Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Mature conifers assimilate nitrate as efficiently as ammonium from soils in four forest plantations.

Conifers are considered to prefer to take up ammonium (NH4+ ) over nitrate (NO3- ). However, this conclusion is mainly based on hydroponic experiments that separate roots from soils. It remains unclear to what extent mature conifers can use nitrate compared to ammonium under field conditions where both roots and soil microbes compete for nitrogen (N). We conducted an in situ whole mature tree nitrogen-15 (15 N) labeling experiment (15 NH4+ vs 15 NO3- ) over 15 d to quantify ammonium and nitrate uptake and assimilation rates in four 40-yr-old monoculture coniferous plantations (Pinus koraiensis, Pinus sylvestris, Picea koraiensis and Larix olgensis, respectively). For the whole tree, 15 NO3- contributed 39% to 90% to total 15 N tracer uptake among four plantations during the study period. At day 3, the 15 NO3- accounted for 77%, 64%, 62% and 59% by Larix olgensis, Pinus koraiensis, Pinus sylvestris and Picea koraiensis, respectively. Our study indicates that mature coniferous trees assimilated nitrate as efficiently as ammonium from soils even at low soil nitrate concentration, in contrast to the results from hydroponic experiments showing that ammonium uptake dominated over nitrate. This implies that mature conifers can adapt to increasing availability of nitrate in soil, for example, under the context of globalization of N deposition and global warming.

[Carbonic anhydrase III and mRNA expression levels in quadriceps femoris muscle of chronic obstructive pulmonary disease patients].

OBJECTIVE: To explore the expression status of carbonic anhydrase III (CAIII) from quadriceps femoris muscle in two kinds of muscle clinical phenotype (skeletal muscle atrophy group and skeletal muscles non-atrophy group) of chronic obstructive pulmonary disease (COPD). METHODS: Totally 37 inpatients from our hospital, were divided into 11 patients without COPD and 26 patients with COPD, in addition, according to body mass index, fat free mass index and quadriceps cross-section diameter, patients with COPD were divided into 14 skeletal muscles non-atrophy patients (SMNA) and 12 skeletal muscle atrophy patients (SMA). CAIII concentration of femoris quadriceps specimens was quantitatively determined using Western blot methods, CAIIImRNA expression levels of femoris quadriceps specimens were also quantitatively measured using RT-PCR, then compared among the 3 groups. RESULTS: There was significant difference in CAIII quantitative concentration and CAIIImRNA expression level in each group (P < 0.05) , further more, CAIII concentration expression level was significantly higher (P < 0.01) in SMA group (1.260 ± 0.068) than in SMNA group (1.110 ± 0.014) , the latter was significantly higher (P < 0.01) than in the control group (1.000 ± 0.062) . CAIIImRNA expression level was significantly higher (P < 0.01) in SMNA group (2.170 ± 0.412) than in the control group (1.000 ± 0.115) , and was significantly lower than in SMA group (3.770 ± 0.788; P < 0.01). CAIII concentration and CAIIImRNA expression level increased at equal pace in SMNA group and SMA group, however, CAIII quantitative concentration and CAIIImRNA expression level were inconsistent in the two groups. CONCLUSION: The expression status of CAIII in quadriceps femoris muscle was different in two kinds of muscle clinical phenotype of COPD.

Phosphorus-based soil prophylactics for managing Pb contamination in soil: Slow-release kinetics and microbiological effects.

Soil remediation poses significant challenges due to its spatial heterogeneity, surpassing the complexities of atmospheric and water remediation. This study introduces an innovative approach to prevent soil heavy metal pollution by developing three phosphorus slow-release heavy metal soil prophylactic agents (SLPs) - Sap-11, Sap-12, and Sap-21. At a liquid-to-solid ratio of 1:20, the three types of SLPs achieve phosphorus sustained slow release amounts of 1.586 g/L, 4.259 g/L, and 1.444 g/L within 30 days, respectively. Over a cultivation period of 120 days, after amendment with the three SLPs, the surface soil demonstrates stabilization capacities for Pb of 29.56 mg/g, 46.24 mg/g, and 25.77 mg/g, respectively, representing enhancements of 283.64 %, 500.12 %, and 250.74 % compared to the control. Firstly, the direct contribution of P (up to 3.778 mg/g) released from SLPs chemically binding with Pb, and secondly, a significant proportion of the indirect contribution originating from the microbial activity and soil organic matter. In summary, SLP emerges as an effective strategy for soil heavy metal management, stabilizing heavy metals by stimulating the soil's inherent physiological and biochemical reactions. This approach provides a practical solution for the application of P-containing materials and introduces novel perspectives for soil heavy metal management strategies.

[Relationship between mitochondrial cytochrome oxidase mRNA expression and maternal inheritance of asthma].

OBJECTIVE: To explore the relationship between the mRNA expression level of mitochondrial cytochrome oxidase and the maternal inheritance of asthma. METHODS: From January to December 2009, 220 asthma patients, 162 patient kins and 260 healthy subjects were recruited from Departments of Respiratory Critical Care Medicine and Pediatric Medicine at First Affiliated Hospital, Kunming Medical College. Lung function tests were performed and serum IgE level measured. The polymorphism of mitochondrial cytochrome oxidase gene polymorphisms was detected by direct sequencing. And the peripheral level of COX mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: No significant difference existed in age, gender among 3 groups. For 3 groups, the first second forced expiratory volume (FEV1)/forced vital capacity (FVC) were 90.6 ± 6.2, 92.3 ± 2.3, 102.3 ± 2.3 and FEV1 percentage of expected value (FEV1%) were (82.9 ± 10.8)%, (94.8 ± 5.4)% and (98.3 ± 8.6)% respectively. The lung function was not significant difference among three groups. The mRNA expression level of mitochondrial cytochrome oxidase in peripheral blood were 0.357 ± 0.217, 0.637 ± 0.473 and 0.975 ± 0.260 in the asthma, kin and control groups respectively. No significant difference existed in the expression level of COX3 mRNA among 3 groups (F = 21.45, P = 0.012). The serum level of lgE was the highest for the asthma patients. And it was significantly higher in the asthma group than that in the control group ((283.6 ± 62.4) vs (52.3 ± 13.7) µg/L, F = 48.31, P < 0.05). Moreover, the serum level of IgE was significantly higher in the kin group than that in the control group ((116.4 ± 57.5) vs (52.3 ± 13.7) µg/L, F = 20.45, P < 0.05). However, there was a negative correlation between the mRNA expression level of mitochondrial cytochrome oxidase and the serum level of IgE among 3 groups. CONCLUSIONS: The down-regulated mRNA expressin of mitochondrial cytochrome oxidase may participate in allergic inflammation by regulating the level of IgE. And the maternal inheritance of asthma is in effect.

Remote regulation of rs80245547 and rs72673891 mediated by transcription factors C-Jun and CREB1 affect GSTCD expression.

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is influenced by genetic factors. The genetic signal rs10516526 in the glutathione S-transferase C-terminal domain containing (GSTCD) gene is a highly significant and reproducible signal associated with lung function and COPD on chromosome 4q24. In this study, comprehensive bioinformatics analyses and experimental verifications were detailly implemented to explore the regulation mechanism of rs10516526 and GSTCD in COPD. The results suggested that low expression of GSTCD was associated with COPD (p = 0.010). And C-Jun and CREB1 transcription factors were found to be essential for the regulation of GSTCD by rs80245547 and rs72673891. Moreover, rs80245547T and rs72673891G had a stronger binding ability to these transcription factors, which may promote the allele-specific long-range enhancer-promoter interactions on GSTCD, thus making COPD less susceptible. Our study provides a new insight into the relationship between rs10516526, GSTCD, and COPD.

[Preliminary proteomic analysis of peripheral skeletal muscle atrophy in chronic obstructive pulmonary disease].

OBJECTIVE: To conduct a preliminary proteomic study of chronic obstructive pulmonary disease (COPD) with peripheral skeletal muscle atrophy. METHODS: A total of 16 COPD patients and 8 aged-matched persons because of bone fractures were recruited in First Hospital Affiliated to Kunming Medical College from February to July in 2010. According to body mass index, fat free mass index, quadriceps femoris perimeter and quadriceps femoris active contraction, they were divided into those with muscle atrophy (group A, n = 8) and those without (group B, n = 8). There were 6 males and 2 females with an average age of (70 ± 8) years in the group A and 5 males and 3 females with an average age of (74 ± 8) years in the group B. And the control group had 6 males and 2 females with an average age of (72 ± 6) years. All samples of total quadriceps protein were separated by two-dimensional gel electrophoresis. The abnormal protein points on electrophoresis were compared by PDQuest image software. And the differential protein expression was detected. Then the corresponding peptide quality fingerprint spectrum was analyzed by mass spectrometer. Finally the differential protein points were partially detected by a search of database. RESULTS: The two-dimensional gel electrophoresis yielded an excellent profile of resolution and repeatability. And 12 proteins likely to cause skeletal muscle atrophy in COPD were identified. Among them, 8 proteins belonged to structural proteins (actin alpha cardiac muscle isoform CRA_c, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myoglobin isoform myosin heavy polypeptide 7 cardiac muscle beta isoform CRA_c, actin, alpha skeletal muscle, actin alpha cardiac muscle isoform CRA_b, hemoglobin alpha 1 globin chain & myosin light chain 6B) and 4 proteins were of functional proteins (chain A, crystal structure of human enolase; troponin T, slow skeletal muscle isoform alpha, carbonate anhydrase, troponin T & slow skeletal muscle isoform b). CONCLUSIONS: COPD patients are often accompanied with obvious peripheral skeletal muscle atrophy. It may be caused by quantitative or qualitative changes of peripheral skeletal structural and functional proteins.

Relationship between polymorphisms in the 5' leader cistron, positions 16 and 27 of the adrenergic ß2 receptor gene and asthma in a Han population from southwest China.

BACKGROUND AND OBJECTIVE: Adrenergic ß2 receptors (ADRB2) play an important role in regulating pulmonary function. Many previous studies have investigated possible associations between polymorphisms in the ADRB2 gene and asthma, but have yielded conflicting results. Furthermore, little is known regarding the possible role of the Arg19Cys polymorphism in susceptibility to asthma among Chinese. METHODS: This case-control association study involved 238 patients with asthma and 265 healthy subjects from a Han population in southwest China. For all subjects, the 5' leader cistron Arg19Cys, Arg16Gly and Gln27Glu polymorphisms in the ADRB2 gene were characterized by direct sequencing. Genotype, allele and haplotype frequencies were determined. In addition, to evaluate the association between the ADRB2 polymorphisms and lung function, bronchodilator response to inhaled ß2 agonists (400 µg of albuterol) was assessed in the asthmatic patients. RESULTS: There were no significant differences in genotype or allele frequencies for the three ADRB2 polymorphisms between the two cohorts. The Arg19/Arg16/Gln27 haplotype was more frequent among asthmatic patients than control subjects (odds ratio 2.24, 95% confidence interval (CI): 1.05-4.73, P=0.04). Moreover, the Arg19/Cys19 genotype was associated with a lower FEV1% (mean difference -4.5, 95% CI: -12.5 to 3.6, P=0.02) and FEV1/FVC (mean difference 8.9, 95% CI: 8.5-9.4, P=0.01). The bronchodilator response to albuterol was also marginally lower in individuals who were homozygous for the Arg19 genotype (mean difference 4.2, 95% CI: 3.7-4.8, P=0.03). CONCLUSIONS: The Arg19/Cys19 genotype was an independent risk factor for lower FEV1% and FEV1/FVC. Asthmatic patients with the Arg19/Arg19 genotype showed decreased responsiveness to albuterol. Furthermore, the Arg19/Arg16/Gln27 haplotype may contribute to increased susceptibility to asthma in the Chinese population.

Measurements of Chemical Compositions in Corn Stover and Wheat Straw by Near-Infrared Reflectance Spectroscopy.

Rapid, non-destructive methods for determining the biochemical composition of straw are crucial in ruminant diets. In this work, ground samples of corn stover (n = 156) and wheat straw (n = 135) were scanned using near-infrared spectroscopy (instrument NIRS DS2500). Samples were divided into two sets, with one set used for calibration (corn stover, n = 126; wheat straw, n = 108) and the remaining set used for validation (corn stover, n = 30; wheat straw, n = 27). Calibration models were developed utilizing modified partial least squares (MPLS) regression with internal cross validation. Concentrations of moisture, crude protein (CP), and neutral detergent fiber (NDF) were successfully predicted in corn stover, and CP and moisture were in wheat straw, but other nutritional components were not predicted accurately when using single-crop samples. All samples were then combined to form new calibration (n = 233) and validation (n = 58) sets comprised of both corn stover and wheat straw. For these combined samples, the CP, NDF, and ADF were predicted successfully; the coefficients of determination for calibration (RSQC) were 0.9625, 0.8349, and 0.8745, with ratios of prediction to deviation (RPD) of 6.872, 2.210, and 2.751, respectively. The acid detergent lignin (ADL) and moisture were classified as moderately useful, with RSQC values of 0.7939 (RPD = 2.259) and 0.8342 (RPD = 1.868), respectively. Although the prediction of hemicellulose was only useful for screening purposes (RSQC = 0.4388, RPD = 1.085), it was concluded that NIRS is a suitable technique to rapidly evaluate the nutritional value of forage crops.

Quantifying nitrogen uptake and translocation for mature trees: an in situ whole-tree paired 15N labeling method.

Nitrogen (N) is one of the major nutrients limiting plant growth in terrestrial ecosystems. To avoid plant-microbe competition, previous studies on plant N uptake preference often used hydroponic experiments on fine roots of seedlings and demonstrated ammonium preference for conifer species; however, we lack information about N uptake and translocation in the field. In this paper, we described a method of in situ paired 15N labeling and reported the rates and time course of N uptake and translocation by mature trees in situ. We added 15N-enriched ammonium or nitrate, together with the nitrification inhibitor dicyandiamide, to paired Larix kaempferi (Lamb.) Carr (larch) trees from 30-, 40- and 50-year-old plantations. Fine roots, coarse roots, leaves and small branches were collected 2, 4, 7, 14 and 30 days after labeling. Nitrate uptake and translocation averaged 1.59 ± 0.16 µg 15N g-1 day-1, which is slightly higher than ammonium (1.08 ± 0.10 µg 15N g-1 day-1), in all tree organs. Nitrate contributed 50-78% to N uptake and translocation, indicating efficient nitrate use by larch in situ. We observed no age effect. We suggest that sampling leaves after 4 days of 15N labeling is sufficient to detect mature tree N uptake preference in situ. Whole-tree 15N-ammonium recovery equaled that of 15N-nitrate 30 days after 15N addition, implying the importance of both ammonium and nitrate to mature larch N use in the long run. We conclude that our method is promising for studying mature tree N uptake preference in situ and can be applied to other conifer and broadleaf species. We suggest using highly enriched 15N tracer to overcome soil dilution and a nitrification inhibitor to minimize ammonium transformation to nitrate. Our study revealed mature tree N preference in situ and demonstrated the strong contribution of nitrate toward mature larch growth on soils rich in nitrate.

T-Helper 17 Cell/Regulatory T-Cell Imbalance in COPD Combined with T2DM Patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often combined with type 2 diabetes mellitus (T2DM) in clinical, and with poor prognosis. In recent years, research shows that inflammation is a common characteristic of COPD and T2DM. T-helper 17 cell (Th17)/regulatory T-cell (Treg) balance controls inflammation and may be important in the pathogenesis of COPD combined with T2DM patients. This study investigated the characteristics of Th17, Treg and related inflammatory factors in COPD combined with T2DM patients and the potential mechanism. METHODS: Application of flow cytometry technology, real-time fluorescent quantitative PCR and ELISA to detect the changes in peripheral blood of Th17 and Treg number and the expression of key transcription factors and related cytokines in COPD combined T2DM patients were performed. RESULTS: Patients with COPD combined with T2DM revealed significant increase in peripheral Th17, Th17 related cytokines (IL-17A, IL-17F, IL-21, IL-23, IL-6) and transcription factor (RORγt) levels and significant decrease in Treg, Treg-related cytokines (IL-10, TGFß1) and transcription factor (Foxp3) as compared with patients with COPD, T2DM and healthy controls. CONCLUSION: Th17/Treg functional imbalance exists in patients with COPD combined with T2DM, indicating a potential role of Th17/Treg imbalance in the formation and progression of COPD combined with T2DM.

Hospitalization Due to Asthma Exacerbation: A China Asthma Research Network (CARN) Retrospective Study in 29 Provinces Across Mainland China.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.

Absence of association between SERPINE2 genetic polymorphisms and chronic obstructive pulmonary disease in Han Chinese: a case-control cohort study.

BACKGROUND: Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians. However, this issue still remained controversial. Additional evidences from populations with different environments and/or genetic backgrounds, such as East Asian, would be helpful to elucidate the issue. METHODS: In this study, five proposed causal SNPs in SERPINE2 were genotyped in 327 COPD patients and 349 controls, all of which belonged to the Han population sampled from Southwest China. The frequency of each SNP was compared both individually and in combination between patients and controls. The potential relationship between these SNPs and severity of COPD was also investigated. RESULTS: Three SNPs (rs3795877, rs6747096, and rs3795879) showed complete linkage disequilibrium (r2 = 1), and the minor allele frequencies were 13.0% and 12.9% in case and control cohorts, respectively, with no significant difference observed (P = 0.96). We also failed to observe any significant correlation between these SNPs and COPD severity (P = 0.67). The other two SNPs (rs7579646 and rs840088) also presented a similar pattern. Moreover, four major haplotypes were observed in our sample but none showed a significant difference between case and control groups (P > 0.1). CONCLUSION: Our results failed to obtain the evidence that these SNPs in SERPINE2 contributed to the COPD susceptibility in the Han Chinese population.

Qing Chang Hua Shi granule ameliorate inflammation in experimental rats and cell model of ulcerative colitis through MEK/ERK signaling pathway.

Ulcerative colitis (UC), a bowel disease with significant morbidity, is associated with inflammation. In this study, the effect of Qingchang Huashi granule (QCHS) on UC and its underlying mechanisms were explored using both animal and cell culture experiments. A rat UC model was induced with trinitro-benzene-sulfonic acid (TNBS), concentrations of the cytokines IL-1α, IL-6, IL-8, IL-1ß, and TNF-α were significantly up-regulated and the concentrations of IL-4, IL-10, and IL-13 were significantly down-regulated compared with the control group (P < 0.05). In contrast, the QCHS and salicylazosulfapyridine (SASP) groups reversed these modulations (P < 0.05). A UC cell model in HT-29 cells was generated using TNF-α combined with lipopolysaccharide treatment. Cells treated with QCHS were used to investigate the possible mechanisms. The expression of apoptosis-related proteins, including Bax/Bcl-2, caspase-3, caspase-9, Fas/Fas-L, and Rafl in the QCHS and SASP groups, were significantly lower than that in the control group in both animal and cell experiments (P < 0.05). In addition, the in vitro results indicate changes in these indicators mediate the MEK/ERK signaling pathways via SGK1. Our results suggested that QCHS could be beneficial in preventing UC progression as an alternative drug for UC treatment.

Uptake Patterns of Glycine, Ammonium, and Nitrate Differ Among Four Common Tree Species of Northeast China.

Fundamental questions of how plant species within secondary forests and plantations in northeast China partition limited nitrogen (N) resource remain unclear. Here we conducted a 15N tracer greenhouse study to determine glycine, ammonium, and nitrate uptake by the seedlings of two coniferous species, Pinus koraiensis (Pinus) and Larix keampferi (Larix), and two broadleaf species, Quercus mongolica (Quercus) and Juglans mandshurica (Juglans), that are common in natural secondary forests in northeast China. Glycine contributed 43% to total N uptake of Pinus, but only 20, 11, and 21% to N uptake by Larix, Quercus, and Juglans, respectively (whole plant), whereas nitrate uptake was 24, 74, 88, and 68% of total uptake for these four species, respectively. Retention of glycine carbon versus nitrogen in Pinus roots indicated that 36% of glycine uptake was retained intact. Nitrate was preferentially used by Larix, Quercus, and Juglans, with nitrate uptake constituting 68∼88% of total N use by these three species. These results demonstrated that these dominant tree species in secondary forests in northeast China partitioned limited N resource by varying uptake of glycine, ammonium and nitrate, with all species, except Pinus, using nitrate that are most abundant within these soils. Such N use pattern may also provide potential underlying mechanisms for the higher retention of deposited nitrate than ammonium into aboveground biomass in these secondary forests.

[Combination of inhaled salmeterol/fluticasone and tiotropium in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial].

OBJECTIVE: To observe the efficacy of combination therapy with inhaled salmeterol/fluticasone and tiotropium in reducing the frequency of acute episodes of symptom exacerbation and improving lung function and health status in chronic obstructive pulmonary disease (COPD). METHODS: One hundred and twenty-six patients (M/F: 92/34) with COPD were treated in a randomised, parallel-group, controlled study with salmeterol/fluticasone (50/250 microg) twice daily and tiotropium 18 microg once daily (n = 33, M/F: 23/10); salmeterol/fluticasone (50/250 microg) twice daily (n = 32, M/F: 24/8); or tiotropium 18 microg once daily (n = 32, M/F: 23/9) for 12 months. Patients in the blank control group (n = 29, M/F: 22/7) did not receive any inhaled anticholinergic drugs, long-acting beta(2) agonists or glucocorticoid therapy. Intention-to-treat analysis (n = 161) and per-protocol analysis (n = 126, age 45 - 71 years) were performed. RESULTS: Three active treatments significantly improved symptoms and health status. The use of rescue medication in the combination group [1 (0 - 7) time, 95% CI] was significantly decreased compared with those in the blank group [2 (0 - 29) times], salmeterol/fluticasone alone [2 (0 - 13) times], tiotropium alone [1 (0 - 11) time], F = 4.914, P < 0.01. The frequency of exacerbations in the combination group was (0.7 +/- 0.5) time, significantly lower than that in the blank group [(1.5 +/- 0.9) times], salmeterol/fluticasone alone [(1.2 +/- 0.6) times], and tiotropium alone [(1.1 +/- 0.5) times], F = 8.513, P < 0.01. The FEV(1) in the combination group after the trial was (1.19 +/- 0.03) L, significantly improved compared to that before treatment (1.09 +/- 0.04) L, a 9.5% increase, which was greater than the blank (0.9%), tiotropium alone (8.2%) and salmeterol/fluticasone alone (6.3%), t = -5.024 to -15.58, P < 0.01. CONCLUSION: Combination therapy with salmeterol/fluticasone and tiotropium leads to better control of symptoms and improved lung function, with no greater risk of side-effects, as compared to salmeterol/fluticasone or tiotropium alone in the treatment of COPD.

[Diagnostic and prognostic value of procalcitonin and common inflammatory markers combining SOFA score in patients with sepsis in early stage].

OBJECTIVE: To study the diagnostic and prognostic value of procalcitonin (PCT), common inflammatory markers combining with scores for estimating organ failure of infection related organs (SOFA) in patients with sepsis in early stage. METHODS: Patients were observed continuously in a perspective study with diagnostic tests. According to the definition of ACCP/SCCM Consensus Conference, patients were classified into 5 groups, including non-systemic inflammatory response syndrome (SIRS) (control) group, SIRS group, sepsis group, severe sepsis group and septic shock group. Indexes of inflammation, SOFA and concentration of PCT were determined at 24 hours, and their correlation was analyzed. RESULTS: Two hundred and eight patients were enrolled, including 59 in non-SIRS group, 57 in SIRS group, 52 in sepsis group, 28 in severe sepsis group and 12 in septic shock group. PCT concentrations were positively correlated with the severity of sepsis. Spearman's correlation coefficient was 0.909 (P=0.000). According to the receiver operating characteristic curves (ROC-curves) analysis principle, ROC curves were drawn and areas under these curves (AUC) was calculated. In the diagnosis of sepsis, AUC values were 0.936+/-0.020 for PCT, 0.973+/-0.011 for SOFA (both P=0.000). The best cutoff values in the diagnosis of sepsis were 0.375 microg/L for PCT, and 3. 5 for SOFA score. The Youden index of PCT and SOFA scores was 0.808 and 0.801, respectively. Binary Logistic regression analysis confirmed that PCT and SOFA score were highly correlated with sepsis (OR=84.794,10.761, respectively, both P=0.000) after eliminating confusion factors including age and C-reactive protein (CRP) etc.. PCT and SOFA score could be used to predict the incidence of sepsis. SOFA score was the best prognostic indicator of sepsis (OR=2.084, P=0.0002). CONCLUSION: The traditional inflammatory markers and CRP are useful parameters to differentiate SIRS from non-SIRS, but are not reliable indicators for the early diagnosis in patients with sepsis. PCT is more specific indicator in early diagnosis of sepsis to differentiate from SIRS. PCT combining with SOFA score can be used to predict the incidence of sepsis. SOFA score can be used to define objectively the severity of sepsis according to PCT level and is helpful for estimation of prognosis in patients with sepsis.

1H-NMR-based metabolic profiling of healthy individuals and high-resolution CT-classified phenotypes of COPD with treatment of tiotropium bromide.

BACKGROUND: Heterogeneity of COPD results in different therapeutic effects for different patients receiving the same treatment. COPD patients need to be individually treated according to their own characteristics. The purpose of this study was to explore the differences in different CT phenotypic COPD by molecular metabolites through the use of metabolomics. METHODS: According to the characteristics of CT imaging, 42 COPD patients were grouped into phenotype E (n=20) or phenotype M (n=24). Each COPD patient received tiotropium bromide powder for inhalation for a therapeutic period of 3 months. All subjects were assigned into phenotype E in pre-therapy (EB, n=20), phenotype E in post-therapy (EA, n=20), phenotype M in pre-therapy (MB, n=22), phenotype M in post-therapy (MA, n=22), or normal control (N, n=24). The method of metabolomics based on 1H nuclear magnetic resonance (1H-NMR) was used to compare the changes in serum metabolites between COPD patients and normal controls and between different phenotypes of COPD patients in pre- and post-therapy. RESULTS: Patients with COPD phenotype E responded better to tiotropium bromide than patients with COPD phenotype M in terms of pulmonary function and COPD assessment test scores. There were differences in metabolites in COPD patients vs normal control people. Differences were also observed between different COPD phenotypic patients receiving the treatment in comparison with those who did not receive treatment. The changes of metabolites involved lactate, phenylalanine, fructose, glycine, asparagine, citric acid, pyruvic acid, proline, acetone, ornithine, lipid, pyridoxine, maltose, betaine, lipoprotein, and so on. These identified metabolites covered the metabolic pathways of amino acids, carbohydrates, lipids, genetic materials, and vitamin. CONCLUSION: The efficacy of tiotropium bromide on COPD phenotype E is better than that of phenotype M. Metabolites detected by 1H-NMR metabolomics have potentialities of differentiation of COPD and healthy people, discrimination of different COPD phenotypes, and giving insight into the individualized treatment of COPD.

A functional SNP upstream of the ADRB2 gene is associated with COPD.

Background: Previous studies have suggested that ß2-adrenergic receptor (ADRB2) is associated with COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet. Methods: In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively. Results: One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034). The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1. In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017). Conclusion: Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.