[Overview of the role of inhaled corticosteroids in chronic obstructive pulmonary disease from evolution of guidelines].

In the treatment of stable chronic obstructive pulmonary disease (COPD), international guidelines have updated the recommendations for inhaled corticosteroids (ICS) based on the accumulated clinical evidences, and the understanding has gone further from "controversy" to "affirmation" until the presence of the lastest guideline that indicates patients are divided into two phenotypes according to the clinical characteristics of dyspnea and acute exacerbation for adjustments in treatment strategy, and for patients with frequent acute exacerbations during the last one year, combined with their blood eosinophil counts, the individualized treatments including ICS are recommended.

[Bioinformatics analysis of severe emphysema genome microarray based on GEO database].

Objective: To investigate differential genes (DEGs) between no/mild and severe emphysema by bioinformatics analysis. Methods: The microarray dataset GSE1650, of lung tissue in no/mild and severe emphysema, was downloaded from the GEO database, and DEGs were obtained by t test. Analysis of DEGs based on DAVID database was used to obtain gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway. The protein-protein interaction network (PPI) was established using STRING database to identify hub genes. Results: A total of 76 DEGs were obtained, of which 62 genes were up-regulated and 14 genes were down-regulated in severe emphysema group. Gene ontology showed that the DEGs were mainly involved in neutrophil chemotaxis, cellular response to interleukin-1, extracellular matrix organization, immune response, and KEGG pathway involved cytokine-cytokine receptor interaction, ECM-receptor interaction, PI3K-Akt signaling pathway, platelet activation. Seventeen hub genes were recognized by PPI analysis, including CXCL8, RRAD, CLU, TIMP1, SEPP1, ISLR, BGN, COL1A1, COLIA2, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3 and TAGLN. Among them, fifteen genes (CLU, TIMP1, SEPP1, ISLR, BGN, COLIA2, COL1A1, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3, TAGLN) were up-regulated and two genes (CXCL8, RRAD) were down-regulated. Conclusion: Bioinformatics analysis based on GEO database showed that there were DEGs between non/mild and severe emphysema patients.

[Association of plasma roundabout 4 concentration with pulmonary ventilation function decline in COPD patients].

Objective: To investigate the association of plasma roundabout 4 concentration with pulmonary ventilation function decline in chronic obstructive pulmonary disease (COPD) patients. Methods: To get the effective data, the study was conducted in the outpatient department of West China Hospital from September 2017 to September 2018. The subjects meeting the inclusion and exclusion criteria were continuously included. Among them, the COPD group (75 cases) was from the respiratory outpatient department, and the healthy control group (57 cases) was from the health examination center at the same time. Data of basic demographic characteristics, clinical characteristics, pulmonary ventilation function parameters and blood samples were collected. The concentrations of roundabout 4, C reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1b and tumor necrosis factor (TNF)-α in plasma were detected, and the differences among groups were compared, the correlation between plasma roundabout 4 and pulmonary ventilation function parameters and inflammatory factors was analyzed. The diagnostic efficiency of roundabout 4 to COPD was analyzed according to receiver operating characteristic (ROC) curve. Results: The plasma concentration of roundabout 4 in COPD group was significantly higher than that in healthy control group [(41.3±14.2) vs (27.7±13.3) ng/L; P<0.001], the sensitivity and specificity of roundabout 4 in the diagnosis of COPD were 0.827 and 0.702 respectively. Correlation analysis showed that the plasma concentration of roundabout 4 was negatively correlated with lung function parameters forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), the first second forced expiratory volume as a percentage of the estimated value (FEV(1)%pred), forced exhalation of 50% and 25% lung capacity (MEF50, MEF25) and maximal mid-expiratory flow (MMEF) (r=-0.399, -0.321, -0.439, -0.363, -0.458; all P<0.001), positively correlated with CRP (adjusted r=0.311, P<0.001). Conclusion: The increased concentration of roundabout 4 in plasma leads to the decline of pulmonary ventilation function in COPD patients.

[Prevalence and clinical characteristics of blood eosinophilia in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To investigate the prevalence and clinical characteristics of peripheral blood eosinophilia (EOS) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: From July 2014 to June 2016, AECOPD patients in the Department of Respiratory Medicine of Affiliated Hospital of Chengdu University, were retrospectively stratified into two groups according to two standards of eosinophilic exacerbations (the peripheral blood eosinophil count ≥2% or ≥3% on admission). Demography, clinical symptoms, laboratory results, length of stay, total hospitalization expenses, and defined daily expenses were compared between groups. Results: A total of 559 cases with AECOPD were finally recorded, the prevalence of eosinophilia was 43.1% (241 cases by EOS≥2%) and 27.2% (152 cases by EOS≥3%), respectively. According to either standard, there were no significant differences in sexes, age, course of disease (P>0.05), and there were no significant differences in global initiative for chronic obstructive lung disease (GOLD) grades, parameters of pulmonary function, modified british medical research council (mMRC) scores, rate of antibiotic use, systemic glucocorticoids administration, and average daily expenses (P>0.05). According to 2% standard, leucocytes, neutrophils, monocytes, hs-CRP were lower than non-eosinophilic patients [(5.9±2.0)×10(9)/L vs (8.2±4.0)×10(9)/L, (3.9±1.6)×10(9)/L vs (6.5±3.8)×10(9)/L, (0.446±0.169)×10(9)/L vs (0.501±0.276)×10(9)/L, (25.8±35.9) vs (46.2±55.6) mg/L, all P<0.01]; basophils, lymphocytes were higher than non-eosinophilic patients [(0.043±0.025)×10(9)/L vs (0.029±0.021) ×10(9)/L, (1.3±0.6) ×10(9)/L vs (1.1±0.6) ×10(9)/L, both P<0.01]; length of stay, total hospital expense were shorter (or lower) than non-eosinophilic patients [(10.6±5.0) vs (11.6±5.8) d, (11 851±7 491) vs (14 254±10 751) RMB, both P<0.05]. According to 3% standard, leucocytes, neutrophils, monocytes, hs-CRP were lower than non-eosinophilic patients (all P<0.05), and basophil were higher than non-eosinophilic patients (P<0.01), but no significant differences were observed in lymphocytes, length of stay and total hospital expense (all P>0.05). Conclusion: Eosinophilia is of relative high prevalence in AECOPD patients, and basophil in eosinophilic patients is higher than non-eosinophilic patients.

Serum angiopoietin-like 4 is over-expressed in COPD patients: association with pulmonary function and inflammation.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is both a pulmonary and systematic disease, which will cause abnormal expression of some circulating factors. Angiopoietin-like protein 4 (ANGPTL4) has been reported to play important role in inflammatory responses and several diseases. However, whether it contributes to COPD is an open question. The aim of this study is to explore the potential relationship between ANGPTL4 and COPD. PATIENTS AND METHODS: In this study, circulating levels of ANGPTL4, C-reactive protein (CRP), adiponectin, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-9 and monocyte chemotactic protein (MCP)-1 in 73 COPD patients and 40 healthy volunteers were investigated using multiplex enzyme-linked immunosorbent assay Kits. Then, we analyzed the correlations between ANGPTL4 with other inflammatory mediators and pulmonary function. RESULTS: Serum ANGPTL4 levels were significantly elevated in COPD patients compared with healthy controls (122.86 ± 38.59 ng/mL versus 99.03 ± 31.84 ng/mL, p = 0.001). Besides, serum ANGTPL4 levels were much higher in ever-smokers with COPD than in never-smokers with COPD (131.71 ± 32.92 ng/mL versus 113.25 ± 42.34 ng/mL, p = 0.03). More importantly, the concentrations of circulating ANGPLT4 correlated inversely with forced expiratory volume in 1 second (FEV1) % predicted, an index of lung function in COPD (r = -0.450, p < 0.001) and in all participants (r = -0.369, p < 0.001), while correlated positively with CRP (r = 0.312, p = 0.007 for COPD; r = 0.404, p < 0.001 for total subjects), adiponectin (r = 0.266, p = 0.004 for total subjects), and MMP-9 (r = 0.254, p = 0.03 for COPD). CONCLUSIONS: Our results suggest that circulating ANGPTL4 levels are up-regulated in COPD patients, and have correlations with pulmonary function and systematic inflammation in COPD, which provides a novel idea to further dig the pathogenic mechanisms of COPD, and justifies more studies to determine how ANGPTL4 contributes to COPD.

TRAM-34 attenuates hypoxia induced pulmonary artery smooth muscle cell proliferation.

OBJECTIVE: Hypoxia is an important risk factor for pulmonary arterial remodeling in pulmonary arterial hypertension (PAH). Pulmonary artery smooth muscle cell (PASMC) proliferation is a major contributor to pulmonary vascular remodeling. The intermediate-conductance Ca2+-activated K+ channel (Kca3.1) has been implicated in disease states characterized by excessive cell proliferation, but its role in hypoxia-induced PASMC proliferation is unknown. In the present study, we sought to investigate the effect of TRAM-34 (triarylmethane-34), a selective blocker of Kca3.1, on hypoxia-induced PASMC proliferation and underlying mechanisms. METHODS: PASMC was exposed to hypoxia (2% O2) for 24 hours, cell proliferation and cell cycle analysis were measured by cell counting kit (CCK-8) and flow cytometry. Cell signaling were examined using Quantitative real-time PCR and Western blotting. RESULTS: CCK8 results showed that TRAM-34 reduced PASMC proliferation under hypoxia. Flow cytometry revealed that TRAM-34 inhibited PASMC proliferation by G0/G1 arrest. Quantitative real-time PCR and western blotting results showed that Kca3.1 mRNA and protein levels were greater in PASMC after hypoxia exposure for 24 hours. Elevated BMP2 (bone morphogenetic protein 2) levels and decreased BMPR2/Smad1 signaling activation were also observed under hypoxia, which were significantly attenuated by TRAM-34 intervention. CONCLUSIONS: These results suggest that Kca3.1 inhibition with TRAM-34 inhibited hypoxia-induced PASMC proliferation in the G0/G1 phase. The capability of TRAM-34 to increase BMPR2/p-Smad1 signaling may be part of the mechanisms for hypoxia-induced cell proliferation. Thus, our study implies that blockade of kca3.1 might provide benefits to attenuating PAH vascular remodeling.

Association of a disintegrin and metalloproteinase 33 (ADAM33) gene polymorphisms with chronic obstructive pulmonary disease in the Chinese population: a meta-analysis.

Numerous studies have evaluated the association between polymorphisms of a disintegrin and metalloproteinase 33 (ADAM33) gene and chronic obstructive pulmonary disease (COPD) risk; however, the results remain conflicting. The aim of this study was to investigate whether ADAM33S2 and -T1 polymorphisms are associated with susceptibility to COPD risk in the Chinese population. Publications addressing the association between ADAM33S2 or T1 polymorphisms and COPD risk were selected from the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases. Two independent reviewers extracted data from the studies. Statistical analysis was performed using the RevMan 5.0.25 and STATA 11.0 software. Six case-control studies were retrieved, including a total of 1201 COPD patients and 1203 controls. Meta-analysis results showed a significant association between the T1 polymorphism and COPD risk in both dominant model [odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.40-4.61, P = 0.002] and recessive model (OR = 3.50, 95%CI = 2.11-5.81, P < 0.00001) comparisons. For S2, no significant association was found in any genetic model. This suggests that the T1 polymorphism of ADAM33 would increase the risk of COPD in a Chinese individual, whereas the S2 polymorphism might not be a risk factor for COPD. To further evaluate the gene-to-gene and gene-to-environment interactions on ADAM33 genetic variations and COPD risk, more studies using large sample sizes of patients are needed.

Polymorphisms in the XRCC1 gene are associated with treatment response to platinum chemotherapy in advanced non-small cell lung cancer patients based on meta-analysis.

X-ray repair cross complementing group 1(XRCC1) polymorphisms have been implicated in interindividual variability of efficacy of platinum chemotherapy for treating non-small cell lung cancer (NSCLC); however, results of different studies have been inconsistent. We conducted a meta-analysis to investigate the association between polymorphisms in the XRCC1 gene and response rate of platinum chemotherapy in advanced NSCLC patients. Searches were performed on MEDLINE, PubMed, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, and Wangfang Data, covering all relevant studies published up to August 1, 2012. Statistical analyses were performed using the Revman 5.0 and STATA 10.0 software. Two polymorphisms, Arg399Gln (G>A) and Arg194Trp (C>T), were investigated in 19 studies, involving 2152 advanced NSCLC patients. For XRCC1 Arg399Gln, patients carrying two G alleles had a significantly increased response rate of platinum chemotherapy, when compared with those carrying the A allele [odds ratio (OR) = 2.05, 95% confidence interval CI = 1.62-2.60 for GG vs GA+AA]. Similarly, the AA carriers had a 54% decreased response rate compared with the G allele carriers (OR = 0.46, 95%CI = 0.30-0.70 for AA vs GA+GG). For XRCC1 Arg194Trp, patients carrying two C alleles had a 62% decreased response rate compared with those carrying either one or two variant T alleles (OR = 0.38, 95%CI = 0.30-0.48 for CC vs CT+TT). However, although TT carriers had a better response rate compared with the C allele carriers, the difference was not significant (OR = 1.27, 95%CI = 0.92-1.77 for TT vs CC+CT). Based on this meta-analysis, we conclude that XRCC1 polymorphisms are associated with treatment response to platinum chemotherapy in advanced NSCLC patients.

Different risk factors of recurrent pulmonary tuberculosis between Tibetan and Han populations in Southwest China.

OBJECTIVE: The geographical environment and living habits are different between Tibetan and Han populations. The present study aimed to investigate the risk factors of recurrent pulmonary tuberculosis (TB), and analyze the differences between the two populations. PATIENTS AND METHODS: A total of 480 TB patients, including 80 Tibetan and 80 Han patients with recurrent pulmonary TB, and 320 patients without recurrent pulmonary TB, were included in present study. All patients with pulmonary TB were diagnosed between 2000 and 2001 and followed until December 2012. Multivariate logistic regression was used for the statistical analysis. RESULTS: Among all patients, the independent risk factors associated with recurrent pulmonary TB were no use of directly observed therapy, short course (DOTS) (HR 5.867, 95% CI 2.557-13.461), diabetes (HR 3.288, 95% CI 1.301-8.312), smoking (HR 2.387, 95% CI 1.328-4.291) and malnutrition (HR 1.910, 95% CI 1.110-3.285). The independent risk factors of recurrent pulmonary TB for the Tibetan patients included no use of DOTS and malnutrition, while the independent risk factors for the Han patients were diabetes and smoking. CONCLUSIONS: The risk factors of pulmonary TB recurrence were different between Tibetan and Han patients. To reduce the recurrent rate of pulmonary TB, especially for Tibetan populations, pursuing high-quality DOTS is essential.

Hydrogen-rich saline reduces airway remodeling via inactivation of NF-κB in a murine model of asthma.

BACKGROUND AND OBJECTIVES: Recent studies suggest that hydrogen has great therapeutic and prophylactic potential against organ injury caused by oxidative stress and inflammation. Here we investigated the effect of hydrogen-rich saline on airway inflammation and remodeling in a murine model of asthma. MATERIALS AND METHODS: Asthma was induced by ovalbumin (OVA) sensitization and challenge. Then mice were treated with normal saline or hydrogen-rich saline at low and high doses. Cell counts and cytokine levels in bronchoalveolar lavage fluid (BALF) were determined, bronchial tissue was analyzed for pathology, and expression of MUC5AC, collagen III, VEGF, and total and phosphorylated NF-κB p65 was measured. Immunohistochemistry was used to identify levels and localization of VEGF expression in lung. RESULTS: The results showed that hydrogen-rich saline reduced cell counts and levels of cytokines IL-4, IL-5, IL-13 and TNF-α in BALF. Hydrogen-rich saline treatment also significantly decreased mucus index, collagen deposition, and expression of MUC5AC, collagen III and VEGF. The ratio of phospho-NF-κB p65 to total NF-κB p65 was much lower in mice treated with hydrogen-rich saline than in untreated mice. These effects of hydrogen-rich saline on airway inflammation and remodeling were dose-dependent. CONCLUSIONS: These findings suggest that hydrogen-rich saline reduces airway inflammation and remodeling in OVA-exposed mice by inhibiting NF-κB.

Serum N-terminal pro-brain natriuretic peptide level is a significant prognostic factor in patients with severe sepsis among Southwest Chinese population.

BACKGROUND: This study aimed to determine the predictive value of elevated N-terminal pro-brain natriuretic peptide (NTproBNP) for mortality in patients with severe sepsis. PATIENTS AND METHODS: This was a retrospective study in Emergency Department of Sichuan Provincial People's Hospital, and patients were screened between January 1, 2009 and December 31, 2011. Demographic and clinical data as well as Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sepsis Organ Failure Assessment (SOFA) scores were collected within the first day of admission. Survival was determined to establish its association with the NT-proBNP using logistic regression and receiver operating characteristic (ROC) curve. RESULTS: A total of 171 patients with severe sepsis were analyzed. The median APACHE IIⅡ and SOFA scores were 11 (IQR, 7-16) and 3 (IQR, 1-5), respectively. The median C-reactive protein (CRP), procalcitonin (PCT) and NT-proBNP was 10.3 mg/dL (IQR, 3.4-21.4 mg/dL), 0.4 ng/mL (IQR, 0.2-3.6 ng/mL), and 954 (321-1576) pg/mL, respectively. The median NT-proBNP in survivors was 584 pg/mL (IQR, 321-875 pg/mL) versus 1271 (IQR, 851-1576 pg/mL) in nonsurvivors (p < 0.001). In the ROC curves, the area value was 0.89 for serum NT-proBNP, and its potent cutoff value was 1500 pg/mL. After multivariate regression analysis, NT-proBNP was significantly correlated with the mortality of severe sepsis (OR = 1.58, 95% CI 1.36-1.77). CONCLUSIONS: Serum NT-proBNP is frequently increased in severe sepsis patients, and non-survivors have higher levels than survivors. High levels of admission NT-proBNP are associated with mortality.

Diagnostic Value of p16 Methylation for Malignant Pleural Effusions: A Meta-analysis.

OBJECTIVE: To evaluate the overall diagnostic performance of the p16 methylation for diagnosing malignant pleural effusion (MPE). METHODS: All published literature in English and Chinese were reviewed. Sensitivity, specificity, likelihood ratio and diagnostic odds ratio (DOR) were pooled by using random-effects model or fixed-effects model. Summary receiver operating characteristic (SROC) curve was used to evaluate the overall diagnostic value. RESULTS: Six studies were included with a total of 378 cases. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and DOR of p16 methylation in the diagnosis of MPE were 0.41 [95% confidence interval (CI) 0.35, 0.48], 0.97 [95% CI 0.93, 0.99], 9.57 [95% CI 4.53, 20.20], 0.61 [95% CI 0.45, 0.82] and 19.82 [95% CI 8.35, 47.04], respectively. The area under the curve (AUC) was 0.864. CONCLUSION: Pleural p16 methylation test plays a useful role in the diagnosis of MPE.