Yanqiu Wu

CT-Base Pulmonary Artery Measurementin the Detection of Pulmonary Hypertension: A Meta-Analysis and Systematic Review

AbstractTo summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis.A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance.This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72–0.84); specificity, 0.83 (95% CI 0.75–0.89); PLR, 4.68 (95% CI 3.13–6.99); NLR, 0.26 (95% CI 0.20–0.33); DOR, 18.13 (95% CI 10.87–30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66–0.80); specificity, 0.81 (95% CI 0.74–0.86); PLR, 3.83 (95% CI, 2.70–5.43); NLR, 0.33 (95% CI 0.24–0.44); DOR, 11.77 (95% CI 6.60–21.00); and AUC 0.84.Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography.To summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis. A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance. This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72-0.84); specificity, 0.83 (95% CI 0.75-0.89); PLR, 4.68 (95% CI 3.13-6.99); NLR, 0.26 (95% CI 0.20-0.33); DOR, 18.13 (95% CI 10.87-30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66-0.80); specificity, 0.81 (95% CI 0.74-0.86); PLR, 3.83 (95% CI, 2.70-5.43); NLR, 0.33 (95% CI 0.24-0.44); DOR, 11.77 (95% CI 6.60-21.00); and AUC 0.84. Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography.

Silymarin attenuates cigarette smoke extract-induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells

Cigarette smoke (CS) is a major risk of chronic obstructive pulmonary disease (COPD), contributing to airway inflammation. Our previous study revealed that silymarin had an anti-inflammatory effect in CS-exposed mice. In this study, we attempt to further elucidate the molecular mechanisms of silymarin in CS extract (CSE)-induced inflammation using human bronchial epithelial cells. Silymarin significantly suppressed autophagy activation and the activity of ERK/p38 mitogen-activated protein kinase (MAPK) pathway in Beas-2B cells. We also observed that inhibiting the activity of ERK with specific inhibitor U0126 led to reduced autophagic level, while knockdown of autophagic gene Beclin-1 and Atg5 decreased the levels of ERK and p38 phosphorylation. Moreover, silymarin attenuated CSE-induced upregulation of inflammatory cytokines TNF-α, IL-6 and IL-8 which could also be dampened by ERK/p38 MAPK inhibitors and siRNAs for Beclin-1 and Atg5. Finally, we validated decreased levels of both autophagy and inflammatory cytokines (TNF-α and KC) in CS-exposed mice after silymarin treatment. The present research has demonstrated that CSE-induced autophagy in bronchial epithelia, in synergism with ERK MAPK pathway, may initiate and exaggerate airway inflammation. Silymarin could attenuate inflammatory responses through intervening in the crosstalk between autophagy and ERK MAPK pathway, and might be an ideal agent treating inflammatory pulmonary diseases.

WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway.

The mechanisms of WNT/β-catenin signaling involved in airway inflammation of chronic obstructive pulmonary disease (COPD) remain unknown, although recent observations have suggested an important contribution of the pathway in pulmonary parenchymal tissue repair and airway epithelium differentiation. We investigated the role of WNT/β-catenin signaling in cigarette smoke (CS)-related airway inflammation using patient lung tissues, human bronchial epithelial cells (16HBECs), and mouse models. Reduced activity of WNT/β-catenin signaling was observed in the airway epithelium of smokers with or without COPD. The mRNA expression of WNT transcription factor TCF4 negatively correlated with the pack year. The mRNA levels of WNT receptor FZD4 negatively correlated with the mRNA levels of IL-1β. CS exposure decreased the activity of WNT/β-catenin signaling in both 16HBECs and mice. In vitro studies demonstrated the upregulation of inflammatory cytokines TNF-α and IL-1β secretion induced by CS extract (CSE) could be attenuated by β-catenin activator SB216763 and be exacerbated by β-catenin small-interfering RNA (siRNA), respectively. Furthermore, the decrease in the expression of peroxisome proliferator-activated receptor (PPARδ) induced by CSE stimulation could be rescued by SB216763. SB216763 also attenuated the upregulation of phosphorylated p38 mitogen-activated protein kinase (MAPK) stimulated by CSE. Both PPARδ agonist and p38 MAPK inhibitor could suppress the TNF-α and IL-1β release induced by CSE treatment. In addition, PPARδ activation could abolish β-catenin siRNA-mediated aggravation of phosphorylated p38 MAPK in response to CSE. Finally, SB216763 treatment significantly ameliorated peribronchial inflammatory cell infiltration, leukocyte influx, and the release of TNF-α and IL-1β in the bronchoalveolar lavage fluid of CS-exposed mice. Taken together, our findings indicate that the reduced activity of WNT/β-catenin signaling induced by CS may promote inflammatory cytokine production in airway epithelium and have an essential role in airway inflammation in COPD by PPARδ/p38 MAPK pathway.

Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

Background Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. Methods Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. Results First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007). Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV3/FVC, MMEF25–75/Pre (justified r=−0.289, P=0.001; justified r=−0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively). Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1. Conclusion Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD.

Diagnostic Performance of Bronchoalveolar Lavage Fluid CD4/CD8 Ratio for Sarcoidosis: A Meta-analysis.

Background The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed a meta-analysis to estimate the overall diagnostic accuracy of BALF CD4/CD8 ratio based on the bulk of published evidence. Methods Studies published prior to June 2015 and indexed in PubMed, OVID, Web of Science, Scopus and other databases were evaluated for inclusion. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deekss funnel plot was used to detect publication bias. Results Sixteen publications with 1885 subjects met our inclusion criteria and were included in this meta-analysis. Summary estimates of the diagnostic performance of the BALF CD4/CD8 ratio were as follows: sensitivity, 0.70 (95%CI 0.64–0.75); specificity, 0.83 (95%CI 0.78–0.86); PLR, 4.04 (95%CI 3.13–5.20); NLR, 0.36 (95%CI 0.30–0.44); and DOR, 11.17 (95%CI 7.31–17.07). The area under the SROC curve was 0.84 (95%CI 0.81–0.87). There was no evidence of publication bias. Conclusion Measuring the BALF CD4/CD8 ratio may assist in the diagnosis of sarcoidosis when interpreted in parallel with other diagnostic factors.

Increased serum TRAIL and DR5 levels correlated with lung function and inflammation in stable COPD patients

Background Chronic obstructive pulmonary disease (COPD) is associated with abnormal systemic inflammation, and apoptosis is one of the pathogenic mechanisms of COPD. Several studies have suggested that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors were not only involved in diseases associated with apoptosis but also in inflammatory diseases. However, limited data about the possible relationship between COPD and TRAIL/TRAIL-receptors are available. Objective To evaluate the potential relationship between TRAIL/TRAIL-receptors and COPD. Methods Serum levels of TRAIL, decoy receptor 5 (DR5), C-reactive protein, and tumor necrosis factor-α were analyzed using multiplex enzyme-linked immunosorbent assay kits. Then, serum levels of TRAIL and DR5 in 57 COPD patients with 35 healthy controls were compared and correlated with lung function and systemic inflammation. Results Mean levels of serum TRAIL and DR5 were significantly higher in COPD patients than those in controls (50.17±17.70 versus 42.09±15.49 pg/mL, P=0.029; 48.15±22.88 versus 38.94±10.95 pg/mL, P=0.032, respectively). Serum levels of TRAIL and DR5 correlated inversely with forced expiratory volume in 1 second % predicted, an index of lung function in COPD (r=-0.354, P=0.007 for TRAIL; r=−0.394, P=0.002 for DR5) in all participants (r=-0.291, P=0.005 for TRAIL; r=−0.315, P=0.002 for DR5), while DR5 correlated positively with C-reactive protein (r=0.240, P=0.021 for total subjects) and TRAIL correlated positively with tumor necrosis factor-α (r=0.371, P=0.005 for COPD; r=0.349, P=0.001 for total subjects). Conclusion Our results suggested that circulating TRAIL and DR5 increased in COPD patients and were associated with lung function and systemic inflammation in COPD. Future studies are needed to verify whether and how TRAIL and its receptors play roles in COPD.

Adipokine CTRP-5 as a Potential Novel Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease.

AbstractLocal and systemic inflammation often present in chronic obstructive pulmonary disease (COPD). Adipokines are secretory protein mediators by adipose tissue, which have been found to involve in inflammatory responses in many chronic inflammatory diseases. Therefore, we performed this preliminary clinical study to investigate the possible association between 2 adipokines, C1q/tumor necrosis factor-related protein-3 and -5 (CTRP-3 and CTRP-5), with lung function and other markers of inflammation in COPD. Serum CTRP-3 and CTRP-5 levels were measured in 73 COPD patients and 54 health controls, together with lung function and levels of adiponectin, CRP, TNF-&agr;, and MPO in both groups. Pearsons partial correlation was used to analyze the correlations between CTRPs and other serum markers or lung function. Serum CTRP-5 was significantly elevated in COPD patients (0.41 ± 0.35 versus 0.29 ± 0.28 &mgr;g/ml, P = 0.01) and correlated inversely with FEV1/FVC ratio in all patients (r = −0.31, P = 0.001). In COPD patients, CTRP-5 was also correlated negatively with FEV1% predicted (r = −0.464, P < 0.001) and had a positive association with CRP levels (r = 0.262, P = 0.04). However, serum CTRP-3 levels were not correlated with measures of lung function or systemic inflammation. In conclusion, circulating CTRP-5 was associated with the severity of airflow obstruction and systemic inflammation in patients with COPD, which suggests that it may be used as a potential novel inflammatory biomarker in COPD. Further studies should be performed to clarify the exact role of CTRP-5 on the pathogenesis and outcomes of COPD.

Diagnostic value of thyroid transcription factor-1 for pleural or other serous metastases of pulmonary adenocarcinoma: a meta-analysis.

The role of thyroid transcription factor 1 (TTF-1) in the diagnosis of metastatic pulmonary adenocarcinomas in pleural, pericardial, and peritoneal effusions has not been defined. This study aimed to assess the overall diagnostic accuracy of TTF-1 for metastatic pulmonary adenocarcinomas in pleural or other effusions. Literature search was conducted in PubMed, EMBASE, and other databases to find eligible publications. Quality was assessed according to standardized QUADAS-2 criteria. Sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic (SROC) curves were used to assess overall performance of the TTF-1 assay. A systematic search revealed 20 studies comprising a total of 1,213 subjects in this meta-analysis. The summary estimates were listed as follows: sensitivity, 0.74 (95% CI: 0.69–0.79); specificity, 0.99 (95% CI: 0.97–1.00); PLR, 78.16 (95% CI: 27.15–225.05); NLR, 0.26 (95% CI: 0.22–0.32); and diagnostic odds ratio, 297.75 (95% CI: 104.16–851.19). Estimated positive and negative post-probability values for metastatic pulmonary adenocarcinomas prevalence of 20% were 95% and 6%, respectively. The area under the SROC curve was 0.96. TTF-1 shows significant potential as a diagnostic marker to differentiate metastatic pulmonary from non-pulmonary adenocarcinomas in pleural or other effusions. These results justify larger, more rigorous studies to confirm such a diagnostic role.

Accuracy of the Bronchoalveolar Lavage Enzyme-Linked Immunospot Assay for the Diagnosis of Pulmonary Tuberculosis: A Meta-analysis.

AbstractAssessing of local immune response may improve the accuracy of pulmonary tuberculosis (PTB) diagnosis. Many studies have investigated diagnosing PTB based on enzyme-linked immunospot (ELISPOT) assay of bronchoalveolar lavage (BAL) fluid, but the results have been inconclusive. We meta-analyzed the available evidences on overall diagnostic performance of ELISPOT assay of BAL fluid for diagnosing PTB.A systematic literature search was performed using PubMed, Embase, Wangfang, Weipu, and CNKI. Data were pooled on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Overall test performance was summarized using summary receiver operating characteristic curves and the area under the curve (AUC). Deeks test was used to test for potential publication bias.Seven publications with 814 subjects met our inclusion criteria and were included in this meta-analysis. The following pooled estimates for diagnostic parameters were obtained: sensitivity, 0.90 (95% CI: 0.85–0.94); specificity, 0.80 (95% CI: 0.77–0.84); PLR, 5.08 (95% CI: 2.70–9.57); NLR, 0.13 (95% CI: 0.06–0.28); DOR, 49.12 (95% CI: 12.97–186.00); and AUC, 0.96. No publication bias was identified.The available evidence suggests that ELISPOT assay of BAL fluid is a useful rapid diagnostic test for PTB. The results of this assay should be interpreted in parallel with clinical findings and the results of conventional tests.

Gender difference in plasma fatty-acid-binding protein 4 levels in patients with chronic obstructive pulmonary disease

Plasma FABP4 levels were higher in females with COPD compared with both males with COPD and healthy females. FABP4 levels correlated inversely with lung function, and positively with adiponectin and TNFα in COPD.