Jianmiao Wang

Body mass index and mortality in chronic obstructive pulmonary disease: a meta-analysis.

Background The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades. However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up. Methods We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies. Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD. In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association. Results 22 studies comprising 21,150 participants were included in this analysis. Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR  = 1.34, 95% CI  = 1.01–1.78), whereas overweight (RR  = 0.47, 95% CI  = 0.33–0.68) and obese (RR  = 0.59, 95% CI  = 0.38–0.91) patients were associated with lower mortality. We further performed a baseline risk-adjusted analysis and obtained statistically similar results. Conclusion Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality. However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies.

Comparison of tiotropium plus formoterol to tiotropium alone in stable chronic obstructive pulmonary disease: a meta-analysis.

Background and objective:  It is not clear whether combination therapy with tiotropium plus formoterol has greater efficacy, without increasing the burden of adverse events, compared with tiotropium alone. This meta‐analysis was performed to evaluate the differences in efficacy and adverse events associated with combination therapy compared with tiotropium alone, in patients with stable COPD.

Effect of long-acting beta-agonists on the frequency of COPD exacerbations: a meta-analysis

What is Known and Objective:  Inhaled long‐acting beta‐agonists have been licensed for the treatment of chronic obstructive pulmonary disease (COPD) since the late 1990s, and they improve lung function and symptoms of dyspnoea. However, the evidence that long‐acting beta‐agonists alone can reduce the rate of COPD exacerbations is not conclusive. This meta‐analysis was performed to evaluate their effect on the frequency of exacerbations.

Increased IL-33 expression in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by inflammatory cell activation and the release of inflammatory mediators. Interleukin-33 (IL-33) plays a critical role in various inflammatory and immunological pathologies, but evidence for its role in COPD is lacking. This study aimed to investigate the expression of IL-33 in COPD and to determine whether IL-33 participates in the initiation and progression of COPD. Levels of serum IL-33 and its receptors were measured by ELISA, and serum levels of IL-33, ST2, and IL-1 receptor accessory protein were elevated in patients with COPD compared with control subjects. Flow cytometry analysis further demonstrated an increase in peripheral blood lymphocytes (PBLs) expressing IL-33 in patients with COPD. Immunofluorescence analysis revealed that the main cellular source of IL-33 in lung tissue was human bronchial epithelial cells (HBEs). Cigarette smoke extract and lipopolysaccharide could enhance the ability of PBLs and HBEs to express IL-33. Furthermore, PBLs from patients with COPD showed greater IL-33 release in response to the stimulus. Collectively, these findings suggest that IL-33 expression levels are increased in COPD and related to airway and systemic inflammation. Therefore, IL-33 might contribute to the pathogenesis and progression of this disease.

Tumour necrosis factor alpha ‐308G/A polymorphism and risk of the four most frequent cancers: a meta‐analysis

The latest data show that breast, prostate, lung and colorectal cancer are the four most frequent cancers in both sexes worldwide. A number of molecular epidemiological studies have been conducted to examine the association between TNF alpha ‐308G/A and the risk of those cancers. However the results have been inconclusive or inconsistent. We then performed a meta‐analysis to derive a precise estimation of this association. We carried out a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database for studies using related keywords. The inclusion criteria were (i) in English or Chinese; (ii) case–control study on this association; (iii) provide usable genotype frequencies; and (iv) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI). ORs and 95% CIs were calculated to assess the strength of this association under homozygote comparison (AA vs GG), heterozygote comparison (GA vs GG), dominant (AA/GA vs GG) and recessive (AA vs GA/GG) genetic model comparison. Thirty case–control studies with a total number of 16 507 cases and 19 749 controls were selected for analysis. Overall, no significant association was found between this polymorphism and the risk of total four cancers (GA vs GG: OR = 1.02, 95% CI = 0.91–1.14, P = 0.78). However, there was a significant association between this polymorphism and breast cancer risk in western populations (GA vs GG: OR = 0.91, 95% CI = 0.85–0.96, P = 0.002). This meta‐analysis also revealed that this polymorphism was not associated with susceptibility to the other three cancers.

Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: a meta-analysis.

PURPOSE Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case-control studies. To clarify these associations, we conducted a meta-analysis. METHODS We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association. RESULTS There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR=1.14, 95%CI=1.03-1.26, P=0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR=0.63, 95%CI=0.46-0.88, P=0.0006; recessive, OR=0.61, 95%CI=0.38-0.99, P=0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR=0.38, 95%CI=0.19-0.75, P=0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models. CONCLUSIONS MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found that MMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.

Mannose-binding lectin two gene polymorphisms and tuberculosis susceptibility in Chinese population: A meta-analysis

Numerous studies have been done to explore the association between mannose-binding lectin two (MBL2) gene polymorphisms and the risk of tuberculosis (TB). However, the results are inconsistent. We performed a meta-analysis to investigate whether polymorphisms in the MBL2 gene were associated with TB risk. Databases including PubMed, Medline, Chinese Biomedicine Database, China National Knowledge Infrastructure, Wanfang Database, and Weipu Database were searched to find relevant articles published up to 2 October, 2012. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. All statistical tests were performed by using Revman 5.1 software and STATA 11.0 software. Six case-control studies including 1106 cases and 1190 controls were accepted in the meta-analysis. The results indicated that individuals carrying the MBL2 codon 54 B allele may have an increased risk of TB as compared with AA homozygotes (BB+AB vs. AA: OR=1.52, 95% CI: 1.22–1.88), whereas MBL2 +4 P/Q was possibly not associated with TB susceptibility in Chinese population.SummaryNumerous studies have been done to explore the association between mannose-binding lectin two (MBL2) gene polymorphisms and the risk of tuberculosis (TB). However, the results are inconsistent. We performed a meta-analysis to investigate whether polymorphisms in the MBL2 gene were associated with TB risk. Databases including PubMed, Medline, Chinese Biomedicine Database, China National Knowledge Infrastructure, Wanfang Database, and Weipu Database were searched to find relevant articles published up to 2 October, 2012. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. All statistical tests were performed by using Revman 5.1 software and STATA 11.0 software. Six case-control studies including 1106 cases and 1190 controls were accepted in the meta-analysis. The results indicated that individuals carrying the MBL2 codon 54 B allele may have an increased risk of TB as compared with AA homozygotes (BB+AB vs. AA: OR=1.52, 95% CI: 1.22–1.88), whereas MBL2 +4 P/Q was possibly not associated with TB susceptibility in Chinese population.

Susceptibility of N-acetyltransferase 2 slow acetylators to antituberculosis drug-induced liver injury: a meta-analysis

AIM This study aimed to evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATLI). MATERIALS & METHODS A meta-analysis was performed including 27 studies with 1289 cases and 5462 controls. Odds ratio with 95% CI was used to evaluate the strength of association. RESULTS Our meta-analysis found that NAT2 slow acetylators were associated with increased risk of ATLI compared with fast and intermediate acetylators when standard dose of isoniazid was administrated (odds ratio: 3.08; 95% CI: 2.29-4.15). CONCLUSION Individuals with NAT2 slow acetylators may have increased risk of ATLI when standard dose of isoniazid was used. Detection of NAT2 genotype may benefit to the prevention of ATLI.

Risk profile of bevacizumab in patients with non-small cell lung cancer: a meta-analysis of randomized controlled trials.

Background. Severe adverse events (AEs) have been reported in cancer patients treated with bevacizumab. Currently, safety of bevacizumab in patients with non-small cell lung cancer (NSCLC) is not clear. We conducted a meta-analysis to evaluate the risk profile of bevacizumab in NSCLC patients. Methods. Relevant trials were identified by searching databases and conference proceedings. Data on treatment-related deaths and grade 3 or 4 AEs were extracted and pooled to calculate relative risks (RRs) with 95% confidence interval (CI) for bevacizumab compared with chemotherapy alone. Results. A total of 2210 patients were included in the analysis. Compared with chemotherapy alone, high-dosage (15 mg/kg) bevacizumab was associated with an increased risk of treatment-related deaths (RR = 2.04, 95% CI = 1.18–3.52), but not for low-dosage (7.5 mg/kg) group (RR = 1.20, 95% CI = 0.60–2.41). In addition, treatment with bevacizumab was associated with several grade 3 or 4 AEs in patients with NSCLC, especially in high-dosage bevacizumab group. Conclusion. The use of the bevacizumab increases the risk of treatment-related deaths and several grade 3 or 4 AEs in patient with NSCLC. The risk may be dose-dependent. Close monitoring and adequate management are recommended to decrease severe AEs.

Increased Expression of Interleukin-18 and its Receptor in Peripheral Blood of Patients with Chronic Obstructive Pulmonary Disease

Abstract Chronic obstructive pulmonary disease (COPD) is a complex systemic disorder characterized by both local pulmonary and systemic inflammation. Many studies suggested that activation of circulating inflammatory cells and increased circulating levels of inflammatory cytokines occur in COPD. Interleukin (IL)-18 is a unique proinflammatory cytokine that mediates its effects by binding to the IL-18 receptor (IL-18R). In the present study, the expression of IL-18 in serum and IL-18R on peripheral blood T lymphocytes was analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of IL-18 and interferon (IFN)-©, and high sensitivity C-reactive protein (hsCRP) were measured by chemiluminiscent immunoassay. Expression of IL-18R was examined using a three-color flow cytometry method. In total, 120 subjects were recruited including 32 nonsmokers, 30 current smokers and 58 stable COPD patients. Serum levels of IL-18 and hsCRP were significantly higher in stable COPD patients than those in nonsmokers and current smokers. A significant negative correlation existed between pulmonary function and serum level of IL-18 rather than hsCRP in stable COPD patients. The proportions of IL-18R〈-expressing T lymphocytes and CD8+ T lymphocytes were significantly higher in stable COPD patients than in nonsmokers and current smokers. The current study extended prior analyses by examining IL-18R expression in peripheral blood. The results suggested that IL-18/IL-18R system was active in peripheral blood of COPD patients.