Capsaicin Cough Sensitivity and the Association with Clinical Parameters in Bronchiectasis

Background

Cough hypersensitivity has been common among respiratory diseases.

Objective

To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis.

Methods

We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C₂) and 5 coughs (C₅).

Results

Despite significant overlap between healthy subjects and bronchiectasis patients, both C₂ and C₅ were significantly lower in the latter group (all P<0.01). Lower levels of C₅ were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C₅ being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35–7.83, P<0.01), HRCT total score between 7–12 (OR: 2.57, 95%CI: 1.07–6.173, P = 0.04), BSI between 5–8 (OR: 4.05, 95%CI: 1.48–11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48–12.93, P<0.01).

Conclusion

Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials.     

Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

Background

There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.

Methods

Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.

Results

Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV₁] <80% of predicted value). The mean FEV₁ decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV₁>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV₁ decline. Initial FEV₁>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).

Conclusions

NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.     

Budesonide/Formoterol Enhances the Expression of Pro Surfactant Protein-B in Lungs of COPD Patients

Rationale & Aim

Pulmonary surfactants are essential components of lung homeostasis. In chronic obstructive pulmonary disease (COPD), surfactant expression decreases in lungs whereas, there is a paradoxical increase in protein expression in plasma. The latter has been associated with poor health outcomes in COPD. The purpose of this study was to determine the relationship of surfactants and other pneumoproteins in bronchoalveolar lavage (BAL) fluid and plasma to airflow limitation and the effects of budesonide/formoterol on this relationship.

Methods

We recruited (clinical trials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00569712","term_id":"NCT00569712"}}NCT00569712) 7 smokers without COPD and 30 ex and current smokers with COPD who were free of exacerbations for at least 4 weeks. All subjects were treated with budesonide/formoterol 400/12 µg twice a day for 4 weeks. BAL fluid and plasma samples were obtained at baseline and the end of the 4 weeks. We measured lung-predominant pneumoproteins: pro-Surfactant Protein-B (pro-SFTPB), Surfactant Protein-D (SP-D), Club Cell Secretory Protein-16 (CCSP-16) and Pulmonary and Activation-Regulated Chemokine (PARC/CCL-18) in BAL fluid and plasma.

Results

BAL Pro-SFTPB concentrations had the strongest relationship with airflow limitation as measured by FEV₁/FVC (Spearman rho = 0.509; p = 0.001) and FEV₁% of predicted (Spearman rho =  0.362; p = 0.028). Plasma CCSP-16 concentrations were also significantly related to airflow limitation (Spearman rho = 0.362; p = 0.028 for FEV₁% of predicted). The other biomarkers in BAL fluid or plasma were not significantly associated with airflow limitation. In COPD subjects, budesonide/formoterol significantly increased the BAL concentrations of pro-SFTPB by a median of 62.46 ng/ml (p = 0.022) or 48.7% from baseline median value.

Conclusion

Increased severity of COPD is associated with reduced Pro-SFTPB levels in BAL fluid. Short-term treatment with budesonide/formoterol increases these levels in BAL fluid. Long term studies will be needed to determine the clinical relevance of this observation.     

Testing Two Different Doses of Tiotropium Respimat? in Cystic Fibrosis: Phase 2 Randomized Trial Results

Background

Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 µg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis.

Methods

This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV₁ area under the curve from 0 to 4 hours (FEV₁ AUC_0–4h), and trough FEV₁ at the end of week 12.

Findings

A total of 510 subjects with cystic fibrosis aged 5–69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV₁ AUC_0–4h: 2.5 µg: 2.94%, 95% confidence interval 1.19–4.70, p = 0.001; 5 µg: 3.39%, 95% confidence interval 1.67–5.12, p = 0.0001; in percent-predicted trough FEV₁∶2.5 µg: 2.24%, p = 0.2; 5 µg: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 µg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium.

Conclusions

Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00737100","term_id":"NCT00737100"}}NCT00737100 EudraCT 2008-001156-43.     

Lack of Association between Insulin Receptor Substrate2 rs1805097 Polymorphism and the Risk of Colorectal and Breast Cancer: A Meta-Analysis

Background

Insulin receptor substrate-2 (IRS-2), a signaling adaptor protein, was involved in two cancer-related pathways (the phosphatidylinositol 3′-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathways). Several studies have evaluated the association between IRS2 rs1805097 (G>A) polymorphisms and the risk of colorectal and breast cancer. However, the results were inconsistent.

Methodology/Principal Findings

A meta-analysis of seven published case-control studies (4 studies with 4798 cases and 5478 controls for colorectal cancer and 3 studies with 2108 cases and 2507 controls for breast cancer) were conducted to assess the strength of association using crude odd ratios (ORs) with 95% confidence intervals (CIs). For colorectal cancer, no obvious associations were found for all genetic models (homozygote comparison OR = 0.96, 95%CI 0.85–1.08, P_{heterogeneity} = 0.97; heterozygote comparison: OR = 0.91, 95%CI 0.73–1.13, P_{heterogeneity}<0.01; dominant model: OR = 0.92, 95%CI 0.80–1.06, P_{heterogeneity} = 0.05; recessive model: OR = 1.02, 95%CI 0.91–1.14, P_{heterogeneity} = 0.60). In the subgroup analysis by ethnicity, control source and consistency of frequency with Hardy-Weinberg equilibrium (HWE), still no significant associations were observed. For breast cancer, also no obvious associations were found for all genetic models (homozygote comparison: OR = 0.95, 95%CI 0.71–1.26, P_{heterogeneity} = 0.10; heterozygote comparison: OR = 1.00, 95%CI 0.89–1.14, P_{heterogeneity} = 0.71; dominant model: OR = 0.98, 95%CI 0.87–1.10, P_{heterogeneity} = 0.55; recessive model: OR = 0.95, 95%CI 0.72–1.25, P_{heterogeneity} = 0.07). We performed subgroup analyses by sample size and did not find an association.

Conclusions

This meta-analysis indicated that IRS2 rs1805097polymorphism was not associated with colorectal and breast cancer risk.     

Tolerance and Physiological Correlates of Neuromuscular Electrical Stimulation in COPD: A Pilot Study

Rationale

Neuromuscular electrical stimulation (NMES) of the lower limbs is an emerging training strategy in patients with COPD. The efficacy of this technique is related to the intensity of the stimulation that is applied during the training sessions. However, little is known about tolerance to stimulation current intensity and physiological factors that could determine it. Our goal was to find potential physiological predictors of the tolerance to increasing NMES stimulation intensity in patients with mild to severe COPD.

Methods

20 patients with COPD (FEV₁ = 54±14% pred.) completed 2 supervised NMES sessions followed by 5 self-directed sessions at home and one final supervised session. NMES was applied simultaneously to both quadriceps for 45 minutes, at a stimulation frequency of 50 Hz. Spirometry, body composition, muscle function and aerobic capacity were assessed at baseline. Cardiorespiratory responses, leg discomfort, muscle fatigue and markers of systemic inflammation were assessed during or after the last NMES session. Tolerance to NMES was quantified as the increase in current intensity from the initial to the final NMES session (ΔInt).

Results

Mean ΔInt was 12±10 mA. FEV₁, fat-free-mass, quadriceps strength, aerobic capacity and leg discomfort during the last NMES session positively correlated with ΔInt (r = 0.42 to 0.64, all p≤0.06) while post/pre NMES IL-6 ratio negatively correlated with ΔInt (r = −0.57, p = 0.001). FEV₁, leg discomfort during last NMES session and post/pre IL-6 ratio to NMES were independent factors of variance in ΔInt (r² = 0.72, p = 0.001).

Conclusion

Lower tolerance to NMES was associated with increasing airflow obstruction, low tolerance to leg discomfort during NMES and the magnitude of the IL-6 response after NMES.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00809120","term_id":"NCT00809120"}}NCT00809120     

Alcohol Use and Subsequent Sex among HIV-Infected Patients in an Ethnic Minority Area of Yunnan Province,China

Objective

To examine alcohol use and subsequent HIV risky behaviors among a sample of predominately ethnic minority people living with HIV/AIDS (PLWHA) in a rural community in Yunnan Province, China.

Method

A cross-sectional study with a face-to-face questionnaire interview was conducted among eligible participants.

Results

In total, 455 (94.4%) out of 482 eligible HIV patients participated in the study. Of them, 82.6% were ethnic minorities; 15.4% were never married; 96.5% were sexually experienced; 55.4% had used drugs, 67% were receiving antiretroviral therapy (ART). Over 65% were ever drinkers; of whom 61.5% were current drinkers. Among current drinkers, 32.4% drank daily and 41.2% were hazardous drinkers. Chinese white wine was the preferred choice. Higher level of alcohol use among drinkers in the preceding month was positively associated with being males (OR = 2.76, 95%CI: 1.03–7.43), ethnic minorities (OR _Jingpo = 2.21, 95%CI: 1.06–4.59; OR _{other minorities} = 3.20, 95%CI: 1.34–7.62), higher education (OR_1–6 = 1.98, 95%CI: 0.99–3.96; OR_≥7 = 2.35, 95%CI: 1.09–5.06) and being ART-naive (OR = 2.69, 95%CI: 1.67–4.32). About 39% of ever drinkers reported having engaged in sex after drinking since HIV diagnosis. Those who were younger than 46 years (OR_16–25 = 7.77, 95%CI: 1.22–49.60, OR_26–35 = 2.79, 95%CI: 1.06–7.35, OR_36–45 = 2.96, 95%CI: 1.57–7.58), hazardous drinkers (OR = 1.99, 95%CI: 1.00–3.97) and drug users (OR = 3.01, 95%CI: 1.19–7.58) were more likely to have had sex after drinking. Approximately 56% of drug users had used drugs after drinking.

Conclusions

High prevalence of alcohol use and subsequent risky behaviors including sexual engagement and drug use among HIV patients in rural Yunnan require tremendous and integrated efforts for prevention and control of alcohol and drug abuse and HIV spreading.     

Association between Milk and Milk Product Consumption and Anthropometric Measures in Adult Men and Women in India: A Cross-Sectional Study

Background

The nutritional aetiology of obesity remains unclear, especially with regard to the role of dairy products in developing countries.

Objective

To examine whether milk/milk product consumption is associated with obesity and high waist circumference among adult Indians.

Methods

Information on plain milk, tea, curd and buttermilk/lassi consumption assessed using a Food Frequency Questionnaire was obtained from the cross-sectional sib-pair designed Indian Migration Study (3698 men and 2659 women), conducted at four factory locations across north, central and south India. The anthropometric measures included were Body Mass Index (BMI) and Waist Circumference (WC). Mixed-effect logistic regression models were conducted to accommodate sib-pair design and adjust for potential confounders.

Results

After controlling for potential confounders, the risk of being obese (BMI≥25 kg/m²) was lower among women (OR = 0.57;95%CI:0.43−0.76;p≤0.0001) and men (OR = 0.67;95%CI: 0.51−0.87;p = 0.005), and the risk of a high WC (men: >90 cm; women: >80 cm) was lower among men (OR = 0.71;95%CI:0.54−0.93;p = 0.005) and women (OR = 0.79;95%CI:0.59−1.05;p>0.05) who consume ≥1 portions of plain milk daily than those who do not consume any milk. The inverse association between daily plain milk consumption and obesity was also confirmed in sibling-pair analyses. Daily tea consumption of ≥1 portion was associated with obesity (OR = 1.51;95%CI:1.00−2.25;p>0.050) and high WC (OR = 1.65;95%CI:1.08−2.51;p>0.019) among men but not among women but there was no strong evidence of association of curd and buttermilk/lassi consumption with obesity and high waist circumference among both men and women.

Conclusions

The independent, inverse association of daily plain milk consumption with the risk of being obese suggests that high plain milk intake may lower the risk of obesity in adult Indians. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. Therefore, confirmatory studies are needed to clarify this relationship.     

Inflammation and Airway Microbiota during Cystic Fibrosis Pulmonary Exacerbations

Background

Pulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.

Objective

To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.

Methods

Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0–3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.

Results

Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = −0.67, p<0.001), decreased FEV_1% predicted (r = 0.49, p = 0.03) and increased CRP (r = −0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.

Conclusions

Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.     

Association between Glutathione S-Transferase T1 Null Genotype and Gastric Cancer Risk: A Meta-Analysis of 48 Studies

Background

Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several carcinogens and may play an important role in carcinogenesis of cancer. Previous studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk reported inconclusive results. To clarify the possible association, we conducted a meta-analysis of eligible studies.

Methods

We searched in the Pubmed, Embase, and Wangfang Medicine databases for studies assessing the association between GSTT1 null genotype and gastric cancer risk. The pooled odds ratio (OR) and its 95% confidence interval (95%CI) was calculated to assess the strength of the association. A total of 48 studies with a total of 24,440 individuals were ultimately eligible for meta-analysis.

Results

Overall, GSTT1 null genotype was significantly associated with increased risk of gastric cancer (Random-effect OR = 1.23, 95%CI 1.13–1.35, P _OR <0.001, I² = 45.5%). Significant association was also found in Caucasians, East Asians, and Indians (P _Caucasians = 0.010; P _{East Asians} = 0.003; P _Indians = 0.017). After adjusting for other confounding variables, GSTT1 null genotype was also significantly associated with increased risk of gastric cancer (Random-effect OR = 1.43, 95%CI 1.20–1.71, P _OR <0.001, I² = 48.1%).

Conclusion

The meta-analysis provides strong evidence for the significant association between GSTT1 null genotype and increased risk of gastric cancer.     

KCNE1 rs1805127 Polymorphism Increases the Risk of Atrial Fibrillation: A Meta-Analysis of 10 Studies

Background

Atrial fibrillation (AF) is one of the most common types of arrhythmia in humans. Recently, many studies have investigated the relationship between human atrial fibrillation and the single nucleotide polymorphism (SNP) of rs1805127 (A>G) in KCNE1 gene, but the results were still inconsistent and inconclusive.

Method

Electronic databases and bibliographies of retrieved studies were searched. We performed a meta-analysis of ten case-control studies, including 2099 cases and 2252 controls, to evaluate the association of rs1805127 polymorphism (A>G) with the risk of AF. Random-effects model was used when the heterogeneity was obvious; otherwise, fixed-effects model was applied. Meta-regression was performed to examine potential source of heterogeneity. Egger''s test and Begg''s test were used to detect publication biases.

Results

The results showed a significantly increased risk of AF in homozygote comparison (GG vs. AA:OR = 1.899, 95%CI: 1.568, 2.300; P_{heterogeneity} = 0.217), heterozygote comparison (GA vs. AA:OR = 1.436, 95% CI:1.190, 1.732; P_{heterogeneity} = 0.739), dominant model(GA /GG vs. AA: OR = 1.624, 95%CI: 1.361, 1.938; P_{heterogeneity} = 0.778) and recessive model (GG vs. GA/AA: OR = 1.394, 95%CI:1.152, 1.686; P_{heterogeneity} = 0.03). Meta-regression revealed that the sample size and the types of AF were the source of the heterogeneity.

Conclusion

The rs1805127 polymorphism (A>G) of KCNE1 is associated with an increased risk of AF, which suggests the rs1805217 polymorphism of KCNE1 gene may play an important role in the pathogenesis of AF.     

Association of Thymidylate Synthase Polymorphisms with Acute Pancreatitis and/or Peripheral Neuropathy in HIV-Infected Patients on Stavudine-Based Therapy

Background

Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy.

Methods

We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student’s t test, Pearson’s correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done.

Results

Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10–5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33–6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23–7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; OR_A+B = 0.34 [95%CI: 0.08 to 1.44], OR_B+A = 3.38 [95%CI: 1.33 to 8.57], OR_B+B = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm³ (OR = 0.38; 95%CI: 0.17–0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18–0.85, P = 0.018).

Conclusions

Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients.     

Significant Association of Glutathione S-Transferase T1 Null Genotype with Prostate Cancer Risk: A Meta-Analysis of 26,393 Subjects

Background

Recent studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and risk of prostate cancer showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies.

Methods

Data were collected from the following electronic databases: Pubmed, Embase, and Chinese Biomedical Database (CBM). The odds ratio (OR) and its 95% confidence interval (95%CI) was used to assess the strength of the association. We summarized the data on the association between GSTT1 null genotype and risk of prostate cancer in the overall population, and performed subgroup analyses by ethnicity, adjusted ORs, and types of controls.

Results

Ultimately, a total of 43 studies with a total of 26,393 subjects (9,934 cases and 16,459 controls) were eligible for meta-analysis. Overall, there was a significant association between GSTT1 null genotype and increased risk of prostate cancer (OR = 1.14, 95%CI 1.01–1.29, P = 0.034). Meta-analysis of adjusted ORs also showed a significant association between GSTT1 null genotype and increased risk of prostate cancer (OR = 1.34, 95%CI 1.09–1.64, P = 0.006). Similar results were found in the subgroup analyses by ethnicity and types of controls.

Conclusion

This meta-analysis demonstrates that GSTT1 null genotype is associated with prostate cancer susceptibility, and GSTT1 null genotype contributes to increased risk of prostate cancer.     

Association between Fat Mass- and Obesity- Associated (FTO) Gene Polymorphism and Polycystic Ovary Syndrome: A Meta-Analysis

Aims

Many studies have investigated the relationship between FTO gene polymorphism and polycystic ovary syndrome (PCOS) susceptibility but revealed mixed results. In this study, we aimed to perform a meta-analysis to clarify this association.

Methods

Published literature from PubMed, Embase and CNKI was retrieved. Meta-analysis was performed to calculate pooled odds ratio (OR) with 95% confidence interval (CI) using the random- or fix- effects model.

Results

A total of 5 studies (4778 cases and 4272 controls) were included in our meta-analysis. The results suggested that FTO rs9939609 polymorphism (or its proxy) was marginally associated with PCOS risk after adjustment for body mass index (BMI) (OR = 1.26; 95%CI: 1.02–1.55). However, the marginal association was not stable after sensitivity analysis. In the subgroup analysis by ethnicity, the association was significant in East Asians (OR = 1.43, 95%CI = 1.30–1.59) but not in Caucasians (OR = 1.04, 95%CI = 0.85–1.29).

Conclusions

Our present meta-analysis indicated that FTO rs9939609 polymorphism (or its proxy) might not be associated with risk of PCOS in overall population. However, in East Asians, there might be a direct association between FTO variant and PCOS risk, which is independent of BMI (adiposity).     

Asthma Is Inversely Associated with Helicobacter pylori Status in an Urban Population

Background

Microbial exposures have been suggested to confer protection from allergic disorders and reduced exposures to gastrointestinal microbiota have been proposed as an explanation for the increase in asthma prevalence. Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma.

Methods

Adults were recruited to participate in the New York University (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and controls (N = 208) were identified and serum IgG antibodies to H. pylori whole cell antigens or the immunodominant CagA antigen were measured.

Results

As expected, the asthma cases and controls differed with respect to atopy and lung function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the total case and control study population. Asthma was inversely associated with CagA seropositivity (OR = 0.57, 95% CI = 0.36–0.89). Median age of onset of asthma (doctor''s diagnosis) was older (21 years) among individuals with CagA+ strains than among H. pylori- individuals (11 years) (p = 0.006).

Conclusion

These data are consistent with the hypothesis that colonization with CagA+ H. pylori strains is inversely associated with asthma and is associated with an older age of asthma onset in an urban population. The data suggest H. pylori as a marker for protection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00212537","term_id":"NCT00212537"}}NCT00212537     

Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

Background

Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.

Methods

There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.

Results

After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.

Conclusions

The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.     

The Effect of Ginseng (The Genus Panax) on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Importance

Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.

Objective

To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.

Data sources

MEDLINE, EMBASE, CINAHL and the Cochrane Library (through July 3, 2013).

Study selection

Randomized controlled trials ≥30 days assessing the glycemic effects of ginseng in people with and without diabetes.

Data extraction

Relevant data were extracted by 2 independent reviewers. Discrepancies were resolved by consensus. The Heyland Methodological Quality Score and the Cochrane risk of bias tool were used to assess study quality and risk of bias respectively.

Data synthesis

Sixteen trials were included, in which 16 fasting blood glucose (n = 770), 10 fasting plasma insulin (n = 349), 9 glycated hemoglobin (n = 264), and 7 homeostasis model assessment of insulin resistance (n = 305) comparisons were reported. Ginseng significantly reduced fasting blood glucose compared to control (MD =  −0.31 mmol/L [95% CI: −0.59 to −0.03], P = 0.03). Although there was no significant effect on fasting plasma insulin, glycated hemoglobin, or homeostasis model assessment of insulin resistance, a priori subgroup analyses did show significant reductions in glycated hemoglobin in parallel compared to crossover trials (MD = 0.22% [95%CI: 0.06 to 0.37], P = 0.01).

Limitations

Most trials were of short duration (67% trials<12wks), and included participants with a relatively good glycemic control (median HbA1c non-diabetes = 5.4% [2 trials]; median HbA1c diabetes = 7.1% [7 trials]).

Conclusions

Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. In order to address the uncertainty in our effect estimates and provide better assessments of ginseng''s anti-diabetic efficacy, larger and longer randomized controlled trials using standardized ginseng preparations are warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01841229","term_id":"NCT01841229"}}NCT01841229     

The Association between Disturbed Eating Behavior and Socioeconomic Status: The Online Korean Adolescent Panel Survey (OnKAPS)

Background

A limited amount of research, primarily conducted in Western countries, has suggested that higher socioeconomic status (SES) is associated with higher risk of eating disorders (EDs). However, little is known about this association in Asian countries. We examined the association of SES with disturbed eating behavior (DEB) and related factors in Korean adolescents.

Subjects

A nationwide online panel survey was conducted in a sample of adolescents (n = 6,943, 49.9% girls). DEB was measured with the 26-item Eating Attitudes Test (EAT-26). Participants who scored ≥20 on the EAT-26 were considered to have DEB. Participants’ SES was determined based on self-reported household economic status.

Results

The prevalence of DEB was 12.7%: 10.5% among boys and 14.8% among girls. Both boys and girls with DEB were more likely to perceive themselves as obese, experience higher levels of stress, and have lower academic achievement. The risk for DEB was significantly higher in boys of higher SES than in those of middle SES (OR = 1.45, 95%CI = 1.05–1.99 for high SES; OR = 5.16, 95%CI: 3.50–7.61 for highest SES). Among girls, higher risk of DEB was associated with the highest and lowest SES (OR = 1.52, 95%CI: 1.13–2.06 for lowest SES; OR = 2.22, 95%CI: 1.34–3.68 for highest SES).

Conclusions

Despite the lower prevalence of obesity in Korea compared with Western countries, the prevalence of DEB in Korean adolescents was high, especially among girls. Moreover, the association between SES and DEB followed a U-shaped curve for girls and a J-shaped curve for boys.     

Determinants of the Changes in Glycemic Control with Exercise Training in Type 2 Diabetes: A Randomized Trial

Aims

To assess the determinants of exercise training-induced improvements in glucose control (HbA_1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.

Methods

A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).

Results

Changes in HbA_1C were associated with changes in adiponectin (r = −0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA_1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = −0.26; P<0.03), and PGC-1α (r = −0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA_1C.

Conclusions

Decreases in HbA_1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00458133","term_id":"NCT00458133"}}NCT00458133     

Association of Three Common Single Nucleotide Polymorphisms of ATP Binding Cassette G8 Gene with Gallstone Disease: A Meta-Analysis

Background

In this study, we evaluated the association between these polymorphisms and gallstone disease using meta-analysis and compared the hepatic ABCG5/G8 mRNA expression and biliary lipids composition in patients with different genotypes of T400K and Y54C.

Methods

Data were analyzed using the Stata/SE 11.0 software and a random- effects model was applied irrespective of between-study heterogeneity. Hepatic mRNA expression of ABCG5/G8 genes in 182 patients with gallstone disease and 35 gallstone-free patients who underwent cholecystectomy were determined using real-time PCR. Genotypes of Y54C and T400K in the ABCG8 gene were determined by allelic discrimination using either genomic DNA or hepatic cDNA as template by Taqman assays. Biliary compostion in gallbladder bile was assayed in these patients as well.

Results

Ten papers including 13 cohorts were included for the final analysis. In the genotype model, the overall association between genotype with gallstone was significant for D19H (OR = 2.43, 95%CI: 2.23–2.64, P<0.001), and for Y54C (OR = 1.36, 95%CI: 1.01–1.83, P = 0.044), or T400K (OR = 1.17, 95%CI: 0.96–1.43. P = 0.110). In allele model, minor alleles of D19H polymorphism (allele D: OR = 2.25, 95%CI: 2.10–2.42, P<0.001) and of T400K polymorphism (allele K: OR = 1.18, 95%CI: 1.06–1.31, P<0.001) were related with an increased risk of gallstone disease. However, minor allele of Y54C polymorphism (allele Y, OR = 1.08, 95%CI: 0.96–1.21, P = 0.146) was not related with gallstone disease. I ² statistics indicated no significant between-study heterogeneity for all genetic models for any of the three polymorphisms. Funnel plot and Egger’s test suggested the absence of publication bias as well. However, no association of T400K and Y54C polymorphism with hepatic ABCG8/G5 mRNA expression or biliary lipids composition was found.

Conclusions

Our study showed strong association of D19H polymorphism with gallstone disease. T400K and Y54C polymorphism, though to a less extent, may also relate with gallstone disease.