyroptosis ; HMGB1 Protein/genetics* ; Hypertension, Pulmonary/etiology* ; Pulmonary Disease, Chronic Obstructive/genetics*

OBJECTIVE: This study evaluated the effect of maximal oxygen pulse (O ₂P _max) on patients with chronic obstructive pulmonary disease (COPD) and confirmed the predictive effect on acute exacerbations of COPD (AECOPD). METHODS: This retrospective study included 91 participants who underwent cardiopulmonary exercise testing (CPET), lung function testing, a dyspnea scale assessment, and a 3-year follow-up. The participants were divided into two groups according to the O ₂P _max value. Exercise capacity, ventilatory conditions, gas exchange efficiency, and dyspnea symptoms were compared, and the correlations between O ₂P _max and these indices were evaluated. The ability of O ₂P _max to predict AECOPD was examined. RESULTS: Exercise capacity, ventilatory conditions, and gas exchange efficiency were lower, and dyspnea symptom scores were higher in the impaired O ₂P _max group ( P < 0.05). O ₂P _max was positively correlated with forced vital capacity (FVC)%, forced expiratory volume in 1 sec (FEV ₁)%, FEV ₁/FVC%, anaerobic threshold (AT), work rate (WR)%, aximal oxygen uptake (V̇O _2max)%, V̇O ₂/kg _max, V̇O ₂/kg _max%, WR _AT, WR _max, V̇O _2AT, V̇O _2max, and V̇ _Emax, and was negatively correlated with EqCO _2AT, and EqCO _2max ( P < 0.05). Most importantly, O ₂P _max could be used to predict AECOPD, and the best cut-off value was 89.5% (area under the curve, 0.739; 95% CI, 0.609-0.869). CONCLUSION O ₂P _max reflected exercise capacity, ventilation capacity, gas exchange capacity, and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.
Dyspnea/etiology* ; Exercise Tolerance ; Humans ; Oxygen ; Oxygen Consumption ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies

BACKGROUND: The incidence of symptomatic radiation pneumonitis (RP) and its relationship with dose-volume histogram (DVH) parameters in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and concurrent once-daily thoracic radiotherapy (TRT) remain unclear. We aim to analyze the values of clinical factors and dose-volume histogram (DVH) parameters to predict the risk for symptomatic RP in these patients. METHODS: Between 2011 and 2019, we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and once-daily TRT simultaneously (EGFR-TKIs group) and 129 patients who had received concurrent chemoradiotherapy (CCRT group). The symptomatic RP was recorded according to the Common Terminology Criteria for Adverse Event (CTCAE) criteria (grade 2 or above). Statistical analyses were performed using SPSS 26.0. RESULTS: In total, the incidences of symptomatic (grade≥2) and severe RP (grade≥3) were 43.5% (37/85) and 16.5% (14/85) in EGFR-TKIs group vs 27.1% (35/129) and 10.1% (13/129) in CCRT group respectively. After 1:1 ratio between EGFR-TKIs group and CCRT group was matched by propensity score matching, chi-square test suggested that the incidence of symptomatic RP in the MATCHED EGFR-TKIs group was higher than that in the matched CCRT group (χ2=4.469, P=0.035). In EGFR-TKIs group, univariate and multivariate analyses indicated that the percentage of ipsilateral lung volume receiving ≥30 Gy (ilV30) [odds ratio (OR): 1.163, 95%CI: 1.036-1.306, P=0.011] and the percentage of total lung volume receiving ≥20 Gy (tlV20) (OR: 1.171, 95%CI: 1.031-1.330, P=0.015), with chronic obstructive pulmonary disease (COPD) or not (OR: 0.158, 95%CI: 0.041-0.600, P=0.007), were independent predictors of symptomatic RP. Compared to patients with lower ilV30/tlV20 values (ilV30 and tlV20cut-off point values) and COPD had a significantly higher risk for developing symptomatic RP, with a hazard ratio (HR) of 1.350 (95%CI: 1.190-1.531, P<0.001). CONCLUSIONS Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy. The ilV30, tlV20, and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.
Carcinoma, Non-Small-Cell Lung/radiotherapy* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/radiotherapy* ; Protein Kinase Inhibitors/adverse effects* ; Pulmonary Disease, Chronic Obstructive/complications* ; Radiation Pneumonitis/etiology* ; Radiotherapy Dosage ; Retrospective Studies

Adrenergic beta-Antagonists ; Heart Failure/etiology* ; Humans ; Pulmonary Disease, Chronic Obstructive/complications*

OBJECTIVE: To establish and evaluate the model of chronic obstructive pulmonary disease (COPD) with osteoporosis induced by elastase in mice. METHODS: Twenty four healthy female 8-week-old C57BL / 6 mice (weighing about 18 g) were randomly divided into three groups. The control group was given intratracheal drip of normal saline, the experimental group 1 and the experimental group 2 were given intratracheal drip of elastase, the control group and the experimental group 1 were kept for 8 weeks and then killed, the experimental group 2 was kept for 12 weeks and then killed. HE staining was used to evaluate the histopathological changes of lung and tibia in the control and experimental groups. The levels of serum inflammatory factors and broncho alveolar lavage factors (BALF) were detected by ELISA. Micro CT was used to detect the bone mass related parameters of mouse femur. The expression of osteoclastic and osteogenic genes was detected by real-time fluorescence quantitative PCR. RESULTS: Lung histopathology showed that the structure of alveoli in the experimental group was disordered, the walls of alveoli became thin or broken, and the alveoli cavity expanded. IL-6 and TNF-α in BALF were significantly higher than those in control group (<0.001), while IL-1β and TNF-α in serum inflammatory factors were significantly higher than those in control group (<0.001). BV / TV(bone volume fraction), TB.Th(average bone trabecular thickness) and TB.N(average bone trabecular number) in the experimental group were significantly lower than those in the control group (<0.05), TB.Sp (average bone trabecular separation) and BS / BV (bone surface area fraction) in the experimental group were significantly higher than those in the control group (<0.01). Compared with the control group, the expression of osteoclast related marker genes increased in the experimental group (<0.05), but decreased in the experimental group(<0.05). The results of experiment 1 and experiment 2 were time-dependent. CONCLUSION In this study, elastase was used to construct a COPD model with osteoporosis successfully, which provides a suitable animal model for the future study of the pathogenesis of COPD with osteoporosis.
Animals ; Bone Density ; Female ; Mice ; Mice, Inbred C57BL ; Osteoporosis ; etiology ; Pancreatic Elastase ; Pulmonary Disease, Chronic Obstructive ; complications

OBJECTIVE: To investigate the risk factors of postoperative pulmonary infection (PPI) in patients over 60 years of age with gastric cancer after radical gastrectomy. METHODS: Clinicopathological data of 373 patients over 60 years of age who underwent radical gastrectomy at Department IV of Gastrointestinal Cancer Center, Peking University Cancer Hospital, from April 2009 to December 2016 were retrospectively collected in this case-control study. The clinicopathological characteristics of patients with postoperative pulmonary infection (including postoperative atelectasis) and those without pulmonary infection were compared. A Student t-test (reported as Mean±SD if data matching normal distribution) or Mann-Whitney U test [reported as median (quartile) if data did not conform to normal distribution] was used to analyze continuous variables. A χ² test or Fisher exact tests (reported as number and percentage) was used for categorical variables. Multivariable logistic regression was used to analyze the risk factors for pulmonary infection after operation of gastric cancer.PPI was defined as postoperative patients with elevated body temperature (>38.0 degrees centigrade) for more than 24 hours; cough and expectoration; positive sputum bacteria culture;recent infiltration, consolidation or atelectasis confirmed by chest imaging examination. RESULTS: Among 373 patients, 50 cases had PPI(13.4%, PPI group), 323 cases had no PPI(86.6%, non-PPI group). There were 39 (78.0%) and 178(55.1%) patients with comorbidities (including hypertension, diabetes and cardiopulmonary disease) preoperatively in PPI and non-PPI group, respectively. The difference between two groups was statistically significant (χ²=9.325,P=0.002). The incidence of preoperative hypoalbuminemia in PPI group was also significantly higher than that in non-PPI group [10.0%(5/50) vs. 3.1% (10/323),χ²=4.098, P=0.048]. Compared to non-PPI group, the rate of total gastrectomy [54.0%(27/50) vs. 34.4% (111/323), χ²=12.501, P=0.002], postoperative wound pain [34.0%(17/50) vs. 11.8% (38/323),χ²=16.928, P<0.001], secondary operation [6.0%(3/50) vs. 0.6% (2/323), χ²=6.032, P=0.014] and the rate of gastric tube removal later than 7 days postoperatively [96.0%(48/50) vs. 84.5%(273/323),χ²=4.811, P=0.028] were significantly higher in PPI group, respectively. The postoperative hospital stay was also prolonged in PPI group [16.0(9.5) days vs. 12.0(5.0) days, U=4 275.0, P<0.001]. Multivariate logistic regression analysis showed that preoperative comorbidities (OR=4.008, 95%CI:1.768-9.086, P=0.001), abdominal infection (OR=3.164, 95%CI:1.075-9.313, P=0.037), and wound pain (OR=3.428, 95%CI:1.557-7.548, P=0.002) were independent risk factors for PPI in patients over 60 years of age with gastric cancer. Furthermore, 50 patients with pulmonary infection were classified according to the length of latency and the type of infection. The patients with PPI latency ≤ 3 days were classified as early onset (34 cases, 68.0%), and those with latency ≥ 4 days as delayed onset (16 cases, 32.0%); PPI combined with surgical infection (including anastomotic leakage, abdominal infection, duodenal stump leakage, wound infection, etc.) was classified into mixed infection group (13 cases, 26.0%), with non-surgical infection as simple infection group (37 cases, 74.0%). The results showed that the pulmonary infection occurred 0 to 12 days (median 3 days) before surgical infection in mix infection group. The incidence of previous chronic obstructive pulmonary disease (COPD) in patients with early onset was significantly higher than that in patients with delayed onset [17.6%(6/34) vs. 0, χ²=5.005, P=0.025], and the incidence of mixed infection in patients with delayed onset was significantly higher than that in patients with early onset [50%(8/16) vs. 14.7%(5/34), χ²=6.730, P=0.009],but there was no significant difference in postoperative hospital stay between the two groups[17.0(9.8) days vs. 14.0(9.5) days, U=224.0, P=0.317]. CONCLUSIONS Postoperative pulmonary infection is common in gastric cancer patients over 60 years of age. Preoperative comorbidities, abdominal infection and wound pain are independent risk factors for postoperative pulmonary infection. Pulmonary infection within 3 days after operation is associated with preoperative COPD. For patients suffering from PPI after the 4th day,attentions should be paid to abdominal infection and anastomotic leakage.
Age Factors ; Anastomotic Leak ; etiology ; Case-Control Studies ; Gastrectomy ; adverse effects ; methods ; Humans ; Intraabdominal Infections ; etiology ; Middle Aged ; Pneumonia ; etiology ; Pulmonary Atelectasis ; etiology ; Pulmonary Disease, Chronic Obstructive ; complications ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; complications ; surgery

BACKGROUND: Chronic obstructive pulmonary disease (COPD) will reduce the cardiopulmonary function and increase perioperative risk. The aim of this study is to investigate the effect of preoperative short-term high intensity lung rehabilitation training on lung function and postoperative complications in patients with COPD who are eligible for lung cancer surgery. METHODS: We analysis of 101 patients with COPD and a diagnosis of lung cancer, with 43 patients in pulmonary rehabilitation group and 58 patients in conventional group. The pulmonary function, postoperative pulmonary complications (PPCs) and length of stay (LOS) will be compared between the two groups, the lung function will be compared before and after the rehabilitation at the same time. RESULTS: There were no significant difference between the two groups in general information, lung function before surgery, postoperative pulmonary infection [8 (18.6%) vs 17 (29.3%)], atelectasis [1 (2.3%) vs 1 (1.7%)], respiratory failure [1 (2.3%) vs 2 (3.4%)] and postoperative LOS [(8.93±3.78) d vs (9.62±3.98) d, P>0.05]. In the rehabilitation group, the FEV1 [(2.06±0.45) L vs (2.15±0.45) L, P<0.001] and PEF [(4.32±0.90) L/s vs (5.15±1.05) L/s, P<0.001) were higher, and PCO2 [(42.42±2.79) mmHg vs (41.58±2.98) mmHg, P=0.009] was lower after rehabilitation, significantly. The increase value of FEV1 in moderate to severe COPD group was higher than that of the mild COPD group after the rehabilitation [(0.16±0.05) L, 8.6% vs (0.06±0.05) L, 2.8%, P<0.001). CONCLUSIONS The short-term highly-intensity lung rehabilitation can improve lung function in lung cancer patients with COPD, and the improvement of pulmonary function in moderate to severe COPD patients is more obviously.
Female ; Humans ; Lung Neoplasms ; complications ; rehabilitation ; surgery ; Male ; Middle Aged ; Perioperative Period ; Postoperative Complications ; etiology ; Pulmonary Disease, Chronic Obstructive ; complications ; Retrospective Studies ; Safety

Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10). We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.
Aged ; Biomarkers, Tumor ; genetics ; Cohort Studies ; Female ; Gene Expression Profiling ; Genome, Human ; Humans ; Male ; MicroRNAs ; genetics ; Neoplasms ; diagnosis ; etiology ; genetics ; Prognosis ; Pulmonary Disease, Chronic Obstructive ; complications

INTRODUCTIONThe presence of trigger factors may help to distinguish asthma from chronic obstructive pulmonary disease (COPD). Knowing and avoiding trigger factors for both asthma and COPD can facilitate the design of comprehensive management programmes that can aid disease control. This study aimed to describe the relative frequency and range of various trigger factors in asthma and COPD.

METHODSWe conducted a telephone-based survey involving asthma and COPD patients on follow-up at a university hospital in Singapore.

RESULTSA total of 779 asthma patients and 129 COPD patients participated in this study. Among these patients, 93.8% of those with asthma and 42.6% of those with COPD had trigger factors (p < 0.001). The median number of trigger factors was greater among asthma patients than among those with COPD (3 vs. 0, p < 0.001). Trigger factors found to be significantly more prevalent among asthma patients compared to those with COPD include tobacco smoke, alcohol, upper respiratory tract infections, incense smoke, perfume, laughter, a dusty environment, air-conditioning, heavy rain, heavy traffic fumes, citrus fruits, gastro-oesophageal reflux, household pets, flowers/pollen, medications and psychological triggers. Trigger factors that were not previously described, such as bathing, fatigue, insufficient sleep, crowded places and overeating, were also reported.

CONCLUSIONTrigger factors, although found in both groups of patients, were more common among asthma patients. Knowledge of these trigger factors may be useful in distinguishing between the two diseases and optimising disease management.

Adult ; Aged ; Allergens ; Asthma ; epidemiology ; etiology ; Chronic Disease ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Gastroesophageal Reflux ; Humans ; Male ; Middle Aged ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; epidemiology ; etiology ; Singapore ; Telephone

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