Shan Cai

Local inflammation occurs before systemic inflammation in patients with COPD.

Background and objective:  COPD is associated not only with an abnormal inflammatory response in the lung but also with systemic inflammation, including systemic oxidative stress, activation of circulating inflammatory cells and increased circulating levels of inflammatory cytokines. Understanding the nature and course of systemic inflammation in COPD is important given the potential for anti‐inflammatory therapy. This study explored whether local and systemic inflammation occur concurrently in patients with COPD.

Intraperitoneal injection of cigarette smoke extract induced emphysema, and injury of cardiac and skeletal muscles in BALB/C mice.

ABSTRACT Background: Chronic obstructive pulmonary disease (COPD) is a chronic, progressive, airway disease. In order to recognize mechanisms of COPD, various types of COPD animal models have been established, and the pathogenesis are different. The present study was designed to establish a COPD animal model by intraperitoneal injection of cigarette smoke extract (CSE) in BALB/C mice. Methods: Mice were injected intraperitoneally with PBS/CSE and sacrificed at day 28. Pulmonary function, pathology of lung tissue, morphology of hearts and skeletal muscle, leukocytes count and antioxidant activity of bronchoalveolar lavage fluid (BALF), pulmonary parenchymal apoptosis index (AI), expression of cleaved caspase-3, expression of MMP-2 and MMP-9 mRNA, and activity of MMP-2 and MMP-9 in lung tissue were measured. Results: Intraperitoneal injection of CSE induced pulmonary parenchymal destruction, pulmonary function reduction, leukocytes count, injury of cardiac and peripheral muscles, and increased pulmonary parenchymal AI, cleaved caspase-3 protein, expression of MMP-2 and MMP-9 mRNA, activity of MMP-2 and MMP-9 protein in lung tissue, and suppressed antioxidant activity in BALF (P < 0.05). Conclusions: Intraperitoneal injection of CSE produced emphysema, pulmonary parenchymal apoptosis, and injury of cardiac and skeletal muscles in mice. All pathobiologically relevant mechanisms in this model are shared with the COPD patients.

The effect of pollutional haze on pulmonary function.

Detrimental health effects of atmospheric exposure to ambient particulate matter (PM) have been investigated in numerous studies. Exposure to pollutional haze, the carrier of air pollutants such as PM and nitrogen dioxide (NO2) has been linked to lung and cardiovascular disease, resulting increases in both hospital admissions and mortality. This review focuses on the constituents of pollutional haze and its effects on pulmonary function. The article presents the available information and seeks to correlate pollutional haze and pulmonary function.

Effectiveness of individual counseling for smoking cessation in smokers with chronic obstructive pulmonary disease and asymptomatic smokers

Few studies have examined the effect of individual counseling for smoking cessation in China. The present study evaluated the efficacy of individual counseling in patients with chronic obstructive pulmonary disease (COPD) and asymptomatic smokers. This prospective randomized study evaluated 85 smokers with COPD and 105 asymptomatic smokers with normal lung function. The individuals were randomly allocated to intervention and control groups. Subjects in the intervention group were provided with individual cognitive counseling based on face-to-face individual consultation, self-help materials and nine telephone follow-ups. Subjects in the control group were provided with simple smoking cessation advice. The smoking status for all subjects and the St. George’s Respiratory Questionnaire (SGRQ) for COPD patients were assessed at baseline, week 4 and month 6. The COPD patient exacerbations during the 6 months were recorded. In the total study population, individual counseling resulted in higher abstinence rates compared with those in the control: Intervention vs. control, 23.4 vs. 10.4% (P=0.007), respectively. Similar results were observed in the smokers with COPD: Intervention vs. control, 40.5 vs. 18.6% (P=0.027), respectively. However, for asymptomatic smokers, the effect of individual counseling was identified to be statistically insignificant: Intervention vs. control, 9.6 vs. 3.8% (P=0.230), respectively. SGRQ scores and COPD exacerbations were significantly improved in patients who abstained from smoking compared with those in the patients who failed to stop smoking. Airway obstruction, quitting motivation and individual counseling were predictors associated with smoking cessation. Airway obstruction was the most significant predictor of smoking cessation (odds ratio, 4.215; 95% confidence interval, 2.215–7.865). The results of the present study show that individual counseling is an effective method for smoking cessation, particularly in COPD patients. However, its efficacy in asymptomatic smokers requires confirmation in further studies.

Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer

Background Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA). Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD. In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer. Methods Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 without COPD, undergoing pneumonectomy were enrolled. The apoptotic index (AI) of pulmonary vascular endothelial cells was analyzed by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. The expression of mtTFA mRNA and protein was measured using PCR, immunohistochemistry and Western-blot. Methylation of the mtTFA promoter was detected using bisulfite sequencing PCR. Results Compared to the non-COPD group, the AI was higher, and expression of mtTFA mRNA and protein was lower in the COPD group (P<0.001). Expression of the mtTFA protein was positively correlated with FEV1/Pre (r = 0.892, P<0.001), and negatively correlated with AI (r = −0.749, P<0.001) and smoke index (r = −0.763, P<0.001). Percentage of mtTFA promoter methylation in the COPD patients was significantly higher compared to the non-COPD patients (P<0.05). Conclusion These results suggest that the expression of mtTFA mRNA and protein is down-regulated in the lung tissue from the COPD patients with squamous cell lung cancer, and the level of mtTFA protein is related to apoptosis of pulmonary vascular endothelial cells. Aberrant mtTFA methylation may also play an important role in the pathogenesis of COPD.

Effects of One-Hour Training Course and Spirometry on the Ability of Physicians to Diagnose and Treat Chronic Obstructive Pulmonary Disease

Backgrounds In China, the prevalence of chronic obstructive pulmonary disease (COPD) in persons 40 years of age or older is estimated at 8.2%, but this is likely a substantial underestimate. Methods Eight secondary hospitals which didn’t have spirometries were chosen randomly in Hunan province of central south China. Physician subjects at these hospitals underwent a one-hour training course on the Chinese COPD guidelines. Physicians answered questionnaires assessing their knowledge of the guidelines before and after the training session. The mean correct scores of questionnaires were compared before and after training. Four out of the eight hospitals were given access to spirometry. Eligible patient subjects underwent spirometry testing prior to the physician visit. After seeing the patient, physicians were asked to answer a questionnaire relating to the diagnosis and severity of COPD. Physicians were then given the results of the spirometry, and asked to answer the same questionnaire. Physicians’ responses before and after receiving the spirometry results were compared. Results 225 physicians participated in the training session. 207 questionnaires were completed. Mean scores (out of 100) before and after the training were 53.1 ± 21.7 and 93.3 ± 9.8, respectively. 18 physicians and 307 patient subjects participated in the spirometry intervention. Based on spirometric results, the prevalence of COPD was 38.8%. Physicians correctly identified the presence of COPD without spirometric data in 85 cases (76.6%); this increased to 117 cases (97.4%) once spirometric data were available. Without spirometric data, physicians incorrectly diagnosed COPD in 38 patients; this decreased to 6 patients once spirometric data were available. Spirometric data also improved the ability of physicians to correctly grade COPD severity. Conclusions Simple educational training can substantially improve physicians’ knowledge relating to COPD. Spirometry combined with education improves the ability of physicians to diagnose COPD and to assess its severity.

Notch1 regulates endothelial apoptosis via ERK pathway in chronic obstructive pulmonary disease

The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis. In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD). We obtained surgical specimens from 10 patients with COPD and 10 control participants. Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells. Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE). Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE. The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis. However, this activation can be abolished by N1ICD overexpression. Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis. These results suggest that CS alters Notch signaling in pulmonary endothelial cells. Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor.

The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model

Background Cigarette smoke exposure is the most common risk factor for emphysema, which is one of the major pathologies of COPD. Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that specially catalyzes dimethylation of R2 in histone H3 (H3R2me2a). H3R2me2a prevents trimethylation of H3K4 (H3K4me3), which is located in the transcription start sites of genes in mammalian genomes. We attempted to determine the expression of PRMT6 in human samples, and investigate whether the upregulation of PRMT6 expression can attenuate the development of cigarette smoke extract (CSE)-induced emphysema. Further experiments were performed to elucidate the molecular mechanisms involved. Materials and methods Human lung tissues were obtained from patients undergoing pneumonectomy for benign pulmonary lesions. BALB/c mice were treated with lentiviral vectors intratracheally and injected with CSE three times. The protein expression of PRMT6, H3R2me2a, and H3K4me3 in human and mouse samples, as well as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and endothelial nitric oxide synthase (eNOS) in mice were detected in lung homogenates by Western blotting. The mRNA expression of cyclooxygenase-2, interleukin-6, Bcl-2, Bax, and eNOS in mice was measured by quantitative real-time polymerase chain reaction. Results The expression of PRMT6 was significantly downregulated in the pulmonary parenchyma in smokers with COPD as well as in mice treated with CSE. Overexpression of PRMT6 was detected in the CSE + Lenti-PRMT6 group of mice, which reversed the expression of H3R2me2a and H3K4me3. Inflammation, apoptosis, and oxidative stress levels were severe in the CSE-treated emphysema mice compared with the control group, which was inhibited by the overexpression of PRMT6. Conclusion The overexpression of PRMT6 might inhibit inflammation, apoptosis, and oxidative stress in CSE-induced emphysema mediated by H3R2me2a.

Exercise assessments and trainings of pulmonary rehabilitation in COPD: a literature review

Skeletal muscle dysfunction leads to reduction in activity in patients with COPD. As an essential part of the management of COPD, pulmonary rehabilitation (PR) alleviates dyspnea and fatigue, improves exercise tolerance and health-related quality of life, and reduces hospital admissions and mortality for COPD patients. Exercise is the key component of PR, which is composed of exercise assessment and training therapy. To evaluate PR’s application in clinical practice, this article summarizes the common methods of exercise measurement and exercise training for patients with COPD. Exercise assessments should calculate patients’ symptoms, endurance, strength, and health-related quality of life. After calculation, detailed exercise therapies should be developed, which may involve endurance, strength, and respiratory training. The detailed exercise training of each modality is mentioned in this review. Although various methods and therapies of PR have been used in COPD patients, developing an individualized exercise training prescription is the target. More studies are warranted to support the evidence and examine the effects of long-term benefits of exercise training for patients with COPD in each stage.

Effect of a Patient Education Intervention on Asthma Control and Patient-Doctor Relationship

To the Editor: Asthma control is the focus of modern asthma management, while only 2% of Chinese patients are controlled.[1] A good patient‐doctor relationship is one of the first steps in the successful management of asthma; patients can know more information about their condition and the processes of their health through talking thoroughly with doctors. Due to large numbers of outpatients, most physicians in China spend no more than 5 min with a patient in clinics, limiting the opportunity to give the appropriate treatment and discuss further knowledge about asthma with the patients.[2]