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Aim To determine the diagnostic accuracy of pulmonary artery to aorta ratio in screening for pulmonary hyperten - sion in advanced chronic obstructive pulmonary disease (COPD) patients. Methods A prospective, diagnostic study was conducted in University Hospital Center Zagreb between January 2015 and March 2018. The study enrolled 100 patients who con - secutively underwent chest computed tomography (CT), echocardiographic exam, and right heart catheterization. Two independent observers measured pulmonary artery and ascending aorta diameters. The correlation between the ratio and mean pulmonary artery pressure, measured invasively, was assessed. Patients with echocardiographic signs of moderate systolic or diastolic left ventricular dys - function were excluded (n =44). Results Sixty-six patients (55.5% men), with a median age of 61, were identified. Median forced expiratory vol - ume during the first second (FEV1) was 34 ±12, FEV1/ forced vital capacity

Contains fulltext : 244079.pdf (Publisher’s version ) (Closed access) BACKGROUND: The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting. METHODS: We conducted a retrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records. RESULTS: Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was a significant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003). CONCLUSION: The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.

Background: Besides the burden of acute covid care, a fraction of patients report symptoms after the period of acute covid illness which affect quality of life and prolong recovery. Aim: To assess the profile of patients reporting to our post-covid clinic, their quality of life and frequency of persisting symptoms. Methods: Covid- 19 survivors, referred (at least a month after the acute illness) from December 2020 to January 2021 to our Centre’s post-covid clinic. Patients entered this study by filling out a questionnaire which also included current symptoms and standardised Post-Covid Functional Scale (PCFS) score. Results: 112 patients were included in the study. Males predominated (62.5% ; mean age 56) over females (37.5% ; mean age 48). In the acute phase, 72.3% were treated as outpatients, 27.6% at the ward and 7.1% in the ICU. Most common comorbidities were hypertension (21.4%), various chronic lung diseases (22.3%) and type 2 diabetes (5.4%). Corticosteroid therapy was given in 45.5% of patients, either in the acute phase, post-covid period, or both. The most frequent post- covid complaints were exhaustion (63.4%), shortness of breath (48.2%), muscle weakness (31.3%), dry cough (34.8%) and chest pain (25.0%). Of 110 patients with known PCFS value, 27 (24.5%) reported 0, while 34 (30.9%), 31 (28.2%), 17 (15.5%), and one (0.9%) patient reported scores of 1, 2, 3, and 4, respectively. Conclusion: Even though the majority of our patients were treated as outpatients in the acute phase and presumably had milder disease forms, three-quarters of them still experience impairment of life quality (PCFS >1) with pronounced respiratory symptoms months after the illness.

Background Patients with head and neck squamous cell carcinoma (HNSCC) can develop lung squamous cell carcinoma (LuSCC), which could be the second primary tumor or HNSCC metastasis. Morphologically it is difficult to distinguish metastatic HNSCC from a second primary tumor which presents a significant diagnostic challenge. Differentiation of those two malignancies is important because the recommended treatments for metastatic HNSCC and primary LuSCC differ significantly. We investigated if the quantification of the promotor methylation status in HNSCC and LuSCC differs. Methods Primary HNSCC (N = 36) and LuSCC (N = 17) were included in this study. Methylation status in the ASC/TMS1/PYCARD (apoptosis-associated speck-like protein containing a caspase recruitment domain; 8 CpG sites) and MyD88 (Myeloid differentiation primary response protein 88; 10 CpG sites) promoters was analyzed. Bisulfite converted DNA, isolated from tumor tissue was quantified using pyrosequencing. Results of pyrosequencing analysis were expressed as a percentage for each tested CpG site. Receiver-operating characteristic (ROC) curve analysis was used for the evaluation of the diagnostic properties of selected biomarkers. Results CpG sites located in the promoters of ASC/TMS1/PYCARD_CpG8 (− 65 upstream) and MyD88_CpG4 (− 278 upstream) are significantly hypermethylated in the HNSCC when compared with LuSCC (p ≤ 0.0001). By performing ROC curve analysis we showed that corresponding areas under the curve (AUC) were 85–95%, indicating that selected CpG sites are useful for a distinction between primary LuSCC and primary HNSCC. Conclusions Results of the present study indicate that there is a significant difference in the methylation status of tested genes between primary HNSCC and LuSCC. However, to prove this approach as a useful tool for distinguishing second primary LuSCC from HNSCC metastasis, it would be necessary to include a larger number of samples, and most importantly, metastatic samples.

Background and Aims: Limited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy. Methods and Results: The study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI- I, CRI-II), and monocyte to HDL ratio (MHR) were calculated. HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C- reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742 - 0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases. Conclusion: Lipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.

Malignant pleural mesothelioma (MPM) is an aggressive tumor that develops from the mesothelial cells lining the pleural cavity. The most relevant risk factor is asbestos exposure. Despite therapy the median survival is poor ranging from four to 18 months. The aims and objectives of this study were to assess the clinical characteristics and survival of patients with MPM treated at UHC Zagreb. This study included 101 patients diagnosed and treated for MPM at UHC Zagreb from September 1999 to September 2012. We analyzed the overall survival (OS), progression free survival (PFS) and OS depending on histological subtype, clinical stage, age, treatment method and pleurodesis performed using the Kaplan-Meier method. Eighty-nine patients were male and 12 female with the median age of 62 years. Using the TNM staging system, 69.3% were stage IV, 26.73% were stage III and 3.96% were stage II. 73.26% of MPM were epitheloid, 4.95% sarcomatous and 20.79% were NOS (non otherwise specified) histological subtype. 14.85% of patients had surgery, 55.44% of patients received chemotherapy and 9.9% radiotherapy. Median OS was 11 months and PFS was ten months. OS by histological subtype was 11 months for epitheloid, 12.5 months for NOS and 5.5 months for sarcomatous MPM. OS by TNM stage was seven months for stage II, 17.5 months for stage III and 11 months for stage IV disease. Median OS was longer for patients younger than 65 (12 vs. 8.5 months, p=0.28), patients treated with pleurodesis (13 vs. 7.5 months, p=0.06) and patients who received chemotherapy (12.5 vs. 7.5 months, p=0.10). The overall survival and prognosis of patients with malignant pleural mesothelioma in Croatia is poor in accordance with the literature. The studied treatment methods offer only a modest survival benefit to our patients.

Background: Smoking is one of the major preventable risk factor for respiratory diseases and a global public health problem. Public awareness and access to smoking cessation schools should be one of the principal goals in disease prevention and public health initiatives. Cognitive-behavioral treatment has proven to be efficient in smoking cessation. Aim: The aim of this paper is to present the results of a two year ongoing smoking cessation school. Methods: Smoking cessation program started in 2017 as a public health interdisciplinary initiative. It consists of 12 visits, organized in a group, over one month, free of charge and accessible to all adult smokers motivated to quit. Education, psychoeducation, cognitive-behavioural techniques (self-monitoring, cognitive restructuring, reframing, breathing and progressive muscle relaxation, relapse prevention, etc.) and group counseling are included. It also includes measurement of exhaled CO at the beggining and end of the programme, and spirometry to screen for early stages of respiratory obstruction. Attendants evaluate the program in a written form on their last visit. Results: In two years, nine cycles of smoking cessation schools were completed. The program completed 91 person and 39 (42,9%) sucsessfuly quit smoking. Follow up at six months after the end of program showed a success rate reduction of 3% in average. Futher follow up is needed. Conclusion: Interdisciplinary, cognitive-behavioraly based, publicly accessible smoking cessation school represent an efficient way of smoking cessation. Due to its remarkable results so far, it is considered to be adopted as a nation–wide prevention program, during national lung cancer screening program.

Background. There is a lack of real-world data on the safety and efficacy of nivolumab in patients with previously treated advanced non-small-cell lung cancer (NSCLC) especially in South East Europe, a region with particularly high incidence and an unfavorable mortality-to-incidence ratio for lung cancer. Objectives. To evaluate the real-world safety and efficacy of nivolumab in patients with previously treated advanced squamous and nonsquamous NSCLC in South East Europe. Methods. This is a multicenter, retrospective cohort study on patients with stage IIIB or IV disease with at least one previous systemic treatment who received nivolumab through an expanded-access program between 2015 and 2017 in Croatia, Malta, and Hungary. The primary endpoint was the proportion of patients whose therapy was discontinued because of toxicity. Secondary endpoints were the incidence of adverse events (AEs), objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results. We analyzed data on 239 patients with a median (IQR) age of 62 (57–68), and 33% of them were women. Treatment was discontinued because of toxicity in 11.6% (95% CI 7.8% to 16.5%) of patients. The PFS was 6.4 (95% CI 5.2 to 8.6) months, and the median OS was 14.1 (10.6 to 18.0) months. Conclusions. The safety and efficacy of nivolumab in previously treated patients with advanced NSCLC in the real-world South East Europe clinical settings were consistent with the results of randomized clinical trials and comparable to the results from other countries.

Introduction. Lung cancer is a complex disease and requires a multidisciplinary approach to achieve the best results in treatment, to increase the survival rate while preserving the quality of life of the sufferer. The nutritional status of the patient is an important factor affecting outcome and recovery from disease or injury. We question whether there is a link between nutritional status and malignant pain in lung cancer patients. Aim. A prospective trial was conducted to determine the distribution of respondents by frequency of pain according to a validated Visual Analog Scale (VAS), distribution of respondents who reported reduced food intake and distribution of factors that have led to the reduced food intake. Methods. A prospective trial was conducted at the Department for respiratory diseases Jordanovac, University Hospital Center Zagreb, Croatia, on a sample of patients with advanced non-small cell lung cancer to determine the frequency, characteristics and treatment of chronic malignant pain (N=76). These are the results from November 2013 to June 2014. For pain assessment, we used a validated VAS. For the identification of patients at risk of malnutrition we used Nutritional risk screening tool (NRS 2002). For a rough estimate of total body adiposity, we measured dermal thicknesses using a standard calliper. Monitoring of patients was documented in the form of nursing documentation. A component of nursing documentation was designed to monitor the nutritional status of cancer patients and has been implemented at the Department for respiratory diseases Jordanovac as required documentation. The component included collecting the following data: the stage and type of cancer and treatment, demographic characteristics, age, gender, vital signs, body weight and height, body mass index (BMI), subjective symptoms such as pain, fatigue and nausea, reduction ad rezones of food consumption. Results. During the study 417 measurements were made: 1) 32,1% of patients reported reduced food intake, and 67,9% of respondents indicated that have not reduced their regular diet; 2) as a reason for the reduced food intake 37,7% respondents stated loss of appetite, 31,2% fatigue and 24,6% pain; 3) 59,5% subjects mainly reported absence of pain, while none of the respondents reported the existence of the highest degree of pain. Conclusion. By regular monitoring of the intensity of the pain we achieved good control in malignant pain management, which is an important data in the assessment of nutritional status. The fact is that poorly controlled pain is present in 24% of patients and has been the reason for the reduced food intake., Uvod. Rak pluća jest kompleksna bolest i zahtijeva multidisciplinarni pristup kako bi se postigli što bolji rezultati u liječenju i povećala stopa preživljavanja uz istodobno očuvanje kvalitete života oboljelog. Nutritivni status bolesnika pokazao se važnim čimbenikom koji utječe na ishod i oporavak od bolesti ili ozljede. Postavljamo pitanje postoji li poveznica između nutritivnog statusa i maligne boli u bolesnika s rakom pluća. Cilj. Provedeno je prospektivno istraživanje kako bi se utvrdila raspodjela ispitanika prema učestalosti bolova prema validiranoj vizualnoj analognoj skali (VAS), raspodjela ispitanika koji su prijavili smanjeni unos hrane i raspodjela čimbenika koji su doveli do smanjenog unosa hrane. Metode. Istraživanje je provedeno na Zavodu za tumore pluća i sredoprsja Klinike za plućne bolesti Jordanovac Kliničkoga bolničkog centra Zagreb, na uzorku bolesnika s uznapredovalim rakom pluća nemalih stanica (N = 76). u periodu od studenoga 2013. do lipnja 2014. Za procjenu boli primijenjen je validirani VAS. Za identifikaciju pacijenata s rizikom od pothranjenosti primijenjen je alat za provjeru prehrambenih rizika (NRS 2002). Za grubu procjenu količine masnog tkiva koristili smo se kaliperom. Praćenje bolesnika dokumentirano je u obliku sestrinske dokumentacije. Sastavnica sestrinske dokumentacije osmišljena je za praćenje prehrambenog stanja oboljelih od karcinoma i implementirana je na Odjelu za respiratorne bolesti Jordanovac kao potrebna dokumentacija. Sastavnica je obuhvatila prikupljanje sljedećih podataka: stadij bolesti i tip karcinoma, tip i stadij liječenja, demografske karakteristike ispitanika, debljina kožnog nabora, standardizirani upitnik o pothranjenosti Nutritional NRS 20021, vitalni znakovi, tjelesna težina, tjelesna visina, indeks tjelesne mase, subjektivna procjena pacijenta; bol, umor i mučnina, razlozi smanjene prehrane. Rezultati. Tijekom provedenog istraživanja izvedeno je 417 mjerenja: 1) 32,1 % ispitanika prijavilo je smanjeni unos hrane, a 67,9 % istaknulo kako nisu smanjivali redovitu prehranu; 2) najučestaliji uzroci smanjenog unosa hrane u ispitanika su bili nedostatak apetita (37,7 %), prisutnost umora/slabosti (31,2 %) i prisutnosti boli (24,6 %); 3) 59,5 % ispitanika prijavilo je nepostojanje boli, dok nijedan ispitanik nije prijavio postojanje najvećeg stupnja boli. Zaključak. Redovitim praćenjem intenziteta boli ostvarena je dobra kontrola maligne boli kod ispitivane populacije, što je važan podatak kod procjene nutritivnog statusa. Činjenica je da je loše kontrolirana bol u 24 % ispitanika razlog smanjenog unosa hrane.

Novel hematological parameters such as immature granulocytes (IG), activated neutrophils (NEUT-GI, NEUT-RI) and lymphocytes (RE-LYMP, AS-LYMP) are shown to be valuable for detecting and monitoring infections and inflammations. Our aim was to assess the connection between these parameters and the severity and outcome of COPD exacerbations (AECOPD). 90 patients with AECOPD who visited our pulmonary emergency room from May to August 2018 were included in this retrospective study. Patients’ sex, age, therapy, smoking status, laboratory findings, comorbidities, spirometry results, blood gas analysis, hospitalization or discharge from the ER, duration of hospitalization and survival were evaluated. Hematological parameters were determined by flow cytometry method on a SYSMEX XN-1000 hematological analyzer. Pearson’s correlation test, Chi square and t-test were used for data analysis. 52 patients were male (58%) and 38 female (42%). There were 57 active smokers (64%), 5 former smokers (5.5%) and 28 non- smokers (31%). All patients had comorbidities, mostly hypertension (75, 5%) and diabetes (20%). 19 were admitted to the hospital (21%), and 4 died (4.4%). Correlation between CRP and IG (r=0.363) and NEUT-GI (r=0.230) was low positive, and between CRP and AS-LYMP (r=-0.068), RE-LYMP (r=-0.039) and NEUT-RI (r=-0.251) was low negative. There was no significant difference in these parameters between patients who were discharged from the ER and those who were hospitalized, as well as between patients who died and those who survived. In conclusion, further research on a larger number of patients is required, given these parameters could be promising new biomarkers of inflammation.

Background: Carbohydrate sulfotransferases (CHST) were shown to be involved in carcinogenesis. The aim of the study was to assess the diagnostic value of serum CHST7 concentration in differentiation between lung cancer and non-malignant pulmonary inflammations. Methods: Clinical case-control study involving 125 participants was conducted: the control group containing cases of pneumonia and chronic obstructive pulmonary disease was compared to the lung cancer group composed of primary and metastatic cancers. Serum concentrations of CHST7 and routinely used markers including carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) were determined for each participant using immunochemical methods. Statistical association, receiver operating characteristic (ROC) analysis and cross-validation were used for the evaluation of CHST7 either as a standalone biomarker or as a part of a biomarker panel. Results: In comparison to the control group, serum CHST7 was elevated in lung cancer (p Conclusions: Serum CHST7 is a promising biomarker for the differentiation between lung cancer and non-malignant pulmonary inflammations.

We present unusual treatment outcome in a 59-year- old male diagnosed with metastatic lung adenocarcinoma with a very good response to ruxolitinib as monotherapy. In June 2017, this patient was diagnosed with myeloproliferative neoplasm - Janus-associated kinases 2 positive - and in December 2017 ruxolitinib therapy was started. At the same time, patient was diagnosed with lung adenocarcinoma in the left lower lobe with positive anaplastic lymphoma kinase mutation and with right lower lobe metastasis. Because of partial regression of tumor size noted on the computed tomography (CT) scans during tumor investigation, we did not apply any therapy for lung adenocarcinoma. A follow-up CT scan done in March 2018 showed further size reduction of tumor lesion in lower left lobe (91%), while follow-up CT scan done in June 2018 showed further size reduction of tumor lesion in lower right lobe (82%).

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the “one-fits-all” paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.

Th e aim of this study was to investigate the role of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) in detecting latent tuberculosis in immunocompromised patients before introducing tumor necrosis factor (TNF-α) antagonists. Th e study included 300 subjects of similar age. Th e study group comprised of 150 QuantiFERON (QFT) positive subjects with rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis and psoriatic arthritis, while control group comprised of 150 QFT negative respondents with the same diseases. Exhaustive medical history was documented for all patients. Screening tests were performed including QFT-GIT, tuberculin skin test (TST), chest radiography and detection of Mycobacterium tuberculosis in sputum culture 2 times. A positive QFT-GIT test result, regardless of TST result, was considered as an indication for latent tuberculosis infection (LTBI) treatment. Results of this study showed good correlation between the conclusive results of QFT-GIT and TST. All study group patients had normal clinical fi ndings, normal radiologic fi ndings and negative results of sputum microbiological analysis during the course of prophylaxis and after its completion and during the course of biological therapy. Conversion of positive QFT-GIT test to negative was observed in 4% of study group patients, while QFT negative respondents remained negative. Th ere was a statistically signifi cant positive correlation between QFTGIT, TST results and patient age, smoking habit and contact with tuberculosis. Study results showed that along with good clinical evaluation and detailed medical history, it is important to conduct testing in order to avoid disease progression or unnecessary isoniazid prophylaxis

Objective: Weight loss and an underweight status are serious problems in chronic obstructive pulmonary disease (COPD), independent of the degree of airflow obstruction. Body mass index (BMI), does not reflect changes in body composition that may occur with aging or with the level of disease. BIA is a simple, inexpensive, quick and non-invasive technique for measuring body composition, due to ability to identify malnutrition. Aim: To analyze values of BIA- Phase angle (PA), Fat Free Mass (FFM), Visceral Mass (VM) and obstruction level (FEV1) and their importance in the prediction of exercise capacity measured by six-minute-walking test (6MWT). Method: We analyzed results from 68 stable COPD male (44) and female (24) patients, aged M= 55.9 who attended standard PRP five days weekly, during four weeks. Nutritional status during rehabilitation was evaluated by BIA. Data analysis was performed using linear regression with following predictor variables: patient’s age, BIA values (PA, FFM, VM), FEV1 and 6MWT as a criterion variable. Results: Our results showed that chosen predictors explain a significant 40% (p Conclusion: Age, FEV1 and PA are significant predictors of exercise capacity. Therefore, PA as a measure of body composition status is an important tool in PRP to detect early changes in body composition in COPD patients so they can start immediately with nutrition support and pulmonary rehabilitation which in combination produce the best results regarding patient’s functionality.

Introduction: Clinical differences between M. avium and M. intracellulare haven’t been fully studied. Aims and Objectives: to asses the relevance of M. avium complex (MAC) members; record treatment outcomes and long term survival of MAC pulmonary disease (MAC-PD) patients. Methods: retrospective study on all Croatian residents with MAC respiratory isolates from 2006 to 2016 with follow up to 2018. ATS/IDSA guidelines were used to establish MAC-PD and evaluate treatment adequacy. Results: Medical records were available for 93/149 (62.4%) isolates. MAC-PD was diagnosed in 36/49 (73.4%) of M. avium and 24/44 (54.5%) of M. intracellulare isolates. Fibrocavitary form and smear positivity were more common with M. intracellulare than M. avium - 33.3 vs. 22.2% and 61 vs. 27.6%, respectively. Treatment was started in 23/36 (63.9%) of M. avium and 21/23 (91.3%) of M. intracellulare. Adequate regimen was administered in 26.1% (6/23) of M. avium and 55% (11/20) of M.intracellulare patients, and microbiological cure was achieved in 83.3% and 72.7% of cases, respectively. One-year mortality of M. avium patients was 19.4% compared to 8.3% of M. intracellulare. 5-year all-cause mortality amounted to 36% and 30% of M. avium and M. intracellulare cases, respectively (p=0.876). Conclusions: M. avium showed a higher percentage of isolates meeting the MAC-PD criteria. Still, M.intracellulare disease was more severe in its presentation, which partly explains the higher rate and adequacy of treatment. Although one-year mortality of M. avium cases was doubled compared to M. intracellulare, there were no differences in long term survival between the two groups.

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1&beta, induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1&beta, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients&rsquo, overall survival was analyzed with the Kaplan&ndash, Meier method with the log-rank test. Serum IL-1&beta, concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1&beta, compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220, OR = 0.55, p = 0.03) and NLRP4 (rs12462372, OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

AIM: To assess the diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in lung cancer (LC). We compared the ratios between healthy participants and all LC patients, as well patients with different pathohistological LC subtypes. ----- METHODS: We retrieved the data on neutrophil, lymphocyte, and platelet levels in 449 patients with different pathohistological LC subtypes (non-small cell LC, small-cell LC, atypical or metastatic LC, neuroendocrine, and sarcomatoid carcinoma) and 47 healthy controls. NLR and PLR were calculated by dividing the absolute number of neutrophils or platelets with the absolute number of lymphocytes. ----- RESULTS: There were significant differences in both NLR and PLR (P

Introducion: Lung carcinoid(LC)tumors account for 1–2% of all lung malignancies. They are classified as typical(TC)or atypical(AC)based on the mitotic index and/or the presence of necrosis. The utility of Ki-67 to differentiate between TCs and ACs has yet to be established and it is not presently recommended Aim: To investigate the predict value of Ki 67 indeks in overal survival, in multivariate analysis Methods: A cohort of 60 pts with LC treated in 5 year period in our department were analysed.LC were classified according to WHO histotype criteria after surgical resection Results: 6pts were excluded before the statistic analysis. Remaining 60pts;35 male(58.4%)and 25 female(41.6%);mean age of 53.6years. The histopathology revealed 44pts with TC and 16pts with AC. The mean Ki-67 indices for the TC(5.0)and theAC(18.4)were significantly different(p Conclusion: These findings don`t provide best evidence for the routine use of Ki-67 index to predict overall short-term survival in pts with LC

Background: Asthma patients, due to their symptoms, often experience fear and anxiety when faced with daily activities. Such functional impairment over time causes lowered quality of life (QoL) and additional psychological distress expressed with depression, anxiety and stress symptoms. Objective: To evaluate the role of aerobic treadmill training among asthma patients attending pulmonary rehabilitation (PR) in their walking capacity (6 minute walking test - 6MWT), in improving QoL and reducing psychological distress. Method: We analyzed the results from 77 patients with persistent asthma divided in two groups. Patients in both groups had the same level of obstruction. They attended standard PR program five days weekly, during four weeks. In one group aerobic treadmill exercise training was added three times a week. Intensity was set at 60% of maximal work rate. Baseline and post PR status were evaluated by 6MWT in both groups, QoL, Depression (D), Anxiety (A) and Stress (S) symptoms. Results: All patients had a significant increase in 6MWT after PR (p

Introduction: Transbronchial criobiopsy is less invasive diagnostic technique for interstitial lung disease. According to published paper is safe with good diagnostic yield. Aim: to analyse safety and diagnostic yield of cryobiopsy in our centre. Methods: Prospective study which included 36 patients with clinical and radiographic features of interstitial lung disease who underwent transbronchial cryobiopsy without fluoroscopy. Results: Safety: Pneumothorax occurred in 2 patients (5,5%). There was no severe bleeding. In 26 cases (72%) there was mild bleeding and in 2 cases no bleeding. The mean number of samples was 4 (1-5) and mean diameter was 5,4 mm (5,4+/-2,3). Definitive diagnosis by pathologist was obtained in 14 (38%) cases (NSIP in 6 cases, 2 granulomatosis, 1 DAD, 1 UIP, 1 hypersensitivity pneumonitis, 1 drug related, 1 adenocarcinoma, 1 aspiration pneumonitis). In 15 cases cryobiopsy was inconclusive, in 5 cases nonspecific fibrosing changes were found and in 3 cases normal lung tissue. After multidisciplinary team discussion definitive diagnosis was obtained in 25 (69%) cases (6 NSIP, 4 IPF, 3 pulmonary manifestations of connective tissue disease, 3 chronic hypersensitivity pneumonitis, 2 sarcoidosis, 2 RB ILD, 2 cryptogenic organising pneumonia, 1 drug induced interstitial lung disease, 1 adenocarcinoma, 1 aspiration pneumonitis). Conclusion: Cryobiopsy is safe procedure with low incidence of serious complications (major bleeding or pneumothorax) even when it is performed without fluoroscopy. Results in our study showed lower proportion of definitive diagnosis established after cryobiopsy which can be partly explained with the lack of pathologist9s experience when we started the study.

Aim: to determine in-hospital and post-discharge mortality, readmission rates, and predictors of invasive mechanical ventilation (IMV) in patients treated at intensive care unit (ICU) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods: a retrospective observational cohort study included all patients treated at a respiratory ICU for AECOPD during one year. A total of 62 patients (41 men) with mean age 68.4 ± 10.4 years were analyzed for outcomes including in-hospital and post-discharge mortality, readmission rates, and IMV. Patients’ demographic, hematologic, biochemical data and arterial blood gas (ABG) values were recorded on admission to hospital. Mean duration of followup time was 2.4 years. Results: of 62 patients, 7 (11.3%) died during incident hospitalization and 21 (33.9%) died during the follow-up. The overall 2.4-year mortality was 45.2%. Twenty nine (46.8%) patients were readmitted due to AECOPD. The average number of readmissions was 1.2. Multivariate analysis showed that blood pH, bicarbonate levels, low albumin, low serum chloride, and low hemoglobin were significant predictors of IMV during incident hospitalization (P < 0.001 for the overall model fit). Conclusion: high in-hospital and post-discharge mortality and high readmission rates in our patients treated due to AECOPD at ICU indicate that these patients represent a high risk group in need of close monitoring. Our results suggested that anemia, hypoalbuminemia, and elevated troponin levels were risk factors for the need of IMV in severe AECOPD. Identification of such high-risk patients could provide the opportunity for administration of an appropriate and timely treatment.

Sažetak. U posljednja dva desetljeća znatno je porasla upotreba neinvazivne mehaničke ventilacije (NIV) kao učinkovite metode zbrinjavanja akutne i kronične respiracijske insuficijencije. U bolesnika s kroničnom respiracijskom insuficijencijom NIV se može primijeniti u kućnim uvjetima. Najčešće bolesti koje dovode do razvoja kronične respiracijske insuficijencije jesu: kronična opstruktivna plućna bolest, sindrom hipoventilacije u pretilih, restriktivne plućne bolesti i neuromuskularne bolesti. Primjena NIV-a poboljšava vrijednosti dišnih plinova, simptome, kvalitetu života i produžuje životni vijek bolesnika s kroničnom respiracijskom insuficijencijom. Danas se NIV uglavnom provodi primjenom pozitivnog tlaka zraka na dišne putove bolesnika, a dvorazinska tlačna potpora najčešći je način ventilacije. Izbor adekvatnog sučelja osnova je uspješne primjene NIV-a. Kućni NIV može se indicirati i započeti u specijaliziranim centrima. Liječnik je odgovoran za postavljanje indikacija, izbor ventilatora, načina i parametara ventilacije. Ciljevi ovih smjernica jesu: pružanje informacija o tehničkim aspektima kućnog NIV-a kliničarima i određivanje indikacija, kontraindikacija te preporučenih postavka ventilacije za svaku skupinu bolesti., Summary. The use of noninvasive ventilation (NIV) has been markedly increased over the past two decades, as an effective method of managing acute and chronic respiratory failure. Patients suffering from chronic respiratory failure can be introduced to home NIV. The most frequent diseases leading to chronic respiratory failure are chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), restrictive thoracic diseases and neuromuscular diseases (NMD). NIV application improves blood gases, symptoms, quality of life and prolongs survival of these patients. Nowadays, noninvasive ventilation is mostly performed by positive pressure ventilators and bilevel positive airway pressure (BiPAP) is the most common mode used. The choice of appropriate interface is the key to successful application of noninvasive ventilation. Home NIV must be introduced through specialized centers. The physicians are responsible for indicating home NIV, choosing the type of ventilator, the ventilation mode and ventilation parameters. The objective of this document is to provide clinicians with information on technical aspects of home NIV, to establish diagnostic and therapeutic strategies for initiating home NIV, indications, contraindications and recommended settings for each group of diseases.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence. Its underdiagnosis and hence under-treatment is a general feature across all countries. This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease. A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms. Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity = 80% predicted. In recent years, an elegant series of studies has shown that exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment. In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation. Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy. This is an essential issue in COPD. In fact, on one hand, airflow limitation, even mild, can unduly limit the patient's physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease. Therefore, we thought that it was worthwhile to analyze further and discuss this stage of mild COPD. To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with mild airflow limitation. The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind mild COPD. Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both., The authors acknowledge the scientific contribution of the following European Pulmonology Societies: AIPO - Italian Association of Hospital Pulmonologists, Croatian Pulmonology Society, Croatian Thoracic Society, HTS Hellenic Thoracic Society, SEPAR - Spanish Society of Pneumology and Thoracic Surgery, Slovenian Respiratory Society. The authors would like to thank the staff of AIPO Ricerche (Milan, Italy) for editing assistance. This consensus document has been funded through an unrestricted educational grant from Teva.

Incorrect catheter placement for drainage of malignant pericardial effusion in a 43-year-old woman with a metastatic lung adenocarcinoma.

The aim of this study was to investigate the consequences of insulin-like growth factors (IGF) and IGF receptor dysfunction in lung carcinomas. A correlation between increased expression (at mRNA and protein levels) for IGF-1 and IGF-1R and decreased apoptosis were found in large-cell carcinomas and adenocarcinomas. In 40% of informative adenocarcinomas expressing the highest values of IGF-2 and Ki-67 proteins, M6P/IGF-2R gene had LOH at one allele and a mutation in another allele. All four squamous cell carcinoma samples expressed LOH/mutation in the M6P/IGF-2R gene. The alphaIR3 strongly diminished proliferation and increased apoptosis in cultures established from squamous cell carcinomas overexpressing IGF-2 and IGF-1R. Telomerase activity was assessed in four squamous cell carcinomas. Cell treatment with IGF-1 increased telomerase activity. The opposite was observed when the cells were treated with alphaIR3, which inhibits the activity of IGF-1 receptors. Our findings suggest that disruption of the IGF/IGF receptors axis is involved in lung cancer formation.

Haemangiopericytoma is a rare soft tissue tumour originating from the contractile pericapillary cells. Relatively little is known about its molecular pathogenesis. To address this issue, the insulin-like growth factor family (IGFs) was analysed in 19 tumours collected from a human tumour bank network. Seven of the tumours were associated with severe hypoglycaemia. Of these, six were retroperitoneal and one was located in the leg. 3 out of the 19 tumours (15·8 per cent) were positive for insulin-like growth factor I (IGF I) mRNA and 11 were positive for IGF II mRNA (57·9 per cent). Almost 90 per cent of haemangiopericytomas expressed IGF I receptor (IGF IR) mRNA (17 out of 19), five (26·3 per cent) expressed IGF binding protein 1 (IGF BP1), three (15·8 per cent) expressed IGF BP2, and four (21 per cent) exhibited IGF BP3 mRNA. All of the 14 haemangiopericytomas examined with regard to specific receptor binding were IGF IR positive, ranging from 1·2 to 16·2 per cent. Binding was much higher in IGF I/IGF IR positive tumours (15·3±0·7) than in IGF I negative/IGF IR positive tumours (5·1±3·3). The potential role of IGF IR as a growth promoting factor in malignant haemangiopericytoma was studied using antisense oligonucleotides and monoclonal antibody αIR3 that specifically inhibit IGF IR synthesis or activity. 10 µM IGF IR antisense oligonucleotides significantly inhibited the growth of haemangiopericytoma cells in culture, by around 50 per cent; monoclonal antibody against IGF IR (αIR3) also significantly inhibited proliferation. The data suggest that IGF IR may play an important role in the genesis and progression of malignant haemangiopericytomas. Copyright © 1999 John Wiley & Sons, Ltd.

Rates in targetable gene changes varies between different populations of lung cancer patients. Targetable genes changes include changes in EGFR and ALK gene, as well as KRAS gene. Primary aim of this study was to determine mutation status in purely Caucasian Croatian population.

AIM: To describe and interpret lung cancer incidence and mortality trends in Croatia between 1988 and 2008. ----- METHODS: Incidence data on lung cancer for the period 1988-2008 were obtained from the Croatian National Cancer Registry, while mortality data were obtained from the World Health Organization mortality database. Population estimates for Croatia were obtained from the Population Division of the Department of Economic and Social Affairs of the United Nations. We also calculated and analyzed age-standardized incidence and mortality rates. To describe time incidence and mortality trends, we used joinpoint regression analysis. ----- RESULTS: Lung cancer incidence and mortality rates in men decreased significantly in all age groups younger than 70 years. Age-standardized incidence rates in men decreased significantly by -1.3% annually. Joinpoint analysis of mortality in men identified three trends, and average annual percent change (AAPC) decreased significantly by -1.1%. Lung cancer incidence and mortality rates in women increased significantly in all age groups older than 40 years and decreased in younger women (30-39- years). Age-standardized incidence rates increased significantly by 1.7% annually. Joinpoint analysis of age-standardized mortality rates in women identified two trends, and AAPC increased significantly by 1.9%. ----- CONCLUSION: Despite the overall decreasing trend, Croatia is still among the European countries with the highest male lung cancer incidence and mortality. Although the incidence trend in women is increasing, their age standardized incidence rates are still 5-fold lower than in men. These trends follow the observed decrease and increase in the prevalence of male and female smokers, respectively. These findings indicate the need for further introduction of smoking prevention and cessation policies targeting younger population, particularly women.

Background. Massive haemoptysis is a clinical state characterized by the expectoration of blood at a rate of 300-600 mL/24 h, thus causing life-threatening asphyxia. The aim of our study is to review use of transcatheter bronchial artery embolization (BAE) in the treatment of massive haemoptysis. Materials and methods. Series of 11 patients with the clinical picture of massive haemoptysis was referred to our hospital for digital subtraction angiography and BAE within a 33 months period. There were 8 male (aged 43-69, mean age 56) and 3 female patients (aged 63-65, mean age 64). Aortography of thoracic aorta was initially performed in all patients, followed by selective angiography of bronchial and intercostal arteries, and intercostobronchial tree as indicated. A selective arterial embolization was done in 9 patients (9 primary and 3 secondary embolizations). The embolization was performed under fluoroscopy control by manual injection of the mixture of contrast solution (1 ccm) and embolization material, Embosphere (BioSphere Medical Inc., MA, USA), particle size 350-500 μm. Results. Bronchiectasis was the most common cause of bleeding (45.4%), while hypervascularization and intensive parenchymal opacification were the most frequent angiographic indicators of bleeding (100%), followed by tortuous and hypertrophic arteries (72.7%). Primary BAE proved successful in 81.9% and secondary BAE performed within 24 months in 33.3% of patients, whereas the tertiary (operative) treatment was required in 22.2% of patients. In 44.4% of patients, BAE was associated with only mild discomforts, like pain and cough. Conclusions. BAE is a reliable and minimally invasive method in the management of massive haemoptysis. Therefore, it should be considered as the primary method of the treatment or as a procedure for the stabilization the patient before the surgery.

Subclinical lead poisoning with no clinical symptoms is a dilemma for the occupational health physician. He is supposed to assess when and how to treat workers at risk mainly by the results of biological monitoring. The aim of this study was to demonstrate different responses of biological indices in 50 lead-exposed workers who have been working in the same plant of lead pigment production factory. Twenty-one had normal, that is, permissible blood lead concentrations (PbB), erythrocyte protoporphyrin (EP), and aminolevulinic acid activity (ALAD) measured during regular periodic examinations (group 1). No differences between two measurements were found, although they were continuously working with lead. In 18 of the 50 workers (group 2). PbB and EP concentrations increased, whereas ALAD activity decreased: those parameters improved after a 3- to 6-month cessation of lead exposure. Seven of the 50 workers also had altered values of biological indices, but their condition improved spontaneously without cessation of lead exposure (group 3), while in the remaining four workers, elevated concentrations of biological indices did not change during the observation period. The reasons for such discrepancies and indications for chelation therapy are discussed. Am. J. Ind. Med. 31:631–635, 1997. © 1997 Wiley-Liss, Inc.