Prevalence, patterns and prognosis of multimorbidity among middle-aged and elderly inpatients with chronic obstructive pulmonary disease / 中华预防医学杂志

Objective: To explore the characteristics, patterns of multimorbidity and the impact on quality of life and the prognosis of middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD). Methods: This is a cross-sectional study. From January 2012 to December 2021, 939 middle-aged and elderly COPD patients hospitalized in Beijing Hospital were selected by the convenient sampling method. The basic data of patients and the date of 16 common chronic diseases were collected. Patterns of multimorbidity were depicted by cluster analysis. Generalized linear regression model and logistic regression were used to evaluate the multimorbidity patterns and their prognosis. Results: At least one multimorbidity existed among 93.40% of COPD patients, and the median number of multimorbidity was 3. The top five multimorbidity among the patients were hypertension (57.93%, 544/939), coronary heart disease (33.76%,317/939), heart failure (31.95%,300/939), hyperlipidemia (31.63%,297/939) and arrhythmia (27.37%,257/939). Four multimorbidity patterns were identified, cardiometabolic and metabolic multimorbidity, kidney disease multimorbidity, respiratory-digestive-tumor multimorbidity and other multimorbidity. Cardiometabolic and metabolic multimorbidity was most common (590/939, 62.83%). Compared with non-cardiometabolic and metabolic multimorbidity, the incharge ADL score of patients with this multimorbidity decreased by 7 points (95%CI:-11.22- -3.34), Correspondingly, patients with kidney disease multimorbidity decreased by 14 points (95%CI:-24.12- -3.30) on the incharge score. The presence or absence of kidney disease multimorbidity had the greatest impact on discharge score, which was reduced by 12 points in comparison with patients without this multimorbidity (95%CI:-22.43- -2.40). ICU admission is mostly affected by the presence of cardiometabolic and metabolic multimorbidity (OR=2.44, 95%CI: 1.51-3.92) and kidney disease multimorbidity (OR=2.58, 95%CI: 1.01-6.60). The risk of death is the highest for cardiometabolic and metabolic multimorbidity (OR=2.24, 95%CI: 1.19-4.21). Conclusion: Multimorbidity is common in COPD patients. The most common pattern is cardiometabolic and metabolic multimorbidity. Cardiometabolic and metabolic multimorbidity and kidney disease multimorbidity significantly affect the quality of life and often associate with a poor prognosis.

Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats / 中华医学杂志(英文版)

BACKGROUND@#Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms.@*METHODS@#COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-β) by enzyme-linked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured.@*RESULTS@#Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ± 6.1 vs. 20.1 ± 3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ± 1.2 vs. 6.7 ± 0.5 pg/mL, P = 0.01; lung TGF-β: 122.4 ± 20.8 vs. 81.9 ± 10.8 pg/mL, P < 0.01; serum TGF-β: 38.9 ± 8.5 vs. 20.6 ± 2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ± 0.1 fold of control vs. 0.2 ± 0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ± 0.4 μmol/μg vs. 17.4 ± 1.1 μmol/μg, P < 0.01; activity: 1.1 ± 0.1 unit vs. 1.4 ± 0.1 unit, P < 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7 ± 0.4 μmol/μg vs. 14.1 ± 0.9 μmol/μg, P < 0.01; activity: 1.3 ± 0.1 unit vs. 1.0 ± 0.1 unit, P < 0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1 ± 0.0 fold of control vs. 0.3 ± 0.1 fold of control, P < 0.01).@*CONCLUSIONS@#This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway.

Prevalence and clinical prognosis of heteroresistant vancomycin-intermediate Staphylococcus aureus in a tertiary care center in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The emergence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is increasingly challenging the methods for detection in diagnostic microbiology laboratories. However, the report of hVISA is rare in China. This study summarizes the prevalence and clinical features associated with hVISA infections at our institution and the local impact they have on clinical outcome.</p><p><b>METHODS</b>A total of 122 methicillin-resistant Staphylococcus aureus (MRSA) isolates which were of the causative pathogens were collected. One hundred and two patients for whom we had full information of MRSA pneumonia were included. Isolates of MRSA were collected using PCR to detect the mecA gene. Both Etest and macro Etest were performed to screen for hVISA. The Staphylococcal chromosome cassette mec (SCCmec) types were determined by multiplex PCR strategy. Logistic regression analysis was used to determine the risk factors.</p><p><b>RESULTS</b>Among the 122 MRSA isolates collected, 25 (20.5%) strains were identified as hVISA. There were 119 (97.5%) SCCmec III isolates, two (1.6%) SCCmec II isolates, and one (0.8%) SCCmec V isolate. The 30-day mortality of MRSA-hospital acquired pneumonia (HAP) was 37.3%, and 62.5% for hVISA-HAP. Vancomycin treatment was the independent risk factor of hVISA. Factors independently associated with 30-day mortality in all patients were acute physiology and Chronic Health Evaluation (APACHE) II score >20, multiple lobe lesions, and creatinine clearance rate (CCR) < 15 ml/min.</p><p><b>CONCLUSIONS</b>The prevalence of hVISA is 20.5% at our institution. hVISA-HAP patients had a poor clinical outcome. Vancomycin treatment was the independent predictors for hVISA infection. Factors independently associated with 30-day mortality in all patients were APACHE II score > 20, multiple lobe lesions and CCR < 15 ml/min.</p>

Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting β(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775).</p><p><b>METHODS</b>A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life.</p><p><b>RESULTS</b>Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated.</p><p><b>CONCLUSIONS</b>In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.</p>

Regulation of NOD like receptors and inflammasome during the inflammation / 生理学报

The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the nucleotide binding oligomerization domain (NOD)-like receptor (NLR) families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the cysteine protease Caspase-1, a central mediator of innate immunity. Caspase-1 initiates a novel form of cell death called pyroptosis. Inflammasome activation by pathogen-associated signatures results in the autocatalytic cleavage of Caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1β and IL-18. Here, we review the recent advancements of negative regulatory functions and mechanisms leading to the activation of NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes.

Flagellin of Pseudomonas aeruginosa induces transforming growth factor beta 1 expression in normal bronchial epithelial cells through mitogen activated protein kinase cascades / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lung infection due to Pseudomonas aeruginosa (P. aeruginosa) is a serious problem, especially in patients with structural lung conditions or immune compromised hosts, leading to an overwhelming threat with a high risk of morbidity and mortality. As an outcome of infection, fibrosis can be linked with chronic lung diseases. But some fibrotic manifestations, such as an irreversible decrease of lung function and fibrous bands seen on chest imaging, have been found after an acute infection with P. aeruginosa. Fibrogenesis/remodeling resulting from acute lung infection by P. aeruginosa is rarely reported. This study was designed to explore the relation between fibrogenesis/remodeling and acute infection by P. aeruginosa in vitro. We used flagellin protein from P. aeruginosa, a key initiator of acute P. aeruginosa lung infection, to elucidate mechanisms by which acute lung infection with P. aeruginosa can cause fibrogenesis/remodeling.</p><p><b>METHODS</b>We studied the effect of flagellin from P. aeruginosa (flagellin for short) on the transforming growth factor beta 1 (TGF-β1) and interleukin-8 (IL-8) expression, and the possible involvement of the signaling pathway, tumor necrosis factor receptor-associated factor 6 (TRAF6)/mitogen activated protein kinase (MAPK) pathway. Flagellin was purified from the P. aeruginosa standard strain, PAO1. Normal bronchial epithelial cells BEAS-2B were challenged with different concentrations of flagellin, and cell viability assessment was performed by cell counting kit-8. BEAS-2B cells were incubated with flagellin with the specific MAPK inhibitors or TRAF6 siRNA. Cell lysates and the cultured supernatant were collected. The level of TGF-β1 and IL-8 were detected by enzyme-linked immunosorbant assay (ELISA). Western blotting was used to detect the protein levels of MAPK signal proteins p38, c-Jun NH(2)-terminal kinase (JNK) and extracellular regulated kinase (ERK).</p><p><b>RESULTS</b>Expression of TGF-β1 in BEAS-2B cells was elevated by flagellin vs. control groups ((104.3 ± 20.8) vs. (44.6 ± 4.4) pg/ml (P < 0.01)) and was ablated by either p38 or JNK inhibitors compared with flagellin treatment ((45.1 ± 18.8) vs. (104.3 ± 20.8) pg/ml and (48.1 ± 20.8) vs. (104.3 ± 20.8) pg/ml, respectively (P < 0.05)). Flagellin also elevated the expression of IL-8 in BEAS-2B cells vs. the control groups ((554.9 ± 57.7) vs. (51.4 ± 22.9) pg/ml (P < 0.01)), and p38 MAPK inhibitors weaken the expression by flagellin ((301.1 ± 155.1) vs. (554.9 ± 57.7) pg/ml (P < 0.05)). Western blotting revealed that all three MAPK proteins, p38, JNK and ERK were activated by flagellin challenge in an early phase, respectively in 15 minutes (P < 0.01), 30 minutes (P < 0.01) and 15 minutes (P < 0.01). TRAF6 siRNA which decreased expression of TRAF6, altered the activation of JNK, p38, and ERK following flagellin treatment, but its influence on the expression of TGF-β1 and IL-8 has no statistical significance.</p><p><b>CONCLUSIONS</b>Flagellin from P.aeruginosa PAO1 induces TGF-β1 expression in normal bronchial epithelial cells, BEAS-2B, through the MAPK signal cascade in vitro. It suggests that the fibrogenesis/remodeling process may be initiated from an early stage of acute lung infection due to P. aeruginosa.</p>

Effect of different levels of environmental oxygen on the biofilm production of Pseudomonas aeruginosa / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship among oxygen concentration, quorum sensing system, type secretion system, and biofilm production of Pseudomonas aeruginosa.</p><p><b>METHODS</b>A total of 23 clinical strains of Pseudomonas aeruginosa were cultured at different levels of environmental oxygen for three days. Then biofilm mass and alginate were quantified. The expression levels of LasI and RhlI were detected by real time polymerase chain reaction (PCR). The secretion of exoenzyme S was examined by Western blot.</p><p><b>RESULTS</b>Both the biofilm mass (R=0.455, P=0.000) and alginate (R=0.367, P=0.000) were positively correlated with oxygen concentration. Real time PCR showed that the expression levels of LasI and RhlI were not significantly correlated with oxygen concentration (R=0.025, P=0.794; R=-0.044, P=0.653), the production of biofilm (R=0.001, P=0.990; R=0.011, P=0.909), or alginate(R=0.029, P=0.770; R=0.193, P=0.064). Western blot showed that the optimal oxygen concentration range for exoenzyme S secretion of Pseudomonas aeruginosa ranged 10% to 30%.</p><p><b>CONCLUSIONS</b>Hyperoxia can promote the production of biofilm and alginate by Pseudomonas aeruginosa. Las/Rhl system may not participate in biofilm production at the early stage due to the low bacteria amount. The increased production of biofilm may inhibit the expression of Type Secretion system and thus inhibit bacterial virulence.</p>

Early application of non-invasive ventilation in treating elderly patients with acute left ventricular failure and respiratory failure / 中华急诊医学杂志

Objective To study effects of early non-invasive ventilation (NIV) application in treating elderly patients with acute left ventricular failure induced respiratory failure. Method Totally 32 elderly patients with acute left ventrieular failure induced respiratory failure, admitted from August 1997 to February 2007, received NIV treatment, and were retrospectively studied. There were 22 male and 10 female, aged (81.5?8.6) yearsdd. The changes of rahs, respiration rate, heart rate, arterial blood gas, cardiac function before and after NIV application were compared. According to the application time of NIV, 32 patients were divided into two groups: group A (early NIV application group, n=17) and group B (non-early NIV application group, n= 15). The time to improve the symptoms, the application time of NIV, cure rates, tracheal intubation rates and mortality were compared between the two groups. Results Thirty of the 32 patients survived, cardiac function was improved from New York classⅣtoⅠ～Ⅱ, respiratory rate, heart rate and blood pressure significantly decreased, PaO_2 and SaO_2 significantly increased and PaCO_2 significantly decreased. The tracheal intubation was performed in 4 patients. The time needed to improve the symptoms and the application time of NIV were significantly different between group A and group B (P

The role of serum leptin and tumor necrosis factor-alpha in malnutrition of male chronic obstructive pulmonary disease patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha.</p><p><b>METHODS</b>Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed.</p><p><b>RESULTS</b>Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group.</p><p><b>CONCLUSIONS</b>Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.</p>