Institute Of Lung Diseases Research Articles

Association of Inflammatory Markers with Disease Severity and Outcome in Covid-19 Patients.

Objectives: The coronavirus pandemic was associated with a high mortality rate in the Republic of North Macedonia. Finding early markers of the disease's severity may predict outcomes and guide the treatment of the disease. The aim of our study was to evaluate the role of inflammatory markers in predicting the outcome of COVID-19 in hospitalized patients. Methods: The study included 104 PCR-confirmed COVID-19 patients who underwent hospital treatment at the Institute of Lung Diseases and Tuberculosis in Skopje, North Macedonia, between November 2020 and May 2021. Inflammatory markers were assessed in all patients and correlated with the disease severity and outcome in terms of survival or death. Results: IL-6 and LDH at admission were significantly elevated in patients with a severe or critical form of the disease and among non-survivors. In addition, IL-6 showed 87.9% of sensitivity and 61.8% of specificity for distinguishing non-survivors from survivors with a cut-off value of 21.7 pg/ml in the receiver operator curve (ROC). Procalcitonin was significantly increased in non-survivors. Parallel to the increase of disease severity, the values of CRP and LDH increased significantly during hospitalization. Conclusion: The results of the study indicate that a significant association exists between the highly increased levels of CRP, LDH, IL-6 and procalcitonin and the severity of the disease and mortality in COVID-19 patients. Their measurements and follow-up during the course of the disease could be used as predictors for prognosis and outcome but also as a subject for targeted therapy.

Secondary respiratory microflora in patients with COVID-19

The incidence of secondary lung infections in hospitalized patients with COVID-19 is not well understood. The results of bacteriological research for nonspecific flora of sputum or flushing from the respiratory tract were analyzed for 820 out of 3040 patients with COVID-19 hospitalized at the Research Institute of Lung Diseases in Baku. Secondary respiratory microflora was detected in 771 (94%) patients. in 347 (42.3%) cases, fungi of the genus Candida were found, and in 211 (25.7%) patients this was observed simultaneously with the bacterial microflora. Among bacterial infections, the most common pathogens were Staphylococcus aureus (n109), Klebsiella Pneumoniae (n41), Escherichia Coli (n38), Enterobacter (n33), Streptococcus pneumoniae (n32).

Tuberculosis in the Prisons in the Republic of Macedonia, 2008-2017.

BACKGROUND:Tuberculosis (TB) is a major health problem in penitentiary institutions (prisons), and its prevalence was reported to be multiple times higher compared to that of the general population. Conditions such as overcrowding, malnutrition and limited access to medical care which often exist in prisons increase the risk of reactivation, transmission and poor prognosis of tuberculosis disease among inmates.AIM:The main objective of this study was to present the epidemiological situation of TB in the prisons from 2008 till 2017 in the Republic of Macedonia (RM).PATIENTS AND METHODS:There are 13 different penitentiary institutions in the RM with a total capacity to house 2600 prisons inmates. Management of TB in the prisons is part of the National TB program in RM, and the Institute for Lung Diseases and Tuberculosis in Skopje is in charge of it. All prisoners with TB in the RM are registered in the Central Register for TB within this Institute. We use the data from the Central Register, and with the method of description, we present the epidemiological data and clinical characteristics of the prisoners about TB in prisons in RM for 10 years’ period.RESULTS:From 2008 till 2017 there were 58 TB cases registered in prisons in total. The absolute number of TB cases in the prisons is not big, but the incidence rate is higher than 100/100,000 population, or several times bigger than in the general population (except in 2012 and 2016). In 2017 there were 10 TB cases registered in the prisons with an incidence rate of 323.9/100,000 population which is many times higher than in the general population in RM. The majority of inmates with TB were young men with risk factors for TB infection or TB disease before incarceration such as drug abuse, alcohol, smoking, but there was no association with HIV infection. The most of the patients diagnosed in prison were new cases (54), secondary TB due to reactivation from the latent TB infection or secondary TB due to the environment. From 2008-2017 there were 82.75% successfully treated TB cases in the prisons, and there were no cases of multi-drug resistant tuberculosis (MDR-TB).CONCLUSION:The results from our study showed that the TB control in the prisons in RM is good with satisfactory treatment outcome. On the other hand, the high incidence rate showed that the prisons in RM provide conditions for TB transmission and with other additional risk factors present place for high TB prevalence. The study findings can be used for planning more effective TB control interventions for the prison population in RM.

Evaluation of the Directly Observed Treatment's Acceptance by Tuberculosis Patients in the Republic of Macedonia.

BACKGROUND:Directly observed therapy (DOT) is a specific strategy endorsed by the World Health Organization in 1994 to improve adherence by requiring health workers, community volunteers or family members to observe and record tuberculosis (TB) patients for taking each dose. The implementation of DOT strategy in the National Tuberculosis Programme (NTP) in Macedonia was introduced in 2006 and was realised by 6 nurses engaged through the Project of Global Fund against HIV/AID and TB.AIM:This study aimed to evaluate how these visits conducted by the DOT nurses engaged through the GF were accepted by TB patients and to evaluate the impact on the treatment outcomes.PATIENTS AND METHODS:In this prospective study 105 TB patients who started treatment in 2016 and who were supposed to be visited by DOT nurses at their homes were included. All of these patients filled out a questionnaire compiled of 6 questions related to their opinion about the efficacy and usefulness of the visits managed by the nurses when they would come for check-ups at the Institute for Lung Diseases and Tuberculosis. The assessment of the efficacy of the work of DOT nurses was performed by analysis of the answers received by TB patients. The data were analysed with the method of description and was statistically prepared in the program SPSS for Windows, 17.0.RESULTS:The results from the analyses showed that the number of visited patients were not satisfied, because 29.52%% were never visited by a DOT nurse at their homes. A lot of patients (61.91%) were not willing to take medicines under the observed control by nurses. Those TB patients who were visited by DOT nurses thought that this type of visit is useful for them: they were satisfied by the attitude of the nurses during the visits, and they received enough explanations regarding TB.CONCLUSION:We can conclude that the DOT visits to TB patients are useful, contribute patients to complete the therapeutic regime without interruption, take care for every individual patient effectively, and protect the rest of society by preventing the development and spread of TB, including drug-resistant strains.

Primary pulmonary sarcomas: The results of surgical treatment.

e22540 Background: Primary pulmonary sarcomas (PPS) are the very rare cancer type (0.01% - 0.4% of all malignant tumours of the lung). PPS can derive from stromal elements of the bronchial wall, blood vessels and connective tissue steep of lung parenchyma. The aim of the study was evaluation of PPS patients’ outcome. Methods: The analysis included 23 patients (11 males, 12 females) age 28-70 years (median 49.6 years) with PPS treated surgically in the Department of Surgery, Institute of Lung Diseases and Tuberculosis in Warsaw from 1994 to 2009. Results: There were 3 leiomyosarcomas (13%), 3 hemangiopericitomas (13%), 3 MFH (13%), 3 malignant peripheral nerve sheath tumours (13%), 3 PNET (13%), 2 fibrosarcomas (8.8%), 2 liposarcomas (8.8%), 2 sarcomas synoviale (8.8%), 1 angiosarcomas (4.3%), 1 chondrosarcomas (4.3%) (according to the 3rd edition of the WHO Classification of Tumours of Soft Tissue and Bones). There were performed 5 pneumonectomies (21.7%), 5 lobectomys (21.7%), 5 wedge resection (21.7%), 6 exploratory thoracotomys (26.1%), 2 stent inserts (8.8%). In the case of 15 patients (65%) were performed operation R0. Adjuvant therapy was used in 7 patients (30%), 3 patients (13%) received chemotherapy, 2 patients (13%) radiotherapy and 1 patient (4%) chemo-radiotherapy. Palliative chemotherapy and or radiotherapy were given to 6 patients (26%). Median overall survival (OS) was 22 months (5- and 10-years OS was 26% and 17%, respectively) and depended on sex (p = 0.006), tumor size (p = 0.02), operation R0 (p = 0.07). Conclusions: Surgery, especially operation R0, is the most effective treatment method of PPS. Subsequent studies on larger groups are necessary.

Evaluation of C-Reactive Protein in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND:Chronic Obstructive Pulmonary Disease (COPD) is associated with evidence of systemic oxidative stress, activation of circulating inflammatory cells and increased plasma level of proinflamatory cytokines which include C-reactive protein (CRP). CRP is one biomarker of extrapulmonary or systemic consequences of COPD that can be detected.AIM:The aim of this research is to determine whether the level of CRP statistically significantly correlates with the level of bronchial obstruction and the accompanying co-morbidities in patients with COPD.MATERIAL AND METHODS:This study included 80 patients with exacerbation of COPD, hospitalised at the Institute for Lung Diseases and Tuberculosis in Skopje. We measured the level of CRP in the blood in all of these patients in fasting conditions. The classification of COPD patients by the severity of airflow limitation was made according to the actual version of the Global initiative for chronic Obstructive Lung Disease (GOLD). The Student’s Independent Samples t-test was used for the statistic analysis of the data.RESULTS:In 52 (65%) of the patients with exacerbation of COPD we detected an increase of the mean value of CRP. The statistical analysis using the Student’s t-test showed statistically significant differences in the mean value of CRP in patients with different level of bronchial obstruction. Hypertension, heart failure, diabetes mellitus, hyperlipidemia, coronary disease, and CVI were confirmed as co-morbidities in 45 (73.1%) of the patients, hypertension being the most frequent one (40%). The statistical analysis using the Student’s t-test showed statistically significant difference of the mean value of CRP (p< 0.01) depending on the number of co-morbidities.CONCLUSION:In 52 (65%) of the patients with exacerbation of COPD, were detected an increase of the mean value of CRP. The mean values of CRP statistically significantly correlate with the level of bronchial obstruction and the number of co-morbidities in patients with COPD.

Vasculitis - Wegener’s granulomatosis in pulmonary practice

Introduction and Review of Literature. Diagnosis of Wegener?s granulomatosis in the early stage is difficult because nonspecific symptoms of the disease mimic other disorders. Our Experience. A retrospective review of case records of 37 patients with Wegener?s granulomatosis referred to the Institute for Lung Diseases in Belgrade to be diagnosed and treated over a 15-year period was carried out. There were 37 patients (20 males and 17 females), ranging in age from 18 to 73 years (mean age 46.2 years). The mean period from the onset of first symptoms to diagnosis of Wegener?s granulomatosis was 4.59?6.15 months. The American College of Rheumatology criteria were fulfilled in all patients. Twenty-five of 37 patients had evidence of systemic, generalized form of Wegener?s granulomatosis and a limited involvement of the upper and lower respiratory system occurred in 12 cases. The frequency of different system involvement expressed in percents was as follows: the upper respiratory tract 64.8%, the lower respiratory tract 100%, the kidneys 67.5%, the musculoskeletal system 40.5%, the skin 27.2%, the eyes 8.1%, the nervous system in two patients. Anti-neutrophil cytoplasmic antibodies test was positive in 32 (6.5%) patients, and negative in 5 (13.5%). All patients were antinuclear antibodies negative. Histological evidence of granulomatous vasculitis was obtained in 34 (91.9%), whereas in three patients the diagnosis was based on clinical manifestations and positive c-anti-neutrophil cytoplasmic antibodies test.

Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes.

Corresponding author: Dr Dragan SUBOTIC, MD, PhD, FCCP Institute for lung Diseases, Belgrade, Visegradska 26/20 Serbia E-mail: vilusi@yubc.net; Tel: +38 11 1361 5559 Since the latest revision of the TNM system reclassified T3N0 tumours into the IIB stage, N2 lesions became the major determinant of the IIIA stage. Concerning the minority of patients with T3N1 tumours in this stage, their prognosis depends on characteristic of T3 tumours: localised chest wall invasion is associated with more favourable prognosis compared to those T3 tumours that either directly invade the mediastinum, or have the proximal propagation < 2 cm from the central carina. The significance of preoperative confirmation of metastases in mediastinal lymph nodes was recognized long ago, based on survival differences depending on whether N2 lesions were confirmed preoperatively or not (Tab 1).

Economic aspects of hospital treated pneumococcal pneumonia and the results of Pneumo 23 vaccine use in Serbia

In Serbia, there is a significant number of persons suffering of pneumococcal pneumonia. Persons aged 65 years or older, immunocompromised patients, patients with co-morbidities, such as chronic obstructive lung disease and congestive heart failure, are at the highest risk for developing pneumococcal pneumonia. Most of the patients are treated empirically, although it is often overlooked that Streptococcus pneumoniae can be resistant to the used antibiotics. The treatment costs of such inpatients and outpatients are very high. In Serbia, immunization of persons at risk to develop the diseases caused by Streptococcus pneumoniae is carried out using pneumococcus polysaccharide vaccine according to clinical indications. The exact number of immunized persons and the total number of registered patients are still unknown, but it is certain of being unjustifiably low. The goal of the study was to investigate, during a one-year period, the number and basic characteristics of persons hospitably treated for pneumonia, the type of cause of the infection, applied antibiotic medications, duration and costs of hospital treatment at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade. We retrospectively analyzed the medical records of patients with pneumonia treated at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade during 2006. During the observed one-year period, 290 patients underwent hospital treatment, of whom the cause of the infection was confirmed in 116 (40%). The average duration of hospitalization was 12 days, with treatment cost of 32,031.74 RSD (402.42 EUR) per patient. The treatment cost per patient including general and intensive care was 18,290.01 RSD (229.78 EUR). The distribution cost of Pneumo 23 vaccine in Serbia, without purchase tax, was 746.90 RSD (9.38 EUR). Pneumococcal pneumonia is a significant medical and economic problem for the healthcare system of Serbia. The use of antipneumococcal vaccination can be useful in decreasing the overall treatment costs related to pneumococcal infection.

P1-050: Lung cancer in patients under 50 years old

Lung cancer in young patients is increasing in frequency.In 2005 in Institute for Lung Diseases and TB were registered 1471 patients(pts)with lung cancer and 186 pts(12.65%)were under 50 years old.There were significantly more male than female(70.9%:29.3%);mean age 45.8.The majority of them were smokers (76.1%).The diagnosis was established by fiberoptic bronchoscopy in 176(94.6%),percutaneus lung biopsy in 5pts((2,6%)and in 5pts(2,6%) by lymphnode biopsy. In this group of patients the non-small-lung cancer(NSCLC) is found in 75,8%,compared to 24,2% for small cell lung cancer(SCLC).Unfortunately 40,4% from them were with the metastatic disease.Surgical procedure was applied in 67pts (36,02%)chemotherapy was performed in 91(48,9%)pts,radiotherapy in 14(7,5%)pts.In 14pts(7,5%)the only treatment was symptomatic. In the group of patients with lung cancer under 50 years old there were significantly more male,smokers,with advanced stage lung cancer.Squamous cell carcinoma was the most frequent histological type.

P1-281: Clinical features of bronchial carcinoid tumor- 10 years experience (1996-2006)

The aim of the study was to analyse clinical features and 1-yr survival rate of bronchial carcinoid patients diagnosed at the Institute of Lung Diseases and TB in Belgrade 1996-2006. The group consists of 58 pts (30 females and 28 males), the average age of 48 ys (17 – 75). 57 of them underwent operation: lobectomy in 34pts (58.6.%), pneumonectomy in 11pts(19%), atypical resection in 9pts (15.5%), bilobectomy in 3pts (5.2%). Hystologic finding of typical carcinoid tumor was in 39pts (67.2%), while atypical in 19pts (32.8%). Central tumor type was noted in 30pts(51.7%) and peripheral in 28pts (48.3%). CT scan showed that majority of peripheral tumors were 3-3.5cmX4-4.5cm in diameter, with the exception of 1 case with the tumor size 8x7cm and 2 of size 6x5cm. The most frequent symptoms were cough −30pts (51.7%), chest pain-25pts (43.1%), dyspnoea −20pts (34.5%), haemoptysis-19pts (32.7%), fever-18pts(31.0%), weight loss-13pts (22.4%) and fatigue-12pts (20.7%). Majority of pts had disease symptoms lasting either 1 year and longer-25pts (43.1%) or less than 3 months −16pts (27.6%). Five pts (8.6%) had associated neuroendocrine disorder or tumor either in the previous history or at the same time of bronchial carcinoid tumor diagnosis. Only one pt with Kushing Sy persisting after operation of gonadotropic adenoma of pituitary gland, has shown to have hormonal activity of the peripheral bronchial carcinoid tumor since this Sy resolved after lung operation. The 1-year follow-up analysis shows 1-year survival rate of 86.2% (50pts): 8pts died within the first year after diagnosis or operation. One pt died 6th day after operation due to fatal pulmonary embolism, and other 7 pts died due to metastatic disease relapse

P-152 The increase in number of intervent pulmonology procedures indiagnostics and therapy of lung cancer at the Institute of Lung Diseases in Sremska Kamenica

P-152 The increase in number of intervent pulmonology procedures indiagnostics and therapy of lung cancer at the Institute of Lung Diseases in Sremska Kamenica

Low-intensity laser therapy of pleuritis

Low-intensity lasers have been utilized in medicine in two ways: for local stimulation and for stimulation of acupuncture points. Literature data reveal that this method has been indiscriminately applied in psychiatry, rheumatology, gynecology, dermatology, otorhinolaryngology, in diverse acute and chronic pains, inflammations, vascular disorders, angina pectoris, bronchial asthma. Most commonly reported clinical effects are analgesia, spasmolytic and anti-inflammatory effects, as well as faster wound and bone healing. This prospective study analyses effects of laser biostimulation on patients with pleurisy. The analysis included 25 patients treated at the Institute of Lung Diseases in Sremska Kamenica during 2000, 2001 and 2002. Apart from conservative treatment, these patients were treated with laser biostimulation of acupuncture points and local region for ten days. During treatment, changes of present clinical signs, general symptoms, radiological findings, as well as changes of some relevant biochemical parameters were recorded. Results were compared with the control group which included the same number of patients, who differed from the examined group only by not being exposed to laser biostimulation. The examined group of patients with pleuritis presented with quicker resorption of pleural effusion, less pleural adhesions, more significant decrease of clinical symptoms, especially pain, as well as more significant increase of cortisol and immunoglobulin A and decrease of circulating immune complexes (CIC), leukocytes and sedimentation rate than the control group. Mechanisms of laser biostimulation in treatment of pleurisy were described in detail and the obtained results were correlated to those reported by other authors. 1. Patients with pleurisy undergoing laser stimulation presented with faster resorption of effusion and remission of the subjective symptoms, as well as significant decrease of biochemical acute inflammation parameters in the peripheral blood and therefore with faster recovery. 2. In patients with pleurisy laser treatment increases regenerative mechanisms of the pleural surface, thus decreasing the quantity of formed adhesions and resulting in better mobility of the diaphragm.

Diagnostic approach to solitary peripheral pulmonary lesions

Peripheral localization and lack of symptoms are reasons why it is difficult to establish the diagnosis of peripheral pulmonary lesions commonly of malignant nature. Therefore thoracotomy often represents a diagnostic and therapeutic method at the same time. There is a need to define an adequate and optimal diagnostic approach to these lesions in order to establish their etiology, if possible, at low costs. This retrospective study included 50 patients with peripheral solitary pulmonary lesions (PSPL) who underwent thoracotomy at the Institute of Lung Diseases in Sremska Kamenica. In all patients both bronchoscopy and transthoracic puncture were performed prior to surgery. Having evaluated the diagnostic procedures, their proper sequence has then been applied in the prospective group of another 50 patients admitted to the Institute for similar lesions. In the retrospective group the etiology of PSPL was established by bronchoscopy in 4% and using transthoracic puncture in 58% of patients, with sensitivity, specificity and accuracy of 78.78%, 100% and 85.1%, respectively. In the prospective group, transthoracic puncture (TTP) provided the final diagnosis in 70% of patients, with 86.2% sensitivity, 100% specificity and 90% accuracy. Transthoracic puncture is a method of choice in preoperative diagnostics of solitary peripheral pulmonary lesions, quite like thoracotomy in cases where applied diagnostic procedures were inefficient.

Wartime migration and the incidence of tuberculosis in the Zagreb region, Croatia.

The objective of the present study was to investigate the rate of decline in the incidence of tuberculosis (TB) in residents (1985-1994) and in refugees and displaced persons (1992-1994) during prewar and war periods (1985-1994) in the region of Zagreb, Croatia, and to examine a possible change in the trend of decline in the resident population. Data on the incidence of TB were obtained from the Epidemiology Department, Institute for Lung Diseases, Zagreb, Croatia. The sample comprised two groups of subjects: residents (800,000-1,000,000 inhabitants) and all refugees and displaced persons temporarily residing in the Zagreb region (78,000-95,000 persons). Data were analysed by stepwise logistic regression. The most significant predictors of the TB incidence rate were the square of the year and residence status. The rate of TB incidence in nonresidents was significantly higher than in residents. The decline in incidence in residents was significantly slower than in the nonresident group. The results did not indicate a potential change in the natural decline of the incidence of tuberculosis in the resident population during the study periods. The difference between the regression trends of the incidence of tuberculosis in residents and nonresidents was the result of various concomitant factors, including artefacts of the war.

260-PA12 TB among refugees from former SFRJ treated in 1993 at the Institute for Lung Diseases and TB, Belgrade

260-PA12 TB among refugees from former SFRJ treated in 1993 at the Institute for Lung Diseases and TB, Belgrade

261-PA12 Analysis of pulmonary TB in young adults treated in 1994 at the institute for lung diseases and TB

261-PA12 Analysis of pulmonary TB in young adults treated in 1994 at the institute for lung diseases and TB

Why do our patients die of active tuberculosis in the era of effective therapy?

Setting: All patients with tuberculosis as a primary or underlying cause of death who were autopsied at the Institute for Lung Diseases and Tuberculosis, Sremska Kamenica, in the former Yugoslavia, between 1981 and 1990 were investigated. Objective: To study why people die of active tuberculosis in the era of effective chemotherapy and to identify factors contributing to death. Design: In a retrospective investigation, this index group was compared with a control group consisting of patients who suffered from tuberculosis over the same period but who improved and were discharged from hospital. Results: A significant difference in age ( P < 0.05) was found between those patients who died with an antemortem-established diagnosis and those who died with unrecognised tuberculosis (median 49 and 60 years respectively). When it came to the index group, 28 patients (56%) had one or more risk factors and the frequency of alcohol abuse was significantly higher ( P < 0.001). Antituberculosis treatment had been introduced in 27 cases (54%). The median duration of hospitalization before therapy was 2 days and the median duration of antituberculosis therapy was 7 days. Of the 23 untreated tuberculosis patients, 74% died within the first 4 days. Conclusion: Delay in the detection of tuberculosis was the main factor contributing to death in our patients.

Mutagenic effect of cytostatic therapy on chromosomes of patients with lung carcinoma : V. Kačar-Kukrić, G. Radosavljević-Asić, Institute for Lung diseases, Belgrade, Serbia

Mutagenic effect of cytostatic therapy on chromosomes of patients with lung carcinoma : V. Kačar-Kukrić, G. Radosavljević-Asić, Institute for Lung diseases, Belgrade, Serbia

Human leukocyte interferon alpha (HLI-α) for treatment of pleural effusion caused by non small cell lung cancer. A pilot study : Tercelj-Zorman M, Mermolja M, Jereb M, Oman M, Soos E, Petric-Grabnar G et al. Institute for Lung Diseases, Golnik YU-64204 Golnik, Slovenia. Acta Oncol 1991;30:963-5

Human leukocyte interferon alpha (HLI-α) for treatment of pleural effusion caused by non small cell lung cancer. A pilot study : Tercelj-Zorman M, Mermolja M, Jereb M, Oman M, Soos E, Petric-Grabnar G et al. Institute for Lung Diseases, Golnik YU-64204 Golnik, Slovenia. Acta Oncol 1991;30:963-5