Prognostic value of serum galactomannan index in critically ill patients with chronic obstructive pulmonary disease at risk of invasive pulmonary aspergillosis

Background Critically ill chronic obstructive pulmonary disease （COPD） patients admitted to an intensive care unit （ICU） due to respiratory failure are at particularly high risk of Aspergillus infection.The serum galactomannan index （GMI） has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis （IPA） in classical immunocompromised patients.However,the prognostic value of serum GMI in critically ill COPD patients needs evaluation.The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.Methods In this single-center prospective cohort study,serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients＇ discharge or death.Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission.Univariate analysis and survival analysis were tested in these two groups.Results One hundred and fifty-three critically ill COPD patients were included and were divided into survival group （106 cases） and non-survival group （47 cases） according to their outcome.Univariate analysis showed that the highest GMI level during the first week after admission （GMI-high 1st week） was statistically different between the two groups.Independent prognostic factors for poor outcome in severe COPD patients were：GMI-high 1st week ＞0.5 （RR：4.04,95％ CI：2.17-7.51） combined with accumulative dosage of corticosteroids ＞216 mg before the RICU admission （RR：2.25,95％ CI：1.11-4.56） and clearance of creatinine （Ccr） ＜64.31 ml/min （RR：2.48,95％ CI：1.22-5.07）.Conclusions The positive GMI-high 1st week （＞0.5） combined with an accumulative dosage of corticosteroids ＞216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.     

High levels of interleukin-6 and 8-iso-prostaglandin in the exhaled breath condensate and serum of patients with chronic obstructive pulmonary disease related pulmonary hypertension

Background Pulmonary hypertension （PH） is a common complication of chronic obstructive pulmonary disease （COPD）. Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. Methods We measured the levels of interleukin-6 （IL-6） and 8-iso-prostaglandin （8-iso-PSG） in exhaled breath condensate （EBC） and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure （PASP） was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. Results Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH （（8.27±2.14） ng/L vs. （4.95±1.19） ng/L, P 〈0.01）. The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group （（72.8±21.6） ng/L vs. （43.58±13.38） ng/L, P 〈0.01 ）. Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group （EBC： （9.00±2.49） ng/L vs. （5.96±2.31） ng/L, P 〈0.01 and serum： （41.87±9.75） ng/L vs. （27.79±11.09） ng/L, P 〈0.01）. Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum （r=0.477-0.589, P 〈0.05）. Conclusion The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.     

Catheter ablation of paroxysmal atrial fibrillation in a young patient with a partial anomalous pulmonary venous connection

It has been demonstrated that pulmonary veins （PV）play an important role in the initiation and perpetuation of paroxysmal atrial fibrillation （PAF）.1-5 Therefore, PV isolation has become the cornerstone for catheter ablation in the majority of these AF patients.3-5 In addition, ectopic foci in the non-PVs areas, such as superior vena cava（SVC）,     

Potential biomarkers predicting risk of pulmonary hypertension in congenital heart disease: the role of homocysteine and hydrogen sulfide

Background Pulmonary hypertension （PH） is a common complication of congenital heart disease （CHD）.Although risk stratification is vital for prognosis and therapeutic guidance,the need for understanding the role of novel biomarkers cannot be overlooked.The aim of the present study was to investigate the changes of homocysteine and hydrogen sulfide levels and find potential biomarkers for early detection and treatment.Methods Between September 2012 and April 2013,we prospectively collected data on 158 pediatric patients with left to right shunt CHD at our institution.Standard right heart catheterizations were performed in all cases.Seventy-seven cases were associated with PH.The levels of homocysteine and hydrogen sulfide were detected with fluorescence polarization immunoassay and a sensitive silver-sulphur electrode,respectively.Enzyme-linked immunosorbent assay was used to determine the expression of methylenetetrahydrofolate reductase （MTHFR）,cystathionine β-synthase （CBS）,and cystathionine gamma-lyase （CSE）.Radioimmunoassays were used to obtain folic acid and vitamin B12 levels.Results The difference in the levels of homocysteine,folic acid,vitamin B12,hydrogen sulfide,as well as the MTHFR and CSE expression between patients with PH and without PH were statistically significant （all P ＜0.05）.Homocysteine had the best sensitivity and specificity to predict PH （P ＜0.001）.Subgroup analysis showed that the levels of homocysteine and hydrogen sulfide,and the expression of CSE and MTHFR between patients with dynamic and obstructive PH were significantly different （all P ＜0.05）.Based on the ROC curve,homocysteine had the best sensitivity and specificity to predict obstructive PH （P=0.032）,while CSE had the most significant sensitivity and specificity to predict the dynamic PH （P=0.008）.Conclusions Increased levels of homocysteine and decreased levels of hydrogen sulfide were significantly negatively correlated in PH associated with CHD.The underlying mechanism involved the decreased expression of MTHFR and CSE along with vitamin B12 deficiency.Homocysteine and hydrogen sulfide are potential biomarkers to predict PH.     

Basic and clinical research into chronic obstructive pulmonary

Chronic obstructive pulmonary disease （COPD）, one of the most common public health problemsworldwide, is the fourth leading cause of death in the world. In China, respiratory diseases （of which COPD is a major component） are the third leading cause of death in rural areas and the fourth leading cause of death in urban area, accounting for 1 million deaths and over 5 million disabilities each year. COPD ranks first among the burdens in China.1 Hence, medical workers and governments at different levels pay close attention to this disease~ The Respiratory Group under the Chinese Medical Association published the Guidelines for Diagnosis and Management of COPD in 2002^2 and the revised version in 2007^3. This publication serves as a milestone of the development of basic and clinical investigation in China. The guidelines are likely to affect the way for the treatment of COPD in addition to reflect the current knowledge about the underlying causes of COPD and recommend the proper diagnosis and management of COPD.     

Unique association of adiponectin isoforms with serum cytokines and redox molecules in patients with chronic obstructive pulmonary disease

In serum,adiponectin can exist as either full-length form that can form trimers,hexamers and high molecular weight (HMW) multimers,or as globular adiponectin (gAd).Adiponectin-deficiency leads to an increase in proinflammatory mediators and an emphysemalike phenotype,1 also protects against tobacco-induced inflammation and the increased emphysema.2 The mechanism underlying this apparent paradox remains unclear.We therefore analyzed serum levels of adiponectin isoforms,thioredoxin (Trx)/thioredoxin reductase (TrxR) activity,tumor necrosis factor (TNF)-α,IL-6and 4-hydroxynonenal (4-HNE) in patients with chronic obstructive pulmonary disease (COPD) and in control individuals.     

Symptomatic pulmonary lipiodol embolism after transarterial chemoembolization for hepatic malignant tumor: clinical presentation and chest imaging findings

Background Pulmonary lipiodol embolism after transarterial chemoembolization （TACE） was rare and life-threatening,occasionally reported in previous literatures.We aimed to review the records of 11 patients with pulmonary oily embolism and analyze their characteristics of radiographic findings and risk factors.Methods Records of 478 consecutive patients who underwent 1 026 percutaneous TACE procedures were retrospectively analyzed.Eleven cases with respiratory symptoms were identified as having symptomatic pulmonary lipiodol embolism after TACE.Data of these patients,including clinical presentation,techniques of TACE,imaging features of tumor and chest imaging findings,were assessed.Results Eleven （2.3%） of 478 consecutive patients who underwent percutaneous TACE procedures had a pulmonary oily embolism after procedures.The mean size of target tumors embolized was （13.6＆#177;2.0） cm.All were hyper-vascular.The mean volume of lipiodol was （21.8＆#177;8.2） ml.Pulmonary oily embolisms were revealed within 12-48 hours after TACE.The most severe respiratory symptoms and imaging abnormalities of the eight patients who survived presented between 2 and 5 days after TACE,becoming normal between 12 and 35 days after TACE.Three patients died.Chest CT revealed retention of radiopaque lipiodol in lungs.Conclusions Pulmonary lipiodol embolism occurs easily in patients who have large hyper-vascular hepatic malignant tumor.The high-density lipiodol deposition in the lung field can be used as diagnostic feature.     

Determinants of health-related quality of life worsening in patients with chronic obstructive pulmonary disease at one year

Background Chronic obstructive pulmonary disease （COPD） is a major cause of morbidity and mortality worldwide and has been the leading cause of death in China.Patients with COPD have significant decrements in their health-related quality of life （HRQL）.It is necessary to identify the factors involved in worsening HRQL in order to improve the HRQL of COPD patients.However,evidence from longitudinal studies is limited.The aim of the study was to evaluate the determinants of the deterioration of HRQL in patients with COPD.Methods At baseline,a total of 491 patients with stable COPD received comprehensive assessments,including psychosocial and clinical variables,six minutes walk distance （6MWD）,dyspnea grade measured by the 5-grade Medical Research Council （MRC） dyspnea scale,anxiety and depression measured by the hospital anxiety and depression scale and HRQL measured by St.George＇s Respiratory Questionnaire （SGRQ）.Patients were then monitored monthly for 12 months to document COPD exacerbations.At the end of the study period,the SGRQ values were reassessed.A 1-year change in SGRQ total score ≥4 was defined as a deterioration of the HRQL and as the outcome.A total of 450 patients completed the 12-month follow-up and were analyzed in the present study.Results The age （mean±SD） was （65.0±10.6） years and 68.7％ of subjects were men.The deterioration of the HRQL was 26.4％.In multivariate Logistic regression,independent and graded associations were found between the baseline MRC dyspnoea grade and the deterioration of HRQL （P=0.012）,OR 3.03 （95％ CI 1.11-8.24） for patients with MRC dyspnoea grade ≥4 versus patients with MRC dyspnoea grade =1.Similarly,the number of exacerbations during the follow-up was independently and gradually increased with the deterioration of HRQL （P ＜0.001）,OR 3.03 （95％ CI 1.9-5.6） for the participants with exacerbations ≥3 versus participants with no exacerbation.The 6MWD evaluated by quartiles was negatively associated with the deterioration of HRQL with borderline statistical significance.Conclusion MRC dyspnea grade and the number of exacerbations impair the HRQL of patients with COPD.     

Interleukin-32, not reduced by salmeterol/fluticasone propionate in smokers with chronic obstructive pulmonary disease

Background The interleukin （IL）-32/tumor necrosis factor （TNF） a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease （COPD） inflammation. Inhaled corticosteroids （ICS） in combination with long-acting I]2-agonists （LABA） have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain. Methods Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate （SF; Seretide, GlaxoSmithKline） Diskus （50/500 pg twice daily） or ipratropium bromide/salbutamol （IS; Combivent, Boehringer Ingelheim） MDI （42 IJg/240 IJg quartic daily） for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-a, the number of neutrophUs and eosinophils were measured. Results Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-a in sputum （P=0.004） was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance （P=0.028） but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George＇s respiratory questionnaire in both the SF （P=0.004） and IS （P=0.030） treatment groups, but no evidence of improvement in lung function was observed in either group. Conclusion The sputum TNF-a and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.     

Surgical treatment of right atrial myxoma and pulmonary embolism

Myxomas are rare benign tumours,with an estimated incidence of 0.5 per million of population per year.1It is most commonly of left atrial origin （75% to 90%）,less commonly right atrial （10% to 25%）,and rarely ventricular （1% to 4%）.2 Right atrial myomata generally presents as right heart failure,with signs of tricuspid valve disease.The association of pulmonary embolism with right atrial myxoma has been recognized at autopsy for many years.     

A rare case of Castleman disease presenting as pulmonary mass mimicking central pulmonary malignancy

Castleman disease is a rare disorder of the lymphoid system characterized by noncancerous growths that may develop in lymph node tissues throughout the body. Most often this occurs in the neck, mediastinum, and abdomen where lymph nodes aggregate. Here we describe a case of asymptomatic intrapulmonary Castleman disease adjacent to the left pulmonary hilum that mimicked central pulmonary malignancy in a 27-year-old man who underwent curative surgical removal of the mass.     

An adult case of isolated unilateral pulmonary agenesis under general anesthesia

Pulmonary agenesis is a rare congenital malformation of unknown etiology that is defined as the complete absence of the bronchus,lung parenchyma,and pulmonary vasculature.The exact incidence of this rare abnormality is not known but is believed to range from 0.003 4% to 0.009 7%.1 Pulmonary agenesis affects men and women almost equally.Left sided agenesis is more common.More than half of the reported cases are associated with anomalies involving cardiovascular,gastrointestinal,skeletal,and urogenital systems and patients die within the first five years of life.Although some cases are compatible with long-term survival and normal growth,completely symptom free and well tolerated surgery is extremely rare.Here we present a case of congenital left lung agenesis in an adult woman tolerating general anesthesia well for modified radical mastectomy.     

Computed tomography in predicting smear-negative pulmonary tuberculosis in AIDS patients

Background The correct diagnosis of sputum smear-negative pulmonary tuberculosis in AIDS patients is very important to their therapy.We aimed to assess the value of the computed tomography (CT) and cli...     

Association between body mass index and pulmonary function of patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease （COPD） is a major cause of chronic morbidity and mortality throughout the world. It is a preventable and treatable disease with significant extra pulmonary effects that may contribute to the severity in individual patients. It is characterized by airflow limitation that is not fully reversible. The diagnosis of COPD should be confirmed by spirometry. Body mass index （BMI） is an important indicator that can well reflect nutritional status of patients, and low BMI is an independent risk factor for mortality in patients with COPD.     

Diffusion-weighted magnetic resonance imaging with short T1 inversion recovery-echo planar imaging combined with dual-head coincidence single photon emission computed tomography for diagnosing solitary pulmonary nodule

Positron emission tomography （PET） using 18F-fluorodeoxyglucose （FDG） has not been widely used in China for expensive cost （$1200）. Dual-head coincidence single photon emission computed tomography （DHC-SPECT） can depict many of the lesions depicted with a PET scanner in the lungs, which is used in place of PET-CT for discriminating malignant from benign pulmonary nodules in many studies. However, DHC-SPECT has inevitable false-negative results because the sensitivity for small lesions less than 2.0 cm is limited, and has high false-positive rate for active inflammatory nodules. Furthermore,DHC-SPECT also has a considerably higher cost （$300 in China） than other imaging examination.     

Clinical and radiographic predictors in diagnosing sputum smear-negative pulmonary tuberculosis in HIV-negative patients: a cross-sectional study in China

Background In county-level tuberculosis （TB） dispensaries in China,the accurate diagnosis of sputum smear-negative pulmonary tuberculosis （SNPT） needs to be improved by developing and validating clinical and radiographic predictors.Methods The study was conducted simultaneously in three counties per province in Chongqing Municipality and Liaoning Province in China between May 2005 and May 2006.A total of 432 new SNPT patients who are HIV-negative and more than 15 years old diagnosed by expert panels in county-level TB dispensaries were recruited.Their sputum samples were collected for culture before anti-TB treatment,and the treatment outcomes （changes of X-rays） were followed up at the end of the 6th month.Results Of the 432 SNPT patients,sputum culture positive （9.7%） or culture negative with good changes of X-rays at the end of the 6th month （73.6%） was validated as SNPT.Four predictive variables were associated with validated SNPT in the multivariate logistic regression model：age ≤55 years old （odds ratio （OR） 5.66; 95% CI 2.69-11.91）,〉60 days of cough （OR 3.73; 95% CI 1.10-12.65）,≥10% of pulmonary consolidation in the lungs （OR 5.40; 95% CI 2.90-10.06）,and pulmonary consolidation in the upper lobe anterior segment （OR 3.00; 95% CI 1.57-5.72）.The area under the receiver operating characteristic curve of the model was 0.77 （95% CI 0.71-0.83）.Conclusion Four predictors of clinical and radiological characteristics that had a good diagnostic performance of SNPT deserve to be recommended as index indicators of SNPT diagnosis in county-level TB dispensaries in China.     

Decreased and dysfunctional circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease

Background It has been widely demonstrated that endothelial progenitor cells are involved in several diseases and that they have therapeutic implications. In order to define the altered pulmonary vascular homeostasis in chronic obstructive pulmonary disease, we sought to observe the level and functions of circulating endothelial progenitor calls in patients with chronic obstructive pulmonary disease. Methods The total study population included 20 patients with chronic obstructive pulmonary disease and 20 control subjects. The number of circulating endothelial progenitor cells （CD34＋/CD133＋/IVEGFR-2＋cells） was counted by flow cytometry. Circulating endothelial progenitor cells were also cultured in vitro and characterized by uptake of Dil- acLDL, combining with UEA-I, and expression of von Willebrand factor and endothelial nitric oxide synthase. Adhesion, proliferation, production of nitric oxide, and expression of endothelial nitric oxide synthase and phosphorylated-endothelial nitric oxide synthase were detected to determine functions of circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease. Results The number of circulating endothelial progenitor cells in the chronic obstructive pulmonary disease group was lower than in the control group： （0.54±0.16）% vs. （1.15±0.57）%, P 〈0.05. About 80% of adherent peripheral blood mononuclear cells cultured in vitro were double labeled with Dil-acLDL and UEA-I. The 92% and 91% of them were positive for von Willebrand factor and endothelial nitric oxide synthase, respectively. Compared with the control, there were significantly fewer adhering endothelial progenitor cells in chronic obstructive pulmonary disease patients： 18.7±4.8/field vs. 45.0±5.9/field, P 〈0.05. The proliferation assay showed that the proliferative capacity of circulating endothelial progenitor cells from chronic obstructive pulmonary disease patients was significantly impaired： 0.135±0.038 vs. 0.224±0.042, P 〈0.05. Furthermore, nitric oxide synthase （112.06±10.00 vs. 135.41±5.38, P 〈0.05）, phosphorylated endothelial nitric oxide synthase protein expression （88.89±4.98 vs. 117.98±16.49, P 〈0.05） and nitric oxide production （（25.11±5.27） Iμmol/L vs. （37.72±7.10） μmol/L, P 〈0.05） were remarkably lower in endothelial cells from the chronic obstructive pulmonary disease group than the control. Conclusion Circulating endothelial progenitor cells were decreased and functionally impaired in patients with chronic obstructive pulmonary disease.     

Role of voltage-gated potassium channels in pathogenesis of chronic pulmonary heart disease

The influence of hypoxia on the activity of voltage-gated potassium channel in pulmonary artery smooth muscle cells （PASMCs） of rats and its roles in the pathogenesis of chronic pulmonary heart disease were investigated. Eighty male Sprague-Dawley rats were randomly allocated into control group （n=10）, acute hypoxic group （n=10）, and chronic hypoxic groups （n=60）. The chronic hypoxic groups were randomly divided into 6 subgroups （n=10 each） according to the chronic hypoxic periods. The rats in the control group were kept in room air and those in acute hypoxic group in hypoxia envi- ronmental chamber for 8 h. The rats in chronic hypoxic subgroups were kept in hypoxia environmental chamber for 8 h per day for 5, 10, 15, 20, 25, and 30 days, respectively. The mean pulmonary arterial pressure （mPAP）, right ventricular hypertrophy index （RVHI）, and the current of voltage-gated potas- sium channel （IK） in PASMCs were measured. Results showed that both acute and chronic hypoxia could decrease the IK in PASMCs of rats and the I-V relationship downward shifted to the right. And the peak Ir density at ＋60mV decreased with prolongation of hypoxia exposure. No significant difference was noted in the density oflK （at ＋60 mV） and I-V relationship between control group and chronic hy- poxic subgroup exposed to hypoxia for 5 days （P〉0.05）, but there was a significant difference between control group and chronic hypoxic subgroup exposed to hypoxia for 10 days （P〈0.05）. Significant dif- ferences were noted in the IK density （at ＋60 mV） and I-V relationships between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days （P〈0.01）. Compared with con- trol rats, the mPAP and RVHI were significantly increased after chronic exposure to hypoxia for 10 days （P〈0.05）, which were further increased with prolongation of hypoxia exposure, and there were signifi- cant differences between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days （P〈0.01）. Both the mPAP and the RVHI were negatively correlated with the density OflK （r---0.89769 and -0.94476, respectively, both P〈0.01）. It is concluded that exposure to hypoxia may cause decreased activity of voltage-gated potassium channel, leading to hypoxia pulmonary vasocon- striction （HPV）. Sustained HPV may result in chronic pulmonary hypertension, even chronic pulmonary heart disease, contributing to the pathogenesis of chronic pulmonary heart disease.     

Major advances in respiratory medicine in China

Respiratory disease is the term for diseases of the respiratory system. These diseases range from mild and self-limiting such as the common cold to life-threatening such as bacterial pneumonia or pulmonary embolism. They are common and important causes of illness and death. In the US, people suffer 1 billion colds per year. One out of 7 people in the UK are affected by some kinds of chronic lung diseases, most commonly chronic obstructive pulmonary disease （COPD） and asthma. Respiratory disease accounts for over 10% of hospitalizations and over 16% of deaths in Canada.