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CURRICULUM VITAE Personal data First Name: Dionisios Last Name: Spyratos Date of birth: 15/08/1973 Place of birth: Athens, Greece Specialty: Pulmonologist Residence: Thessaloniki, Greece Address: Filikis Eterias 26 Kalamaria, Greece (55132) Work address: Pulmonary Department, Aritotle University of Thessaloniki, “G. Papanikolaou” Hospital, Exohi, Thessaloniki,57010 Phone: 00302310410876 Mobile: 00306979490052 E-mail: [email protected] Marital state: Married and one child Academic qualifications Medical Degree: Medical School, University of Patras, Greece (7.3/10) PhD: Pathogenetic mechanisms of orthopnea in patients with congestive heart failure. Studying respiratory mechanics with impulse oscillometry system, Thessaloniki 2008 Medical School, Aristotle University of Thessaloniki, Greece Medical Specialty Postgraduate education Pulmonary Medicine Pulmonary Department, Medical School, Aristotle University of Thessaloniki, Greece (19/3/2007) Professional activities Publications (PubMed) / Citations Hufeland Clinic, Bad Ems (Taunusallee 5, Bad Ems, Germany) on pulmonary rehabilitation for 3 months St. Elisabeth und St. Barbara Clinic of Martin-Luther-Universitat HalleWittenberg (Mauerstraβe 5, Halle Saale, Germany) on medical thoracoscopy for 2 months Lecturer of Pulmonary Medicine, Medical School, Aristotle University of Thessaloniki, Greece since 04/02/2011 25 / 166 Research programs As sub-investigator in the following international, multicenter clinical studies accepted by Research Committee of Aristotle University of Thessaloniki, Greece: 1 INSPIRE, code D5125C00288: comparing formoterol as inhaler and turbuhaler in asthmatic patients Uplift, code bi205235: 4-year study investigating the effect of tiotropium on the rate of lung function decline in patients with COPD Smile, code SD-039-074: comparing formoterol/budesonide, formoterol and terbutaline administered in an as-needed basis in asthmatic patients who receive standard doses of formoterol/budesonide SUN, code D5899C00001: comparing efficacy and safety of the combination formoterol/budesonide as pMDI with formoterol as turbuhaler in patients with COPD REACT, code RO-2455-404RD (phase 3/4): investigating the effect of roflumilast on the frequency of COPD exacerbations versus placebo in patients with COPD who receive fixed combination of LABA/ICS DB2114930: comparing the efficacy and safety of the combination umeclidinium/vilanderol with fluticasone propionate / salmeterol in patients with COPD CQMF149F2202 (phase ΙΙ): comparing the efficacy and safety of the combination QMF149 (indacaterol 150 μg/ Mometasone furoate 160 μg o.d.) with salmeterol hydroxynaphthoate / fluticasone propionate (50 μg / 500 μg b.i.d.) in patients with COPD Clinical study investigating the effects of fluticasone furoate / vilanterol (100/25mcg) compared with placebo for the survival of patients with moderate COPD and medical history or increased risk for cardiovascular diseases. Table of publications Type of Number of 1st publication publications author Full articles in peer 25 6 reviewed journals (PubMed) Full articles in journals 4 1 not included in PubMed Abstracts in 21 5 journals included in PubMed Full articles 9 in Greek medical journals 2nd 3rd 4 >3 Corresp. author 6 9 4 8 4 3 3 3 2 3 2 Abstracts in Greek medical journals Chapters in Greek medical educational books PhD 31 5 4 9 13 10 1 Table of full publications in peer reviewed journals according to their impact factor Journals Impact factor Total 3.486 Number of articles 1 Drug Design, Development and Therapy Onco Targets Ther Int J Pharm Subst Abuse Treat Prev Policy Arch Environ Occup Health Virol J J Aerosol Med Pulm Drug Deliv Prim Care Respir J Am J Clin Oncol Heart Lung Am J Ind Med Ther Adv Respir Dis Int J Environ Res Public 2.073 1 2.073 3.458 1.56 1 1 3.458 1.56 1.194 1 1.194 2.09 2.894 1 1 2.09 2.894 2.19 2 2Χ2.19=4,38 2.552 2 2Χ2.552=5,104 1.404 1.973 0.795 1 2 1 1.404 2Χ1.973=3,946 0.795 2.197 1 2.197 3.486 3 Health Respiration Int J Tuberc Lung Dis Allergol Immunopathol (Madr) 2.615 2.731 2 1 2Χ2.615=5,23 2.731 1.229 1 1.229 Total 43,771 Hirsh index (H-index ή H-factor): 7 Citations: 166 Table of medical congresses International Congresses 18 Greek Congresses 9 Workshops (ERS) 4 EDUCATION – CAREER – TITLES I was born in Athens, Greece the 15th of August in 1973. I finished High School in Mytilene, Greece (degree: 197/11/20) in 1991. I passed the examination for the Certificate of Proficiency in English (University of Michigan). In 1991 I successfully passed the National Examinations and enrolled in Medical School, University of Patras, Greece. I graduated from the Medical School in July 1997 with a degree “Very Well (7.3/10). I worked as a doctor in a Primary Care Center in Mytilene, Greece from September 1997 to March 1999. I served my military service as a doctor from March 1999 to September 2000. 4 Then I worked as a primary care doctor in two Nursing Homes (“St. Dimitrios” and “12 Apostles”) in Thessaloniki from October 2000 to November 2011. I worked as a resident in the Pulmonary Department, Medical School, Aristotle University of Thessaloniki from January 2002 to January 2007. I successfully passed the examinations for Pulmonary Medicine and I was awarded the title of Pulmonologist on March 2007 (Identity Number: Γ2/1812, 19-3-2007, Section of Public Health, Prefecture of Thessaloniki, Greece). From May 2007 to January 2011 I worked as collaborator of the Pulmonary Department, Aristotle University of Thessaloniki (AUTh) on research programs of the clinic and paid through the Research Committee of AUTh. I was teaching for some months (16/1/08 to 29/02/08 and 01/04/08 to 30/04/08) the topic of Pulmonary Medicine for the medical students of the 5th year of AUTh. On the 17th of March in 2008 I was entitled Doctor (PhD) of Aristotle University of Thessaloniki with the degree of “Excellent”. My PhD Thesis was “Pathogenesis of orthopnea in patients with congestive heart failure. Studying the mechanics of respiratory system with impulse oscillometry system”. During the time period 16/06/2008 to 15/09/2008 I was trained at Hufeland Clinic, Bad Ems (Taunusallee 5, Bad Ems, Germany) on pulmonary rehabilitation. On the 12th of September 2009 I successfully passed the examinations for the European Diploma in Adult Respiratory Medicine. I was elected as a Lecturer of Pulmonary Medicine by the General Meeting of Medical School, Aristotle University of Thessaloniki on the 08/07/2009 and I undertook my duties on 04/02/2011 in Pulmonary Department. Since then I have been working as a clinical doctor in 5 Pulmonary Department while taking part in theoretical and practical education of medical students and residents on Pulmonology. During the time period 14/05/2012 to 13/07/2012 I was trained at St. Elisabeth und St. Barbara Clinic of Martin-Luther-Universitat HalleWittenberg (Mauerstraβe 5, Halle Saale, Germany) on medical thoracoscopy. Regarding my research activity I am author in 23 studies already published in PubMed while two additional papers have been accepted for publication (Citation index: 166, H index:7). My main research interest is COPD in the primary care setting and Occupational related pulmonary diseases. 6 Full text publications in peer reviewed journals that are included in PubMed Intratumoral chemotherapy for lung cancer: rechallenge current targeted therapies. Hohenforst-Schmidt W, Zarogoulidis P, Darwiche K, Vogl T, Goldberg EP, Huang H, Simoff M, Li Q, Browning R, Turner FJ, Pivert P, Spyratos D, Zarogoulidis K, Celikoglu SI, Celikoglu F. Drug Des Devel Ther 2013:7 571–583 (In Press) 1. Abstract: Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with nonsmall cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa– IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive nonsmall cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented. 2. Measurement of exhaled alveolar nitrogen oxide in patients with lung cancer: a friend from the past still precious today. 7 Kallianos A, Tsimpoukis S, Zarogoulidis P, Darwiche K, Charpidou A, Tsioulis I, Trakada G, Porpodis K, Spyratos D, Panoutsopoulos A, Veletza L, Kostopoulos K, Kostopoulos C, Karapantzos I, Tsakiridis K, Hohenforst-Schmidt W, Zarogoulidis K, Rapti A, Syrigos K. Onco Targets Ther 2013 May 31;6:609-13 Abstract: Nitric oxide (NO) is a marker of airway inflammation and indirectly a general indicator of inflammation and oxidative stress. NO is a contributing factor in lung cancer at an early stage and also after chemotherapy treatment of lung cancer. We studied whether exhaled NO levels were altered by three cycles of chemotherapy at diagnosis and after chemotherapy, and whether, directly or indirectly, these changes were related to the course of disease. Also, a correlation of NO levels with other markers of inflammation was performed. We studied 42 patients diagnosed early: 26 men and 16 women with lung cancer. We analyzed blood tests for control of inflammatory markers, functional pulmonary tests, and alveolar exhaled NO. We recorded a decrease in exhaled NO after three cycles of chemotherapy in all patients, regardless of histological type and stage: there were 42 patients with mean 9.8 NO after three cycles (average 7.7). Also, a strong correlation appeared between NO measurements before and after chemotherapy and C-reactive protein (P , 0.05, r = 0.42, before) and (P , 0.045, r = 0.64, after). NO alveolar measurement as an indicator of airway inflammation indicates response to chemotherapy in lung cancer. Also, the inflammatory process in lung cancer was confirmed and indicated response to chemotherapy through an index that is sensitive to inflammatory disease of the airways. Establishing the optimal nebulization system for paclitaxel, docetaxel, cisplatin, carboplatin and gemcitabine: Back to drawing the residual cup. Zarogoulidis P, Petridis D, Ritzoulis C, Darwiche K, Spyratos D, Huang H, Goldberg EP, Yarmus L, Li Q, Freitag L, Zarogoulidis K. Int J Pharm 2013 Jun 14. doi:10.1016/j.ijpharm.2013.06.011. [Epub ahead of print] 3. Background: Chemotherapy drugs have still the major disadvantage of non-specific cytotoxic effects. Although, new drugs targeting the genome of the tumor are already in the market, doublet chemotherapy regimens still remain the cornerstone of lung cancer treatment. Novel modalities of administration are under investigation such as; aerosol, intratumoral and intravascular. Materials and methods: In the present study five chemotherapy drugs; paclitaxel, docetaxel, gemc-itabine, carboplatin and cisplatin were nebulized with three different jet nebulizers (Maxineb®, Sunmist®, Invacare®) and six different residual cups at different concentrations. The purpose of the study was to identify the “ideal” combination of nebulizer-residual cup designdrug–drug loading for a future concept of aerosol chemotherapy in lung cancer patients. The Mastersizer® 2000 was used to evaluate the aerosol droplet mass median aerodynamic diameter. Results: The drug, nebulizer and residual cup design greatly influences the producing droplet size (p < 0.005, in each case). However; the design of the residual cup is the most important factor affect-ing the produced droplet size (F = 834.6, p < 0.001). The drug loading plays a vital role in the production of the 8 desired droplet size (F = 10.42, p < 0.001). The smallest droplet size was produced at 8 ml loading (1.26 _m), while it remained the same at 2, 4 and 6 mls of drug loading. Conclusion: The ideal nebulizer would be Maxineb®, with a large residual cup (10 ml maximum loading capacity) and 8 mls loading and the drug with efficient pulmonary deposition would be docetaxel. Smoking among adolescents in Northern Greece: a large cross-sectional study about risk and preventive factors. Spyratos DG, Pelagidou DT, Chloros D, Haidich AB, Karetsi E, Koubaniou C, Konstantopoulos S, Gourgoulianis K, Sichletidis LT. Subst Abuse Treat Prev Policy 2012 Sep 10;7:38 4. Abstract Background: The aim of the present study was to investigate epidemiological data about cigarette smoking in relation with risk and preventive factors among Greek adolescents. Methods: We randomly selected 10% of the whole number of schools in Northern Greece (133 schools, 18,904 participants were included). Two anonymous questionnaires (smoker's and non-smoker's) were both distributed to all students so they selected and filled in only one. A parental signed informed consent was obtained using an informative leaflet about adolescent smoking. Results: The main findings of the study were: a) 14.2% of the adolescents (mean age+/−SD: 15.3+/−1.7 years) reported regular smoking (24.1% in the age group 16– 18 years), b) 84.2% of the current smokers reported daily use, c) students who live in urban and semirural areas smoke more frequently than those in rural areas, d) students in technically oriented schools smoke twice as frequent compared to those in general education, e) risk factors for smoking: male gender, low educational level of parents, friends who smoke (OR: 10.01, 95%CI: 8.53-11.74, p<0.001), frequent visits to internet cafes (OR:1.53, 95%CI: 1.35-1.74, p<0.001), parents, siblings (OR:2.24, 95%CI: 1.99-2.51, p<0.001) and favorite artist (OR:1.18, 95%CI: 1.04-1.33, p=0.009) who smoke, f) protective factors against smoking:participation in sports (OR:0.59, 95%CI: 0.53-0.67, p<0.001), watching television (OR:0.74, 95%CI 0.66-0.84, p<0.001) and influence by health warning messages on cigarette packets (OR:0.42, 95%CI: 0.37, 0.48, p<0.001). Conclusions: Even though prevalence of cigarette smoking is not too high among Greek adolescents, frequency of everyday cigarette use is alarming. We identified many social and lifestyle risk and preventive factors that should be incorporated in a national smoking prevention program among Greek adolescents. Chest imaging and lung function impairment after long-term occupational exposure to low concentrations of chrysotile. Spyratos D, Chloros D, Haidich B, Dagdilelis L, Markou S, Sichletidis L. Arch Environ Occup Health. 2012;67(2):84-90 5. 9 ABSTRACT. The aim of the present study was the investigation of radiographic findings in relation to lung function after occupational exposure to permissible levels of relatively pure chrysotile (0.5–3% amphiboles).We studied 266 out of the total 317 employees who have worked in an asbestos cement factory during the period 1968– 2004 with chest x-ray, high-resolution computed tomography (HRCT) and lung function tests. Sensitivity of chest x-ray was 43% compared to HRCT. Abnormal HRCT findings were found in 75 subjects (67%) and were related to age, occupational exposure duration, and spirometric data. The presence of parenchymal or visceral pleural lesions (exclusively or as the predominant abnormality) was being accompanied by lower total lung capacity and diffusion capacity. HRCT was much more sensitive than chest x-ray for occupational chrysotile exposure. Lung function impairment was related with parenchymal but not with pleural HRCT abnormalities. Diagnosis of chronic obstructive pulmonary disease in the primary care setting Spyratos D, Chloros D, Sichletidis L. Hippokratia 2012;16(1):402-7 (In Press) 6. Abstract Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality with increasing rates during the last decades. Due to the progressive nature of the disease, underestimation of symptoms by the patients, lack of knowledge and underuse of spirometry by the Primary Care providers the disease remains underdiagnosed in about half of the cases. Patients with a smoking history of ≥20 packyears and relevant symptoms (e.g. dyspnea, chronic cough and sputum production) are considered a high risk group. Measurement of spirometric parameters after administration of a short acting bronchodilator confirms the presence of irreversible airflow obstruction and establishes the diagnosis. However in the primary care spirometry is usually not available and differential diagnosis with other obstructive pulmonary diseases (e.g. asthma, bronchiectasis) is not always easy. General Practitioners (GPs) need simple screening tools to decide if a patient belong to a high risk group and pulmonary consultation is necessary. Early and accurate diagnosis of COPD in the primary care setting allowing for a timely and effective management which reduces the rate of decline in lung function improves survival of patients, their quality of life and reduces health-care utilization. The aim of the present review is to provide the existing information about COPD diagnosis and the related problems in the Primary Care. Also we reviewed numerous simple COPD diagnosis questionnaires as well as the use of hand-held flow meters which could be used as effective screening tools. Long-term respiratory follow-up of H1N1 infection. Zarogoulidis P, Kouliatsis G, Papanas N, Spyratos D, Constantinidis TC, Kouroumichakis I, Steiropoulos P, Mabroudi M, Matthaios D, Kerenidi T, Courcoutsakis N, Zarogoulidis K, Maltezos E. Virol J 2011 Jun 25;8:319 7. Background: The first case of 2009 pandemic influenza A (H1N1) virus infection was documented in our Hospital on 10th August 2009. 10 Metdods and findings: Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm the diagnosis. All patients were treated with oseltamivir from the first day of hospitalization. Upon admission 12/44 had local patchy shadowing in their chest x-ray and additionally antibiotic regimen was added to these patients as pneumonia was suspected based on clinical evidence. In total 44 patients were hospitalized 15/44 had asthma, 6/44 COPD, 5/44 leukemia. Lung function was evaluated with forced vital capacity, forced expiratory volume in 1 sec and diffused carbon monoxide upon discharge and every 3 months, until 6 months of observation was completed after discharge. The purpose of this retrospective cohort study was to evaluate whether influenza A (H1N1) had an impact on the respiratory capacity of the infected patients. Conclusions: An improvement of pulmonary function tests was observed between the first two measurements, implicating an inflammatory pathogenesis of influenza A (H1N1) to the respiratory tract. This inflammation was not associated with the severity or clinical outcome of the patients. All patients had a mild clinical course and their respiratory capacity was stable between the second and third measurement, suggesting that the duration of respiratory inflammation was two months. Early treatment with antiviral agents and vaccination represent the mainstay of management. Inhaled insulin: too soon to be forgotten? Zarogoulidis P, Papanas N, Kouliatsis G, Spyratos D, Zarogoulidis K, Maltezos E. J Aerosol Med Pulm Drug Deliv 2011;24(5):213-23 8. Inhalation is a potentially viable route of administration for numerous agents. In diabetes mellitus, the need for frequent injections to achieve ideal glycemic control remains a significant limitation for initiating and complying with insulin therapy in a large number of patients. To overcome this barrier, inhaled insulin was developed. The inhalation form of regular human insulin has been tested and administered in a large number of trials. Respiratory capacity was evaluated in patients with normal lung parenchyma in whom inhaled insulin was administered without complications. However, issues like cost, bulky device, fear for lung safety, and the small number of studies in subjects with underlying respiratory disease prevented widespread use of this new mode of delivery. In the present review, we will suggest a number of methods that could be applied in this form of administration to maximize drug absorption and fully exploit the advantages of this route of administration. A combination of the IPAG questionnaire and PiKo6® flow meter is a valuable screening tool for COPD in the primary care setting. Sichletidis L, Spyratos D, Papaioannou M, Chloros D, Tsiotsios A, Tsagaraki V, Haidich AB. Prim Care Respir J 2011;20:184-9 9. Aims: To investigate the validity of the International Primary Care Airways Guidelines (IPAG) questionnaire and PiKo-6R (Ferraris Respiratory Europe Ltd.) 11 flow meter as screening tools for diagnosing chronic obstructive pulmonary disease (COPD) in the primary care setting. Methods: The first 50 patients in 25 general practice offices completed the IPAG questionnaire and underwent spirometry with the handheld PiKo-6R flow meter. The results were compared with official spirometry parameters after bronchodilation. All participants had no previous medical diagnosis of respiratory diseases. Results: Data from 1,078 out of 1,250 subjects (462 males, mean age 65.3•}11.4 years) were analysed. The percentage of smokers was 48.4% (38•}29 pack-years). COPD was diagnosed in 111 (10.3%) patients. In the subgroup of smokers the sensitivity and specificity for COPD diagnosis were 91% and 49%, respectively, for the IPAG questionnaire; 80% and 95% respectively for the PiKo-6R spirometer; and 72% and 97% for their combination. The negative predictive value of the questionnaire was 97%, whereas the positive predictive value of the questionnaire/ PiKo-6R combination was 82%. Using a cut-off score of 19 points for the IPAG questionnaire, we calculated the best combination of sensitivity (75%) and specificity (72%). Conclusions: The IPAG questionnaire and the hand-held PiKo-6R spirometer can be used in combination to increase the possibility of an early and accurate diagnosis of COPD in the primary care setting. Pulmonary rehabilitation in non-small cell lung cancer patients after completion of treatment. Glattki GP, Manika K, Sichletidis L, Alexe G, Brenke R, Spyratos D. Am J Clin Oncol. 2012;35(2):120-5 10. Objectives: The functional status of patients with non-small cell lungcancer (NSCLC) is often limited not only by cancer itself, but also by the different types of treatment and by comorbidities [eg, chronic obstructive pulmonary disease (COPD), congestive heart failure]. The aim of this study was to investigate the utility of an inpatient multidisciplinary pulmonary rehabilitation (PR) program on pulmonary function and exercise capacity of patients with NSCLC after completion of their treatment. Methods: Forty-seven patients with NSCLC underwent a PR program after completing cancer treatment. Pulmonary function tests, arterial blood gases, 6-minute walk test, and dyspnea severity before and after PR were retrospectively analyzed. Results: After undergoing PR, patients exhibited significantly higher forced expiratory volume in the first second (mean increase, 110±240 mL; P = 0.007), forced vital capacity (mean increase, 130±290 mL; P = 0.001), and 6-minute walk test distance (mean increase, 41 m; P < 0.001). A statistically significant improvement in the severity of dyspnea (mean decrease in the Modified Medical Research Council dyspnea scale: 0.26±0.61; P = 0.007) was observed. We observed that improvement in pulmonary function and exercise capacity was similar among patients with and without COPD and among patients who underwent thoracic surgery or not. Conclusions: Patients with NSCLC who could accomplish PR program, after multidisciplinary treatment for the main disease, seem to benefit in terms of exercise capacity and pulmonary function. These benefits are independent of concurrent COPD and surgical treatment for lung cancer. 12 Therapeutic pneumoperitoneum in a patient with pulmonary tuberculosis and persistent fever. Antoniou M, Chloros D, Spyratos D, Giouleka P, Sichletidis L. BMJ Case Rep. 2011 Feb 2;2011 11. Artificial pneumoperitoneum represents a therapeutic technique fi rst applied in the treatment of pulmonary tuberculosis (TB) in prechemotherapy antimycobacterial era. A 25-year-old patient presented with pulmonary TB diagnosed during the 8th month of her pregnancy. She was febrile and in severe clinical condition. An antituberculous regimen of four primary drugs was initiated immediately after the caesarean section. There was no clinical improvement after 3 months despite full drug sensitivity of Mycobacterium tuberculosis isolates. An artificial pneumoperitoneum was applied along with the drug treatment for 6 months. Soon the patient became afebrile, her body weight increased and sputum smears gave negative results. The combination of the old technique of therapeutic pneumoperitoneum along with the current antituberculosis treatment proved to be effective in this advanced case of pulmonary TB initially unresponsive to drug therapy alone. Interferon α-induced sarcoidosis to a patient with polycythemia vera. Sionidou M, Spyratos D, Chloros D, Sichletidis L. BMJ Case Rep. 2011 May 10;2011 12. Treatment with interferon (IFN) can precipitate a variety of inflammatory conditions, including sarcoidosis. Although many other systems can be affected, the clinical picture in this case mostly includes cutaneous and pulmonary symptoms. The prognosis is better than the idiopathic form of the disease, and the most effective treatment is considered the discontinuation of antivirus therapy alone or in combination with corticosteroid administration. The authors present the case of a 36year-old man who developed sarcoidosis stage I after 2 years of IFNα therapy for polycythemia vera. An unusual cause of spontaneous pneumothorax. Spyratos D, Kalpakidis V, Giouleka P, Chloros D, Sichletidis L. BMJ Case Rep. 2011 May 3;2011 13. Bronchopulmonary sequestration is a congenital pulmonary malformation consisting of a non-functioning region of lung parenchyma that receives systemic arterial blood supply. The authors present the case of a 31-year-old male who presented with spontaneous pneumothorax as the initial clinical manifestation of an intralobar bronchopulmonary sequestration. There was a persistent air leak through the chest tube which remained in the pleural cavity for 12 days. CT revealed an area of increased opacity, with focal calcifi cations and a small eccentric cavity in the posterior basal region of the left lower lobe. Aortography established the fi nal diagnosis. 14. Iliopsoas tuberculous abscess associated cervical and axillary tuberculous lymphadenopathy. with 13 Latsios D, Chloros D, Spyratos D, Dagdilelis L, Sichletidis L. BMJ Case Rep. 2011 Jun 30;2011 The authors report a case of iliopsoas tuberculous abscess without obvious spinal column involvement. Cervical and axillary tuberculous lymphadenopathy were also presented. Despite appropriate antituberculous treatment, patient required percutaneous drainage with CT-guided catheter insertion. Assessment of respiratory mechanics by impulse oscillometry in orthopneic patients with acute left ventricular failure. Spyratos DG, Glattki GP, Sichletidis LT, Patakas D. Heart Lung 2011;40(2):97-104 15. Backround: This study investigated the respiratory function and mechanics of patients with orthopnea caused by acute left ventricular failure (ALVF). Methods: The study comprised 40 patients with ALVF and 15 control subjects. All patients underwent lung function tests and impulse oscillometry in both sitting and supine positions. In a subgroup of 22 patients, isosorbide dinitrate was administered and impulse oscillometry was performed 15 minutes later in the supine position. Results: No patient reported dyspnea while seated, and the orthopnea score was 2.9±1.4. Left ventricular ejection fraction was 43±10%. Patients demonstrated restrictive spirometric pattern in the sitting position, whereas functional residual capacity was comparable to that of the control group. In the supine position, all pulmonary volumes decreased, except inspiratory capacity which increased. Respiratory reactance (Xrs5) was higher in patients in both sitting and supine positions. Respiratory resistance (Rrs5) and Xrs5 improved after nitrates administration. Orthopnea was better correlated with Xrs5%pred in the supine position. Ejection fraction was positively correlated with inspiratory capacity %pred in the sitting position. Conclusion: Patients with ALVF demonstrated increased respiratory reactance that correlated with orthopnea severity and improved after nitrates administration Pleural plaques in dentists from occupational asbestos exposure: a report of three cases. Sichletidis L, Spyratos D, Chloros D, Michailidis K, Fourkiotou I. Am J Ind Med 2009;52:926-30 16. Background White asbestos (chrysotile) has been used in dentistry since 1930 when it was introduced as a lining material for casting rings. Methods All three patients presented with pleural plaques on chest X-rays as well as on CT-scans. They were working as dentists for 35–45 years. Under the instructions of the first dentist we represented precisely the whole process of manipulating a kind of paper that contained asbestos. In order to measure asbestos fibers concentration we used the membrane filter method and phase contrast optical microscopy. Dry asbestos sheets were scanned with x-ray diffraction and electron microscope. 14 Results Analysis of the filter demonstrated 0.008 fibers/cm3 during the sampling period. X-ray diffraction analysis revealed that the material consisted of chrysotile exclusively. Electron microscope pictures confirmed the presence of chrysotile. Conclusion Everyday occupational exposure for many years even to low asbestos levels, under poor ventilation conditions in a closed space, could cause pleural lesions. 17. Sarcoidosis-associated pulmonary hypertension: a role for endothelin receptor antagonists? Pitsiou GG, Spyratos D, Kioumis I, Boutou AK, Nakou C, Stanopoulos I. Ther Adv Respir Dis 2009;3(3):99-101 Abstract: Data on the treatment of sarcoidosis-associated pulmonary hypertension are scarce, while the variety of underlying pathophysiologic mechanisms are a major limitation in the implementation of a universal therapy. We report a 47-year-old male patient who presented with stage II sarcoidosis and associated severe pulmonary hypertension. Corticosteroid treatment resolved parenchymal lesions of the lung while vascular involvement did not respond, with the patient remaining in poor functional status. Addition of bosentan, a dual endothelin receptor antagonist, resulted in marked improvement in functional class and exercise capacity of the patient, allowing gradual tapering of steroids. Prevalence and risk factors for initiation of smoking in Greek high-school students. Sichletidis LT, Chloros DA, Tsiotsios AI, Spyratos DG. Int J Environ Res Public Health 2009;6:971-9 18. Abstract: The smoking habits of 9,276 high-school students (15-18 years old) in six cities of Northern Greece were studied using a questionnaire in order to determine the prevalence and possible risk factors for initiation of smoking. We observed that 29.6% of high-school students (32.6% of boys and 26.7% of girls) were current smokers. A percentage of 43.3% had started smoking before the age of 14. Reactive behaviour towards parents’ and teachers’ advice (40.2%) and the existence of smoking friends (40.1%) were the main reasons of initiation. A well-planned integrated anti-smoking campaign is urgently required, especially among students and teachers. Efficacy and safety of erythromycin as sclerosing agent in patients with recurrent malignant pleural effusion. Balassoulis G, Sichletidis L, Spyratos D, Chloros D, Zarogoulidis K, Kontakiotis T, Bagalas V, Porpodis K, Manika K, Patakas D. Am J Clin Oncol 2008;31(4):384-9 19. Objectives: The aim of pleurodesis in malignant pleural effusions is to prevent reaccumulation of the fluid, symptoms, and avoid the need for repeated hospitalization for thoracentesis. The purpose of this study was to evaluate the efficacy and safety of erythromycin as a pleural sclerosing agent. Methods: Over a 2-year period, 34 patients with a symptomatic, recurrent, malignant pleural effusion who referred for chest tube drainage and pleurodesis were included. 15 They had not received prior intrapleural therapy and had predicted survival of at least 1 month. All underwent pleural drainage and chemical pleurodesis with erythromycin. Complications and response to pleurodesis, according to clinical and radiographic criteria after 90 days, were recorded. Results: The overall response was 88.2%. Complete response (no reaccumulation of pleural fluid after 90 days) was observed in 27 patients (79.4%). Partial response (reaccumulation of fluid but without symptoms, not requiring drainage) was observed in 3 (8.8%). No response (symptomatic reaccumulation of fluid that required drainage) was observed in 4 (11.8%). All patients experienced pleurodynia that was treated with administration of paracetamol and/or dextropropoxyphene. Sinus tachycardia and concurrent mild systemic hypertension were observed 2 and 4 hours after pleurodesis. Both of them were attributed to pleurodynia as there was remission with analgesics. Conclusions: This study suggests that erythromycin is effective and safe as a sclerosing agent for pleurodesis in patients with recurrent malignant pleural effusions. Mortality from occupational exposure to relatively pure chrysotile: a 39-year study. Sichletidis L, Chloros D, Spyratos D, Haidich AB, Fourkiotou I, Kakoura M, Patakas D. Respiration 2009;78:63-8 20. Background: Asbestos exposure is related to serious adverse health effects. However, there is disagreement about the relationship between chrysotile exposure and mesothelioma or lung cancer. Objectives: Our aim was to investigate the mortality rate among workers exposed to relatively pure chrysotile in an asbestos cement factory. Patients and Methods: In an asbestos cement plant opened in 1968, we prospectively studied all 317 workers. A quantity of 2,000 tons of chrysotile, with minimal amphibole contamination, was used annually until 1 January 2005. Asbestos fiber concentration was measured regularly. Date and cause of death were recorded among active and retired workers. Results: Asbestos fiber concentration was always below permissible levels. Fifty-two workers died during the study. The cause was cancer in 28 subjects; lung cancer was diagnosed in 16 of them. No case of mesothelioma was reported. Death was attributed to cardiovascular diseases in 23 subjects and to liver cirrhosis in 1. Overall mortality rate was significantly lower than that of the Greek general population, standardized mortality ratio (SMR) was 0.71 (95% CI 0.53–0.93). Mortality due to cancer was increased (SMR 1.15, 95% CI 0.77– 1.67), mainly due to lung cancer mortality (SMR 1.71, 95% CI 0.98–2.78), but not significantly. Conclusions: Occupational exposure to relatively pure chrysotile within permissible levels was not associated with a significant increase in lung cancer or with mesothelioma. Decreased overall mortality of workers indicates a healthy worker effect, which – together with the relatively small cohort size – could have prevented small risks to be detected. 21. Expiratory flow limitation in patients with pleural effusion. 16 Spyratos D, Sichletidis L, Manika K, Kontakiotis T, Chloros D, Patakas D. Respiration 2007;74:572-8 Background: Expiratory flow limitation (EFL) is one of the main mechanisms contributing to dyspnea in patients with chronic obstructive pulmonary disease but has not been explored in patients with pleural effusion. Objectives: It was the aim of this study to determine whether patients with pleural effusion exhibit EFL and to investigate the effect of therapeutic thoracentesis on EFL. Patients and Methods: The study was performed on 21 patients with pleural effusion who were subjected to thoracentesis and measurement of pleural pressure (PP). Spirometry and estimation of flow limitation by the negative expiratory pressure technique were performed before and after thoracentesis. Results: Statistically significant differences were observed in all spirometric parameters. No correlation between the increase in lung volumes and flows and any of the aspirated fluid parameters was observed. Before thoracentesis, 14 out of 21 patients were flow limited, compared with 7 patients after thoracentesis (x 2= 6.151, p = 0.013). Mean values of flow limitation before and after thoracentesis differed significantly. The decrease in flow limitation did not correlate with the increase in the spirometric parameters, the aspirated fluid volume or PP decrease. Conclusions: In the majority of patients with pleural effusion, flow limitation improves after thoracentesis. Flow limitation may be a contributing factor to the sensation of dyspnea in these patients. The validity of the diagnosis of chronic obstructive pulmonary disease in general practice. Sichletidis L, Chloros D, Spyratos D, Chatzidimitriou N, Chatziiliadis P, Protopappas N, Charalambidou O, Pelagidou D, Zarvalis E, Patakas D. Prim Care Respir J 2007;16:82-8 22. AIM: To determine the validity of the diagnosis of chronic obstructive pulmonary disease (COPD) in general practice in patients given a diagnosis of COPD and treated with bronchodilators. METHODS: From the medical records of eight Health Centres in Northern Greece, 319 subjects aged over 40 years and diagnosed as "COPD" were entered into the study. All filled in a special questionnaire and were subjected to spirometry, rhinomanometry and chest X-ray. RESULTS: One hundred and sixty patients (50.2%) met the GOLD criteria for COPD. Twenty-six of them were non-smokers and underwent further evaluation: blood eosinophil count, serum IgE assay, high resolution computed tomography (HRCT) scan of the chest, and echocardiography; 16 were given a different diagnosis. One hundred and fifty-nine subjects (49.8%) with an FEV1/ FVC ratio >0.7 did not meet the GOLD criteria for COPD; 71 suffered from nasal obstruction, 13 from asthma, six had restrictive pulmonary disease and 69 had no respiratory disease. CONCLUSION: Diagnostic errors in patients with respiratory symptoms in the primary healthcare setting are frequent. Patients suspected to have COPD should undergo spirometry testing after bronchodilation. An alternative diagnosis must be sought for non-smoking patients with irreversible airway obstruction. 17 Tuberculosis in patients receiving anti-TNF agents despite chemoprophylaxis. Sichletidis L, Settas L, Spyratos D, Chloros D, Patakas D. Int J Tuberc Lung Dis 2006;10:1127-32 23. SETTING: A major concern surrounding the use of tumor necrosis factor-alpha (TNF-α) inhibitors is their potential to increase the risk of opportunistic infections, particularly tuberculosis (TB). OBJECTIVE: To estimate the incidence of active TB in patients with rheumatic diseases receiving anti-TNF drug therapy and to evaluate the effectiveness of an antituberculosis chemoprophylaxis regimen. DESIGN: Retrospective study of the files of 613 patients with rheumatic diseases who had received anti-TNF agent (etanercept, infliximab and adalimumab) therapy from July 2000 to June 2004 at the Aristotle University of Thessaloniki, Greece. All patients had a tuberculin skin test (TST) and a postero-anterior chest radiograph (CXR) prior to anti-TNF therapy. When indicated (TST≥10 mm and/or fibrotic lesions on CXR), treatment for latent TB was established (6 months isoniazid [INH] or 3 months INH and rifampicin [RMP]). Anti-TNF agent therapy was started again 2 months later. RESULTS: Of 45 patients who fulfilled the criteria for chemoprophylaxis, only 36 were treated correctly. Eleven patients developed active TB 2–35 months after the beginning of anti-TNF therapy. Six patients developed pulmonary and five extrapulmonary TB. Eight of these had received infliximab and three adalimumab. CONCLUSION: The incidence of active TB in this study population was estimated at 449 cases per 100 000 population annually. Anti-tuberculosis chemoprophylaxis was only of partial preventive success in these patients. Diachronic study of pleural plaques in rural population with environmental exposure to asbestos. Sichletidis L, Chloros D, Chatzidimitriou N, Tsiotsios I, Spyratos D, Patakas D. Am J Ind Med 2006;49:634-41 24. Background: The progress of pleural plaques in persons exposed to environmental asbestos in Almopia, Greece were studied prospectively. Methods: During a 15-year period, 198 individuals, in whom pleural plaques had been observed during the period 1988–1990 were followed. Respiratory function was initially evaluated in 23. All were inhabitants of seven villages of Northern Greece, where rocks with high concentration in asbestos fibers were used for whitewashing until 1935. Results: Out of this population, 126 survived and underwent chest X-ray in 2003 while respiratory function was retested in 18. New radiological findings were compared to previous ones using digital technology. Furthermore, the cause of death of the remaining 72 was recorded. Deterioration of X-ray findings was observed in all survivors. Not only did the surface area of previous plaques increase (8.66±12.6 cm2, mean value_SD) but new ones also appeared. Total lung capacity decreased from 95.6±14.8 in 1998 to 76.5±9.3% predicted in 2003. It was found that out of 72 deaths, 11 people died of malignant lung neoplasm, and 4 of mesothelioma. 18 Conclusions: Radiological appearance of pleural plaques and respiratory function of people previously exposed to asbestos environmental pollution worsens over the years.Prevalence of mesothelioma was found to be higher than expected. The prevalence of allergic asthma and rhinitis in children of Polichni, Thessaloniki. Sichletidis L, Chloros D, Tsiotsios I, Gioulekas D, Kyriazis G, Spyratos D, Charalambidou O, Goutsikas S. Allergol Immunopathol (Madr) 2004;32:59-63 25. Aim: To define the prevalence of asthma and rhinitis in primary school children in the Polichni Municipality of the city of Thessaloniki. Methods and results: The parents of 2005 students living in the area of Polichni completed a questionnaire for the detection of pulmonary disease in childhood. Of 493 children who gave positive answers to the questions about allergies, asthma and rhinitis, 203 were excluded after an interview with the parents, because they suffered from either atopic dermatitis or drug allergy or had normal lgE levels. Of the remaining children, 290 were further examined: methacholine test was positive in 109, exercise test was positive in 67, nasal provocation test with histamine was positive in 244, and rhinodilation test with tramazoline was positive in 206. Skin prick tests were positive in 142 children (90 to grass-cereal pollen, 66 to acarea and 59 to Parietaria officinalis). 19