Multidimensional Frailty Instruments Can Predict Acute Exacerbations Within One Year in Patients with Stable Chronic Obstructive Pulmonary Disease: A Retrospective Longitudinal Study.

Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People's Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P<0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663-0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693-0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.

Cognition, attitude, practice toward health checkup and associated factors among urban residents in southwest China, Sichuan province, 2022: a community-based study.

Aim: Research on the health checkup status of urban residents in Southwest China is limited. In this study, we aimed to investigate the current status of health checkups and explore their influencing factors by analyzing the cognition, attitudes, and practices of urban residents in Southwest China. Methods: We sampled 1200 urban residents for a questionnaire survey. Statistical analysis was performed using SPSS 23, and logistic regression analysis was used to analyze the factors affecting cognition, attitudes, and practices regarding health checkups. A P value < 0.05 was used to identify variables significantly associated with the outcome variable. Results: Overall, 29% of the residents understood the importance of health checkups. The main ways urban residents acquire health-related knowledge are through the use of mobile media and medical staff health education. Only 40% of residents had undergone a regular checkup. Health self-assessment, economic reasons, and time are the factors that interfere with urban residents' health checkups. Logistic regression analysis showed that occupation status, educational background, self-assessed health status, exercise status, and monthly income level were the common influencing factors of health checkup cognition and planning. Whether residents had participated in a medical checkup program was also related to sex and age. Conclusions: Urban residents in Southwest China generally had a high willingness to undergo physical examinations, but there were differences in knowledge and practice; at the same time, residents lacked understanding of respiratory assessments. Improving the health literacy of medical staff, strengthening urban residents' health education, and enhancing the utilization rate of health checkups in urban residents are necessary and urgent.

A pilot study of differential gene expressions in patients with cough variant asthma and classic bronchial asthma.

BACKGROUND: Despite extensive exploration of asthma, the mechanism of asthma has not been fully elucidated. Cough variant asthma (CVA) is considered as precursor to classical asthma (CA). Comparative study between CA and CVA may be helpful in further understanding the pathogenesis of asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from CVA, CA and healthy adults. Each group consisted of five cases. Total RNA was extracted from the PBMCs. Agilent 4 × 44 K human genome oligo microarray was used to detect whole genome expression. Allogeneic clustering, Gene Ontology and KEGG analysis were performed to investigate differentially expressed genes (DEGs). Then, ten candidate genes were screened and verified by real-time PCR. RESULTS: Gene expressions were significantly different among the three groups, with 202 DEGs between the CA and the CVA groups. The Gene Ontology analysis suggested that the DEGs were significantly enriched in 'histone H4-K20 demethylation' and 'antigen processing and presentation of endogenous antigens'. HDC, EGR1, DEFA4, LTF, G0S2, IL4, TFF3, CTSG, FCER1A and CAMP were selected as candidate genes. However, the results of real-time PCR showed that the expression levels of FCER1A, IL4 and HDC in the cough variant asthma group were significantly different from those in the other two groups (p < 0.05). CONCLUSIONS: The pathogenesis of CVA and CA may be related to genes such as FCER1A, HDC and IL4. Further studies incorporating a larger sample size should be conducted to find more candidate genes and mechanisms.

The Serum Citrulline and D-Lactate are Associated with Gastrointestinal Dysfunction and Failure in Critically Ill Patients.

OBJECTIVE: This study attempted to screen and combine effective biomarkers to analyse the association between these biomarkers and gastrointestinal failure (GIF) in critically ill patients. METHODS: A total of 110 critically ill patients with acute gastrointestinal injury (AGI) admitted to ICU were enrolled. The AGI grade was determined by the AGI classification proposed by ESICM. There were 67 patients in gastrointestinal dysfunction (GID) group (AGI grade II), 43 patients in GIF group (AGI grade III-IV), and 41 healthy adults in healthy control (HC) group. APACHE II and SOFA score were used to evaluate the disease severity. Peripheral blood samples of patients were collected within 24 hours of admission to the ICU (prior-treatment) and after the conventional medication therapy for 7 consecutive days (post-treatment). Citrulline serum level was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and D-lactate and lipopolysaccharide (LPS) serum levels were measured by ELISA. Pearson correlation, logistic regression, and ROC curve analysis were used. RESULTS: Patients with GID or GIF had lower serum level of citrulline, while higher levels of D-lactate and LPS than HC. Compared with GID patients, serum level of citrulline was reduced, while D-lactate and LPS were elevated in GIF patients. Correlation analysis displayed that serum levels of citrulline, D-lactate, and LPS were associated with the APACHE II and SOFA score in patients with GID or GIF. Logistics regression analysis showed that citrulline and D-lactate were risk for both GID and GIF. ROC curve analysis exhibited that combination of citrulline and D-lactate had relatively high value to distinguish GID from HC, GIF from GID, and GIF from HC. CONCLUSION: Serum citrulline and D-lactate were associated with severity of GIF, combination of citrulline and D-lactate improved the diagnostic efficacy to identify GIF in critically ill patients.

Attitudes Toward Advance Directives Among Patients and Their Family Members in China.

OBJECTIVES: Chinese people are generally unfamiliar with the concept of advance care planning or advance directives (ACP/ADs), which raises dilemmas in life-support choice and can even affect clinical decision making. To understand and address the issues involved better, we investigated the awareness of ACP/ADs in China, as well as people's attitudes toward medical autonomy and end-of-life care. DESIGN: A multicenter cross-sectional survey, conducted from August 1 to December 31, 2016. SETTING: Twenty-five hospitals located in 15 different provinces throughout mainland China. PARTICIPANTS: Pairs of adult patients without dementia or malignancies, and a family member. MEASUREMENTS: Participants self-filled anonymous questionnaires, and the data collected were analyzed to relate patients' sociodemographic characteristics to their awareness of ACP/ADs and attitudes to health care autonomy and end-of-life care. RESULTS: Among 1084 patients who completed the questionnaire, 415 (38.3%) had heard about ACP/ADs. Having been informed about ACP/ADs, 995 (91.8%) were willing to find out their true health status and decide for themselves; 549 (50.6%) wanted to institute ACP/ADs. Regarding end-of-life care, 473 (43.6%) chose Do Not Resuscitate, and 435 (40.1%) wished to forgo life-support treatment if irreversibly moribund. Patients predominantly (481, 44.4%) chose general hospital as their preferred place to spend their last days of life; only 114 (10.5%) favored a special hospice facility. Patients' main concerns during end-of-life care were symptom control (35.1%), followed by functional maintenance and quality of life (29.8%), and prolonging life (18.9%). More highly educated patients had significantly greater awareness of ACP/ADs than less well educated ones (χ2 = 59.22, P < .001) and were more willing to find out the truth for themselves (χ2 = 58.30, P ≤ .001) and make medical decisions in advance (χ2 = 55.92, P < .001). Younger patients were also more willing than older ones to know the truth (χ2 = 38.23, P = .001) and make medical decisions in advance (χ2 = 18.42, P = .018), and were also more likely to wish to die at home (χ2 = 96.25, P < .001). Only 212 patients' family members (19.6%) wanted life-support treatment for themselves if irreversibly moribund, whereas 592 (54.6%) would want their relative to receive such procedures in the same circumstances; a similar discrepancy was evident for end-of-life invasive treatment (18.3% vs 42.7%). CONCLUSIONS: Awareness about ACP/ADs in China is still low. Providing culturally sensitive knowledge, education, and communication regarding ACP/ADs is a feasible first step to promoting this sociomedical practice.

A Patient with a Right Atrium Mass and Congenital Heart Disease: A Challenging Diagnosis of a Stubborn Disease.

Cardiac lymphoma is extremely rare. An intracardiac mass has rarely been reported to be the cardiac involvement of extranodal lymphoma. It is difficult to establish a final diagnosis via routine examinations. The ability of an echocardiogram to characterize tissue is limited; systemic (18)F-FDG PET/CT scans provide important information for both staging and response assessment in patients with lymphoma. A 68-year-old Chinese male with a second patent foramen ovale (PFO) and an interventricular septal defect presented at our institute with persistent fever, shortness of breath, repeated paroxysmal supraventricular tachycardia (PSVT) attack, and rapidly progressing superior vena cava syndrome. The patient also presented with a mass located in the upper right atrium and superior vena cava which was detected by echocardiogram. (18)F-FDG PET/CT scan revealed a pathological increase of (18)F-FDG uptake in the atrial mass and several other extracardiac lymph nodes. Lymph node biopsy was positive for large B-cell lymphoma. Immunohistochemistry revealed intense and diffuse expression of CD20, CD10, BCL-6, and Ki-67. The patient died without any chemotherapy 18 days after hospital discharge.

The Toll-like receptor 4 polymorphism Asp299Gly but not Thr399Ile influences TLR4 signaling and function.

The common, co-segregating Toll-like receptor 4 (TLR4) non-synonymous single nucleotide polymorphisms (SNPs), Asp299Gly and Thr399Ile, are associated with hyporesponsiveness to inhaled lipopolysaccharide (LPS) and increased susceptibility to Gram negative pathogens in humans. The purpose of this study was to identify the relative contributions of the Asp299Gly and the Thr399Ile variants in inhibiting the function of TLR4. 293/hMD2-CD14 cell line was transfected with lentiviral constructs containing human wild type (WT) TLR4-EGFP or TLR4-EGFP with Asp299Gly, Thr399Ile or Asp299Gly/Thr399Ile complementary DNA (cDNA). Multiple stable cell lines were established for each construct: three for WT TLR4, Asp299Gly, and Thr399Ile, and only two for Asp299Gly/Thr399Ile mutants and EGFP control. We did not observe a significant effect of polymorphisms on cell surface and intracellular TLR4 expression nor were there any significant differences in TLR4 and EGFP protein levels assessed by Western blotting and confocal microscopy among the multiple cell lines of each of the constructs. All cell lines had a dose-dependent responsiveness to LPS stimulation. However, compared to the WT TLR4, cells expressing TLR4 with Asp299Gly but not Thr399Ile polymorphism produced significantly less (P<0.05) IL-8 following LPS stimulation. Similarly, cells expressing TLR4 Asp299Gly but not Thr399Ile allele had significantly lower percentage of phosphorylated and total NF-κB P65 following LPS stimulation. While we could not do statistics on the Asp299Gly/Thr399Ile group, we observed a reduced responsiveness to LPS compared to WT TLR4. Taken together, we observed that the TLR4 Asp299Gly variant, but not the Thr399Ile variant, is responsible for impaired responsiveness of TLR4 to LPS and corresponding activation of NF-κB.

[Effects of epidermal growth factor receptor on airway inflammation in a rat asthmatic model].

OBJECTIVE: To explore the possible roles of epidermal growth factor receptor (EGFR) in the process of acute and chronic airway inflammation in a rat asthmatic model. METHODS: Forty-five Sprague-Dawley (SD) rats were randomly divided into control groups (subgroups A1, A2, A4), asthmatic groups (subgroups B1, B2, B4) and treatment groups (subgroups C1, C2, C4), with 5 mice in each subgroup. Mice in the asthmatic and treatment groups were exposed to OVA challenge for 1 week, 2 weeks and 4 weeks. Rats in the treatment groups received intraperitoneal injection of a tyrosine kinase inhibitor Genistein (Rongli China) with the dose of 20 mg/kg 1 hour before OVA exposure. Total cell counts and cell differentials in bronchoalveolar lavage fluid (BALF) were performed. A semi-quantified method of airway inflammation score was used to evaluate airway inflammation by hematoxylin-eosin (HE) staining. Expression of EGFR and tyrosine phosphorylation (EGFR activation) in airway epithelium at different times of OVA exposure were evaluated by immunohistochemical and immunofluorescence. All data were expressed as mean +/- SD. One-way ANOVA was used for comparison between 2 groups and post-hoc multiple comparisons of means were performed by using Least Significant Difference. RESULTS: (1) The total cell counts and cell differentials in the BALF of subgroups B1, B2 and B4 were higher than those of subgroups A1, A2 and A4. The total cell counts and eosinophils (EOS) in the BALF of subgroups C1, C2, and C4 [Total cells (48 +/- 6) x 10(5), (51 +/- 9) x 10(5), (57 +/- 12) x 10(5); EOS (2.5 +/- 0.5) x 10(5), (2.7 +/- 0.6) x 10(5), (2.6 +/- 0.5) x 10(5), respectively] decreased significantly as compared to those of subgroups B1, B2 and B4 [Total cells (70 +/- 10) x 10(5), (88 +/- 8) x 10(5), (72 +/- 10) x 10(5); EOS (5.6 +/- 0.8) x 10(5), (6.6 +/- 0.6) x 10(5), (4.3 +/- 0.4) x 10(5)], all P < 0.05. There was no significant difference in the counts of neutrophils and lymphocytes in BALF between the treatment groups and the asthmatic groups. The count of epithelial cells in group C1 [(2.5 +/- 0.5) x 10(5)] was lower than that in group B1[(4.9 +/- 0.7) x 10(5)], q = 4.671, P < 0.05. But that in group C4[(5.7 +/- 1.2) x 10(5)] was higher than that in group B4 [(4.3 +/- 0.4) x 10(5)], q = 4.012, P < 0.05. (2) The airway inflammation score in group C4(3.6 +/- 0.6) was less than that in group B4(5.1 +/- 0.6), q = 4.923, P < 0.05. The scores of group C1 and C2 were less than those of group B1 and B2, but the differences did not reach statistical significance. (3) The expression of EGFR and tyrosine phosphorylation in airway epithelium of the OVA sensitized subgroups were increased statistically as compared to the control subgroups (all P < 0.05). Genistein decreased tyrosine phosphorylation of EGFR in subgroups C1, C2 and C4[(3.12 +/- 0.24), (3.00 +/- 0.28), (2.69 +/- 0.54)] as compared to subgroups B1, B2 and B4[(3.69 +/- 0.43), (3.57 +/- 0.29), (4.46 +/- 0.47), respectively] (all P < 0.05). (4) There were positive correlations between expression and activation of EGFR in airway epithelium and total cell counts, EOS counts, neutrophil and lymphocyte counts in BALF, and airway inflammation scores (all P < 0.05). CONCLUSIONS: EGFR is involved in airway inflammation of asthmatic rats. Tyrosine kinase inhibitor Genistein inhibits acute and chronic airway inflammation in the asthmatic model.

[Effect of tyrosine kinase inhibitors on airway remodeling in bronchial asthma].

OBJECTIVE: To investigate the effect of tyrosine kinase inhibitors (TKIs) on asthmatic rat airway remodeling. METHODS: The inhibitive effects of three TKIs (Genistein, jin-zhuan-ting and Tyrphostin AG1478) on proliferation of primary cultures of rat tracheal epithelial cells were assessed by MTT assay. Then, jin-zhuan-ting was adopted in the asthmatic rat model; immunohistofluorescene method was used to stain phosphorylated tyrosine (P-tyr) for disclosing the activation of EGFR; Sirius Red staining of submucosal collagen I and III was performed, and an analysis was made on the correlation between EGFR activation and collagen I and III deposition. RESULTS: All the three TKIs inhibited the growth of tracheal epithelial cells in a time and dose depending manner, and the inhibition rates among them showed no statistical differences; airway subepithelial collagen I and III deposition degrees were markedly elevated in asthmatic groups and jin-zhuan-ting reduced the deposition in a certain degree; EGFR activation (P-tyr) in airways epithelium of asthmatic groups was greatly increased in comparison with that of control groups, and it was evidently decreased in jin-zhuan-ting groups. Correlation analysis demonstrated that the amount of airway subepithelial collagen I and III was positively correlated to EGFR activation. CONCLUSION: TKIs may have preventive implications for asthmatic airway remodeling.

[Effects of epithelial growth factor receptor inhibitor on the growth and repair of airway epithelial cells].

OBJECTIVE: To explore the possible effects of epithelial growth factor receptor inhibitor on the growth and repair of airway epithelial cells. METHODS: MTT assay was used to measure the effects of several concentrations of epithelial growth factor receptor inhibitor Tyrphostin AG1478 on the cell proliferation of rat tracheal epithelial cells in primary culture. And 24 hours after scraping to off a certain amount of cells, we measured the changes of scraped area in two groups of cell culture exposed to Tyrphostin AG 1478 at the concentration of 2.5 mumol/L and low-serum culture medium. RESULTS: Tyrphostin AG 1478 inhibited the proliferation of tracheal epithelial cells depending on concentrations. In the meantime, the scraped area of Tyrphostin AG 1478 group was much larger than that of low-serum group, P < 0.001. CONCLUSION: Epithelial growth factor receptor inhibitor Tyrphostin AG1478 has an inhibitory effect on the growth of rat tracheal epithelial cells and it may prevent the repair of airway epithelium.