Associations between Comorbidities and Acute Exacerbation of Interstitial Lung Disease after Primary Lung Cancer Surgery.

Acute exacerbation (AE) of interstitial lung disease (ILD) is a severe complication of lung resection in lung cancer patients with ILD (LC-ILD). This study aimed to assess the predictive value of comorbidities other than ILD for postoperative AE in patients with LC-ILD. We retrospectively evaluated 68 patients with LC-ILD who had undergone lung resection. We classified them into two groups: those who had developed postoperative AE within 30 days after resection and those who had not. We analyzed patient characteristics, high-resolution computed tomography findings, clinical data, pulmonary function, and intraoperative data. The incidence of postoperative AEs was 11.8%. In univariate analysis, performance status (PS), honeycombing, forced vital capacity (FVC), and high hemoglobin A1c (HbA1c) levels without comorbidities were significantly associated with postoperative AE. Patients were divided into two groups according to cutoff levels of those four variables as determined by receiver operating characteristic curves, revealing that the rates of patients without postoperative AE differed significantly between groups. The present results suggested that preoperative comorbidities other than ILD were not risk factors for postoperative AE in patients with LC-ILD. However, a high preoperative HbA1c level, poor PS, low FVC, and honeycombing may be associated with postoperative AE of LC-ILD.

Cell stress induces upregulation of osteopontin via the ERK pathway in type II alveolar epithelial cells.

Osteopontin (OPN) is a multifunctional protein that plays important roles in cell growth, differentiation, migration and tissue fibrosis. In human idiopathic pulmonary fibrosis and murine bleomycin-induced lung fibrosis, OPN is upregulated in type II alveolar epithelial cells (AEC II). However, the mechanism of OPN induction in AEC II is not fully understood. In this study, we demonstrate the molecular mechanism of OPN induction in AEC II and elucidate the functions of OPN in AEC II and lung fibroblasts. Human lung adenocarcinoma cells (A549) and mouse alveolar epithelial cells (MLE12), used as type II alveolar epithelial cell lines for in vitro assays, and human pulmonary alveolar epithelial cells (HPAEpiC) were treated with either bleomycin, doxorubicin or tunicamycin. The mechanism of OPN induction in these cells and its function as a pro-fibrotic cytokine on A549 and lung fibroblasts were analyzed. The DNA damaging reagents bleomycin and doxorubicin were found to induce OPN expression in A549, MLE12 and HPAEpiC. OPN expression was induced via activation of the extracellular signal-regulated protein kinase (ERK)-dependent signaling pathway in A549 and MLE12. The endoplasmic reticulum (ER) stress-inducing reagent tunicamycin induced OPN mRNA expression in A549, MLE12 and HPAEpiC, and OPN mRNA expression was induced via activation of the ERK-dependent signaling pathway in A549 and MLE12. Another ER stress-inducing reagent thapsigargin induced the expression of OPN mRNA as well as the subsequent production of OPN in A549 and MLE12. Furthermore, OPN promoted the proliferation of A549 and the migration of normal human lung fibroblasts. Inhibition of OPN by small interference RNA or neutralizing antibody suppressed both of these responses. The results of this study suggest that cell stress induces the upregulation of OPN in AEC II by signaling through the ERK pathway, and that upregulated OPN may play a role in fibrogenesis of the lung.

Effects of obesity and smoking on mental stress-induced blood pressure and augmentation index responses in normotensive young males: the J-SHIPP study.

Exaggerated blood pressure (BP) response to mental stress has been known to be a prognostic factor for cardiovascular disease. It has been argued that such unusual vascular reactivity to mental stress may arise from insulin resistance. To examine the vascular responses to mental stress, we evaluated the stress-related changes in BP and the augmentation index (AI), an index of arterial stiffness, in normotensive young males. Changes in late systolic BP (SBP2) representing central aortic pressure were also examined. Subjects were 86 males (21+/-2 years), 13 of whom were classified as obese (>or=25 kg/m(2)). AI was obtained from the radial arterial waveform as a ratio of the height of the late systolic peak to that of the first peak. Blood pressure and AI measurements were taken before, during and after a simple mental arithmetic test (MAT) lasting 3 min. Systolic BP (baseline 125+/-13, during MAT 133+/-13, post-MAT 124+/-11 mmHg; p<0.001) and heart rate (74+/-12, 81+/-13, 74+/-11 beats/min; p<0.001) were significantly increased during the MAT, whereas AI showed a slight reduction. In a separate analysis, the opposite response was observed between obese subjects showing increased AI (54+/-11, 56+/-13, 52+/-11%) and non-obese subjects who showed reduced AI (54+/-12, 51+/-12, 53+/-12%; p=0.032). The responses in SBP and SBP2 (obese 103+/-14, 117+/-12, 104+/-12; non-obese 98+/-13, 104+/-12, 97+/-12 mmHg; p=0.007) were also larger in the obese subjects. Stress-related transient increases in arterial stiffness may be involved in the exaggerated responses in aortic pressure in obese subjects.