Lipoxygenase-derived arachidonic acid metabolites in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by a persistence of inflammation in large and small airways. We hypothesized that this could be caused by the inability of an inflammatory process to resolve. In the resolution of inflammation, a switching of arachidonic acid metabolism from the production of proinflammatory leukotriene B(4) (LtB(4)) to the synthesis of anti-inflammatory lipoxins plays an important role. The aim of our study was to determine the content of lipoxin A(4) (LXA(4)) and LtB(4) in induced sputum of patients with exacerbated COPD and to compare it to healthy controls, as well as to analyze the relationship between proinflammatory and anti-inflammatory mediators and an inflammatory cell spectrum in induced sputum. MATERIAL AND METHODS: Induced sputum from 17 COPD patients and 7 healthy controls were analyzed for LXA(4) and LtB(4) content and inflammatory cell spectrum. RESULTS: COPD patients had a significantly lower sputum LXA(4) concentration and LtB(4)/LXA(4) ratio compared with healthy controls. A significant negative correlation was found between the LXA(4) concentration and the relative neutrophil count and between the LtB(4)/LXA(4) ratio and the relative macrophage count. CONCLUSIONS: COPD patients during the late phase of exacerbation had a suppressed production of LXA(4) and an elevated LtB(4)/LXA(4) ratio in induced sputum demonstrating a proinflammatory imbalance. The correction of a balance between proinflammatory and anti-inflammatory eicosanoids by the administration of stable analogues of lipoxins could improve the treatment of chronic obstructive pulmonary disease in the future.

Different patterns of lung sirtuin expression in smokers with and without chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. MATERIAL AND METHODS: A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study. Immunohistochemical and Western blot methods were used to analyze sirtuin expression in the airways. RESULTS: The obtained results showed the nonuniform sirtuin expression throughout the bronchial tree. Smokers both with and without chronic obstructive pulmonary disease had decreased sirtuin expression in large airways. However, in small airways, sirtuin expression was decreased only in patients with chronic obstructive pulmonary disease. In addition, a correlation between airflow limitation, smoked pack-years and the number of sirtuin-positive cells in airways was found. CONCLUSIONS: Smoking is characterized by suppressed sirtuin expression in large airways, whereas chronic obstructive pulmonary disease is characterized by more severe suppression of sirtuin expression both in large and small airways.

Patterns of inflammatory responses in large and small airways in smokers with and without chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. OBJECTIVES: The aim of our research was to characterise the expression and localisation of NF-κBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. METHODS: Nineteen nonsmokers, 20 smokers with normal lung ventilation function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate NF-κBp65 and HDAC2 expression and identify inflammatory cells in airways. RESULTS: COPD patients had increased NF-κBp65 expression compared to nonsmokers and smokers without COPD, in both large and small airways, which corresponded to increased numbers of macrophages, CD8+ T lymphocytes and neutrophils. COPD patients had more macrophages in large compared to small airways and more CD8+ T lymphocytes and neutrophils in small compared to large airways. HDAC2 expression was significantly downregulated in smokers with COPD in small compared to large airways. CONCLUSIONS: Our findings indicate a nonuniform distribution of inflammatory cells throughout the bronchial tree. However, in both smokers with and without COPD, similar patterns of inflammatory processes occur in both large and small airways. The difference between smokers with and without COPD is only quantitative.

Effects of the prolonged thoracic epidural analgesia on ventilation function and complication rate after the lung cancer surgery.

UNLABELLED: Thoracic epidural analgesia has been considered to have a good anesthetic efficacy and to decrease the postoperative complication rate, while its effect upon the ventilation function is still the topic of many clinical studies. The aim of this study was to evaluate the course of early postoperative period using thoracic epidural analgesia. MATERIAL AND METHODS: A total of 453 patients undergoing the operation due to the non-small cell carcinoma were selected and examined. Their postoperative complications and mortality rate were evaluated. In 79 patients, arterial oxygen saturation (SaO(2)), forced vital capacity, forced expiratory volume in the first second, and the efficacy of analgesia were analyzed within the first 7 days after the operation. These patients were divided into subgroups according to the type of the operation--lobectomy or pneumonectomy--and the type of analgesia--thoracic epidural analgesia or opiates administered intramuscularly (control group). RESULTS: A better statistically significant efficacy of analgesia was observed in thoracic epidural analgesia group than in the control group (visual analog pain scale score 2.5 versus 5.3, P<0.01). There was also a statistically significant lower incidence of postoperative complications (20.5% versus 38.8%, respectively). Thoracic epidural analgesia is a factor decreasing the relative risk of complications (RR=0.53, 95% CI 0.28-0.99, P=0.0233). In the lobectomy group, 24 hours after the surgery, forced vital capacity was 61+/-12% in the group receiving thoracic epidural analgesia and 45+/-13% in the control group (P=0.0152); forced expiratory volume in the first second was 56+/-17% and 41+/-11%, respectively (P=0.0308). In the pneumonectomy group, 24 hours after the surgery, forced vital capacity was 47+/-16% in the group receiving thoracic epidural analgesia, 35+/-8% in the control group (P=0.080). Forced expiratory volume in the first second was 47+/-15% and 36+/-7%, respectively (P=0.0449). CONCLUSION: We conclude that analgesia with intramuscularly administered opioids provides unsatisfactory analgesia, especially in the first days after the operation. Thoracic epidural analgesia is a safe method, which provides a better quality of life for the patient, decreases the postoperative complication rate, and improves the ventilation function after the lung operations.