Depressive symptom-associated IL-1ß and TNF-α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma.

BACKGROUND: Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored. OBJECTIVE: This study aimed to determine whether depressive symptom-associated immune inflammation correlates with impaired bronchodilator response (BDR) and airway inflammatory phenotypes. METHODS: Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Pre- and post-bronchodilator spirometry was performed for BDR. Airway inflammatory phenotypes were defined by sputum cell counts. CRP, IL-1ß, IL-5, IL-6, IL-8, TNF-α, IFN-γ, CCL17 and CCL22 in serum and sputum were detected. RESULTS: Compared with the non-depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS-D scores (P = 0.027 and P = 0.029). Levels of IL-1ß, TNF-α and IFN-γ in the serum and those of IL-1ß and IFN-γ in the sputum were elevated in the depressive group compared to those in the non-depressive group (all P < 0.05). Multiple regression models indicated that TNF-α in the sputum and IL-1ß, IL-6 and IFN-γ in both the serum and sputum were inversely associated with BDR; TNF-α in the sputum and IL-1ß in both the serum and sputum were positively correlated with sputum neutrophils. Mediation analyses revealed that IL-1ß and TNF-α in the sputum and IL-1ß in both the serum and sputum mediate the correlations of the HADS-D scores with BDR and sputum neutrophils, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Asthma patients with depressive symptoms present worse asthma control, which is most likely explained by impaired BDR and neutrophilic airway inflammation. IL-1ß and TNF-α, which are two key pro-inflammatory cytokines that mediate the correlation of depressive symptoms with impaired BDR and neutrophilic airway inflammation, may serve as targeted biomarkers in the neuropsychological phenotype of asthma; however, this result needs to be further validated.

Tumour markers in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: Interstitial lung disease (ILD) is the most common pulmonary extra-articular manifestations of rheumatoid arthritis (RA), but the pathogenesis of RA-ILD is unknown. The purpose of this study was to investigate the tumour markers levels in patients of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to explore the diagnostic value of serum tumour markers for RA-ILD. METHODS: Twenty-eight patients with RA-ILD and 83 patients with RA only were included. Serum levels of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, CA125, and CA19-9 were measured. RESULTS: Tumour markers CA15-3, CA125 and CA19-9 were increased in RA-ILD patients compared with RA without ILD patients. Logistic regression analysis revealed that older age (OR=1.06, 95% CI=[1.02-1.11]) and higher CA125 (OR=1.03, 95% CI=[1.01-1.05]) related to the increased risk of RA-ILD. ROC curve analysis showed the relationship between CA125 and RA-ILD was moderate (area under ROC curve (AUC)=0.78, 95% CI=[0.68-0.88]). In addition, CA125 levels above the normal reference (<35 U/ml) raised the risk of RA-ILD (OR=6.00, 95% CI=[2.37-15.16]). CONCLUSIONS: RA patient with older age and elevated tumour markers especially CA125 levels should be evaluated to check whether there is a potential of ILD.

[Expression of Serotonin Receptor and Transporter Related Genes of CD4+ T Lymphocytes in Patients with Asthma and Depression].

OBJECTIVE: To explore the comorbidity mechanism of asthma and depression. METHODS: A self-developed questionnaire, which also contained Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ) and Hamilton Rating Scale for depression ( HRSD), was administered in 41 participants with asthma (AS), asthma and depression (AD), or none any of these conditions (health control, HC). Lung function and blood levels of eosnophils and IgE were also detected in those in the AS and AD groups. Blood CD4+ T cells were isolated in all of the participants to extract RNA for reverse transcription to cDNA. Real-time polymerase chain reaction (RT-PCR) was performed using cDNA as a template to detected the expression levels of HTR1A, HTR2A, HTR7, SLC6A4, and B2M genes. RESULTS: Participants with AS and AD had lower expression level of SLC6A4 than the healthy controls (P = 0.000). The expression level of HTR2A in participants with AS was lower than that in the healthy controls (P = 0.021) and marginally lower than that in participants with AD (P = 0.077). Participants with AD had lower AQLQ scores than participants with AS (P = 0.004). CONCLUSION: Asthma and depression is correlated at gene level. Decreased expression of SLC6A4 gene may be one of the possible comorbidity mechanisms of asthma and depression.

Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B.

BACKGROUND: The interruption of mother-to-child transmission (MTCT) is considered important to decrease the individual and population morbidity of hepatitis B virus (HBV) infection as well as the global burden of hepatitis B. Serum vitamin D (VD) is associated with hepatitis B. AIM: To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) are associated with the efficacy of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT in pregnant women with high HBV viral loads. METHODS: Thirty-eight pregnant women who were at high risk for MTCT of HBV (those with an HBV DNA level ≥ 2 × 105 IU/mL during 12-24 wk of gestation) receiving antiviral therapy of TDF between June 1, 2019 and June 30, 2021 in Mianyang were included in this retrospective study. The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery. To further characterize the clinical relevance of maternal serum HBV DNA levels, we stratified patients according to HBV DNA level as follows: Those with levels < 2 × 105 (full responder group) vs those levels ≥ 2 × 105 IU/mL (partial responder group) at delivery. Serum levels of 25-hydroxyvitamin D [25(OH)D], liver function markers, virological parameters, VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF. The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups. Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery. Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery. RESULTS: A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study. The MTCT rate was 0%. No mother achieved hepatitis B e antigen or hepatitis B surface antigen (HBsAg) clearance at delivery. Twenty-three (60.5%) participants were full responders, and 15 (39.5%) participants were partial responders according to antiviral efficacy. The present study showed that a high percentage (76.3%) of pregnant women with high HBV viral loads had deficient (< 20 ng/mL) or insufficient (≥ 20 but < 31 ng/mL) VD levels. Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline (25.44 ± 9.42 vs 17.66 ± 5.34 ng/mL, P = 0.006) and delivery (26.76 ± 8.59 vs 21.24 ± 6.88 ng/mL, P = 0.044). Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels [log(10) IU/mL] at delivery after TDF therapy (r = -0.345, P = 0.034). In a multiple linear regression analysis, maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels (P < 0.0001, ß = -0.446), BMI (P = 0.03, ß = -0.245), baseline maternal log10 HBsAg levels (P = 0.05, ß = 0.285) and cholesterol levels at delivery (P = 0.015, ß = 0.341). Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels (OR = 1.23, 95%CI: 1.04-1.44), maternal VDR Cdx2 TT (OR = 0.09, 95%CI: 0.01-0.88) and cholesterol levels at delivery (OR = 0.39, 95%CI: 0.17-0.87) were associated with targeted antiviral effects (maternal HBV DNA levels < 2 × 105 at delivery). CONCLUSION: Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads. Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

Relationship between current psychological symptoms and future risk of asthma outcomes: a 12-month prospective cohort study.

BACKGROUND: Subjects with asthma are more susceptible to psychological symptoms, but it is uncertain whether psychological symptoms are linked to future risk of asthma outcomes. OBJECTIVE: To investigate the relationship between current psychological symptoms and future risk of asthma outcomes. METHODS: We conducted a prospective cohort study with a 12-month follow-up period of 297 patients with asthma. Psychological symptoms, lung function, asthma control test, and Asthma Quality of Life Questionnaire at baseline were assessed. Asthma outcomes including exacerbations, unplanned visits, emergency visits, hospital admissions, intensive care unit admissions, and length of hospital stays were monitored monthly. The time to the first asthma outcomes was analyzed. Furthermore, the association between psychological symptoms and future risk of asthma outcomes was calculated as adjusted relative risk (RR) using logistic regression models. RESULTS: The asthma patients were assigned to one of three groups: neither anxiety nor depression symptoms (NAD, n = 102), either anxiety or depression symptoms (A/D, n = 68), or anxiety and depression symptoms (AD, n = 120). Logistic regression models indicated that asthma patients in the AD group, but not the A/D group, had an increased adjusted RR for unplanned visits and emergency visits (RR = 2.33, 95% confidence interval (CI) = [1.50, 3.61]; and RR = 3.13, 95% CI = [1.90, 5.17], respectively). The time to the first asthma outcomes including exacerbations, unplanned visits, and emergency visits was shorter in patients with psychological symptoms than those without (all p < .001). CONCLUSION: Current psychological symptoms, especially anxiety combined with depression, independently predict the future risk of asthma outcomes. Ting Zhou and Lan Wang contributed equally to this study.

The positive rates of hepatitis B surface antibody in youth after booster vaccination: a 4-year follow-up study with large sample.

BACKGROUND: Hepatitis B virus (HBV) infection is still a public issue in the world. Hepatitis B vaccination is widely used as an effective measure to prevent HBV infection. This large-sample study aimed to evaluate the positive rates of hepatitis B surface antibody (anti-HBs) in youth after booster vaccination. METHODS: A total of 37788 participants were divided into two groups according to the baseline levels of anti-HBs before booster vaccination: the negative group (anti-HBs(-)) and the positive group (anti-HBs(+)). Participants were tested for anti-HBs levels after receiving a booster vaccine at 1 and 4 years. RESULTS: The positive rates of anti-HBs were 34.50%, 73.80% and 67.32% before booster vaccination at 1 and 4 years after vaccination, respectively. At 4 years after the booster vaccination, the positive rates of 13-18 years were 47.54%, which was the lowest level among all youth age groups. In the anti-HBs(-) group, the positive conversion rates of anti-HBs were 74.62% at 1 year after receiving a booster vaccine, and 67.66% at 4 years after vaccination. In the anti-HBs(+) group, the positive maintenance rates of anti-HBs were 70.16% after 1 year, and 66.66% after 4 years. Compared with the baseline anti-HBs (+) group, the positive rates of the baseline anti-HBs(-) group were higher at 1 and 4 years after receiving the booster vaccine. CONCLUSION: The positive rates of anti-HBs declined over time, especially the positive maintenance rates were the lowest at age of 13-18 years.

Psychological status in uncontrolled asthma is not related to airway hyperresponsiveness.

BACKGROUND: Airway hyperresponsiveness (AHR) is the characteristic functional abnormality of asthma, and previous studies have shown the potential for AHR to be influenced by psychological factors, yet the relationship between anxiety and/or depression and AHR remains unclear in patients with asthma. OBJECTIVE: To explore the relationship between psychological status and AHR in asthma patients. METHODS: In a cross-sectional study, 168 adult subjects were recruited with physician-diagnosed uncontrolled asthma and a positive result for AHR in methacholine (Mch) challenge test. Psychological status, asthma control, and asthma quality of life were assessed using Zung self-rating anxiety/depression scale, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ), respectively. AHR severity was evaluated and quantified by the provocative concentration of Mch, which evoked a given decrease of 20% in FEV(1). RESULTS: A total of 70.23% of recruited patients (n = 118) met the diagnostic criteria for anxiety and/or depression. There was a trend between negative psychological status and AHR in asthma patients that did not reach statistical significance, but no independent effects of negative mood states (anxiety, depression, or both) on AHR were established. Further, analyses revealed that only anxiety is associated with worse asthma control (p = 0.029), and a significant interaction effect of depression and anxiety accounted for lower asthma-related quality-of-life scores (p < 0.001). CONCLUSIONS: AHR and psychological status are loosely related to each other even if in uncontrolled asthma.

[Association of 5-hydroxytryptamine transporter gene polymorphism with asthma and comorbid depression].

OBJECTIVE: To explore the molecular genetic mechanism of complicating depression in asthma by detecting two gene polymorphisms of 5-hydroxytryptamine transporter (5-HTTLPR/Stin2) gene. METHODS: One hundred fifty-six adults with asthma were collected, and divided into group of asthma with depression (HAMD score > or = 8) and group of asthma without depression or single asthma (HAMD score <8) according to the score of Hamilton depression scale (HAMD). A total of 508 adults with depression alone and 433 healthy individuals were enrolled as controls. The target gene fragments containing the polymorphic regions of 5-HTTLPR and Stin2 were amplified by polymerase chain reaction (PCR). The amplified fragments were then analyzed using agarose gel electrophoresis (AGE) and motored molecular imaging system. RESULTS: The frequencies of genotype and allele distribution of the Stin2 polymorphism showed that males with genotype Stin2.12/Stin2.10 and allele Stin2.10 had higher risk for asthma than the others (Stin2.12/Stin2.10: OR = 2.291, 95% CI: 1.195 and 4.390; Stin2.10: OR = 1.942, 95% CI: 1.069-3.527). No significant difference was found in the frequencies of genotype and allele distribution of the 5-HTTLPR locus between the asthma and healthy control groups and the two stratified by gender. CONCLUSION: The Stin2 polymorphism may play a role in the onset of male asthma. There might be association between the genetic pathogenesis of asthma and depression.

[The study on relationship between negative mood states and asthma control and quality of life].

OBJECTIVE: To explore the relationship between psychological status including depression and anxiety, and asthma control and quality of life. METHODS: A brief, structured psychiatric interview using the Hamilton depression scale (HAMD) and the Hamilton anxiety scale (HAMA) were applied to 156 consecutive adults with confirmed, physician-diagnosed asthma. Asthma control and asthma-related quality of life were assessed using the asthma control questionnaire (ACQ) and the asthma quality of life questionnaire (AQLQ). Detection of FEV1, FVC and PEF with standard spirometry for all patients was conducted. The patients were divided into depression (DG), anxiety (AG), depression and anxiety (ADG), and non depression and/or non anxiety (NADG) groups according to the scores for depression and anxiety degree. Level of asthma control, quality of life and pulmonary function of different groups were compared and a multiple regression model was set for the analisis. RESULTS: Sixty five percent of patients (n=101) had symptoms of depression or anxiety (18% had depression, 5% had anxiety, and 42% had both). Analyses revealed independent effects for depression but not anxiety, on total ACQ and AQLQ scores (both P<0.05). Moreover, there was no interaction effects on anxiety and depression coupled with anxiety. CONCLUSION: It suggests that depression but not anxiety, is associated with worse asthma control and asthma-related quality of life. Physicians should consider the differential impact of negative mood states when assessing levels of asthma control and quality of life.

Functional polymorphism of CYP2E1 gene and alcohol use disorders in a Tibetan population.

OBJECTIVE: To investigate the relationship between the CYP2E1*c1/*c2 polymorphism and alcohol use disorders, and the potential influence of the CYP2E1*c1/*c2 polymorphism on the severity and dimensions of alcohol use disorders in Tibetan. METHODS: Three hundred and forty Tibetans with Alcohol Use Disorders Identification Test (AUDIT) score >or=10 and another 315 matched control subjects with AUDIT score

The Serum Anti-HBs Level Among Children Who Received Routine Hepatitis B Vaccination During Infancy in Mianyang City, China: A Cross-Sectional Study.

Hepatitis B virus (HBV) prevalence has declined remarkably in children due to nationwide universal vaccination program for HBV in China. However, the persistence of immune response against HBV infection and the optimal time point when a booster vaccination should be performed remain to be elucidated. To assess the persistence and level of antibody against hepatitis B surface antigen (anti-HBs) in a representative population of age 15 and younger who received routine hepatitis B vaccination in Mianyang City, China. A cross-sectional study was conducted in 2011. One thousand five hundred twenty-six children of age 15 and younger who received three doses of 5 µg hepatitis B vaccine series during infancy but did not receive a booster vaccination later were enrolled. Of the 1,526 children, the mean age was 8.2 ± 4.1 and 739 children were male. The median anti-HBs level was 23.0 mIU/mL, and the total percentage of anti-HBs levels ≥10 mIU/mL was 60.9%. With an increase of age, median anti-HBs level, percentage of anti-HBs levels ≥10 mIU/mL, and percentage of anti-HBs levels ≥100 mIU/mL declined remarkably in the early period and reached the lowest level at the age of 3 and then remained relatively stable. The median anti-HBs level, the percentage of anti-HBs levels ≥10 mIU/mL, and the percentage of anti-HBs levels ≥100 mIU/mL in 1- and 2-year-old children were much higher than that in children aged 3-15 (p < 0.05, respectively). Immunity against HBV infection gradually decreased in early ages of children of 15 and younger who received three doses of 5 µg hepatitis B vaccine series during infancy in China. Three dosages of 10 µg hepatitis B vaccine for infants and repeated vaccination or additional booster vaccination for some children at or before age 3 should be provided to get much more powerful immunity to HBV.

The Role of Catalase C262T Gene Polymorphism in the Susceptibility and Survival of Cancers.

Catalase (CAT), one antioxidant enzyme, may provide resistance against many diseases. Many previous studies reported predictive and prognostic values of CAT C262T polymorphism in cancers, with divergent results. This study aimed to summarize the overall relationships between CAT C262T polymorphism and cancer risk or survival. A total of 27 eligible publications were included in susceptibility analysis, while 8 publications contained survival outcomes. The results revealed significant relationship between CAT C262T polymorphism and cancer risk(TT + CT vs CC: OR = 1.05, 95%CI = 1.00-1.10, P = 0.036), subgroup analyses indicated the CAT C262T polymorphism was significantly correlated with an increased risk for prostate cancer (TT vs CC + CT: OR = 1.43, 95%CI = 1.20-1.70, P < 0.001) and increased risk among Caucasians (TT vs CC + CT: OR = 1.19, 95%CI = 1.09-1.31, P < 0.001), while no associations between the polymorphism and Asian or mixed population were established. In the survival analysis, no interactions were identified between this polymorphism and cancer survival (TT + CT vs CC: HR = 1.37, 95%CI = 0.70-2.70, P = 0.36). In conclusion, the CAT C262T polymorphismmay be a candidate markerfor cancer risk with type-specific and population-specific effects but not a fine prognostic factor for cancer survival.

Interleukin-17F 7488T/C polymorphism is associated with protection against asthma: a meta-analysis.

The association between interleukin-17F (IL-17F) 7488T/C polymorphism and asthma risk is conflicting. This study conducted a meta-analysis by pooling all available data to make a more precise estimation of the association. Electronic databases PubMed, EMBASE, and China National Knowledge Infrastructure were searched to identify all eligible studies assessing the association between IL-17F 7488T/C polymorphism and asthma risk. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated. A total of five case-control studies with 1445 cases and 1608 controls were included. Overall, the pooled ORs showed that the IL-17F 7488T/C polymorphism was inversely associated with risk of asthma (OR=0.29, 95% CI=[0.12, 0.70]) using recessive genetic model. Furthermore, this association was found to be exclusive to Asians (OR=0.31, 95% CI= [0.12, 0.84]). Sensitivity analysis by omission of single study in turn showed similar results. In conclusion, the present meta-analysis suggested that homozygote of IL-17F 7488T/C variant could protect against asthma in Asians. However, more studies conducted in different ethnic groups with large sample size are warranted to validate the precise association.

Is Folate Status a Risk Factor for Asthma or Other Allergic Diseases?

PURPOSE: It is controversial whether folate status is a risk factor for the development of asthma or other allergic diseases. This study was conducted to investigate whether indirect or direct exposure to folate and impaired folate metabolism, reflected as methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism, would contribute to the development of asthma and other allergic diseases. METHODS: Electronic databases were searched to identify all studies assessing the association between folate status and asthma or other allergic diseases. Two reviewers independently assessed the eligibility of studies and extracted data. The relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CI) was calculated and pooled. RESULTS: Twenty-six studies (16 cohort, 7 case-control, and 3 cross-sectional studies) were identified. Maternal folic acid supplementation was not associated with the development of asthma, atopic dermatitis (AD), eczema, and sensitization in the offspring, whereas exposure during early pregnancy was related to wheeze occurrence in the offspring (RR=1.06, 95% CI=[1.02-1.09]). The TT genotype of MTHFR C677T polymorphism was at high risk of asthma (OR=1.41, 95% CI=[1.07-1.86]). CONCLUSIONS: It is indicated that maternal folic acid supplementation during early pregnancy may increase the risk of wheeze in early childhood and that the TT genotype of MTHFR C677T polymorphism impairing folic acid metabolism would be at high risk of asthma development. These results might provide additional information for recommendations regarding forced folate consumption or folic acid supplements during pregnancy based on its well-established benefits for the prevention of congenital malformations. However, currently available evidence is of low quality which is needed to further elucidate.

Contribution of Macrophage Migration Inhibitory Factor -173G/C Gene Polymorphism to the Risk of Cancer in Chinese Population.

BACKGROUND: Macrophage migration inhibitory factor (MIF) -173G/C (rs755622) gene polymorphism has been associated with cancer risk. Previous studies have revealed that MIF -173G/C gene polymorphism may increase cancer in the Chinese population, while results of individual published studies remain inconsistent and inconclusive.We performed this meta-analysis to derive a more precise estimation of the relationship. MATERIALS AND METHODS: We conducted a search on PubMed, Embase, MEDLINE, Cochrane Library ,Chinese National Knowledge Infrastructure (CNKI), Wanfang, Weipu on Dec 31, 2014.Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the association. A total of eight studies including 2,186 cases and 2,285 controls were involved in this meta-analysis. RESULTS: The pooled results indicated the significant association between MIF -173G/C polymorphism and the risk of cancer for Chinese population (CC + CG vs GG: OR=1.14, 95%CI=1.02-127, pheterogeneity<0.01; P =0.023; CC vs CG+GG: OR=1.12, 95%CI=1.02- 1.23, pheterogeneity< 001; P =0.017;CC vs GG: OR=1.18, 95%CI=1.04-1.33, pheterogeneity<001; P =0.008; CG vs GG:OR=1.03, 95%CI=0.91-1.15, pheterogeneity<001; P =0.656; C vs G:OR=1.24, 95%CI=1.14-1.25, pheterogeneity<001; P <001). Subgroup analysis showed that in patients with "solid tumors", heterogeneity was very large (OR=0.94,95%CI=0.83-1.06,pheterogeneity=0.044; p=0.297). Within "non-solid tumors", the association became even stronger (OR=6.62, 95 % CI=4.32-10.14, pheterogeneity<0.001; p <0.001). CONCLUSIONS: This study suggested that MIF ?173G/C gene polymorphism may increase increase cancer in the Chinese population.Furthermore, more larger sample and representative population-based casees and well-matched controls are needed to validate our results.

Impact of CYP1A1 Polymorphisms on Susceptibility to Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

OBJECTIVE: Several studies have evaluated the association between CYP1A1 polymorphisms and the susceptibility of chronic obstructive pulmonary disease (COPD) with inconclusive results. We performed the first comprehensive meta-analysis to summarize the association between CYP1A1 polymorphisms and COPD risk. METHOD: A systematic literature search was conducted (up to April 2015) in five online databases: PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WeiPu, and WanFang databases. The strength of association was calculated by odds ratio (OR) and corresponding 95% confidence interval (CI). RESULTS: Seven case-control studies with 1050 cases and 1202 controls were included. Our study suggested a significant association between the MspI polymorphism and COPD risk (CC versus TC + TT: OR = 1.57, CI: 1.09-2.26, P = 0.02; CC versus TT: OR = 1.73, CI: 1.18-2.55, P = 0.005). For the Ile/Val polymorphism, a significant association with COPD risk was observed (GG versus AG + AA: OR = 2.75, CI: 1.29-5.84, P = 0.009; GG versus AA: OR = 3.23, CI: 1.50-6.93, P = 0.003; AG versus AA: OR = 1.39, CI: 1.01-1.90, P = 0.04). Subgroup analysis indicated a significant association between the MspI variation and COPD risk among Asians (CC versus TC + TT: OR = 1.70, CI: 1.06-2.71, P = 0.03; CC versus TT: OR = 1.84, CI: 1.11-3.06, P = 0.02). CONCLUSION: The MspI and Ile/Val polymorphisms might alter the susceptibility of COPD, and MspI polymorphism might play a role in COPD risk among Asian population.

Transcriptomic profiling of peripheral blood CD4⁺ T-cells in asthmatics with and without depression.

BACKGROUND: Cumulative studies have shown that asthma is associated with depression but the underlying mechanisms are poorly understood. This study aimed to determine whether asthma with depression is characterized by unique pathophysiological pathways by analyzing the global gene expression patterns of CD4(+) T-cells from asthmatics with or without depression. MATERIALS AND METHODS: Four groups of subjects (non-depressive asthmatics, depressive asthmatics, depression patients, and healthy controls) consisting of 6 participants in each group were studied. Peripheral CD4(+) T-cells were isolated and the global transcriptomic profiles were defined by using the Agilent SurePrint G3 Human GE 8x60K microarray. The differences in transcriptomic profiles between asthma with or without depression, depression patients and healthy controls were examined. Pathway enrichment analyses of differentially expressed genes were performed using the Ingenuity Pathway Analysis. Selected genes were verified and correlated to the clinical characteristics. RESULTS: A total of 1448 differentially expressed transcripts were identified in any of the non-depressive asthma vs. healthy control, depressive asthma vs. healthy control, or depression vs. healthy control comparisons after correction for multiple comparisons. Among these, 156 were demonstrated as differentially expressed genes only in depressive asthma vs. healthy control. Twenty significant biological pathways were identified and were involved in inflammation, metabolism, immunity, tumor and cell cycle. Increased expression of phosphoinositide-3-kinase, regulatory subunit 1 (alpha) was confirmed in depressive asthmatics and it was inversely correlated with lung function (FEV1/FVC%). CONCLUSIONS: Asthmatics with depression exhibit unique pathophysiological pathways and this result may provide clues for specific molecular mechanisms underlying asthma with depression.

Selection of suitable housekeeping genes for real-time quantitative PCR in CD4(+) lymphocytes from asthmatics with or without depression.

OBJECTIVE: No optimal housekeeping genes (HKGs) have been identified for CD4(+) T cells from non-depressive asthmatic and depressive asthmatic adults for normalizing quantitative real-time PCR (qPCR) assays. The aim of present study was to select appropriate HKGs for gene expression analysis in purified CD4(+) T cells from these asthmatics. METHODS: Three groups of subjects (Non-depressive asthmatic, NDA, n = 10, Depressive asthmatic, DA, n = 11, and Healthy control, HC, n = 10 respectively) were studied. qPCR for 9 potential HKGs, namely RNA, 28S ribosomal 1 (RN28S1), ribosomal protein, large, P0 (RPLP0), actin, beta (ACTB), cyclophilin A (PPIA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase 1 (PGK1), beta-2-microglobulin (B2M), glucuronidase, beta (GUSB) and ribosomal protein L13a (RPL13A), was performed. Then the data were analyzed with three different applications namely BestKeeper, geNorm, and NormFinder. RESULTS: The analysis of gene expression data identified B2M and RPLP0 as the most stable reference genes and showed that the level of PPIA was significantly different among subjects of three groups when the two best HKGs identified were applied. Post-hoc analysis by Student-Newman-Keuls correction shows that depressive asthmatics and non-depressive asthmatics exhibited lower expression level of PPIA than healthy controls (p<0.05). CONCLUSIONS: B2M and RPLP0 were identified as the most optimal HKGs in gene expression studies involving human blood CD4(+) T cells derived from normal, depressive asthmatics and non-depressive asthmatics. The suitability of using the PPIA gene as the HKG for such studies was questioned due to its low expression in asthmatics.

Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study.

BACKGROUND: The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated. This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up. METHODS: This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n = 290). The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models. Further, sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations. RESULTS: The subjects were divided into three groups, which were uncontrolled (U, n = 128), partly-controlled (PC, n = 111), and well controlled (C, n = 51) asthma. After adjustment, the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75, respectively), unplanned visits (OR 8.03 and OR 8.21, respectively) and emergency visits (OR 20.00 and OR 22.60, respectively) over a 12-month follow-up period. The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P < 0.05). The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%. CONCLUSION: Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and predict future risk of asthma exacerbations in clinical practice.