The role of transforming growth factor-ß2 in cigarette smoke-induced lung inflammation and injury.

AIMS: Transforming growth factor-ß2 (TGF-ß2) plays an important role in pleiotropic functions and has been reported to be involved in the pathogenesis of chronic obstructive lung disease. The role of TGF-ß2 in regulating cigarette smoke (CS)-induced lung inflammation and injury has not been investigated, and its underlying mechanism remains unclear. MAIN METHODS: Primary bronchial epithelial cells (PBECs) were treated with cigarette smoke extract (CSE), and the signaling pathway of TGF-ß2 regulating lung inflammation was investigated. Mice were exposed to CS and treated with TGF-ß2 i.p. or bovine whey protein extract containing TGF-ß2 p.o., and the role of TGF-ß2 in alleviating lung inflammation/injury was studied. KEY FINDINGS: In vitro, we demonstrated that TGF-ß2 attenuated CSE-induced IL-8 production from PBECs through the TGF-ß receptor I (TGF-ßRI), Smad3, and mitogen-activated protein kinase signaling pathways. Selective TGF-ßRI inhibitor (LY364947) and antagonist of Smad3 (SIS3) abolished the effect of TGF-ß2 on alleviating CSE-induced IL-8 production. In vivo, CS exposure for 4 weeks in mice increased the levels of total protein, inflammatory cell counts, and monocyte chemoattractant protein-1 in bronchoalveolar fluid and induced lung inflammation/injury, as revealed by immunohistochemistry. Administration of TGF-ß2 through intraperitoneal injection or oral feeding with bovine whey protein extract containing TGF-ß2 significantly reduced CS-induced lung inflammation and injury. SIGNIFICANCE: We concluded that TGF-ß2 reduced CSE-induced IL-8 production through the Smad3 signaling pathway in PBECs and alleviated lung inflammation/injury in CS-exposed mice. The anti-inflammatory effect of TGF-ß2 on CS-induced lung inflammation in humans deserves further clinical study.

Predictors of delayed extubation following lung resection: Focusing on preoperative pulmonary function and incentive spirometry.

BACKGROUND: Delayed extubation is one of postoperative pulmonary complications (PPCs). Preoperative pulmonary function test (PFT) is an important assessment for patients undergoing lung resection. Volume-oriented incentive spirometry (IS) is one of physiotherapies to prevent PPCs. Preoperative PFT and IS volume (IS-v) can reflect the physiologic conditions of respiratory system in patients planning to undergo lung resection. However, the relationship between preoperative PFT/IS-v and delayed extubation in patients undergoing lung resection remains unclear. The study investigated the risk factors and impact of delayed extubation after lung resection. We aimed to achieve early recognition of patients being at a higher risk for developing postoperative delayed extubation after lung resection. METHODS: This retrospective observational 4-year cohort study was conducted in a medical center, Taiwan. A total of 353 enrolled patients receiving thoracic surgery for lung resection were further categorized into the delayed extubation (n = 142, 40%) and non-delayed extubation (n = 211, 60%) groups. RESULTS: In multivariate logistic regression analyses, age >65 years (adjusted odds ratio [AOR]: 2.60; 95% confidence interval [CI], 1.52-4.45), American Society of Anesthesiologists score >2 (AOR: 1.72; 95% CI, 1.05-2.82), anesthesia time >6hrs (AOR: 1.80; 95% CI, 1.13-2.88), pneumonectomy (AOR: 5.58; 95% CI, 1.62-19.19), and IS-v/inspiratory capacity (IC) ratio (AOR: 2.07; 95% CI, 1.16-3.68) were associated with delayed extubation after lung resection (all p < 0.05). Patients with delayed extubation were significantly associated with a higher proportion of other pulmonary complications, reintubation, mortality, and prolonged intensive care unit and hospital stays. CONCLUSION: Older age, poor general health status, longer anesthesia time, pneumonectomy, and IS-v/IC ratio could be the independent factors predictive for delayed extubation after lung resection, which was in turn associated with worse outcomes. Preoperative PFT and IS-v were valuable for early recognition of patients being at a higher risk for developing postoperative delayed extubation after lung resection.

Independent factors associate with hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease requiring intensive care unit admission: Focusing on the eosinophil-to-neutrophil ratio.

BACKGROUND: Factors associated with hospital mortality are unclear in patients with acute exacerbation of COPD (AECOPD) requiring intensive care unit (ICU) admission. We aimed to characterize these patients and identify factors associated with hospital mortality. PATIENTS AND METHODS: We used a retrospective observational case-control design and recruited patients between January 2015 and March 2017. Of 146 patients enrolled, 24 (16.4%) died during their hospital stay, while 122 survived. RESULTS: Multivariate logistic regression analyses revealed factors associated with hospital mortality: age (adjusted odds ratio [AOR] 1.12, 95% CI: 1.03-1.23), C-reactive protein (CRP) level >7.5 mg/dL at the emergency room (AOR 4.52, 95% CI: 1.27-16.04), peak eosinophil-to-neutrophil ratio (ENR)×102 on days 8-14 of treatment (AOR 0.22, 95% CI: 0.08-0.63), and in-hospital complications (AOR 4.23, 95% CI: 1.12-15.98) (all P<0.05). After receiver operating characteristic curve analyses, cutoff level for peak ENR×102 was 0.224. To examine the synergistic effects of CRP level and peak ENR, we divided patients into four groups: (G0, reference group) Peak ENR×102 >0.224 on days 8-14 and initial CRP <7.5 mg/dL; (G1) Peak ENR×102 >0.224 on days 8-14 and initial CRP >7.5 mg/dL; (G2) Peak ENR×102 <0.224 on days 8-14 and initial CRP <7.5 mg/dL; and (G3) Peak ENR×102 <0.224 on days 8-14 and initial CRP >7.5 mg/dL. For G2 and G3 patients, the AOR of mortality was significantly different from that of the reference group (G2: AOR 10.00, P = 0.020; G3: AOR 61.79, P<0.001). The relationship between 28-day mortality and the four groups was statistically significant (log-rank test, P<0.001). CONCLUSION: Older age, initial CRP >7.5 mg/dL, peak ENR on days 8-14, and in-hospital complications were associated with hospital mortality in patients with AECOPD requiring ICU admission. Patients with both biomarkers, initial CRP >7.5 mg/dL, and peak ENR×102 <0.224 on days 8-14 of treatment, had an increased risk of hospital mortality.

Prolonged use of noninvasive positive pressure ventilation after extubation among patients in the intensive care unit following cardiac surgery: The predictors and its impact on patient outcome.

This retrospective, observational cohort study aimed to determine the independent risk factors and impact of prolonged non-invasive positive pressure ventilation (NIPPV) after extubation among patients in the intensive care unit following cardiac surgery. Patients who received prophylactic NIPPV after extubation were categorized into prolonged (NIPPV duration >3 days, n = 83) and non-prolonged groups (NIPPV duration ≤3 days, n = 105). The perioperative characteristics and hospital outcomes were recorded. The multivariate analyses identified the preoperative residual volume/total lung capacity (RV/TLC) ratio (adjusted odds ratio [AOR]: 1.10; 95% CI:1.01-1.19, p = 0.022) and postoperative acute kidney injury (AKI) with Kidney Disease Improving Global Outcomes (KDIGO) stage 2-3, 48 h after surgery (AOR: 3.87; 95% CI:1.21-12.37, p = 0.023) as independent predictors of prolonged NIPPV. Patients with both RV/TLC ratio > 46.5% and KDIGO stage 2-3 showed a highly increased risk of prolonged NIPPV (HR 27.17, p = 0.010), which was in turn associated with higher risk of postoperative complications and prolonged ICU and hospital stays. Preoperative RV/TLC ratio and postoperative AKI could identify patients at higher risk for prolonged NIPPV associated with poor outcomes. These findings may allow early recognition of patients who are at a higher risk for prolonged NIPPV, and help refine the perioperative management and critical care.

The Relationship between Airway Inflammation and Exacerbation in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory response and airflow limitation. Acute exacerbation involves increased inflammatory burden leading to worsening respiratory symptoms, including dyspnea and sputum production. Some COPD patients have frequent exacerbations (two or more exacerbations per year). A substantial proportion of COPD patients may remain stable without exacerbation. Bacterial and viral infections are the most common causative factors that breach airway stability and lead to exacerbation. The increasing prevalence of exacerbation is associated with deteriorating lung function, hospitalization, and risk of death. In this review, we summarize the mechanisms of airway inflammation in COPD and discuss how bacterial or viral infection, temperature, air pollution, eosinophilic inflammation, and concomitant chronic diseases increase airway inflammation and the risk of exacerbation.