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Advances in Experimental Medicine and Biology 934 Neuroscience and Respiration Mieczyslaw Pokorski Editor Pulmonary Dysfunction and Disease Advances in Experimental Medicine and Biology Neuroscience and Respiration Volume 934 Editorial Board Irun R Cohen, The Weizmann Institute of Science, Rehovot, Israel N.S Abel Lajtha, Kline Institute for Psychiatric Research, Orangeburg, NY, USA John D Lambris, University of Pennsylvania, Philadelphia, PA, USA Rodolfo Paoletti, University of Milan, Milan, Italy Subseries Editor Mieczyslaw Pokorski More information about this series at http://www.springer.com/series/13457 Mieczyslaw Pokorski Editor Pulmonary Dysfunction and Disease Editor Mieczyslaw Pokorski Public Higher Medical Professional School in Opole Institute of Nursing Opole, Poland ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-3-319-42009-7 ISBN 978-3-319-42010-3 (eBook) DOI 10.1007/978-3-319-42010-3 Library of Congress Control Number: 2016948844 # Springer International Publishing Switzerland 2016 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland Preface The book series Neuroscience and Respiration presents contributions by expert researchers and clinicians in the field of pulmonary disorders The chapters provide timely overviews of contentious issues or recent advances in the diagnosis, classification, and treatment of the entire range of pulmonary disorders, both acute and chronic The texts are thought as a merger of basic and clinical research dealing with respiratory medicine, neural and chemical regulation of respiration, and the interactive relationship between respiration and other neurobiological systems such as cardiovascular function or the mind-to-body connection The authors focus on the leading-edge therapeutic concepts, methodologies, and innovative treatments Pharmacotherapy is always in the focus of respiratory research The action and pharmacology of existing drugs and the development and evaluation of new agents are the heady area of research Practical, data-driven options to manage patients will be considered New research is presented regarding older drugs, performed from a modern perspective or from a different pharmacotherapeutic angle The introduction of new drugs and treatment approaches in both adults and children also is discussed Lung ventilation is ultimately driven by the brain However, neuropsychological aspects of respiratory disorders are still mostly a matter of conjecture After decades of misunderstanding and neglect, emotions have been rediscovered as a powerful modifier or even the probable cause of various somatic disorders Today, the link between stress and respiratory health is undeniable Scientists accept a powerful psychological connection that can directly affect our quality of life and health span Psychological approaches, by decreasing stress, can play a major role in the development and therapy of respiratory diseases Neuromolecular aspects relating to gene polymorphism and epigenesis, involving both heritable changes in the nucleotide sequence and functionally relevant changes to the genome that not involve a change in the nucleotide sequence, leading to respiratory disorders will also be tackled Clinical advances stemming from molecular and biochemical research are but possible if the research findings are translated into diagnostic tools, therapeutic procedures, and education, effectively reaching physicians and patients All that cannot be achieved without a multidisciplinary, collaborative, bench-tobedside approach involving both researchers and clinicians v vi Preface The societal and economic burden of respiratory ailments has been on the rise worldwide leading to disabilities and shortening of life span COPD alone causes more than three million deaths globally each year Concerted efforts are required to improve this situation, and part of those efforts are gaining insights into the underlying mechanisms of disease and staying abreast with the latest developments in diagnosis and treatment regimens It is hoped that the books published in this series will assume a leading role in the field of respiratory medicine and research and will become a source of reference and inspiration for future research ideas I would like to express my deep gratitude to Mr Martijn Roelandse and Ms Tanja Koppejan from Springer’s Life Sciences Department for their genuine interest in making this scientific endeavor come through and in the expert management of the production of this novel book series Opole, Poland Mieczyslaw Pokorski Contents Adiponectin and Mortality in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Graciela E Delgado, Rỹdiger Siekmeier, Winfried Maărz, and Marcus E Kleber Heart Rate Variability and Arrhythmic Burden in Pulmonary Hypertension C Witte, J.U Meyer zur Heide genannt Meyer-Arend, R Andrie´, J.W Schrickel, C Hammerstingl, J.O Schwab, G Nickenig, D Skowasch, and C Pizarro Cardiac Vagal Control and Depressive Symptoms in Response to Negative Emotional Stress 23 I Tonhajzerova, Z Visnovcova, A Mestanikova, A Jurko, and M Mestanik Effect of Simulated Microgravity and Lunar Gravity on Human Inspiratory Muscle Function: ‘Selena-T’ 2015 Study 31 M.O Segizbaeva, N.P Aleksandrova, Z.A Donina, E.V Baranova, V.P Katuntsev, G.G Tarasenkov, and V.M Baranov Airway Evaluation with Multidetector Computed Tomography Post-Processing Methods in Asthmatic Patients 41 Mateusz Patyk, Andrzej Obojski, Łukasz Gojny, Bernard Panaszek, and Urszula Zaleska-Dorobisz Genotyping of EGFR Mutations from Bronchial Cytological Specimens in Slovakian Lung Cancer Patients 49 K Baluchova, M Zahradnikova, P Bakes, S Trubacova, H Novosadova, E Halasova, I Majer, and P Hlavcak Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury 63 P Mikolka, J Kopincova, L Tomcikova Mikusiakova, P Kosutova, A Calkovska, and D Mokra vii viii Pertussis: History of the Disease and Current Prevention Failure 77 E Kuchar, M Karlikowska-Skwarnik, S Han, and A Nitsch-Osuch Awareness of Influenza and Attitude Toward Influenza Vaccination Among Medical Students 83 A Banaszkiewicz, E Talarek, J S´liwka, F Kazubski, I Małecka, J Stryczyn´ska-Kazubska, W Dziubak, and E Kuchar Pathogens Causing Upper Respiratory Tract Infections in Outpatients 89 A Jama-Kmiecik, M Frej-Ma˛drzak, J Sarowska, and I Choroszy-Kro´l Index 95 Contents Advs Exp Medicine, Biology - Neuroscience and Respiration (2016) 25: 1–8 DOI 10.1007/5584_2016_14 # Springer International Publishing Switzerland 2016 Published online: 30 June 2016 Adiponectin and Mortality in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Graciela E Delgado, Rỹdiger Siekmeier, Winfried Maărz, and Marcus E Kleber Abstract Cardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide A decreased concentration of adiponectin has been reported in smokers The aim of this study was to analyze the effect of cigarette smoking on the concentration of adiponectin and potassium in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study, and the use of these two markers for risk prediction Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration The serum concentration of adiponectin was measured by ELISA Adiponectin was binned into tertiles separately for AS and NS and the Cox regression was used to assess the effect on mortality There were 777 AS and 1178 NS among the LURIC patients Within 10 years (median) of follow-up 221 AS and 302 NS died In unadjusted analyses, AS had lower G.E Delgado Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany R Siekmeier Drug Regulatory Affairs, Pharmaceutical Institute, Bonn University, Bonn, Germany W Maărz Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz Medical University, Graz, Austria Synlab Academy, Synlab Services LLC, Mannheim, Germany M.E Kleber (*) Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Leipzig, Germany Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany Mannheim Institute for Public Health, Social- and Preventive Medicine, 7-11 Ludolf-Krehl-St, 68167 Mannheim, Germany e-mail: marcus.kleber@medma.iim-heidelberg.de Pertussis: History of the Disease and Current Prevention Failure raise serious concern about further usefulness of the vaccine currently available and call for its redevelopment Other solutions under consideration or introduced to the vaccination schedule include booster doses at regular intervals for adolescents and adults The interesting new ideas include the immunization of newborns using the acellular pertussis vaccine, as this approach is indicated as safe and effective (Wood et al 2010) The first reports on the newborns immunization seem promising, but further evaluation and large-scale clinical trials are necessary to this end At present, neonatal protection is achieved by the cocooning strategy, ie, immunization of family members and other close contacts of newborns and infants, and also by immunization of pregnant women during the third trimester of pregnancy Conclusions Pertussis, although less prevalent since the introduction of the first vaccines, still remains a grave disease for susceptible persons, especially infants Due to changes in the Bordetella pertussis structure and the epidemiology and natural course of the disease, a careful evaluation of the current immunization schedule is needed to develop new solutions Both whole-cell and acellular types of vaccine provide waning immunity and the development of new vaccines may be necessary to decrease the incidence of pertussis or to maintain it at the current level Conflicts of Interest The authors declare no conflicts of interest in relation to this article References ACIP (1992) Pertussis vaccination: acellular pertussis vaccine for reinforcing and booster use – Supplementary ACIP statement recommendations of the immunization practices advisory committee MMRW Rec Rep Feb 07, 1992/41 (RR-1); 1–10 Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/ 00041801.htm Accessed on Feb 2016 ACIP (1997) Pertussis vaccination: use of acellular pertussis vaccines among infants and young children 81 recommendations of the Advisory Committee on Immunization Practices (ACIP) MMRW Rec and Rep March 28, 1997/46 (RR-7); 1–25 Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/ 00048610.htm Accessed on Feb 2016 Bouchez V, Brun D, Cantinelli T, Dore G, Njamkepo E, Guiso N (2009) First report and detailed characterization of B pertussis isolates not expressing Pertussis Toxin or Pertactin Vaccine 27:6034–6041 Bouchez V, Hegerle N, Strati F, Njamkepo E, Guiso N (2015) New data on vaccine antigen deficient Bordetella pertussis isolates Vaccine 14:751–770 Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA, Brown KH, Mijalski CM, Tiwari T, Weston EJ, Cohn AC, Srivastava PU, Moran JS, Schwartz B, Murphy TV, Advisory Committee on Immunization Practices (ACIP) (2006) Advisory Committee on Immunization Practices (ACIP) Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 55(RR-3):1–34 Cherry JD (2010) The present and future control of pertussis Clin Infect Dis 51(6):663–667 Cherry JD, Brunnel PA, Golden GS, Karzon DT (1988) Report of the task force on pertussis and pertussis immunization – 1988 Pediatrics 81:933–984 Dauer CC (1943) Reported whooping cough morbidity and mortality in the United States Public Health Rep 58:661–676 ECDC (2014) European Center for Disease Prevention and Control Annual epidemiological report 2014 – vaccine-preventable diseases Available from: http:// ecdc.europa.eu/en/publications/Publications/AER2014-VPD-FINAL.pdf Accessed on Feb 2016 Guiso N (2014) Bordetella pertussis: why is it still circulating? J Infect 68:S119–S124 Gustafsson L, Hessel L, Storsaeter J, Olin P (2006) Longterm follow-up of Swedish children vaccinated with acellular pertussis vaccines at 3, 5, and 12 months of age indicates the need for a booster dose at to years of age Pediatrics 118:978–984 Klein NP (2014) Licensed pertussis vaccines in the United States History and current state Hum Vaccin Immunother 10:2684–2690 Klein NP, Bartlett J, Fireman B, Rowhani-Rahbar A, Baxter R (2013) Comparative effectiveness of acellular versus whole-cell pertussis vaccines in teenagers Pediatrics 131:e1716–e1722 Lynfield R, Schaffner W (2014) Can we conquer coqueluche? J Infect Dis 209(Suppl 1):S1–S3 doi:10.1093/infdis/jit487 Miranda C, Porte L, Garcı´a P (2012) Bordetella holmesii in nasopharyngeal samples from Chilean patients with suspected Bordetella pertussis infection J Clin Microbiol 50:1505 Morgan LG (1997) Pertussis immunization: an update J Can Chiropr Assoc 41(2):86–90 82 Olin P, Gustafsson L, Barreto L, Hessel L, Mast TC, Rie AV, Bogaerts H, Storsaeter J (2003) Declining pertussis incidence in Sweden following the introduction of acellular pertussis vaccine Vaccine 21:2015–2021 Romanus V, Jonsell R, Bergquist SO (1987) Pertussis in Sweden after the cessation of general immunization in 1979 Pediatr Infect Dis J 6:364–671 Rucker WC (1912) Whooping cough, its nature and prevention: a popular discussion of a widespread and dangerous disease for which familiarity has bred Contempt Public Health Rep 27:1736–1739 Sato Y, Sato H (1999) Development of acellular pertussis vaccines Biologicals 27:61–69 Sheridan SL, Ware R, Grimwood K, Lambert SB (2012) Number and order of whole cell pertussis vaccines in infancy and disease protection JAMA 308:454–456 E Kuchar et al Tan T, Dalby T, Forsyth K, Halperin SA, Heininge U, Hozbor D, Plotkin S, Ulloa-Gutierrez R, von Koănig CH (2015) Pertussis across the globe: recent epidemiologic trends from 2000–2013 Pediatr Infect Dis J 34: e222–e232 Weston R (2012) Whooping cough: a brief history to the 19th century Can Bull Med Hist/Bulletin canadien d’histoire de la me´decine 29:329–349 WHO/UNICEF (2015) Global immunization data Available from: http://www.who.int/immunization/monitor ing_surveillance/Global_Immunization_Data.pdf? ua¼ Accessed on Feb 2016 Wood N, McIntyre P, Marshall H, Roberton D (2010) Acellular pertussis vaccine at birth and one month induces antibody responses by two months of age Pediatr Infect Dis J 29:209–215 Advs Exp Medicine, Biology - Neuroscience and Respiration (2016) 25: 83–88 DOI 10.1007/5584_2016_20 # Springer International Publishing Switzerland 2016 Published online: 31 May 2016 Awareness of Influenza and Attitude Toward Influenza Vaccination Among Medical Students A Banaszkiewicz, E Talarek, J S´liwka, F Kazubski, I Małecka, J Stryczyn´ska-Kazubska, W Dziubak, and E Kuchar Abstract In Poland, influenza vaccination coverage among both the general population and healthcare workers is low The aim of the study was to evaluate attitudes towards influenza vaccination among final-year medical students compared with first-year students at medical schools in Poland Students were asked about the last season’s influenza vaccination and what the reasons were for having, or not having, the vaccination The knowledge of influenza was assessed using a 10-point visual analog scale The study group consisted of 712 medical students, 404 in the first year and 308 in the final year (35 % and 31 % of all students in those years, respectively) Final-year students believed they had a better knowledge of influenza (OR ¼ 3.33; CI95 %: 2.54–4.39) They answered questions about influenza immunizations (OR ¼ 0.59; CI95 %: 0.44–0.78) and vaccination recommendations in pregnant women correctly more frequently (OR ¼ 0.21; CI95 %: 0.16–0.28) The influenza vaccination rate among students in the 2014/2015 season was similar (17.1 % in the first vs 15.9 % in the final year, NS) Among the final-year students, the reason for not having the vaccination was mainly financial and not any other We A Banaszkiewicz Department of Pediatric Gastroenterology and Nutrition, Warsaw Medical University, Warsaw, Poland E Talarek (*) Department of Children’s Infectious Diseases, Warsaw Medical University, 37 Wolska St., 01-201 Warsaw, Poland e-mail: ewa.talarek@wum.edu.pl I Małecka and J Stryczyn´ska-Kazubska Department of Health Promotion, Poznan University of Medical Sciences, Poznan, Poland J S´liwka Student Research Association, Warsaw Medical University, Warsaw, Poland W Dziubak Student Research Association, Wroclaw Medical University, Wroclaw, Poland F Kazubski Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland E Kuchar Department of Pediatrics with Clinical Decisions Unit, Warsaw Medical University, Warsaw, Poland 83 84 A Banaszkiewicz et al conclude that although medical students’ knowledge about influenza increases in the course of study, it did not much affect their unwilling attitude toward vaccination Keywords Education • Flu • Immunization • Infection • Prophylaxis • Vaccine Introduction The Center for Disease Control and Prevention (ACIP 2015), the World Health Organization (WHO 2015), and many local authorities worldwide strongly recommend that everyone aged months and over receive an influenza vaccination annually Despite those recommendations, influenza vaccination coverage is low in Poland Many studies have analyzed the reasons of the low coverage Firstly, in some countries, including Poland, the cost of the vaccination is not reimbursed Secondly, there is a lack of awareness about the need for the influenza vaccination Thirdly, a fear of adverse effects is observed in both healthy people and people with chronic diseases Additionally, many individuals advocate against vaccinations in general, which could influence the public opinion and, finally, many doctors and nurses not emphasize or neglect to mention the need for the influenza vaccination Of all the factors mentioned, the last one is the most embarrassing Theoretically, in medical schools, during the 6-year medical programme, students have the opportunity to learn about influenza and influenza vaccination on several occasions In the pre-clinical microbiology module, medical students learn how the influenza virus presents itself and replicates Then, during infectious disease, pediatrics or internal medicine modules, they study influenza symptoms, its course and complications, treatment and prevention One would expect the final-year medical students to have enough knowledge of influenza to be convinced that immunization is an important healthy behavior Therefore, the aim of this study was to evaluate the attitude toward influenza vaccination among final-year medical students compared to first-year students in medical schools in Poland Methods The study was approved a by local Ethic Committee and comported with the principles of the Declaration of Helsinki for Human Research This prospective study was conducted in three universities in Poland (cities of Warsaw, Wroclaw, and Poznan) in the period of April and June of 2015 A total of 2126 medical university students were involved into the study (see details in the Results section) First and final-year students of the Medical Faculty were asked to fill out a three-part two-page questionnaire The first part of the questionnaire consisted of questions regarding age, gender, and the year of study In the second part, the students should provide information whether they had been immunized against influenza during the 2014/2015 season and what their reasons were for having, or not having, the vaccination They could choose from several answers The third part of the questionnaire consisted of eight questions regarding the knowledge of influenza (listed below) This part consisted of a 10-point visual analog scale The students were recruited during their classes They marked the point on the scale that they felt best represented their answer out of the following choice: • What I know about influenza? (point 0: I know nothing; and point 10: I know everything) • How often is influenza severe? (point 0: always; and point 10: never) Awareness of Influenza and Attitude Toward Influenza Vaccination Among Medical Students • How often influenza complications occur? (point 0: always; and point 10: never) • How much does having influenza protect you against influenza in the future? (point 0: does not protect you at all; and point 10: protects you for life) • How much does flu vaccination protect you against influenza? (point 0: does not protect you at all; and point 10: protects you for life) • How often adverse events occur after the influenza vaccination? (point 0: always; and point 10: never) • Would you recommend the influenza vaccination to pregnant women? (point 0: always; and point 10: never) • Would you recommend the influenza vaccination to people with chronic obstructive pulmonary disease? (point 0: always; and point 10: never) The odds ratio and its 95 % confidence interval were used as a measure of effect size The confidence intervals for the differences between two independent binomial proportions were estimated using the Agresti-Caffo method The confidence interval for the difference between two dependent proportions was performed using the Wald procedure with the Agresti and Min modification McNemar’s test was used for two dependent proportions A global test for the difference between two sets of dependent proportions was estimated with 9999 bootstrapped samples The Chi-squared test for two proportions and the exact test, if necessary, were used for cross-classification tables The median was used as a location parameter and its statistic was computed as the measure of variability (Rousseeuw and Croux 1993) Confidence intervals for the difference between two medians were estimated using the studentized bootstrap approach Results Of the 2126 medical university students in the first (n ¼ 1140) and final year (n ¼ 986) of 85 medical faculties, 712 (404 from the first and 308 from the final study year) successfully completed the questionnaire Of those who completed the questionnaire, 16.5 % were vaccinated against influenza during the 2014/ 2015 season; 17.1 % (69/404) and 15.9 % (49/308) students in the first and final study year, respectively (p > 0.05) For the first year students the most common reason for being vaccinated was the fear of influenza and its complications Among the reasons for not being vaccinated, non-financial reasons were chosen 11 times less often (OR ¼ 0.09) by the final year than the first year students The reasons why the students chose to be, or not to be, vaccinated against influenza are shown in Table and Table 2, respectively The final year medical students, in their opinion, knew much more about influenza than the first year students did The detailed differences in answers given by the first and final year students are presented in Table Discussion The results of this prospective study indicate that the influenza vaccination rate is low (16.5 %) among medical students, irrespective of the study year For comparison, results of previously published studies assessing the seasonal influenza vaccination rate among medical students in different countries vary from 4.7 % to 58.1 % (Wicker et al 2013; Machowicz et al 2010) In a previous study performed in Poland, vaccination coverage rate has amounted to 15.2 % among medical students (Machowicz et al 2010), which is closely akin to the present results It is worth noting that this rate, as low as it appears, is four times higher than that for the general Polish population, where the influenza vaccination rate was 3.7 % in the 2014/2015 epidemic season Further, vaccination rate in medical students is higher than that among professional healthcare workers in Poland, where it amounts to % (Wozniak-Kosek et al 2015) In contrast, in a study of Herna´ndez-Garcia and Valero (2014), influenza vaccination coverage 86 A Banaszkiewicz et al Table Reasons for receiving influenza vaccination by medical university students I/II III IV 1st year students 6th year students a b Reason IV taken as baseline Reason for vaccination I not want to get influenza I am afraid of influenza complications I believe in vaccine efficacy My doctor recommends vaccination Ratio sixth/first year OR 5.01 CI95 % 3.14 8.01 p< 0.001 1.71 – 3.73 0.90 3.25 0.100 1.75 7.92 0.001 1st as baseline OR CI95 % 0.94 0.24 3.73 0.25 – 0.08 0.80 p< 0.928 0.019 CI confidence interval, OR odds ratio Reason IV, the least frequently cited, was taken as the baseline reference for 1st year students Reasons I and II were cited with equal frequency, fivefold less often than Reason IV; therefore a single statistical data elaboration applies to both these reasons b 1st year data are taken as the baseline reference after years of study for students of 6th year depicted in the rightmost part of the table to show changes in attitude with years of study toward influenza vaccination Here, Reason IV was chosen by students fourfold less frequently compared with 1st year The frequency of citing the other reasons was akin to that in 1st year a Table Reasons for not receiving influenza vaccination by medical university students 1st year students 6th year students a I/II III/IV/V VI Reason VI as baseline Reason for vaccination I am not afraid of getting influenza I not believe in vaccine efficacy I am afraid of vaccine side effects I am afraid of needles My doctor advises against vaccination I not have money to buy vaccine Ratio sixth/first year b OR 18.60 CI95 % 12.42 27.86 p< 0.001 1.22 0.79 1.87 0.370 – 0.09 0.06 0.13 0.001 1st year as baseline OR CI95 % 0.64 0.39 1.06 7.79 – 4.25 14.25 p< 0.080 0.001 CI Confidence interval, OR Odds ratio a Reason VI, the least frequently cited, was taken as the baseline reference for 1st year students Reasons I and II were cited with equal frequency (18.6-fold more often than Reason VI); therefore a single statistical data elaboration applies to both these reasons Similarly, Reasons III, IV and V were cited with equal frequency (1.2-fold more often than Reason VI), therefore a single statistical data elaboration applies to three these reasons b 1st year data are taken as the baseline reference for students of 6th year depicted in the rightmost part of the table to show changes in attitude with years of study towards influenza vaccination Reason VI was chosen almost eightfold more often compared with 1st year Other reasons were cited 1.5-fold less often compared with 1st year rate has amounted to a high 38.1 % level in health care workers and a meager 7.2 % among medical students, although the majority of students (70.8 %) support mandatory influenza vaccination Whatever the vaccination rate, it seems it can be further improved by a managerial strategy In Qatar, for instance, the hospital programmer sends letters promoting the influenza vaccination and a free-of-charge shots, which has improved vaccination coverage among health care workers from 60.2 % to 93.2 % in a 4-year period (Guanche Gacell et al 2015) We demonstrate in the present study that a 6-year-long Polish medical curriculum had no influence on the vaccination coverage rate among medical students Our results are in line with those of a Spanish study in which the vaccination coverage was not significantly higher for clinical students than that for pre-clinical ones (7.2 % vs 4.4 %, respectively) (Herna´ndezGarcı´a et al 2012) These results are, however, Awareness of Influenza and Attitude Toward Influenza Vaccination Among Medical Students 87 Table Awareness of influenza and attitude towards influenza immunization What I know about influenza How often is influenza severe How often influenza complications occur How much protection is acquired against influenza after coming down with the disease How much does a vaccine protect against influenza How often adverse events occur after vaccination Would you recommend influenza vaccination to pregnant women Would you recommend influenza vaccination to people with COPD ORa 3.33 1.08 1.15 0.59 0.96 1.22 0.21 0.07 CI95 % 2.54 4.39 0.83 1.4 0.89 1.5 0.44 0.78 0.73 1.24 0.93 1.58 0.16 0.28 0.05 0.1 p< 0.001 0.582 0.287 0.001 0.734 0.145 0.001 0.001 COPD chronic obstructive pulmonary disease, 10-point visual analog scale CI confidence interval, OR odds ratio a 1st year students’ responses are taken as the baseline reference at variance with a German study in which students at clinical semesters were significantly more likely to be vaccinated against influenza than those at preclinical semesters (58.1 % vs 15.3 %, respectively) (Wicker et al 2013) A possible explanation for the higher immunization rate in clinical students might be a knowledge gained on influenza complications and the need for protection This indicates that there is a strong need for improved teaching on modern vaccinology and the benefits of influenza vaccination in particular In the present study, the most frequently cited arguments for immunization were as follows: “I not want to get influenza” and “I am afraid of influenza complications” These arguments were chosen a similar number of times by first-year and final-year students It appears that students feared the disease and had they been better educated on the need for vaccination, they could have more likely gotten vaccinated When we analyzed the reasons for not getting the influenza vaccination, we found that firstyear students most frequently selected “I am not afraid of getting influenza”or “I not believe in the efficacy of the vaccine” Non-financial reasons were chosen 11 times less often (OR ¼ 0.09) by final-year students than by first-year students In Poland, recommended vaccines are not reimbursed in contrast to so-called mandatory vaccines which are free of charge Although the influenza vaccine is one of the cheapest vaccines available in Poland, a fiscal reason may have an influence over the low vaccination rate That, however, should have been equally observed in first and final-year medical students In fact, the final-year students chose the financial reason for not getting vaccinated nearly times more frequently than those in the first year (OR ¼ 7.79) A low rate of influenza vaccination we observed in the present study is explicable by the specificity of the vaccination policy in Poland above outline The ‘recommended vaccine’ label could suggest that such vaccines are less important Secondly, many individuals advocate against vaccinations in general, which could influence the public opinion Finally, many doctors and nurses express the opinion that they ‘favor immunization in general but are against influenza vaccination’ due to its purported ineffectiveness Taken together, these factors likely have an impact on vaccination status of medical students A second part of the questionnaire assessed awareness of influenza and influenza vaccination The results indicate that the vaccine cost was not the reason for not receiving vaccination among final-year medical students The vaccine price actually had a limited influence on the decision to not vaccinate Although the final-year students cited the price eight times more often than their younger peers as an important factor for a decision to not get vaccinated, yet the percentage of vaccinated students did not vary between the two groups These results confirm the notion that the final-year medical students not receiving the influenza vaccination was not a result of the lack of the appropriate medical knowledge regarding 88 influenza and the vaccination against it These students gave correct answers to this end significantly more often than the first-year students However, increased knowledge alone does not result in a greater proportion of students getting vaccinated Substantial differences in vaccination coverage among regions may be explained by earlier, local pro-vaccination attitudes which may have been developed before the improved knowledge on influenza was available The attitude of medical students toward the influenza vaccination is influenced by many factors, including their knowledge of the subject, emotional attitude to vaccinations, their social environment, and the role models, for instnace, a leading example of medical professors There are data pointing out that emotions are important or decisive factors in decision-making process as exemplified by neurological patients who cannot normally process emotional information due to brain damage, which results in a difficulty in undertaking decisions (Bechara 2004; Bechara et al 2000) In conclusion, the present study demonstrates that medical students’ knowledge of influenza is not a critical factor in the decision-making on immunization against influenza There is an unfulfilled need to implement better influenza vaccination strategies for medical students who will be future highly educated medical professionals A more rounded approach is needed to change the students’ attitude and to increase their immunization rate against influenza Medical curriculum should develop a more pro-health attitude in students through personal examples set by their professors and the creation of positive emotions in relation to vaccination Conflicts of Interest The authors declare no conflicts of interest in relation to this article A Banaszkiewicz et al References ACIP (2015) Advisory Committee on Immunization Practices Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices Available from: http:// www.cdc.gov/mmwr/preview/mmwrhtml/ mm6430a3.htm Accessed 30 Dec 2015 Bechara A (2004) The role of emotion in decisionmaking: evidence from neurological patients with orbitofrontal damage Brain Cogn 55:30–40 Bechara A, Damasio H, Damasio AR (2000) Emotion, decision making and the orbitofrontal cortex Cereb Cortex 10:295–307 Guanche Gacell H, Villanueva Arias A, Guilarte Garcı´a E, Rubiera Jime´nez R, Nonato AR (2015) A successful strategy for improving the influenza immunization rates of health care workers without a mandatory policy Int J Occup Environ Med 6:184–186 Herna´ndez-Garcı´a I, Valero LF (2014) Practices, beliefs and attitudes associated with support for mandatory influenza vaccination among Spanish medical students Vaccine 32:207–208 Herna´ndez-Garcı´a I, Domı´nguez B, Gonza´lez R (2012) Influenza vaccination rates and determinants among Spanish medical students Vaccine 31:1–2 Machowicz R, Wyszomirski T, Ciechanska J, Mahboobi N, Wnekowicz E, Obrowski M, Zycinska K, Zielonka TM (2010) Knowledge, attitudes, and influenza vaccination of medical students in Warsaw, Strasbourg, and Teheran Eur J Med Res 15(Suppl 2):235–240 Rousseeuw PJ, Croux C (1993) Alternatives to the median absolute deviation J Am Stat Assoc 88:1273–1283 WHO (2015) World Health Organization Global action plan for influenza vaccines objectives Global action plan for influenza vaccines Available from: http:// www.who.int/influenza_vaccines_plan/objectives/en/ Accessed 30 Dec 2015 Wicker S, Rabenau HF, von Gierke L, Franc¸ois G, Hambach R, De Schryver A (2013) Hepatitis B and influenza vaccines: important occupational vaccines differently perceived among medical students Vaccine 17:5111–5117 Wozniak-Kosek A, Mendrycka M, Saracen A, Kosek J, Hallmann-Szelin´ska E, Zielnik-Jurkiewicz B, Kempin´ska-Mirosławska B (2015) Vaccination status and perception of influenza vaccination in the Polish population Adv Exp Med Biol 836:41–46 Advs Exp Medicine, Biology - Neuroscience and Respiration (2016) 25: 89–93 DOI 10.1007/5584_2016_19 # Springer International Publishing Switzerland 2016 Published online: 28 May 2016 Pathogens Causing Upper Respiratory Tract Infections in Outpatients A Jama-Kmiecik, M Frej-Ma˛drzak, J Sarowska, and I Choroszy-Kro´l Abstract The aim of the present study was to determine the results of typical and atypical bacteria microbiological tests in patients with symptoms of chronic cough We investigated 230 outpatients aged from to 83 years (112 female, 72 male, and 46 children) who were free of any respiratory tract infection at the time of study The material for the investigation consisted of pharyngeal swabs Two hundred and thirty pharyngeal swabs were examined for Chlamydia pneumoniae antigen and for typical pathogens each Chlamydia pneumoniae antigen was detected using an indirect immunofluorescence test and classical microbiological culture was used for the detection of typical bacteria The antigen was found in 44/230 (19.1 %) patients with chronic cough (23 women, 13 men, and children) Positive culture for typical pathogens was observed in 65/230 (28.3 %) patients (37 women, 14 men, and 14 children) Simultaneous occurrence of Chlamydia pneumoniae and typical pathogens such as Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, and Haemophilus influenzae, was observed in 11/230 (4.8 %) patients The results show that in patients with chronic cough Chlamydia pneumoniae is detected less frequently than the typical pathogens are A search for atypical bacteria in patients with chronic cough is needed to be able to conduct effective and sufficiently long therapy Keywords Atypical bacteria • Chlamydia pneumoniae • Co-infection • Culture • Pathogen detection • Pharyngeal swabs A Jama-Kmiecik (*), M Frej-Ma˛drzak, J Sarowska, and I Choroszy-Kro´l Department of Basic Sciences, Wroclaw Medical University, Chałubin´skiego St, 50-368 Wrocław, Poland e-mail: agnieszka.jama-kmiecik@umed.wroc.pl Introduction Upper respiratory tract infections (URTIs) are caused by many different bacteria (including 89 90 mycobacteria) and viruses, and rapid detection of pathogens in individual cases is crucial in achieving the best clinical management The most common bacteria causing URTIs are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Mycoplasma pneumoniae The viral side is represented mostly by respiratory syncytial viruses (RSV), adenoviruses, influenza, parainfluenza, with all possible types of crisscross co-infections These infections clinically manifest as a group of disorders which include common cold, pharyngitis, tonsillitis, epiglottitis, sinusitis, bronchitis, rhinitis, and nasopharyngitis (Pettigrew et al 2011) The infections are usually viral as only 10 % of cases are attributed to bacteria, although the percentage of bacterial infection is difficult to estimate precisely due to the all too often encountered bacterial superinfections superimposed on the earlier original viral infection Nonetheless, most patients are treated with antibiotics (Kho et al 2013; Costelloe et al 2010) The rationale for the use of antibiotics might be that viral infections damaging the structure of airway epithelium pave the way for bacterial pathogens, cause inflammation, increase permeability of vascular endothelium, and also often times lead to bronchial hyperreactivity Various signs and symptoms of URTIs have been reported, including stuffy and runny nose, sneezing, coughing, sore throat, fever, vomiting, loss of appetite, and watery eyes Transmission of microorganisms causing URTIs has been known to occur by aerosol, droplet, and direct hand-to-hand contact with infected secretions Children are more susceptible to URTIs than adults This might be due to the lack of immunity to the many viruses and bacteria that cause URTIs and close person-to-person contact exercised by children (Hendaus et al 2015; Pavia 2011; Don et al 2009) An important role in URTIs plays the atypical bacterium Chlamydia pneumoniae It is a Gram-negative intracellular bacterium dependent on host cell ATP deposits, forming inclusions in the cytoplasm of infected cells Chlamydia pneumoniae has a unique developmental cycle and can exist in two forms: A Jama-Kmiecik et al elementary body (EB), a form responsible for spreading the infection, and reticulate body (RB), an intracellular metabolically active form Apart from this replication cycle occurring in acute infection, Chlamydia pneumoniae is able to persist in a non-replicating state (Kaăding et al 2014; Batteiger 2012) The purpose of this study was to investigate the frequency of RTIs infections and the underlying bacterial pathogenesis in a cohort representative for outpatient environment The dominant symptom in all patients investigated was chronic cough of unclear origin Methods The investigation was performed in accordance with the Declaration of Helsinki for Human Research and the protocol was accepted by the Ethics Committee of the Medical University of Wroclaw, Poland The study group consisted of 230 outpatients (112 female, 72 male, and 46 children) aged from to 83 years Patients were recruited in the period of September 2014 to September 2015 A major criterion for inclusion in the study was persisting cough The material tested was pharyngeal swabs taken in the morning in fasted state Specimens were collected before starting antibiotic therapy and were examined for the presence of Chlamydia pneumoniae antigen and for typical pathogens The antigen was detected using an indirect immunofluorescence test (Chlamydia Cel PN-IFT Kit; Cellabs Pty Ltd, Sydney, Australia) Specimens were stained in two sequential steps; the first one using a suspension of monoclonal antibodies which bind to Chlamydia pneumoniae antigen and the second using an Fluorescein isothiocyanate (FITC)conjugated goat anti-mouse antibody to visualize Chlamydia pneumoniae microorganisms Identification of four or more chlamydial elementary bodies among epithelial cells was taken as the criterion of a positive diagnosis Typical bacteria were detected using a classical culture of microbiological throat specimens Pathogens Causing Upper Respiratory Tract Infections in Outpatients Results C pneumoniae antigen was detected in 44 (19.1 %) outpatients, which included 23 (20.5 %) of women, 13 (18.1 %) of men, and (17.4 %) of children Typical respiratory tract pathogens such as Staphylococcus aureus strain MSSA, Streptococcus pyogenes, Moraxella catarrhalis and Haemophilus influenzae were detected in 65 (28.3 %) outpatients, which included 37 (33.0 %) of women, 14 (19.4 %) of men, and 14 (30.4 %) of children The most frequently occurring typical pathogen was Staphylococcus aureus strain MSSA Simulataneous occurrence of typical and atypical pathogens was found in 11 (4.8 %) of patients (Table 1) Discussion URTIs are the commonest acute problem dealt with in primary care; the ‘bread and butter’ of daily practice These infections have been suggested to be mild and self-limiting, but are also reported to lead to life threatening complications Different climatic conditions like rainy season, winter, low humidity conditions, and distorted immunity have been listed as being responsible for the occurrence of infection The causative agents involved in URTIs are coronavirus, rhinovirus, human parainfluenza virus, adenovirus, enterovirus and human respiratory syncytial virus The most common bacteria, on the other side, are betahemolytic streptococci, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Chlamydia pneumoniae, Mycoplasma pneumoniae, 91 Streptococcus pneumoniae, Haemophilus influenzae, Bordetella pertussis, and Moraxella catarrhalis In diagnostic microbiology, it is essential to distinguish between a patient’s commensal flora and the causative agent of an infection That is none too often an easy process, since in some cases microbes belong to normal flora of certain anatomical location, but are considered pathogens when isolated from other sites In our previous study that covered a 1-year period of September 2013 to September 2014, ie, preceding that of the current study, typical pathogens such as Staphylococcus aureus strain MSSA, Streptococcus pyogenes, and Moraxella catarrhalis were detected in 73 (34.1 %) out of the 214 patients with chronic cough The main infecting pathogen was then Staphylococcus aureus MSSA, followed by Streptococcus pyogenes, and Moraxella catarrhalis Chlamydia pneumoniae antigen was found in 55 (25.7 %) of patients Co-infections with typical and atypical pathogens occurred in 16 (7.5 %) of those 2014 patients tested positive (Jama-Kmiecik et al 2014) In the present study, all categories of respiratory pathogens were detected less frequently compared with the study above outlined: typical pathogens in 65 (28.3 %), Chlamydia pneumoniae antigen in 44 (19.1 %), and co-infections in 11 (4.8 %) out of the 230 patients studied Zubairi et al (2012) have investigated 124 patients with cough and pneumonia The most common microorganism detected was Mycoplasma pneumoniae (n ¼ 21; 17.0 %), followed by Chlamydia pneumoniae (n ¼ 15; 12.0 %), Streptococcus pneumoniae (n ¼ 9; 7.0 %), Haemophilus influenzae (n ¼ 2; 1.6 %), Klebsiella pneumoniae (n ¼ 2; 1.6 %), and Staphylococcus aureus (n ¼ 1; 0.8 %) Table Incidence of bacterial infections detected in patients with chronic cough Chlamydia pneumoniae Typical pathogensa Co-infection a Women (n ¼ 112) 23(20.5 %) 37 (33.0 %) (5.3 %) Men (n ¼ 72) 13 (18.1 %) 14 (19.4 %) (1.4 %) Children (n ¼ 46) (17.4 %) 14 (30.4 %) (8.7 %) Total (n ¼ 230) 44 (19.1 %) 65 (28.3 %) 11 (4.8 %) Staphylococcus aureus strain MSSA (methicillin-sensitive S aureus), Streptococcus pyogenes, Moraxella catarrhalis, and Haemophilus influenzae 92 Streptococcus pneumoniae was the most common organism isolated from blood cultures That is somewhat in contrast to the present study in which the most frequently detected pathogen was Staphylococcus aureus Tao et al (2012) have investigated 593 patients with community acquired pneumonia and identified 242 strains of bacteria isolated from 225 patients The most common pathogen was Streptococcus pneumoniae (79/242, 32.6 %), followed by Haemophilus influenzae (55/242, 22.7 %), and Klebsiella pneumoniae (25/242, 10.3 %) From a total of 527 patients who underwent serological test for atypical pathogens, Chlamydia pneumoniae infections were identified in 60 (11.4 %) cases Overall, that study demonstrates a high prevalence of atypical and mixed pathogens Miyashita et al (2003) have conducted an investigation on nasopharyngeal specimens and serum samples obtained from 366 adult patients with persistent cough lasting in excess of weeks Chlamydia pneumoniae was detected in (0.5 %) patients by cell culture, in 20 (5.5 %) patients by PCR, and in 24 (6.5 %) patients by enhanced IgG or IgM antibody titer against the pathogen using a fluorescence test There was a positive diagnostic match between PCR and serology in 13 cases The remaining seven PCR positive cases were serologically negative Out of the 24 serologically positive cases, 11 were PCR negative That gives an overall mismatch between the serologic and PCR yield of 18 cases, i.e., in about 41 % of Chlamydia pneumoniae infections The corollary is that either diagnostic method is burdened with a substantial amount of false negative results and both methods should better be used complimentarily Other respiratory tract pathogens noted in the study outlined above, including Bordetella pertussis and Mycoplasma pneumoniae, were identified by serology in 68 (18.5 %) and in (1.1 %) patients, respectively Dual infections by Chlamydia pneumoniae and Bordetella pertussis were found in patients However, no duality of Mycoplasma pneumoniae and Chlamydia pneumoniae or Mycoplasma pneumoniae and Bordetella pertussis infections were noted A Jama-Kmiecik et al In conclusion, the present study demonstrates that the prevalence of Chlamydia pneumoniae infection is overall high and the infection is more prevalent in women than man Co-infections are often associated with Chlamydia pneumoniae infection The available diagnostic methods to detect the pathogen have not yet been accurately standardized, which leads to a wide interlaboratory discrepancy in test results, even when employing the same type of test Conflicts of Interest The authors declare no conflicts of interest in relation to this article References Batteiger BE (2012) Chlamydia infection and epidemiology In: Tan M, Bavoil P (eds) Intracellular Pathogens I: Chlamydiales ASM Press, Washington, DC, pp 1–26 Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD (2010) Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis Br Med J 340: c2096 Don M, Valent F, Korppi M, Canciani M (2009) Differentiation of bacterial and viral community-acquired pneumonia in children Pediatr Int 51:91–96 Hendaus MA, Jomha FA, Alhammadi AH (2015) Virusinduced secondary bacterial infection: a concise review Ther Clin Risk Manag 24(11):1265–1271 Jama-Kmiecik A, Frej-Ma˛drzak M, Sarowska J, TeryksWołyniec D, Gos´ciniak G, Choroszy-Kro´l I (2014) Frequency of detection Chlamydophila pneumoniae antigen in children with cough Fam Med Prim Care Rev 16:233–235 (Article in Polish) Kaăding N, Szaszak M, Rupp J (2014) Imaging of Chlamydia and host cell metabolism Future Microbiol 9:509–521 Kho BP, Ong CM, Tan FT, Wee CY (2013) Antibiotic prescribing for upper respiratory tract infections in sarawak district hospitals Med J Malaysia 68:136–140 Miyashita N, Fukano H, Yoshida K, Niki Y, Matsushima T (2003) Chlamydia pneumoniae infection in adult patients with persistent cough J Med Microbiol 52:265–269 Pavia AT (2011) Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagosis Clin Infect Dis 52:284–289 Pettigrew MM, Gent JF, Pyles RB, Miller AL, NoksoKoivisto J, Chonmaitree T (2011) Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection J Clin Microbiol 49:3750–3755 Pathogens Causing Upper Respiratory Tract Infections in Outpatients Tao LL, Hu BJ, He LX, Wei L, Xie HM, Wang BQ, Li HY, Chen XH, Zhou CM, Deng WW (2012) Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China Chin Med J (Engl) 125:2967–2972 93 Zubairi AB, Zafar A, Salahuddin N, Haque AS, Waheed S, Khan JA (2012) Atypical pathogens causing community-acquired pneumonia in adults J Pak Med Assoc 62:653–656 Advs Exp Medicine, Biology - Neuroscience and Respiration (2016) 25: 95–96 DOI 10.1007/5584_2016 # Springer International Publishing Switzerland 2016 Index A Adipokines, 2, Airway obstruction, 42, 43, 45 Airway remodeling, 42, 44 Antioxidant, 73 Arterial pressure, 12, 14, 18–21 Asthma, 42–45, 79 Atrial fibrillation, 10, 16, 17, 20 Atypical bacteria, 90 B Biochemical markers, 1–7 Bronchi, 43–45, 50 Bronchial smears, 51, 52, 54–59 C Carcinomas, 50, 53, 54, 57, 58 Cardiovascular disease (CVD), 24 Chlamydia pneumoniae, 90–92 Co-infection, 90–92 Culture, 78, 80, 90, 92 D Depression, 24, 26, 28, 29 Diaphragm, 32, 37–39 E Echocardiography, 11, 12, 35 Education, 87, 88 Emotion, 24, 26–28, 88 Epidermal growth factor receptor (EGFR), 49–59 Exercise, 32–39, 90 HIT-a, 51, 57, 59 Hypokinesia, 33, 35, 38 I Immunization, 79–81, 84, 87, 88 Infection, 78, 80, 89–92 Inflammation, 2, 3, 6, 64, 65, 71–73, 90 Inflammatory disease, 42 L Lung cancer, 49–59 M Meconium aspiration syndrome (MAS), 64, 70, 72–74 Mood disturbance, 26–28 Mortality, 1–7, 10, 11, 20, 78, 80 Multidetector computed tomography (MDCT), 41–45 N N-acetylcysteine (NAC), 63–74 Neurocardiac regulation, 28 Non-small cell lung carcinomas (NSCLC), 50–55, 57, 58 O Oxidative damage, 64–69, 73, 74 P Parasternal (PS), 11, 32–38 Pathogen detection, 90 Pertussis vaccine, 79–81 Pharyngeal swabs, 90 Prevention, 77–81, 84 Prophylaxis, 77–81, 83–88 F Fatigue, 32, 35, 37–39 Flu, 85 Frequency-domain analysis, 12, 17, 18, 20 R Right heart catheterization, 11, 12, 15 Risk factors, 4, 7, 24 H Head-down bed rest (HDBR), 32, 33, 35–39 Head-up bed rest (HUBR), 32, 33, 35–39 Heart rate variability (HRV), 9–21, 24–28 S Scalene, 32, 37–39 Smoking, 2, 3, 51, 53, 54, 58, 59 Somatosome, 50 95 96 Sternocleidomastoid (SCM), 32, 34–38 Stress, 2, 23–29, 64 Sudden cardiac death, 10, 20, 21 Surfactant, 63–74 Systolic pulmonary, 12, 14, 15, 18–20 T Targeted molecular therapy, 50, 51, 59 Time-domain analysis, 11, 16–18 Index V Vaccine, 78–81, 86, 87 Volume of interest (VOI), 43 W Whooping cough, 77–81 ... p-value PH pulmonary hypertension, CTEPH chronic thromboembolic pulmonary hypertension, COPD chronic obstructive pulmonary disease, PASP systolic pulmonary arterial pressure, PAH pulmonary arterial... NS PAH pulmonary arterial hypertension, CTEPH chronic thromboembolic pulmonary hypertension, IPAH idiopathic pulmonary arterial hypertension, PVOD pulmonary veno-occlusive disease, PAWP pulmonary. .. the VLF band, is present in hypoxia-induced pulmonary hypertension Since the LF spectral band is equally influenced by the parasympathetic and sympathetic branch, and the HF spectral band solely
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