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Despite the fact, that lung cancer is more common among older smoking men, however it may also develop among young women without a smoking anamnesis. We report here a history of a non-smoking woman, 40 years old, with a diagnosis of lung adenocarcinoma at IV stage. Despite the fact, the woman received three lines of palliative chemotherapy, the disease progressed. After the sample of the tumor was tested by genetic approach, ROS1 mutation was detected, and the patient was treated with a ROS1 inhibitor, Crizotinib. Sharp improvement was observed already after the first week of treatment. After one-month adenocarcinoma shrink, and specific supraclavicular lymph nodes disappeared. Unfortunately, due to problems with financing the treatment was stopped, after what the disease began to progress rapidly, and the patient died after a month due to brain metastasis. This case is noteworthy also because the patient was first diagnosed a thrombophilia with thrombi present in deep calf veins, left heart ventricle and lungs Adenocarcinoma was discovered occasionally when during video-assisted thoracoscopic surgery biopsy specimen was taken from suspicious mass in the lower lobe of the right lung. This story reminds us that lung carcinoma may start with a paraneoplastic syndrome, like thrombophilia as in this case and finding of adenocarcinoma of the lung in young, non-smoking persons is indicative for possible ROS1 gene mutation. In such cases early treatment with ROS1 protein-tyrosine kinase inhibitors should be started as soon as possible.

Background The study aims at solving the problem with the limitations of the homecare CPAP equipment such as sleep apnea devices in the treatment of COVID-19 pneumonia. By adding an advanced, rapid-to-produce oxygenation module to existing CPAP devices we allow distributing healthcare at all levels, reducing the load on intensive care units, promoting treatment in the early stages at homecare. A significant part of the COVID-19 pneumonia patients requires not only an oxygen supply but also additional air pressure. Existing home care devices are able to create precise positive airway pressure, but cannot precisely measure supplied oxygen concentration. Either uses uncertified and potentially unsafe mechanisms. Results The developed system allows using certified and widely available CPAP (constant positive airway pressure) devices to perform the critical function of delivering pressure and oxygen to airways. CPAP device is connected to the designed add-on module that can provide predefined oxygen concentration in a precise and stable manner. Clinical test results include data from 12 COVID-19 positive patients. The device has been compared against certified NIV (non-invasive) equipment under 6–20 hPa pressure and 30–70% FiO2. Tests have proved that the developed system can achieve the same SaO2 (p = 0.93) and PaO2 (p = 0.80) levels as NIV with clinically insignificant differences. Test results show that the designed system can substitute NIV equipment for a significant part of COVID-19 patients while leaving existing NIV devices for unstable and critical patients. The system has been designed to be mass-produced while having medically certified critical components. Conclusion The clinical testing of the new device for oxygen supplementation of patients treated using simple CPAP devices looks promising and could be used for the treatment of COVID-19 pneumonia.

Lung cancer is a very common malignancy with a low five-year survival rate. Artificial olfactory sensor (electronic nose) is a tool that recently has been studied as a probable optimal screening tool for early detection of lung cancer, but still no statistical method has been put forward as the preferable one. The aim of the study was to explore the use of logistic regression analysis (LRA) to analyse patients' exhaled breath samples with electronic nose in order to differentiate lung cancer patients (regardless of the stage of the cancer) from patients with other lung diseases and healthy individuals. Patients with histologically or cytologically verified, untreated lung cancer, patients with other lung diseases such as benign lung tumors, chronic obstructive pulmonary disease, asthma, pneumonia, etc, and healthy volunteers were enrolled in the study, in total 252 cancer patients and 223 patients without cancer. Breath sample collection and analysis were performed with Cyranose 320 sensor device and data further analysed using LRA. The LRA correctly differentiated lung cancer patients from no-cancer patients. The overall sensitivity in detecting patients having cancer was 95.8% for smokers and 96.2% for non-smokers and the overall specificity was 90.6% for non-smokers and 92.3% for smokers. Exhaled breath analysis by electronic nose using LRA is able to discriminate lung cancer patients from patients with other lung diseases and from healthy individuals.

Background: During the past decade, various studies have documented the presence of sinonasal inflammation in lower airways diseases. The influence of airways inflammation on nasal airways patency was demonstrated in asthmatic patients; however, such association was not confirmed in patients with COPD. Purpose: The aim of the study was to compare the relationship between nasal resistance and lower airways patency in COPD patients and healthy controls. Material and Methods: 4-Phase-Rhinomanometry and spirometry were performed on COPD patients (n=26) and in the corresponding age control group (n=15). To compare the effective nasal resistance in inspiration, expiration and total breathing (Reffin, Reffex, Refft) in COPD and the control group, we used one way analysis of variance (ANOVA). To evaluate the relationship between nasal and lung functional parameters for both groups, we used the analysis of covariance (ANCOVA). Results: We did not find a significant difference between nasal resistances in COPD patients and those of the control group. In spite of the different values of FEV1/FVC and FEV1 in compared groups (p Conclusions: Patients with COPD have no increased nasal resistance compared to healthy subjects, but there may exist an inverse association between nasal resistance and bronchial conductivity (comparing FEV1 and FEV1/FVC values), which potentially might be confirmed by further research.

Background and objectives: It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. Materials and methods: A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell count of FOXP3-positive, CD4+ and CD8+ T lymphocytes by immunocytochemistry staining, and the cell count of macrophages and neutrophils by May-Grünwald Giemsa staining. Results: Induced sputum of smokers contained a higher absolute amount of macrophages and neutrophils when compared to nonsmokers. FOXP3-positive cells in the sputum of young smokers showed a statistically significant increase when compared to nonsmokers. Induced sputum of COPD patients contained an increased absolute amount of neutrophils and FOXP3-positive Treg cells when compared to nonsmokers. Regression analysis showed that the amount of FOXP-3 positive cells, neutrophils and macrophages in the induced sputum was increasing with the number of pack years. Conclusions: This study demonstrates that young smokers have early inflammatory changes in their airways that not only initiate nonspecific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T regulatory lymphocytes. The lymphocyte response is probably adaptive.

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.

Electronic Nose for Identification of Lung DiseasesIn the paper, the authors analyze the preliminary results of testing a classical gas sensing instrument - the electronic nose (a metal oxide transistor sensor of chemical substances) in a hospital where patients with different lung diseases are treated. To reveal the correlation between the amplitudes of the sensor's responses and the patients' diagnoses, different statistical analysis methods have been used. It is shown that the lung cancer can easily be discriminated from other lung diseases if short breath sampling and analysis time (less than 1 min) is used in the test. Volatiles obtained from a breath sample of a patient with lung cancer give the major contribution to the responses of different e-nose sensors, so in these cases highly precise identification could be achieved.

Regional Lung Blood Perfusion Measured With Laser Doppler Method During Body Position Change, Valsalva Manoeuvre and Cardiopulmonary Bypass Methodological approaches to investigate local regulatory mechanisms of lung blood supply in humans are restricted. We tried a new approach using laser Doppler technique. During bronchoscopy, an angled laser Doppler flow probe was introduced through a biopsy channel and wedged into small bronchus. Laser light penetrated the wall of small bronchus and was reflected from blood cells running through neighbouring capillaries. Regional blood perfusion changes were recorded during body position change from vertical to supine and back to vertical, while performing Valsalva maneuver and during cardiac bypass surgery. Body position change and Valsalva maneuver markedly influenced the blood perfusion signal. During cardiac bypass when lungs were supplied with blood only through bronchial arteries regional blood perfusion dropped substantially on average from 93 ± 42 to 7.3 ± 4.3 perfusion units. We conclude that blood perfusion measured with this method reflect mainly the pulmonary vascular bed and may be used for investigation of its local regulatory mechanisms.

Background: COPD is frequently associated with comorbidities, the most serious and prevalent include lung cancer. Sirtuin 1 (SIRT1) is known to deacetylate histones and non-histone proteins including transcription factors thereby regulating metabolism, stress resistance, cellular survival, cellular senescence/aging. The aim of our study was to evaluate SIRT-1 expression in patients with lung squamous cell carcinoma and adenocarcinoma and these co-morbid with COPD. Methods: 93 patients with lung nonsmall cell lung carcinoma co-morbid with moderate severity COPD (n=29) or without COPD were enrolled in the study. Lung function testing was performed within one week before lung surgery. SIRT-1 expression in cancer tissue was compared to control tissue (obtained from 15 autopsy cases) and analyzed by immunohistochemistry. Results: Obtained results showed that in patients co-morbid with COPD and lung cancer, the SIRT-1 expression was higher in squamous cell carcinoma compared to patients without COPD (88 ± 26 vs. 42 ± 18 cell/ mm2; p=0.01). At the same time the SIRT-1 expression did not differ in adenocarcinoma and COPD co-morbidity specimens compared to those without COPD. Conclusion: Patients with lung squamous cell carcinoma co-morbid with COPD have increased SIRT-1 expression if compared to carcinoma patients without COPD.

Lung cancer is one of the most common malignancies and has a low 5-year survival rate. There are no cheap, simple and widely available screening methods for the early diagnostics of lung cancer. The aim of this study was to determine whether analysis of exhaled breath with an artificial olfactory sensor using support vector analysis can differentiate patients with lung cancer from healthy individuals and patients with other lung diseases, regardless of the stage of lung cancer and the most common comorbidities. Patients with histologically or cytologically verified lung cancer, healthy volunteers and patients with other lung diseases (e.g. chronic obstructive pulmonary disease (COPD), asthma, pneumonia, pulmonary embolism, benign lung tumors) were enrolled in the study. Breath sample collection and analysis with a Cyranose 320 sensor device was performed and data were further analyzed using a support vector machine (SVM). The SVM correctly differentiated between cancer patients and healthy volunteers in 98.8% of cases. The cancer versus non-cancer group patients (healthy volunteers and patients with other lung diseases) were classified correctly by SVM in 87.3% of cases. In the mixed diagnosis groups (only cancer, only COPD, cancer + COPD and control) all 79 out of 79 patients were predicted correctly in the cancer + COPD group, with the rate of correct prognosis in other patient groups being lower. Exhaled breath analysis by electronic nose using a SVM is able to discriminate patients with lung cancer from healthy subjects and mixed groups of patients with different lung diseases. It can also provide a certain level of discrimination between lung cancer patients, lung cancer patients with concomitant COPD, COPD alone and a healthy control group.

Early diagnosis of lung cancer is important due to high mortality in late stages of the disease. An ideal approach for population screening could be the breath analysis, due to its non-invasiveness, simplicity and cheapness. Using sensitive methods of analysis like gas chromatography/mass spectrometry in exhaled air of cancer patients were discovered some volatile organic compounds - possible candidates for cancer markers. However, these compounds were not specific for cancer cells. At the same time, integrative approaches used to analyze the exhaled breath have demonstrated high sensitivity and specificity of this method for lung cancer diagnosis. Such integrative approaches include detection of smell prints by electronic nose or integrated analysis of wide range of volatile organic compounds detected by gas chromatography/mass spectrometry or related methods. Modern statistical pattern recognition systems like logistic regression analysis, support vector machine or analysis by artificial neuronal network may improve diagnostic accuracy.

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.

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&lt, 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.

This study was undertaken to ascertain whether the use of a valved holding chamber (VHC) during bronchial provocation testing might increase lung deposition and repeatability of the test relative to the tidal breathing method. The 2-min tidal breathing results were compared to five inhalations from a VHC device in patients using the Pari-provoII nebulizer (MMD = 2.1mkm). Lung and mouth deposition, losses though the exhaled air and losses before aerosol delivery to the patient's mouth were measured in patients using a radiolabeled 99Tc-DTPA solution and gamma camera. The study revealed that lung deposition was 67% with the VHC method, and losses with exhaled air were 29% of the inhaled amount. The tidal breathing method resulted in lung deposition of 20.9 +/- 3.4%, and losses with exhaled air were 77.5 +/-3.5%. Mouth deposition did not differ significantly between methods. Variability in lung deposition was 15.3% for the VHC and 32.0% for the tidal breathing method. In addition to greater lung deposition and reproducibility, the VHC method allows easier calculation of the inhaled dose.

35 ROLE OF CXCL4 CHEMOKINE IN ANGIOGENIC ACTIVITY OF NON-SMALL CELL LUNG CANCER (NSCLC) A. Spaks1, D. Isajeva2, I. Spaka3, A. Pirtnieks1, I. Jaunalksne4, J. Grusina-Ujumaza1, J. Basko1, I. Taivans2, D. Krievins5 1Thoracic Surgery, Pauls Stradins Clinical University Hospital, Riga, Latvia, 2Pathology, University of Latvia, Riga, Latvia, 3Biology, Riga Stradins University, Riga, Latvia, 4Clinical Immunology, Pauls Stradins Clinical University Hospital, Riga, Latvia, 5Surgery, University of Latvia, Riga, Latvia