Klotho Regulates Cigarette Smoke-Induced Autophagy: Implication in Pathogenesis of COPD.

INTRODUCTION: Chronic obstructive pulmonary disease is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway, though its role in human diseases remains unclear. We hypothesized that an anti-aging protein, Klotho plays an important role in regulating autophagy in response to cigarette smoke (CS). METHODS: Autophagy was measured by detecting LC3-I and LC3-II expressions. The regulation of autophagy expression by cigarette smoke extract (CSE) was studied in vitro, and small-interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced autophagy. Protein levels and phosphorylation were measured by Western blot assay. RESULTS: CS exposure resulted in induction of autophagy in alveolar macrophages. Pretreatment of cells with Klotho attenuated CS-induced autophagy whereas knockdown of Klotho augmented CS-induced autophagy. Klotho inhibited phosphorylation of ERK, Akt, and IGF-1 in CSE-stimulated cells. CONCLUSIONS: These data suggest that Klotho plays a critical role in the regulation of CS-induced autophagy and have important implications in understanding the mechanisms of CS-induced cell death and senescence.

The Main Pulmonary Artery to the Ascending Aorta Diameter Ratio (PA/A) as a Predictor of Worse Outcomes in Hospitalized Patients with AECOPD.

Purpose: The main pulmonary artery (PA) to ascending aorta diameter ratio (PA/A) greater than one is a promising indicator of pulmonary hypertension (PH) in acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) (AECOPD). This study aims to disclose the associations between the PA/A ratio and clinical outcomes in hospitalized patients with AECOPD. Patients and Methods: Consecutive AECOPD patients admitted to the Department of Respiratory Medicine from September 2017 to July 2021 were reviewed. The treatment success of AECOPD patients was defined as improvement in the clinical condition when discharged from the hospital. Conversely, treatment failure was considered to be an event of in-hospital death or deterioration of the clinical condition prior to discharge. Results: A total of 118 individuals were ultimately reviewed in this study: 74 individuals with a PA/A ratio <1 and 44 individuals with a PA/A ratio ≥1. The outcomes of 21 patients were treatment failure, and 97 patients were considered successes. Patients with a PA/A ratio ≥1 had significantly higher PaCO2, red cell distribution width, brain natriuretic peptide, PA diameters, RICU admission rates, and proportions of treatment failure than patients with PA/A ratios <1 (P < 0.05). The PA diameter and PA/A ratio were significantly increased in the treatment failure group compared with the success group (P < 0.05). A survival analysis indicated that patients with a PA/A ratio ≥1 had worse outcomes than patients with a PA/A ratio <1 during hospitalization (P < 0.05). A multivariate analysis showed that a PA/A ratio ≥1 was an independent risk factor for treatment failure in patients with AECOPD. Conclusions: AECOPD patients with a PA/A ratio ≥1 may have worse outcomes during hospitalization. A PA/A ratio ≥1 may be a promising predictor of treatment failure in patients with AECOPD.

Clinical significance of procalcitonin in critically ill patients with pneumonia receiving bronchoalveolar lavage.

Background: As a useful tool in intensive care units (ICU), fiberoptic bronchoscopy (FOB) may cause a deterioration of infection. This study is to investigate the clinical significance of procalcitonin (PCT) in critically ill patients with severe pneumonia receiving bronchoalveolar lavage (BAL). Methods: A retrospective case-control study was performed in a single respiratory ICU (RICU) with 6-bed. Critically ill patients with severe pneumonia admitted to RICU were consecutively reviewed from March 2017 to October 2019. Chi-square test, Wilcoxon test, Mann Whitney U-test, Kaplan-Meier survival analysis or Cox's proportional hazards regression model was used as appropriate. Results: A total of 72 eligible patients were included in the final analysis, 51 of which received BAL performed by FOB. Serum levels of PCT in group received BAL is markedly increased at 24 hours after FOB (p<0.001). Forty-eight hours later, BAL group with decreased serum levels of PCT had less SOFA score and decreased mortality compared with those with increased serum levels of PCT. Furthermore, Kaplan-Meier analysis indicated that patients with decreased serum levels of PCT had improved survival rate during hospital (Breslow test, p=0.041). However, increased PCT after BAL was not an independent risk factor for in-hospital mortality (hazard ratio: 1.689, 95% CI(0.626 ,4.563), p=0.301). Conclusions: BAL performed by FOB increased serum levels of PCT. However, PCT levels decreased at 48 hours after BAL predicted a good prognosis of patients with severe pneumonia.

Association between asthma and invasive pneumococcal disease risk: a systematic review and meta-analysis.

PURPOSE: Asthma has been shown to be related to an increased risk of invasive pneumococcal disease (IPD), although the results remain inconclusive. Therefore, we performed a meta-analysis to determine whether asthma increases the risk of IPD. This meta-analysis was performed to validate and strengthen the association between asthma and IPD. METHODS: PubMed, EMBASE, Web of Science, and the reference lists of all relevant articles and books were screened until May 2019. Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio was estimated using a random-effects meta-analysis model of aggregated published data. RESULTS: A total of eight studies with 8877 IPD cases and 78,366 controls were included. Our meta-analysis showed that asthma was significantly associated with the increased risk of IPD (OR 2.44 [95% CI, 2.02-2.96]). The children with asthma (0-17 years old) (OR 2.86 [95% CI 1.80-4.55]) had a higher risk of IPD susceptibility compared with the adult patients (≥ 18 years old) (OR 2.45 [95% CI 1.98-3.03]). CONCLUSIONS: Results of this meta-analysis indicated that the patients with asthma had a higher risk of IPD susceptibility, especially among the children with asthma.

Red Blood Cell Distribution Width Predicts Pulmonary Hypertension Secondary to Chronic Obstructive Pulmonary Disease.

Purpose: This study aims at investigating the predictive value of red blood cell distribution width (RDW) in pulmonary hypertension (PH) secondary to chronic obstructive pulmonary disease (COPD). Methods: 213 eligible in-hospital COPD patients were reviewed between May 2016 and May 2018, including 39 cases with PH and 174 without PH. Clinical data including demographic characteristics, comorbidities, and results of ultrasound scans, imaging examinations, and laboratory tests were recorded. Results: Increased RDW level was observed in COPD patients with PH compared with COPD patients without PH, with 15.10 ± 1.72% versus 13.70 ± 1.03%, respectively (p < 0.001). RDW shared positive relationships with brain natriuretic peptide (BNP) (p=0.001, r = 0.513), pulmonary artery (PA) systolic pressure (p=0.014, r = 0.390), and PA-to-ascending aorta (A) ratio (PA : A) (p=0.001, r = 0.502). Multivariate analysis indicated that RDW, BNP, and PA : A > 1 were the independent risk factors of PH secondary to COPD (p < 0.05). The AUC of the RDW in patients with PH was 0.749 ± 0.054 (p < 0.001). The optimal cutoff value of RDW for predicting PH was 14.65, with a sensitivity and a specificity value of 69.2% and 82.8%, respectively. Conclusion: RDW is significantly increased in COPD patients with PH and thus may be a useful biomarker for PH secondary to COPD.

Clinical characteristics of chronic bronchitic, emphysematous and ACOS phenotypes in COPD patients with frequent exacerbations.

PURPOSE: Chronic bronchitis (CB), emphysematous (EM) and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) phenotypes in COPD are well recognized. This study aimed to investigate distinguishing characteristics of these phenotypes in COPD patients with frequent exacerbations (FE). PATIENTS AND METHODS: A retrospective study was carried out. COPD patients with acute exacerbations were consecutively reviewed from November 2015 to October 2016. Patients were divided into FE and infrequent exacerbations (iFE) subgroups. RESULTS: A total of 142 eligible COPD subjects were reviewed. In the CB phenotype subgroup, age, body mass index, forced expiratory volume in 1 second (FEV1) % predicted, COPD assessment test (CAT), modified Medical Research Council breathlessness measurement (mMRC) dyspnea scale, emphysema scores and arterial carbon dioxide pressure (PaCO2) were significantly different in subjects with FE when compared to those in subjects with iFE of CB. In the EM phenotype subgroup, age, CAT, mMRC scores and history of COPD were different in subjects with FE when compared to those in CB subjects with iFE. Multivariate analysis indicated that FEV1% predicted (odds ratio [OR] =0.90, P=0.04) and PaCO2 (OR =1.22, P=0.02) were independent risk factors for FE in COPD with CB phenotype, and CAT (OR =2.601, P=0.001) was the independent risk factor for FE in COPD with EM phenotype. No significant differences in characteristics were observed in ACOS phenotype subgroups with FE or iFE. CONCLUSION: In CB or EM phenotypes, COPD patients with FE present several differential clinical characteristics compared to patients with iFE, while the characteristics of ACOS phenotype in patients with FE need more investigation.

Community-acquired pneumonia and survival of critically ill acute exacerbation of COPD patients in respiratory intensive care units.

PURPOSE: The aim of this study was to appraise the effect of community-acquired pneumonia (CAP) on inhospital mortality in critically ill acute exacerbation of COPD (AECOPD) patients admitted to a respiratory intensive care unit. PATIENTS AND METHODS: A retrospective observational study was performed. Consecutive critically ill AECOPD patients receiving treatment in a respiratory intensive care unit were reviewed from September 1, 2012, to August 31, 2015. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed by Mann-Whitney U-test. Kaplan-Meier analysis was used to assess the association of CAP with survival of critically ill AECOPD patients for univariate analysis. Cox's proportional hazards regression model was performed to identify risk factors for multivariate analysis. RESULTS: A total of 80 consecutive eligible individuals were reviewed. These included 38 patients with CAP and 42 patients without CAP. Patients with CAP had a higher inhospital rate of mortality than patients without CAP (42% vs 33.3%, P<0.05). Kaplan-Meier survival analysis showed that patients with CAP had a worse survival rate than patients without CAP (P<0.05). Clinical characteristics, including Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein, and CAP, were found to be closely associated with survival of AECOPD individuals. Further multivariate Cox regression analysis confirmed that CAP and APACHE II were independent risk factors for inhospital mortality in critically ill AECOPD patients (CAP: hazard ratio, 5.29; 95% CI, 1.50-18.47, P<0.01 and APACHE II: hazard ratio, 1.20; 95% CI, 1.06-1.37, P<0.01). CONCLUSION: CAP may be an independent risk factor for higher inhospital mortality in critically ill AECOPD patients.