Identification of RAGE and OSM as New Prognosis Biomarkers of Severe Pneumonia

Objective. To investigate efficiency of RAGE and OSM as new prognosis biomarkers of severe pneumonia. Methods. Eligible patients were classified into hypoxemia and nonhypoxemia groups. Meanwhile, the same cohort was divided into survival and nonsurvival groups after a post-hospital stay of 30 days. We analyzed risk factors for the hypoxia and death among these patients. Results. Compared with nonsurvival group, significant increase was noticed in PH, lymphocyte, albumin and platelet level in survival group, while significant decline was noticed in neutrophils, RBC, hemoglobin, hematocrit, creatinine, total bilirubin, CRP, PCT, OSM, RAGE and neutrophils/lymphocyte level. Oxygenation index level was related to APACHE II, LIS, SOFA, NUTRIC score, WBC, neutrophils, lymphocyte, RAGE, and albumin level ( p < 0.05 ). LIS, SOFA, NUTRIC score, lac, lymphocyte, platelet, BUN, total bilirubin, PCT, and OSM levels were associated with mortality rate ( p < 0.05 ). Conclusions. RAGE and OSM may serve as a new biomarker for poor prognosis in pneumonia patients.

Ward-Based Noninvasive Ventilation for Acute Hypercapnic Respiratory Failure Unrelated to Chronic Obstructive Pulmonary Disease

Background. The use of ward-based noninvasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF) unrelated to chronic obstructive pulmonary disease (COPD) remains controversial. This study evaluated the outcomes and failure rates associated with NIV application in the ward-based setting for patients with AHRF unrelated to COPD. Methods. A multicentre, retrospective cohort study of patients with AHRF unrelated to COPD was conducted. COPD was not the main reason for hospital admission, treated with ward-based NIV between February 2004 and December 2018. All AHRF patients were eligible; exclusion criteria comprised COPD patients, age < 18 years, pre-NIV pH < 7.35, or a lack of pre-NIV blood gas. In-hospital mortality was the primary outcome; univariable and multivariable models were constructed. The obesity-related AHRF group included patients with AHRF due to obesity hypoventilation syndrome (OHS), and the non-obesity-related AHRF group included patients with AHRF due to pneumonia, bronchiectasis, neuromuscular disease, or fluid overload. Results. In total, 479 patients were included in the analysis; 80.2% of patients survived to hospital discharge. Obesity-related AHRF was the indication for NIV in 39.2% of all episodes and was the aetiology with the highest rate of survival to hospital discharge (93.1%). In the multivariable analysis, factors associated with a higher risk of in-hospital mortality were increased age (odds ratio, 95% CI: 1.034, 1.017–1.051, P < 0.001 ) and pneumonia on admission (5.313, 2.326–12.131, P < 0.001 ). In the obesity-related AHRF group, pre-NIV pH < 7.15 was associated with significantly increased in-hospital mortality (7.800, 1.843–33.013, P = 0.005 ); however, a pre-NIV pH 7.15–7.25 was not associated with increased in-hospital mortality (2.035, 0.523–7.915, P = 0.305 ). Conclusion. Pre-NIV pH and age have been identified as important predictors of surviving ward-based NIV treatment. Moreover, these data support the use of NIV in ward-based settings for obesity-related AHRF patients with pre-NIV pH thresholds down to 7.15. However, future controlled trials are required to confirm the effectiveness of NIV use outside critical care settings for obesity-related AHRF.

Hemosiderin-Laden Macrophages in Bronchoalveolar Lavage: Predictive Role for Acute Exacerbation of Idiopathic Interstitial Pneumonias

Background. Hemosiderin-laden macrophages (HLMs) have been identified in the bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF). This retrospective study examined the ability of HLMs in BALF to predict the acute exacerbation (AE) of chronic idiopathic interstitial pneumonias (IIPs). Methods. Two hundred and twenty-one patients with IIP diagnosed by bronchoscopy were enrolled in the study (IPF, n = 87; IIPs other than IPF, n = 134). Giemsa stain was used to detect HLMs in BALF specimens. Prussian blue stain was used to quantify HLMs in BALF, and a hemosiderin score (HS) was given to the specimens containing HLMs. Results. Twenty-four patients had a positive HS (range: 7‒132). The receiver-operating characteristic curve analysis identified the cutoff HS value for predicting the AE of IIPs to be 61.5. Seven cases had a higher HS (≥61.5) and 214 had a lower HS. AE occurred significantly earlier in the higher HS group (4/7 cases) than in the lower HS group (41/214 cases) during a median observation period of 1239 days (log-rank test, p = 0.026). Multivariate Cox proportional hazard regression analysis showed that a higher HS was a significant predictor of AE in addition to IPF, percent predicted forced vital capacity, and modified Medical Research Council score. The C-statistics for the prediction of AE did not significantly improve by all the above parameters with HS as compared without HS. Conclusions. A higher HS was a significant predictor of AE in IIPs but did not significantly improve the predictive ability of other parameters.

Value of Peak Expiratory Flow Rate in Evaluating Cough Ability in Patients Undergoing Lung Surgery

Introduction. Postoperative ineffective cough is easy to occur after thoracic surgery, and it is also a risk factor for postoperative pulmonary complications (PPCs). Objectives. To explore the value of peak expiratory flow rate (PEF) in evaluating cough ability in patients undergoing lung surgery and evaluate the effectiveness of chest wall compression during the expiratory phase by PEF. Methods. From September 2020 to May 2021, the researchers collected the data of patients who underwent lung surgery. Eventually, 153 patients who met the criteria were included, 102 cases were included in the effective cough group and 51 cases were included in the ineffective cough group. The receiver working curve (ROC curve) was used to analyze whether PEF could evaluate cough ability. At the same time, the researchers collected the pulmonary function data of the first 30 patients of the ineffective cough group while compressing the chest wall during the expiratory phase to evaluate the effectiveness of chest wall compression. Results. The area under the curve (AUC) of postoperative PEF to evaluate the postoperative cough ability was 0.955 (95% CI: 0.927–0.983, P < 0.001 ). The values of PEF (127.17 ± 34.72 L/min vs. 100.70 ± 29.98 L/min, P < 0.001 , 95% CI: 18.34–34.59) and FEV1 (0.72 (0.68–0.97) L vs. 0.64 (0.56–0.82) L, P < 0.001 ) measured while compressing the chest wall were higher than those without compression. Conclusions. PEF can be used as a quantitative indicator of cough ability. Chest wall compression could improve cough ability for patients who have ineffective cough.

Pectoralis Muscle Mass on Chest CT at Admission Predicts Prognosis in Patients with Pneumonia

Background and Objectives. The concept of sarcopenia has been attracting attention in recent years, but its association with in-hospital mortality of patients with pneumonia is still unclear. Therefore, we investigated the relationship between pectoralis muscle mass on chest computed tomography (CT) and in-hospital mortality in patients with pneumonia. Methods. A retrospective cohort study was performed in patients aged 18 years or older with pneumonia who underwent chest CT within 24 hours of admission between April 2014 and March 2019. We measured the thickness, area, and volume of the pectoralis major and minor muscles at the level of the aortic arch. Factors associated with mortality were examined using logistic regression analysis. Results. A total of 483 patients (mean age 77 ± 14 years, 300 men (62%)) were included, and fifty-one patients (11%) died during admission. In univariate analysis, decreased thickness, area, and volume of the pectoralis major and minor muscles were associated with higher in-hospital mortality. Multivariate analysis with adjustment for age, gender, serum albumin, and A-DROP revealed that thinner pectoralis major and minor muscles were independent factors of poor prognosis (odds ratio: 0.878, 95% confidence interval (CI): 0.783–0.985, P = 0.026 and odds ratio: 0.842, 95% CI: 0.733–0.968, P = 0.016 , respectively). Approximately 25% of the patients died when the pectoralis minor muscle thickness was 5 mm or less, and no patients died when it was 15 mm or more. Conclusion. The pectoralis muscle mass may be an independent prognostic factor in hospitalized patients with pneumonia.

LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway

Background. LIM and SH3 domain protein 1 (LASP1), highly expressed in a variety of tumors, is considered as a novel tumor metastasis biomarker. However, it is unknown which signaling pathway works and how the signal transduces into cell nucleus to drive tumor progression by LASP1. The aim of this study is to explore the essential role of LASP1 in TGF-β1-induced epithelial-mesenchymal transition (EMT) in lung cancer cells. Methods. The gene and protein levels of LASP-1 were successfully silenced or overexpressed by LASP-1 shRNA lentivirus or pcDNA in TGF-β1-treated lung cancer cell lines, respectively. Then, the cells were developed EMT by TGF-β1. The cell abilities of invasion, migration, and proliferation were measured using Transwell invasion assay, wound healing assay, and MTT assay, respectively. Western blotting was used to observe the protein levels of EMT-associated molecules, including N-cadherin, vimentin, and E-cadherin, and the key molecules in the TGF-β1/Smad/Snail signaling pathway, including pSmad2 and Smad2, pSmad3 and Smad3, and Smad7 in cell lysates, as well as Snail1, pSmad2, and pSmad3 in the nucleus. Results. TGF-β1 induced higher LASP1 expression. LASP1 silence and overexpression blunted or promoted cell invasion, migration, and proliferation upon TGF-β1 stimulation. LASP1 also regulated the expression of vimentin, N-cadherin, and E-cadherin in TGF-β1-treated cells. Activity of key Smad proteins (pSmad2 and pSmad3) and protein level of Smad7 were markedly regulated through LASP1. Furthermore, LASP1 affected the nuclear localizations of pSmad2, pSmad3, and Snail1. Conclusion. This study reveals that LASP1 regulates the TGF-β1/Smad/Snail signaling pathway and EMT markers and features, involving in key signal molecules and their nuclear levels. Therefore, LASP1 might be a drug target in lung cancer.

Comparison of Clinical Features between the High and Low Serum KL-6 Patients with Acute Exacerbation of Interstitial Lung Diseases

Background. Serum Krebs von den Lungen-6 (KL-6) measurement is widely used to assess disease activity or prognosis in patients with interstitial lung diseases (ILDs). However, the clinical differences between high and low serum KL-6 levels at the time of acute exacerbation (AE) of ILD are not well known. Methods. Clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers, high-resolution CT findings, and disease mortality were retrospectively compared between high and low KL-6 (cutoff value: 1000 U/mL) patients at the time of diagnosis of AE of ILDs. Results. Thirty-eight high serum KL-6 and 57 low serum KL-6 patients were included. There was no significant difference in 6-month mortality between them ( P = 0.685), whereas serum lactate dehydrogenase was a significant predictor of 6-month mortality in the high serum KL-6 patients (odds ratio (OR): 1.006; 95% confidence interval (CI): 1.003–1.009; P < 0.001), and CCIS (OR: 1.502; 95% CI: 1.242–1.838; P < 0.001) and sex (OR: 5.751; 95% CI: 1.121–105.163; P = 0.033) were significant predictors in low serum KL-6 patients. In addition, the incidences of congestive heart failure, symptomatic chronic pulmonary disease, cerebrovascular disease, and second metastatic solid tumours were significantly higher in nonsurvivors with low serum KL-6 than in other groups ( P < 0.05). Conclusions. The clinical features in patients with AEs of ILDs may differ depending on the serum KL-6 level, and clinicopathological examination according to this subtyping guided by the serum KL-6 level is essential.

Neutrophil-to-Lymphocyte Ratio Facilitates Identification of Obstructive Sleep Apnea in Patients with Type B Aortic Dissection

Purpose. To determine whether the neutrophil-to-lymphocyte ratio (NLR) aids in the detection of obstructive sleep apnea (OSA) in patients with type B aortic dissection (TBAD). Methods. 324 patients with TBAD or type B aortic intramural hematoma (TB-AIMH) underwent an overnight sleep study. We divided the eligible 256 studied subjects into three groups: group A (n = 109, TBAD patients with OSA), group B (n = 68, TB-AIMH patients with OSA), and group C (n = 79, TBAD patients without OSA). Baseline characteristics, biochemical and sleep parameters, and STOP-Bang questionnaire scores were collected. To assess the predictive efficacy of potential variables, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used. Results. The study found that about 58% of TBAD patients and 54% of TB-AIMH patients had OSA, a majority of whom had moderate to severe OSA (95.41% and 89.71%, respectively). In the comparison of sleep parameters between patients with TBAD and TB-AIMH, no other than apnea and hypopnea index (AHI) made a significant difference. The multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratio (NLR) (odds ratio (OR): 3.614, 95% confidence interval (CI): 2.273–5.748, and P < 0.05 ) and STOP-Bang scores (OR: 1.97, 95% CI: 1.34–2.90, and P < 0.05 ) were both independent predictors for OSA in patients with TBAD. ROC curves showed NLR had higher sensitivity (65% versus 59%) and specificity (86% versus 57%) for OSA than the STOP-Bang questionnaire. Furthermore, NLR was positively correlated with AHI through the Spearman test (r = 0.398 and P < 0.05 ). Conclusion. NLR was an independent predictor of OSA in TBAD patients with higher sensitivity and specificity than the STOP-Bang questionnaire, and it was positively associated with AHI. NLR may aid in the diagnosis and risk stratification of OSA in TBAD patients.

Relationship between Driving Pressure and Mortality in Ventilated Patients with Heart Failure: A Cohort Study

Background. Heart failure (HF) is a leading cause of mortality and morbidity worldwide, with an increasing incidence. Invasive ventilation is considered to be essential for patients with HF. Previous studies have shown that driving pressure is associated with mortality in acute respiratory distress syndrome (ARDS). However, the relationship between driving pressure and mortality has not yet been examined in ventilated patients with HF. We assessed the association of driving pressure and mortality in patients with HF. Methods. We conducted a retrospective cohort study of invasive ventilated adult patients with HF from the Medical Information Mart for Intensive Care-III database. We used multivariable logistic regression models, a generalized additive model, and a two-piecewise linear regression model to show the effect of the average driving pressure within 24 h of intensive care unit admission on in-hospital mortality. Results. Six hundred and thirty-two invasive ventilated patients with HF were enrolled. Driving pressure was independently associated with in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06–1.18; P < 0.001 ) after adjusted potential confounders. A nonlinear relationship was found between driving pressure and in-hospital mortality, which had a threshold around 14.27 cmH2O. The effect sizes and CIs below and above the threshold were 0.89 (0.75 to 1.05) and 1.17 (1.07 to 1.30), respectively. Conclusions. There was a nonlinear relationship between driving pressure and mortality in patients with HF who were ventilated for more than 48 h, and this relationship was associated with increased in-hospital mortality when the driving pressure was more than 14.27 cmH2O.