慢阻肺急性加重期患者血浆晚期糖基化终末产物和sRAGE研究

目的研究分析慢性阻塞性肺疾病(慢阻肺)患者血浆中晚期糖基化终末产物(AGEs)和可溶性糖基化终末产物受体(sRAGE)的水平及与慢阻肺患者肺功能的关系。方法选取河北省承德县医院收治的120例慢阻肺患者(慢阻肺组)、50例健康人群(对照组),分别检测两组的血浆AGEs、sRAGE及肺功能等指标。结果慢阻肺组患者的血浆中AGEs(36.25±2.98)ug/m L显著的高于对照组的(28.94±2.31)ug/m L,sRAGE为(338.41±194.26)pg/m L显著的低于对照组的(871.50±226.49)pg/m L且差异均具有统计学意义(P0.05)。慢阻肺组患者血浆AGEs与患者的FEV1%呈显著的负相关关系(r=-0.594,P=0.0000.001);慢阻肺组患者血浆sRAGE与患者的FEV1%呈显著的正相关关系(r=0.552,P=0.0000.001)。结论慢阻肺患者血浆中AGEs、sRAGE水平发生显著的改变,AGEs与患者的肺功能呈负相关性、sRAGE与患者的肺功能呈正相关关系。     

A new staging strategy for chronic obstructive pulmonary disease

Background:

The best method for expressing lung function impairment is undecided. We tested in a population of patients with chronic obstructive pulmonary disease (COPD) whether forced expiratory volume in 1 second (FEV₁) or FEV₁ divided by height squared (FEV₁/ht²) was better than FEV₁ percent predicted (FEV₁PP) for predicting survival.

Method:

FEV₁, FEV₁PP, and FEV₁/ht² recorded post bronchodilator were compared as predictors of survival in 1095 COPD patients followed for 15 years. A staging system for severity of COPD was defined from FEV₁/ht² and compared with the Global Initiative for Obstructive Lung Disease (GOLD) staging system.

Result:

FEV₁/ht² was a better univariate predictor of survival in COPD than FEV₁ and both were better than FEV₁PP. The best multivariate model for predicting survival included FEV₁/ht², age and sex. Comparing the GOLD stages with the FEV₁/ht² groups found that survival was more coherent within each FEV₁/ht group than it was within each GOLD stage. FEV₁/ht² had 60% more people in its most severe group than the severest GOLD stage with these extra subjects having equivalently poor survival and had 155% more in the least severe group with equivalent survival. GOLD staging misclassified 51% of subjects with regard to survival.

Conclusion:

We conclude that GOLD criteria using FEV₁PP do not optimally stage COPD with regard to survival. An alternative strategy using FEV₁/ht² improves the staging of this disease. Studies which stratify COPD patients to determine the effect of interventions such as drug trials, rehabilitation, or management guidelines should consider alternatives to the GOLD classification.     

Role of quantitative chest perfusion computed tomography in detecting diabetic pulmonary microangiopathy

Aims

Aim of the study was to determine the role of perfusion chest computed tomography (pCT) in evaluation of pulmonary diabetic angiopathy.

Methods

18 never-smoking patients (10 diabetic patients and 8 healthy controls) underwent chest high resolution CT (HRCT) and then pCT scanning. In both groups, blood tests, biochemical analysis, fibrinogen, HbA_1c, spirometry, diffusion capacity for carbon monoxide (DLCO) and body pletysmography were performed.Following parameters of pulmonary perfusion have been analysed: blood volume (BV), blood flow (BF), mean transit time (MTT), time to peak (TTP) and permeability surface (PS).

Results

There were no statistically significant differences between groups in terms of age, sex, BMI, forced expiratory volume in one second (FEV₁), DLCO. Chest HRCT revealed no pathologies. Significantly higher values of chest pCT for BF (p = 0.05), BV (p = 0.05) and PS (p = 0.01) have been found in diabetics in comparison to controls. No differences were found in MTT.

Conclusions

Significant increase of perfusion parameters in diabetes seems to confirm pulmonary microangiopathy. The results indicate that further studies on application of pCT in diabetic patients may be beneficial for better understanding of lung microangiopathy, its diagnosing and monitoring.     

Glycation of human high density lipoprotein by methylglyoxal: Effect on HDL-paraoxonase activity

Objective

Methylglyoxal (MG), a reactive carbonyl compound formed primarily from triose phosphates, appears to be involved in the molecular mechanisms of diabetes, end-stage renal disease and neurodegenerative diseases. Methylglyoxal exerts several biological activities. Among these it promotes advanced glycation end products (AGEs), which are crucial in pathogenesis of human disease. Previous studies have demonstrated that MG reacts with proteins and compositional modifications reflect loss of biological activity. The aim of the study was to investigate the effect of in vitro MG-induced glycation on human high density lipoprotein (HDL) and on the activity of the enzyme paraoxonase-1 (PON1).

Methods

HDL was incubated in the absence or in the presence of MG (0.2 mmol/L and 1.0 mmol/L) (MG-HDL) for different times (3, 6, 24 h) at 37 ° C. We evaluated apoprotein compositional changes, in both control and MG treated HDL, using intrinsic fluorescence of tryptophan and monitoring the decrease of free amino groups. Furthermore we evaluated fluorescent advanced glycation end products (Ex = 370 nm, Em = 440 nm) and the activity of HDL-paraoxonase.

Results

We demonstrated that human HDL is susceptible to glycation by MG (0.2 mmol/L and 1 mmol/L). The decrease of free amino groups and of intrinsic fluorescence of tryptophan demonstrates HDL apoprotein modifications in HDL incubated with MG. The compositional changes are associated with a significant increase in fluorescent advanced glycation end products and with a significant decrease of paraoxonase-1 enzyme activity associated with the HDL surface.

Conclusions

HDL-associated paraoxonase is responsible for the anti-inflammatory and anti-oxidative properties of HDL and detoxification against homocysteine-thiolactone. Therefore, modifications of apoprotein composition and the decrease of paraoxonase-1 activity in MG-treated HDL could affect the protective effect exerted by HDL against oxidative damage and could contribute to complications in patients affected by diseases associated with aging and oxidative stress.     

Plasma homocysteine is elevated in COPD patients and is related to COPD severity

Background:

Although recent studies have found that total plasma homocysteine (tHCY) and chronic obstructive pulmonary disease (COPD) are both risk factors for cardiac disease, there have been few studies of plasma homocysteine levels in COPD patients. We tested the hypothesis that total plasma homocysteine (tHCY) would be elevated in patients diagnosed with COPD compared with controls.

Methods:

We studied 29 COPD outpatients and 25 asymptomatic subjects (controls) over age 55 years with measurement of forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), St. Georges Respiratory Questionnaire (SGRQ) score, tHCY and serum C-reactive protein (sCRP).

Results:

There was no difference between controls vs. COPD patients in mean age or gender but mean (SD) FEV₁ was 2.25 (0.77) vs 1.43 (0.60) L; FEV₁% predicted 76.1 (17.2) vs 49.1 (16.3) p < 0.001 in both cases. Median (IQR) tHCY was 8.22 (6.63, 9.55) in controls vs 10.96 (7.56, 13.60) micromol/l for COPD, p = 0.006 and sCRP 0.89 (0.47, 2.55) vs 2.05 (0.86, 6.19) mg/l, p = 0.023. tHCY(log) was also higher in (r, p) smokers (0.448, 0.001), patients with low FEV₁% (−0.397, 0.003), males (0.475, <0.001), but high SGRQ Total score (0.289, 0.034), and high sCRP (0.316, 0.038). tHCY(log) was independently related to (regression coefficient, p) sCRP(log) (0.087, 0.024), male gender (0.345, <0.001) and presence of COPD (0.194, 0.031). Median (IQR) tHCY GOLD Stage I and II 8.05 (7.28, 11.04), GOLD Stage III and IV: 11.83(9.30, 18.30); p = 0.023.

Conclusions:

Plasma homocysteine is significantly elevated in COPD patients relative to age and sex-matched controls and is related to serum CRP and COPD severity.     

Low levels of soluble receptor for advanced glycation end products in non-ST elevation myocardial infarction patients

BACKGROUND:

Interaction of the receptors for advanced glycation end products (RAGEs) with advanced glycation end products (AGEs) results in expression of inflammatory mediators (tumor necrosis factor-alpha [TNF-α] and soluble vascular cell adhesion molecule-1 [sVCAM-1]), activation of nuclear factor-kappa B and induction of oxidative stress – all of which have been implicated in atherosclerosis. Soluble RAGE (sRAGE) acts as a decoy for the RAGE ligand and is protective against atherosclerosis.

OBJECTIVES:

To determine whether levels of serum sRAGE are lower, and whether levels of serum AGEs, TNF-α and sVCAM-1 are higher in non-ST elevation myocardial infarction (NSTEMI) patients than in healthy control subjects; and whether sRAGE or the ratio of AGEs to sRAGE (AGEs/sRAGE) is a predictor/biomarker of NSTEMI.

METHODS:

Serum levels of sRAGE, AGEs, TNF-α and sVCAM-1 were measured in 46 men with NSTEMI and 28 age- and sex-matched control subjects. Angiography was performed in the NSTEMI patients.

RESULTS:

sRAGE levels were lower, and levels of AGEs, TNF-α, sVCAM-1 and AGEs/sRAGE were higher in NSTEMI patients than in control subjects. sRAGE levels were negatively correlated with the number of diseased coronary vessels, serum AGEs, AGEs/sRAGE, TNF-α and sVCAM-1. The sensitivity of the AGEs/sRAGE test is greater than that of the sRAGE test, while the specificity and predictive values of the sRAGE test are greater than those of the AGEs/sRAGE test for identifying NSTEMI patients.

CONCLUSIONS:

Serum levels of sRAGE were low in NSTEMI patients, and were negatively correlated with extent of lesion, inflammatory mediators, AGEs and AGEs/sRAGE. Both sRAGE and AGEs/sRAGE may serve as biomarkers/predictors for identifying NSTEMI patients.     

Ethnic differences in spirometry measurements in China: Results from a large community‐based epidemiological study

Background and objective

No previous studies have examined differences in spirometry measurements among ethnic populations in China, and factors which may influence ethnic differences are unclear. Our study aimed to investigate whether forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) differ among Han Chinese and other ethnic minorities in China.

Methods

We recruited 7137 individuals aged 35–70 years from four areas of China inhabited by ethnic minority groups between 2007 and 2009. We conducted spirometry tests for all available participants, and compared FEV₁ and FVC among Uygur, Hui, Mongolian, Dai and Han Chinese ethnicities, using nonlinear multiplicative regression models.

Results

A total of 2005 healthy never‐smokers were enrolled in the analysis. For all ethnicities, spirometry values increased with height and decreased with age; FEV₁ and FVC were consistently higher in males than in females. Compared with Han Chinese, FEV₁ was 4.42% (95% CI: 2.11–6.78%) higher in Mongolians, 4.08% (95% CI: 1.33–6.76%) lower in Uygurs, 4.39% (95% CI: 1.33–7.35%) lower in Hui people and 4.72% (95% CI: 1.80–7.55%) lower in Dai people, after adjusted for potential confounders including height, age, sex and place of residence. We observed similar differences for FVC.

Conclusions

We detected significant differences in spirometry measurements among ethnic populations in China. Such differences cannot be fully explained by demographic, anthropometric or socioeconomic factors, but may also be attributed to genetic background as well as indoor and outdoor environmental exposures that need further investigation.

     

Calcitriol modulates receptor for advanced glycation end products (RAGE) in diabetic hearts

Background

Receptor for advanced glycation end products (RAGE) signaling pathway plays a vital role in diabetic cardiovascular complications. Calcitriol has been shown to exert various beneficial cardiovascular effects. The purpose of this study is to determine whether calcitriol can modulate RAGE expression, and study the potential mechanisms in diabetic hearts.

Methods

Streptozotocin (65 mg/kg, intraperitoneal injection once) induced diabetic rats were treated with or without subcutaneous injections of calcitriol at a dose of 150 ng/kg/day for 4 weeks. Western blot was used to evaluate protein expressions of myocardial RAGE, TNF-α, p65 subunit of NF-κB (p65), α subunit of inhibitor of κB (IκBα), subunits of NADPH oxidase (NOX4 and p22^phox), angiotensin II type 1 receptor (AT1R), TGF-β1, TGF-β receptor I, total and phosphorylated SMAD2/3 and ERK, matrix metalloproteinases 2 (MMP2), tissue inhibitors of metalloproteinases 2 (TIMP2) and procollagen I.

Results

As compared to control, diabetic rats had increased expressions of cardiac RAGE, TNF-α, p22^phox, AT1R, and TGF-β1, which were significantly attenuated in the diabetic rats treated with calcitriol. Calcitriol-treated diabetic hearts also had lesser expressions of p-SMAD2/3 and p-ERK signaling than those of diabetic hearts. Moreover, diabetic hearts had increased expressions of MMP2 and procollagen I and decreased TIMP2. However, calcitriol reverted the diabetic effects in procollagen I but not in MMP2 or TIMP2.

Conclusions

Calcitriol decreased diabetic effects on RAGE and fibrosis, which may be caused by its modulation on AT1R and the anti-inflammatory and antioxidative potentials. Therefore, calcitriol may attenuate diabetic cardiomyopathy.     

Relationship between advanced glycation end products and increased lipid peroxidation in semen of diabetic men

Aims

Majority of diabetic male patients have disturbances in their reproductive systems. However, the mechanisms underlying these disturbances are largely unknown. Since advanced glycation end products (AGE) have a key role in oxidative stress and cell damage in diabetic complications, we hypothesize that AGEs may be involved sperm lipid peroxidation.

Methods

Total AGEs in seminal plasma of 32 diabetic and 35 non-diabetic men was determined by spectrofluorimetric method and carboxy methyl lysine (CML) level was assayed using ELISA. Contents of lipid peroxidation in sperm and seminal plasma were determined by thiobarbituric acid reaction. Total antioxidant capacity (TAC) was measured by a colorimetric assay.

Results

Total AGEs were found significantly higher in seminal plasma of diabetic men than non-diabetic group (p < 0.001) whereas no significant differences in seminal plasma CML values between two groups was observed. Moreover, sperm and seminal plasma lipid peroxidation were significantly higher in diabetic subjects than non-diabetic men and a significantly lower TAC was detected in diabetic group compare to non-diabetics.

Conclusions

These results showed an increment in AGEs in seminal plasma of diabetic subjects and may suggest a key role for glycation process and increased oxidative stress in reproductive system dysfunction.     

COPD in chronic heart failure: Less common than previously thought?

Background

Using a fixed ratio of forced expiratory volume in 1 s to forced vital capacity (FEV₁/FVC) < 0.70 instead of the lower limit of normal (LLN) to define chronic obstructive pulmonary disease (COPD) may lead to overdiagnosis of COPD in elderly patients with heart failure (HF) and consequently unnecessary treatment with possible adverse health effects.

Objective

The aim of this study was to determine COPD prevalence in patients with chronic HF according to two definitions of airflow obstruction.

Methods

Spirometry was performed in 187 outpatients with stable chronic HF without pulmonary congestion who had a left ventricular ejection fraction <40% (mean age 69 ± 10 years, 78% men). COPD diagnosis was confirmed 3 months after standard treatment with tiotropium in newly diagnosed COPD patients.

Results

COPD prevalence varied substantially between 19.8% (LLN-COPD) and 32.1% (GOLD-COPD). Twenty-three of 60 patients (38.3%) with GOLD-COPD were potentially misclassified as having COPD (FEV₁/FVC < 0.7 but > LLN). In contrast to patients with LLN-COPD, potentially misclassified patients did not differ significantly from those without COPD regarding respiratory symptoms and risk factors for COPD.

Conclusions

One fifth, rather than one third, of the patients with chronic HF had concomitant COPD using the LLN instead of the fixed ratio. LLN may identify clinically more important COPD than a fixed ratio of 0.7.     

Comparison of respiratory system impedance in asthma and COPD: A prospective observational study

Background and objective

A single assessment of within‐breath variations of respiratory system reactance (Xrs) at 5 Hz (ΔX5) measured by the forced oscillation technique (FOT) has been reported to be useful for the detection of pathophysiological changes in chronic obstructive pulmonary disease (COPD) and asthma. We examined longitudinal changes in respiratory system resistance (Rrs) and Xrs during tidal breathing between stable asthma and COPD patients in order to clarify the features of changes of respiratory system impedance and airflow limitation for these conditions.

Methods

Between April 2013 and September 2013, outpatients with a COPD or asthma diagnosis were recruited. We examined forced expiratory volume in 1 s (FEV₁) and FOT every 6 months until September 2015. Annual changes were estimated from the linear regression curve slope.

Results

We included 57 and 93 subjects with COPD and asthma, respectively. The median follow‐up period was 26 months (range: 24–29 months). Within‐breath analysis showed that the difference between mean Rrs at 5 Hz and 20 Hz was significantly lower, and ΔX5 more negative, in COPD than in asthma patients. With regard to annual changes, only ΔX5 was significantly different, more negative, in COPD than in asthma patients. Comparing between COPD subjects of Global Initiative Chronic Obstructive Lung Disease (GOLD) stage I/II and those with asthma, there were no significant differences in respiratory system impedance at enrolment, while annual change in ΔX5 was significantly more negative in mild COPD than in asthma patients.

Conclusion

ΔX5 may be useful for long‐term assessment of airflow limitation in COPD.

     

24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis

Objective

Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines through 24 h in patients with previous definite ST. Furthermore, we explored whether increased levels of immature platelets and thrombopoietin are associated with a particularly rapid recovery of platelet function.

Methods

This case–control study included 50 patients with previous definite ST matched with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate^® Analyzer). Cyclooxygenase-1 activity, platelet activation, immature platelets, and thrombopoietin were measured.

Results

Platelet aggregation increased by 109 ± 150 (arachidonic acid) and 47 ± 155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values < 0.0001) with corresponding increases in thromboxane B₂ (5.6 ± 5.1 ng/ml, p < 0.0001) and soluble P-selectin (6.2 ± 15.5 ng/ml, p < 0.0001). Platelet aggregation increased equally in all groups, but patients with previous ST displayed the highest levels of platelet aggregation at 24 h (p-values ≤ 0.05) and the highest levels of immature platelets (p < 0.01) and thrombopoietin (p < 0.0001).

Conclusions

Platelet inhibition declined significantly during the 24-hour dosing interval in aspirin-treated patients with previous definite ST or stable coronary artery disease and in healthy individuals. Increased levels of immature platelets and thrombopoietin were observed in patients with previous definite ST.     

The PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats

Objectives

The present study aimed to investigate the relationship between PI3K/p-Akt signaling pathway and podocyte impairment in DN rats as well as the protective effect of calcitriol.

Methods

SD rats were randomly divided into four groups: normal control (NC), normal treated with calcitriol (NC + VD), diabetic nephropathy (DN) and DN treated with calcitriol (DN + VD); all VD rats were treated with 0.1 μg/kg/d calcitriol by gavage. DN model rats were established by intraperitoneal injections of streptozotocin (STZ). Rats were sacrificed after 18 weeks of treatments.

Results

In the present study, increased albuminuria was observed as early as 3 weeks of diabetes and continued to increase more than six-fold throughout the length of the study (18 weeks). Expectedly, animals receiving the treatment with calcitriol was protected from this increase, lower about one third. Meanwhile, the expression of podocyte specific markers, including nephrin and podocin, together with PI3K/p-Akt was significantly decreased in DN rats, whereas calcitriol reversed these above changes accompanied by elevated the expression levels of VDR. Additionally, a positive correlation was observed between the expression levels of nephrin and VDR (r = 0.776, P < 0.05). Likewise, the expression of nephrin was positively correlated with both PI3K-p85 and p-Akt (r = 0.736, P < 0.05; r = 0.855, P < 0.05, respectively).

Conclusion

PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats. The manipulation of calcitriol might act as a promising therapeutic intervention for diabetic nephropathy.     

Prevalencia de enfermedad pulmonar obstructiva crónica en las Islas Canarias

Introduction

The prevalence of chronic obstructive pulmonary disease (COPD) varies significantly among the different geographical areas reported. In Spain, two epidemiological studies have shown a prevalence of 9-10% in the population aged over 40. However, neither of these studies included the Canary Islands, which are of interest due to their climatic conditions and high incidence of smoking.

Materials and methods

A random group of 1,353 subjects aged between 40 and 70 years was selected from a sample population of 596,478 individuals. Participants completed a questionnaire and then performed spirometry with bronchodilator testing if obstruction was observed. COPD was diagnosed when the post-bronchodilator FEV₁/FVC ratio was less than 0.70.

Results

The prevalence of COPD was 7.3% (95% CI: 5.5-9.5) and was higher in males than in females (8.7% vs. 6.3%, P = .134). The incidence of smoking was 29.4% (95% CI: 25.4-33.1) and was also higher in males than in females (35.1% vs 25.4%, P < .001). The prevalence of COPD stratified by severity of obstruction, according to the GOLD criteria, was 16% in group i, 69.9% in group ii, 10.4% in group iii and 3.3% in group iv. 71.6% of the subjects were underdiagnosed and 63.5% undertreated.

Conclusions

Despite having one of the highest rates of smoking in Spain, the prevalence of COPD in the Canary Islands is lower than in most of the Spanish regions studied.     

Sarcopenia in COPD: relationship with COPD severity and prognosis

Objective:

To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.

Methods:

A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height² only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.

Results:

We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m². Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV₁ (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.

Conclusions:

In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.     

Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults

Background

Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress – such as diabetes, chronic kidney disease and aging – where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined.

Methods

To test the hypothesis that circulating levels of N^?-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older.

Results

During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95% confidence interval [CI] = 1.03–1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke.

Conclusions

In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML’s value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.     

Skin autofluorescence: Correlation with measures of diabetic sensorimotor neuropathy

Objective

Advanced glycation end products (AGE) contribute to the development of diabetes complications. Their accumulation in skin can be non-invasively assessed by measurement of skin autofluorescence (SAF). Our study investigated whether SAF correlates with measures of diabetic peripheral neuropathy (DPN).

Hospitalized patients with COPD: analysis of prior treatment

Objective:

Although COPD is a prevalent disease, it is undertreated, and there are no available data regarding previous treatment of COPD in Brazil. This study aimed to determine the appropriateness of maintenance treatment in COPD patients prior to their hospitalization and to identify variables associated with inappropriate treatment.

Methods:

This was an observational, cross-sectional, analytical study involving 50 inpatients with COPD at two hospitals in the city of Florianópolis, Brazil. The patients completed a questionnaire on parameters related to the maintenance treatment of COPD. Non-pharmacological management and pharmacological treatment were assessed based on the recommendations made by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2011 and by the Brazilian National Ministry of Health in the chronic respiratory diseases section of its Caderno de Atenção Básica (CAB, Primary Care Guidebook).

Results:

In most of the patients, the COPD was classified as being severe or very severe. Regarding non-pharmacological management, 33% of the patients were smokers, only 32% had been advised to receive the flu vaccine, 28% had received pneumococcal vaccine, and only 6.5% of the patients in the B, C, and D categories received pulmonary rehabilitation. Regarding GOLD and CAB recommendations, pharmacological treatment was inappropriate in 50% and 74% of the patients, respectively. Based on GOLD recommendations, 38% were undertreated. A low level of education, low income, not receiving oxygen therapy, and not receiving the flu vaccine were associated with inappropriate treatment.

Conclusions:

The application of various non-pharmacological management recommendations was unsatisfactory. Regarding the GOLD recommendations, the high rate of inappropriate maintenance treatment was mainly due to undertreatment. In Brazil, even in severe COPD cases, optimizing treatment to achieve greater benefits continues to be a challenge.     

Effects of bronchoscopic lung volume reduction using transbronchial infusion of autologous blood and thrombin in patients with severe chronic obstructive pulmonary disease

Background

Existing medical treatments have limitations in the management of very severe chronic obstructive pulmonary disease (COPD).

Methods

We performed bronchoscopic lung volume reduction (BLVR) using transbronchial infusion of autologous blood and thrombin (BLVR with blood) in three patients with very severe COPD whose dyspnea could not be relieved by maximum medical management. Two patients underwent BLVR with blood in the left and right lungs at intervals of a half-year or a year, and one patient underwent this procedure in only the right lung. We assessed the changes in pulmonary function, exercise capacity and quality of life before and after BLVR with blood in a total of five procedures.

Results

The subjects were 58- to 74-year-old males. Their forced expiratory volume in one second (FEV₁) percent predicted ranged from 14.8% to 23.4%. BLVR with blood achieved significant improvements as follows (values before → after the procedure, mean ± standard deviation): FEV₁ 0.45r the L → 0.76r the L (P=0.004), inspiratory capacity 1.50cityo L → 2.05±.05c L (P=0.015), 3-minute walk test 46.8nuteo m → 89.6±34.5 m (P=0.004). Lung function peaked several months after BLVR with blood and returned to nearly the baseline level in 6 months, but exercise capacity was better than that at baseline for at least 12 months. St. George’s Respiratory Questionnaire (SGRQ), measured in two patients before and 12 months after the procedure, showed remarkable improvements (−15.6 and −11.9 units).

Conclusions

BLVR with blood is an effective palliative treatment for very severe COPD.     

Oxidative stress and systemic inflammation as modifiers of cardiac autonomic responses to particulate air pollution

Background

The role of oxidative stress and systemic inflammation on the association between personal exposures to ambient fine particulate matter ≤ 2.5 μm in diameter (PM_2.5) and cardiac autonomic dysfunction, indicated by reduction in heart rate variability (HRV), has not been examined.

Methods

We performed a repeated measures study on community adults in a densely populated inner city neighborhood in Boston, Massachusetts. Continuous ambulatory electrocardiogram (ECG) monitoring and personal exposure to PM_2.5 were measured for up to two consecutive days. Peripheral blood and spot urine samples were collected at 12-hour intervals for the measurements of markers of inflammation including C-reactive protein (CRP), fibrinogen, white blood cell (WBC) and platelet counts as well as for the analysis of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage.

Results

After adjusting for confounders, we found a pronounced decrease in nighttime standard deviation of normal-to normal intervals (SDNN): an interquartile range (IQR) increase in PM_2.5 (13.6 μg/m³) was associated with an 8.4% decrease in SDNN (95% CI: − 11.3 to − 5.5). Compared with the lower eightieth percentile, significantly greater PM_2.5 associated nighttime SDNN reductions were observed among subjects in the upper twentieth percentile of 8-OHdG by − 25.3%, CRP by − 24.9%, fibrinogen by − 28.7%, WBC by − 23.4%, and platelet counts by − 24.0% (all P < 0.0001; all P_interaction < 0.01).

Conclusions

These data suggest that oxidative stress and systemic inflammation exacerbate the adverse effects of PM_2.5 on the cardiac autonomic function even at ambient levels of exposure.