Heat shock protein 27 as a predictor of prognosis in patients admitted to hospital with acute COPD exacerbation.
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ABSTRACT:
SUBMITTER: Zimmermann M
PROVIDER: S-EPMC6985059 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown.MethodsIn this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data.ResultsHSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival.ConclusionsOur findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
| S-EPMC7867877 | biostudies-literature
Project description:ObjectivesChronic obstructive pulmonary disease is a large and increasing problem in low- and middle-income countries; Nepal is no exception. We aimed to obtain information on patient characteristics and the level of care provided to patients admitted for acute exacerbation of chronic obstructive pulmonary disease in two Nepalese hospitals and to compare the given care with the Global Initiative for Chronic Obstructive Lung Disease guidelines.MethodsThis was a cross-sectional, observational, descriptive study. All patients admitted to two Nepalese hospitals due to acute exacerbation of chronic obstructive pulmonary disease between 18 February and 5 April 2019 were asked to participate.ResultsIn total, 108 patients with a median age of 70 years participated. Fifty-three (42.7%) were male, 80 (74.8%) were former smokers, and 46 (45.1%) were farmers. Using the Global Initiative for Chronic Obstructive Lung Disease A-D classification, 97 (90.6%) of the patients were classified in group D. All the patients received supplementary oxygen treatment and 103 (95.4%) were treated with short-acting beta2 agonists. A total of 105 (97.2%) patients received antibiotics, and 80 (74.5%) received systemic corticosteroids. The majority was discharged with triple therapy including long-acting muscarinic antagonist, long-acting beta2 agonist, and inhaled corticosteroids, and 72 (75.8%) were discharged with long-term oxygen treatment.ConclusionAll elements of the Global Initiative for Chronic Obstructive Lung Disease guidelines were applied. However, due to a lack of information, it cannot be concluded whether the treatment was provided on the correct indications. The average patient received almost all the treatment alternatives available. This might indicate a very sick population or over-treatment.
| S-EPMC8935543 | biostudies-literature
Project description:Hospital-acquired acute kidney injury (HA-AKI) is associated with poor prognosis. In this study, we evaluated whether serum cystatin C on admission could predict AKI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The retrospective study was conducted using data on adult inpatients with AECOPD from January 2014 to January 2017. A total of 1035 patients were included, among which 79 (7.6%) with HA-AKI were identified. Univariate and multivariate logistic regression analyses were used to investigate predictors of HA-AKI in patients with AECOPD. HA-AKI was associated with poor prognosis, and patients with HA-AKI had higher inpatient mortality (34.2% vs. 2.6%, p < 0.001). Furthermore, after adjusting for confounders, HA-AKI was an independent risk factor for inpatient mortality for patients with AECOPD (odds ratio (OR) 11.02; 95% confidence interval (CI) 4.77-25.45; p < 0.001). Four independent risk factors for HA-AKI (age, levels of urea and cystatin C, and platelet count on admission) were identified in patients with AECOPD. Cystatin C (OR 5.22; 95% CI 2.49-10.95; p < 0.001) was a significant independent predictor of AKI in patients with AECOPD. HA-AKI in patients with AECOPD could be identified with a sensitivity of 73.5% and a specificity of 75.9% (area under the curve (AUC) = 0.803, 95% CI 0.747-0.859) by cystatin C level (cutoff value = 1.3 mg/L) and with a sensitivity of 75.9% and a specificity of 82.0% (AUC = 0.853, 95% CI 0.810-0.896) using a model comprising all significant predictors. Serum cystatin C has the potential for use to predict the risk of HA-AKI in patients with AECOPD.
| S-EPMC7493270 | biostudies-literature
Project description:Acute exacerbations of COPD involve increased symptoms such as cough, dyspnea and sputum production. These exacerbations are associated with increased mortality as well as decline in lung function. Non-invasive positive-pressure ventilation (NIPPV) is the preferred method of ventilatory support in respiratory failure secondary to AECOPD. NIPPV reduces work of breathing, improves oxygenation and ventilation and decreases both mortality and the risk of invasive ventilation. Other therapies for AECOPD include inhaled bronchodilators and systemic glucocorticoids. Antibiotics are recommended for severe exacerbations. Future areas of interest in treatment for AECOPD include utilization of biomarkers and extracorporeal carbon dioxide removal.
| S-EPMC7121203 | biostudies-literature
Project description:BackgroundRejection is the major obstacle to survival after cardiac transplantation. We investigated whether overexpression of heat shock protein (Hsp)-27 in mouse hearts protects against acute rejection and the mechanisms of such protection.MethodsHearts from B10.A mice overexpressing human Hsp-27 (Hsp-27tg), or Hsp-27-negative hearts from littermate controls (LCs) were transplanted into allogeneic C57BL/6 mice. The immune response to B10.A hearts was investigated using quantitative polymerase chain reaction for CD3+, CD4+, CD8+ T cells, and CD14+ monocytes and cytokines (interferon-?, interleukin [IL]-2, tumor necrosis factor-?, IL-1?, IL-4, IL-5, IL-10, transforming growth factor-?) in allografts at days 2, 5, and 12 after transplantation. The effect of Hsp-27 on ischemia-induced caspase activation and immune activation was investigated.ResultsSurvival of Hsp-27tg hearts (35±10.37 days, n=10) was significantly prolonged compared with LCs (13.6±3.06 days, n=10, P=0.0004). Hsp-27tg hearts expressed significantly more messenger RNA (mRNA) markers of CD14+ monocytes at day 2 and less mRNA markers of CD3+ and CD8+T cells at day 5 compared with LCs. There was more IL-4 mRNA in Hsp-27tg hearts at day 2 and less interferon-? mRNA at day 5 compared with LCs. Heat shock protein-27tg hearts subjected to ischemia or to 24 hr ischemia-reperfusion injury demonstrated significantly less apoptosis and activation of caspases 3, 9, and 1 than LCs. T cells removed from C57BL/6 recipients of Hsp-27tg hearts produced a vigorous memory response to B10.A antigens, suggesting immune activation was not inhibited by Hsp-27.ConclusionHeat shock protein-27 delays allograft rejection, by inhibiting tissue damage, through probably an antiapoptotic pathway. It may also promote an anti-inflammatory subset of monocytes.
| S-EPMC4164282 | biostudies-literature
Project description:Background: Hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality and decreased quality of life. Replicate hospital discharge studies were initiated to examine efficacy and safety of once-daily tiotropium HandiHaler® versus placebo, in addition to usual care, in patients discharged from the hospital after an AECOPD. Methods: Both studies were randomized, placebo-controlled, double-blind, parallel-group, multicenter, with inclusion/exclusion criteria providing a diverse COPD patient cohort hospitalized for ?14 days with AECOPD. Patients received tiotropium or placebo, initiated within 10 days post-discharge. Target recruitment was 604 patients/study and planned duration was event-driven, ending after 631 clinical outcome events across both studies. Inability to reach targeted site numbers and patient recruitment/retention difficulties led to early study termination. Recruitment/retention challenges and protocol amendment impacts were assessed qualitatively to understand the major issues. Results: Over 18 months, 219 patients were enrolled; 158 were randomized and 61 failed screening. Premature treatment discontinuation occurred in 49(31%) patients, of whom 20(41%) completed health status follow-up. All-cause, 30-day hospital readmission was low (8[5%] patients). A total of 154(98%) patients had a concomitant diagnosis and most took pulmonary medication pre-randomization (143[91%]) and during study treatment (144[92%]). Inclusion/exclusion criteria changes failed to improve recruitment. Recruitment/retention barriers were identified, relating to patient and clinician factors, health care infrastructure, and clinical practices. Conclusions: Although AECOPD hospitalization is clinically important and incurs high costs, significant challenges exist in studying this population in clinical trials after hospitalization. Studies are needed to evaluate effective management of AECOPD patients at high risk of adverse clinical outcomes.
| S-EPMC5764840 | biostudies-literature
Project description:ObjectiveAppropriate use of antibiotics in the management of hospitalised patients with COPD exacerbations is defined within the GOLD strategy. This paper analyses the factors associated with antibiotic prescribing in patients to better understand how prescribing may be improved.MethodsThe European COPD audit was a study of clinical care in 384 hospitals from 13 European countries between 2010 and 2011 enrolling 16018 patients. Those admitted to hospital due to a clinician-made diagnosis of exacerbation of COPD at the time of discharge were audited. We defined antibiotic prescribing compliance as consistent with the GOLD 2010 recommendations. Two different multivariate models were used to evaluate factors associated with the prescription of antibiotics and the guideline-compliant prescriptions.ResultsOverall 86% of admissions were given antibiotics but only 61.4% cases met the GOLD recommendations. Antibiotics were more likely to be given in hospital and at discharge if received prior to admission. Antibiotic prescription was more likely in patients who met the GOLD recommendations and in those with radiological consolidation but there was also a significant use of antibiotics in patients who did not meet either criterion. Patients cared for on a Respiratory Ward were more likely to receive GOLD compliant antibiotic management.ConclusionsThe present study describes the audited in-hospital antibiotic prescription for COPD exacerbation across different European countries. In general, there is an apparent overuse of antibiotics likely to be associated with both patient and practice-related variables.
| S-EPMC4408103 | biostudies-literature
Project description:Inhibitors of heat-induced heat shock protein 70 (HSP70) expression have the potential to enhance the therapeutic effectiveness of heat-induced radiosensitization of tumors. Among known small molecule inhibitors, quercetin has the advantage of being easily modified for structure-activity studies. Herein, we report the ability of five monomethyl and five carbomethoxymethyl derivatives of quercetin to inhibit heat-induced HSP70 expression and enhance HSP27 phosphorylation in human cells. While quercetin and several derivatives inhibit HSP70 induction and enhance HSP27 phosphorylation at Ser78, other analogues selectively inhibit HSP70 induction without enhancing HSP27 phosphorylation that would otherwise aid in cell survival. We also show that good inhibitors of HSP70 induction are also good inhibitors of both CK2 and CamKII, kinases that are known to activate HSP70 expression by phosphorylation of heat shock transcription factor 1. Derivatives that show poor inhibition of either or both kinases are not good inhibitors of HSP70 induction, suggesting that quercetin's effectiveness is due to its ability to inhibit both kinases.
| S-EPMC2763579 | biostudies-literature
Project description:The establishment of a guideline for long-term noninvasive ventilation treatment (LTH-NIV) of acute hypercapnic exacerbations of chronic obstructive pulmonary disease (AECOPD) requiring acute ventilation has proven elusive. Most studies thus far have shown no mortality benefit of long-term noninvasive ventilation treatment. Using retrospective analysis of the data of our patients (n = 143) recruited from 2012 to 2019, we aimed to compare patients discharged with and without long-term noninvasive ventilation. The follow-up results showed no significant difference (p = 0.233) between the groups [LTH-NIV (n = 83); non-NIV (n = 60)] regarding readmission due to clinical worsening. However, the first- and second-year survival rates were 82% and 72%, respectively, in the LTH-NIV group and significantly different (p = 0.023) from 67 and 55% in the non-NIV group. The statistical models showed a significant mortality risk for the non-NIV group, with a hazard ratio (HR) of 2.82 (1.31; 6.03). To the best of our knowledge, this is the first study to demonstrate the mortality benefit of long-term NIV therapy for patients with AECOPD under real-world conditions.
| S-EPMC10121675 | biostudies-literature
Project description:Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI.This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI.Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03-2.81; P = 0.038] for the HA-AKI group).AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes.
| S-EPMC6054768 | biostudies-other