CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients.A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways.Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction.To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of 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-ĸBp65 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-ĸBp65 and HDAC2 expression and identify inflammatory cells in airways. Results: COPD patients had increased NF-ĸBp65 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.
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 B4 (LtB4) to the synthesis of anti-inflammatory lipoxins plays an important role. The aim of our study was to determine the content of lipoxin A4 (LXA4) and LtB4 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 LXA4 and LtB4 content and inflammatory cell spectrum. Results. COPD patients had a significantly lower sputum LXA4 concentration and LtB4/LXA4 ratio compared with healthy controls. A significant negative correlation was found between the LXA4 concentration and the relative neutrophil count and between the LtB4/LXA4 ratio and the relative macrophage count. Conclusions. COPD patients during the late phase of exacerbation had a suppressed production of LXA4 and an elevated LtB4/LXA4 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.
Pulmonary sarcomatoid carcinoma (psc) is a rare subtype of non-small-cell lung carcinoma with a poor prognosis and poor response to chemotherapy and radiotherapy. A previous study reported that psc expresses high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumours. We report 2 cases of patients with a lung sarcomatoid carcinoma. Both patients initially underwent curative lung resection, but developed early recurrent disease. Because PD-L1 was highly expressed in the tumour cells, we initiated therapy with nivolumab, which showed good efficacy, almost complete radiologic tumour remission, and a remarkable improvement in the condition of those patients. Immune checkpoint inhibitors targeting PD-1 might be a valuable therapy option for pscs.
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.
Comparison Of Stress Response Performing Endotracheal Intubation By Direct Laryngoscopy, Fibreoptic Intubation And Intubation By The Glidescope Laryngoscope Stress response is regulated by two primary neuroendocrine systems—the hypothalamuspituitary- adrenocortical (HPA) and sympathetic adrenomedullary (SAM) systems. Salivary alphaamylase (AA) levels can be used as an index of the SAM activity, and serum cortisol as an index of HPA activity. The aim of the study was to compare patient stress response to different intubation techniques. Sixty adult patients, ASA I-III, scheduled for elective abdominal surgery were included in this study, with median age of 54±18 years. Patients were prospectively randomly divided into three groups-intubation with a GlideScope (GS), Macintosh laringoscope (ML) and PENTAX fibreoptic bronchoscope (FB). After preoxygenation for 3 min anaesthesia was induced with fentanyl 2 mkg/kg, mivacuronium 0.2 mg/kg and propofol 2 mg/kg, injected intravenously over 20 seconds. Intubation was started 2 min after mivacuronium injection. Anaesthesia was maintained with sevoflurane 1-2 vol% and fentanyl 1 mkg/kg as needed. Intubation time (IT) was measured, blood and saliva samples were collected before and shortly after intubation. Haemodynamic response was recorded. Intubation time was statistically significantly longer in the FB group (120±65 s) versus the ML group (29±5 s) and GS group (26±9 s), P < 0.05. In the three patients groups the initial AA level was similar (54±20 KU/ml, P > 0.05). In GS patients the alpha amylase level after intubation significantly decreased (42±15 KU/ml, P < 0.05), but in ML and FB patients—significantly increased (68±24 KU/ml and 73±32 KU/ml, respectively, P < 0.05). After intubation, blood cortisol did not differ between the ML (377±181 U/ml) and GS (484±61 U/ml) patient groups, but was significantly higher (P < 0.05) in the FB group (530±79 U/ml). Both heart rate and blood pressure increased during intubation, the difference between groups was not significant. All intubations were successful, but in the FB patient group IT was significantly longer than in the ML and GS patient group. IT in the GS and FB patient groups did not statistically significantly differ. In our opinion, shorter and more confident intubations with a GlideScope produce less nociceptive stimulus and less stress to the patient. Intubations using GlideScope videolaryngoscope causes lesser stress response in comparison to intubation with a Macintosh laryngoscope or fibreoptic bronchoscope.
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 (SaO2), 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.
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