World Organization of Family Doctors (Wonca) and realization of the Millennium Development Goals

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1 Review PAPERS World Organization of Family Doctors (Wonca) and realization of the Millennium Development Goals Światowa Organizacja Lekarzy Rodzinnych (Wonca) i realizacja Milenijnych Celów Rozwoju Tomasz Tomasik, Katarzyna Dubas Key words: family physician, Millennium Development Goals, Wonca, Conference in Cancun Słowa kluczowe: lekarz rodzinny, Milenijne Cele Rozwoju, Wonca, konferencja w Cancun Department of Family Medicine, Chair of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow Tomasz Tomasik, MD, PhD Adjunct Health Economics and Social Security Department, Institute of Public Health, Jagiellonian University Medical College, Krakow Katarzyna Dubas, MPH, PhD student CORRESPONDENCE ADDRESS: dr n. med. Tomasz Tomasik Pracownia Medycyny Rodzinnej Uniwersytet Jagielloński Collegium Medicum ul. Bocheńska Kraków mmtomasi@cyf-kr.edu.pl RECEIVED: ACCEPTED: Abstract: The World Organization of Family Doctors (Wonca) supports the development of General Practice/Family Medicine and aspires to improve the standard of primary care all over the world. The aims of this article is to provide information about activities undertaken by Wonca and describe the most important events during the 19th Wonca World Conference, especially in relation to the Millennium Development Goals. On the international level, Wonca cooperates with the United Nations on realization of the Millennium Development Goals (the MDG) that relate not only to diseases and health, but also to poverty, hunger, gender equality and environment. Health related MDG focus on problems that most commonly affect the poor (child and maternal health, communicable diseases). These issues were also the main subject of the 19th World Conference of General Practitioners/Family Physicians in Cancun in May this year. Approximately 3,000 physicians from 80 countries participated in the Conference. The Scientific Committee accepted 1,300 presentations, among them were 11 from Poland. The achievement of the MDG represents one of the greatest challenges and requires primary health care to be prioritized. The world s community of general practitioners should continue its involvement and increase efforts to attain these goals. Polish family doctors who provide comprehensive, continuing care and have strong relationship with their patients and the community should also be involved in this process. Streszczenie: Światowa Organizacja Lekarzy Rodzinnych (Wonca) wspiera rozwój medycyny rodzinnej i dąży do poprawy standardu podstawowej opieki zdrowotnej na całym świecie. Celem niniejszego artykułu jest przedstawienie informacji na temat działań podejmowanych przez Wonca oraz opisanie istotnych wydarzeń, jakie miały miejsce w trakcie 19 Światowej Konferencji Wonca, zwłaszcza w odniesieniu do Milenijnych Celów Rozwoju. Na poziomie międzynarodowym Wonca współpracuje z Organizacją Narodów Zjednoczonych, starając się wspierać realizację Milenijnych Celów Rozwoju. Cele te obejmują nie tylko zagadnienia związane z ochroną zdrowia, ale odnoszą się także do ubóstwa, głodu, równości płci oraz środowiska. Zadania w obszarze zdrowia skupiają się na problemach dotyczących głównie ludzi biednych (zdrowie dzieci, opieka nad matkami, choroby zakaźne). Zagadnienia te były głównymi tematami obrad w czasie 19 Światowej Konferencji Lekarzy Rodzinnych, która odbyła się w maju bieżącego roku w Cancun. Wzięło w niej udział blisko 3000 lekarzy z 80 krajów. Komitet Naukowy zaakceptował do prezentacji 1300 doniesień naukowych, w tym 11 z Polski. Osiągnięcie Milenijnych Celów Rozwoju stanowi ogromne wyzwanie, ale aby było skuteczne, wymaga także wzmocnienia roli podstawowej opieki zdrowotnej. Światowa społeczność lekarzy rodzinnych powinna nadal brać udział, a nawet zwiększać wysiłki zmierzające do realizacji wyżej wymienionych celów. Polscy lekarze rodzinni, zapewniający wszechstronną i skoordynowana opiekę, a także mający silne więzi z pacjentami i społecznością lokalną, także powinni być włączeni w omawiany proces. Introduction Wonca is an acronym comprising the first five initials of the World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians. It is a non-governmental organization and uses its short name World Organization of Family Doctors. (Probl Med Rodz 2010;2(31):39 44) Being a huge association, Wonca brings together primary care physicians from different continents and has an important voice on the international level. Cooperation between the United Nations and Wonca is designed to fully realize the Millennium Development Goals. This is an immense activity which requires the involvement of general practi- 39

2 review PAPERS tioners/family physicians (GP/FP) from all over the world 1. The 19 th Wonca World Conference and its pre-conference meeting were the essential events which created an opportunity to present, discuss and plan actions on how GP/FP can become involved in the fight not only against diseases, but also against poverty and hunger 2. The Conference was organized in Cancun, Mexico from 19 th to 23 rd May 2010, and its title was The Millennium Development Goals: the Contribution of Family Medicine. The aims of this article are to: (1) give information about various activities undertaken by Wonca World and Wonca Europe, (2) describe the most important events during the 19 th Wonca World Conference in Cancun and highlight the contribution of Polish family doctors in it, (3) bring the readers attention to the initiatives related to the Millennium Developments Goals. Wonca World and Wonca Europe Wonca World was founded in 1972 by 18 organizations concerned with the academic aspects of general/family practice. There are now 120 member organizations (colleges, academies, associations) from 99 countries with over 250,000 GP/FP members. The mission of Wonca is to improve the quality of life of people all over the world through defining and promoting its values and by fostering and maintaining high standards of care in general practice/family medicine (GP/FM). It promotes continuous, comprehensive and personal care for the individual patient in the context of the family and the community. Wonca encourages and supports the development of academic organizations of GP/FP and provides a forum for exchange of knowledge and information between member organizations. Wonca interacts with world bodies such as the World Health Organization and acts as a supporter for its members at a global level. Several Committees and Wonca Working Parties undertake activities and implement different projects on an international level (committees/parties/interest group on: (1) Classification, (2) Quality in Family Medicine, (3) Rural Practice, (4) Informatics, (5) Education, (6) Research, (7) Women and Family Medicine, (8) Mental Health, (9) Behavior Change, (10) the Environment, (11) Ethical Issues, (12) Travel Medicine. Wonca Europe is one of seven European regional branches of Wonca. It has more than 40 member organizations and represents more than 45,000 family physicians in Europe. It is an academic and scientific society of GP/FP in Europe and stimulates an interest in research, education and quality improvement. Its main goals are to: expand undergraduate and vocational education in GP/FM; develop family medicine based on research; encourage the debate on professionally led continuous medical education and re-certification; support a proper balance within family medicine in relation to prevention, diagnosis, cure and care; raise the awareness of the responsibility of GP/FP not only for individual patients, but also for society as a whole. Wonca Europe established 4 networks organization: (1) The European Academy of Teachers in General Practice (EURACT), (2) The European Association for Quality in General Practice/Family Medicine (EQuiP), (3) The European General Practice Research Network (EGPRN), (4) The WONCA Europe Working Group for Young and Future General Practitioners (The Vasco da Gama Movement). The European Journal of General Practice (EJGP), an international, peer-reviewed scientific journal, is the official journal of Wonca Europe. Every three years Wonca World organizes world conferences. These are major occasions for GP/FP to present papers, discuss different issues and enhance their professional networks. In 2007 the world conference was held in Singapore and from 19 th to 23 rd May this year, in Cancun, Mexico. Pre-conference meetings Before the official opening of the 19 th Wonca World Conference of Family Doctors in Cancun, the Wonca Europe Council Meeting as well as the Wonca World Council Meeting took place. On the 15 th of May, the Wonca Europe Council Meeting started with a welcome by the president Prof. Igor Svab (Slovenia). Several reports were presented (president s, treasurer s, networks organizations - EURACT, EQuiP, EGPRN) and finally accepted. During the meeting, the most important debate was devoted to the research themes for the next European Union funding program. According to delegates, research in GP/ FM is not sufficiently addressed in the EU funding programs and underrepresented in its funded research. A part of the agenda was assigned to the European Journal of General Practice. The editorial process is on track, and four issues are going to be published in 2010 with a total number of approximately. 250 pages. It was stressed that a very important subject is to start the procedure of acquiring the Impact Factor. Also, more active promotion of the journal was advised. Representatives of national colleges presented reports on preparedness activities related to organization of future Wonca Europe conferences. In 2010 the conference will be organized in Malaga, Spain from 7 th to 9 th October. The next 40

3 review PAPERS one prepared by the College of Family Physician in Poland will be held in Warsaw (8 th 11 th September, 2011). The voting procedures to select new members of the Executive Board of Wonca Europe were conducted. Two candidates for the position of Vice-President received the same number of votes, and the next voting round was postponed until the meeting in Malaga. Prof Igor Svab finished his cadency as the President, and Dr Tony Mathie (Great Britain) undertook this position. Job Metsemakers (the Netherlands) was elected as honorary secretary and Carl Steylaerts (Belgium) as honorary treasurer. The Wonca World Council was held from 16 th to 18 th May. A considerable part of the meeting was devoted to discussion and acceptance of different reports, presenting activities from the last triennium ( ) of Wonca World officials, regional presidents, all committees and working parties. The Council received and adopted the proposed budget for the period Bylaw changes were suggested and discussion started. The Council voted unanimously in favor of ratifying the Wonca Bylaws and Regulations of the Council. These changes strengthened the role of women in Wonca World. The future of Wonca in the light of international cooperation was also the subject of discussion. Wonca - WHO relations were outlined and commented upon. Official recognition and ratification of 7 th Wonca Region (East Mediterranean) was completed. A proposal of establishing a World Family Doctor Day was raised and met with general approval. Sessions on the future of primary care were carried out in 8 groups. A summary of the results was presented during the plenary session. Presentation of the offers for organization of the 21 st Wonca World Conference in 2016 was arranged. Delegates decided that the conference will be organized in Rio de Janeiro, by Brazilian Society of Family and Community Medicine. During the last day of the Wonca World Council Meeting, the election of a President Elect and Executive Members at Large for the triennium was conducted. The appointment of Chairs/Conveners of several Committees and Wonca Working Parties was agreed upon. Prof Richard Roberts (USA) took the position of the Wonca President and Prof Michael Kidd from Australia was elected as the new President-Elect. The next day, the 19 th Wonca World Conference began th Wonca World Conference The 2010 World Wonca Conference brought the world of family medicine/general practice and primary health care to the Yucatan Peninsula, which separates the Caribbean Sea from the Gulf of Mexico and which is located in southeastern Mexico. The Conference started on the 19 th and finished on the 23 rd of May The conference target groups were: practitioners, teachers, researchers and managers in GP/FM. In addition, specialists in other disciplines interested in primary care participated, as well as other health-care professionals, managers and policy makers responsible for medical and social support in the local community. In all, approximately 3,000 delegates coming from 80 countries of all the Wonca Regions participated in this event. Organizers put forth special effort to convince young doctors, especially residents and trainees in GP/FM, to take part in the conference. They accounted for approximately 30% of all participants. The program included a variety of activities oriented towards clinical, educational, research, managerial and ethical areas of GP/FM. There were 1,600 abstracts sent to the Scientific Committee from which 1,300 were accepted for presentation. There were 5 keynote sessions, 10 symposiums, 54 workshops, 554 oral presentations and 685 poster presentations. The sessions were carried out simultaneously in 19 conference rooms. Family doctors from Poland actively participated in the conference. Eleven presentations from Poland were included in the scientific program. A workshop was devoted to patients compliance. The oral presentations were related to cardiovascular diseases (goals achievements in dyslipidemia treatment, hypertension in pregnancy and smoking cessation), psychiatric and psychological problems in family doc- Table I. Selected country Workshop Type of presentation Oral presentation Symposium Poster presentation Poland Czech Republic Number of presentations from selected countries included in the program of the 19th Wonca World Conference in Cancun, Mexico 2 10 Germany Russia 2 USA Canada Brasil Spain

4 review PAPERS tors practices, colorectal cancer screening and barriers to compliance. The poster presentations were linked to education, hyperlipidemia and smoking cessation issues. A comparison of the presentations accepted into the conference scientific program from Poland and other selected countries is shown in Table I. 2. Message from the conference The theme of the 19 th Wonca World Conference was: Millennium Development Goals: the Contribution of Family Medicine. The Millennium Development Goals (MDG) were established in 2000 by the United Nations and became important priorities that constitute international policy targets. They consist of 8 goals with 21 targets and a series of measurable indicators for each of them. The United Nations General Assembly set 2015 as the target date for achieving the MDG, which are as follows: 1. Eradicate extreme poverty and hunger, 2. Achieve universal primary education, 3. Promote gender equality and empower women, 4. Reduce child mortality, 5. Improve maternal health, 6. Combat HIV/AIDS, malaria and other diseases, 7. Ensure environmental sustainability, 8. Develop a global partnership for development. Each year a special expert group presents a detailed report on annual assessment of progress towards the MDG. According to the latest, many parts of the word have made very good progress, which is especially remarkable in east and south Asia 3. Despite many previously achieved successes, realization of the goals is now being threatened by sluggish economic growth and diminished resources 4. Sub-Saharan Africa is in persistent crisis, with rising hunger and extreme poverty 5. Nevertheless, the Millennium Development Goals remain the focus points of the international policy and play a pivotal role in strengthening global cooperation and solidarity 6,7. Three of the MDG directly reflect health issues; however, all of them can be linked to the broadly defined well-being. Eradication of poverty and hunger is crucial for achieving health status improvement. Health related MDG focus on problems that most commonly affect the poor (communicable diseases, child and maternal mortality). The presented issues should be, without any doubts, the center of attention for GP/FP all over the world. The inter-relationship between physical condition and socio-economical status is clear. Poverty is one of the most important factors influencing health 8. It acts through unemployment, poor diet, inappropriate housing, higher stress levels, difficulties to adopt a healthy lifestyle, inability to afford health insurance and limited access to health care. People living in poverty tend to have poor health, more chronic illnesses, severe disease complications and die younger. In turn, sickness and disability can affect productivity and the income of individuals 9. These factors contribute to low or even negative rates of economic growth and thereby to prolonged or even worsened poverty over time. Better health can support economic growth, and as a consequence, the MDG cannot be achieved without strengthening the health care system 10. After 30 years since the Declaration of Alma Ata, the Millennium Development Goals structure and choice of priorities makes primary health care (PHC) contribution an important and undeniable issue. Problems like child mortality, maternal health and fighting disease epidemics such as AIDS and malaria are a direct link to the health care sector especially to its basis constituted by Family Medicine. GP/FP all over the world, being for a majority of patient the first contact point with medical help and providing care for most of a family s health needs, play a crucial role. Additionally, the complexity of family physicians work and their strong professional relationship over time with patients and whole communities emphasize the importance of their influence 11. During the conference, it was highlighted that the role of GP/FP in achieving the MDG was reinforced in 2008 when the World Health Organization issued the report Primary Health Care Now More Than Ever 12. The authors of the publication clearly state that primary health care offers ( ) a way to improve fairness in access to health care and efficiency in the way resources are used. It embraces a holistic view of health that goes well beyond a narrow medical model. PHC recognizes that many root causes of diseases and overall health problems lie beyond the control of the health sector and thus must be tackled through a broad wholeof-society approach. According to the report, four interlinked policy directions should constitute primary health care core principles: 1. Universal coverage, 2. People-centered services, 3. Healthy public policies, 4. Leadership. For a family physician s daily practice, the second point from those listed above seems crucial. Characteristic for family medicine, the continuous and comprehensive character of the doctor-patient relationship as well as a community-oriented approach are basic aspects distinguish- 42

5 review PAPERS Figure 1. Primary health care (PHC) as a holistic, people-oriented approach comprising elements of disease control programs (DCP) and conventional ambulatory care (AC) AC DCP PHC ing conventional health care from people-oriented primary care (see Figure 1). Conventional ambulatory care (AC) focusing on illness is limited to episodic curative care, and interaction with the patient finishes the moment he/she leaves the clinic. Disease control programs (DCP) have a broader scope of influence, but still they focus on specific disease target groups only during the period of program implementation. People-oriented primary health care linked with these two areas and depending on their active cooperation goes far beyond this. Family physicians must focus on the health needs of their patients and take responsibility for the health of the entire community throughout its life cycle. Only by developing a long-term relationship with the patient and taking into account their emotional and social concerns as well as those strictly medical they can provide effective health care. The issues described in The World Health Report 2008 as well as many recent studies provide evidence of primary health care development resulting in: better health outcomes 13 16, lower costs 17,18, and greater equity in health. One of the topics, being a subject of recent studies, is the impact of comorbidity on the use of primary care and specialty services 19. Comorbidity, or even multimorbidity, is common for GP/FM general practitioners often have to care for patients with several concurrent chronic conditions. Comorbidity prevalence becomes an important issue for a family physician s daily practice e.g. in the United States the percentage of Medicare beneficiaries with more than 5 treated conditions increased from 31 to 40 and then to 50 percent respectively in 1987, 1997 and The age-adjusted prevalence increased in the same period for: hyperlipidemia (2.6 to 10.7 to 22.2); osteoporosis (2.2 to 5.2 to 10.3); mental disorders (7.9 to 13.1 to 19.0); heart disease (27.0 to 26.1 to 27.8). The message from the data above is that discretionary diagnoses are increasing in prevalence, particularly those associated with new pharmaceuticals. This has a strong impact on resource use and control of the morbidity burden. As comorbidity (and hence multimorbidity) is increasing, specialist use is also growing. The more different specialists are seen, the higher the costs of medical care provision become. The important conclusion is that high quality and universally available primary health care can assure provision of more appropriate referrals to a specialist and thus more effective use of specialist services. Family physicians can provide continuous and comprehensive medical care, especially concerning chronic diseases, which is often more effective than the one offered by the multiplicity of a narrowly focused specialist. Conclusions This year in September, the 10th anniversary of introducing the MDG is coming, and this is an occasion to discuss the achieved goals in the fight against disease, hunger and poverty. For GP/FP this process started at the 19 th Wonca World Conference in Cancun and may be continued during regional and national conferences. Without any doubts, the MDG have encouraged significant progress, but the various challenges remain huge. Global efforts were often ineffective and disorganized, whilst the MDG are simple, straightforward, practical and undeniable. They became the principles not only for governments developing specific programs or preparing assistance strategies, but also for associations, foundations and other nongovernmental organizations. The world community of GP/FP should continue their involvement and increase efforts to attain these goals, especially in the field of communicable diseases as well as the health of women and children. Polish family doctors should also be involved in this process. It may be concluded that the development and strengthening of family medicine can without any doubt be linked with its contribution towards realization of the MDG. Primary care-focused initiatives can improve access to health care at a reasonably low cost. Regardless of the disparities between its objectives in different regions of the world and the inequalities of patients needs, it remains the cornerstone of the health care systems all over the world. Its overall mis- 43

6 review PAPERS sion is extremely important, irrespective of whether family medicine is tackling epidemics and hunger related health problems in Africa or growing technology and tele-medicine demands in Europe. Achievement of the health-related MDG represents one of the greatest challenges and requires health to be prioritized within overall economic and development policies. It is obvious that investments in health are important means of economic growth. The MDG cannot be met without a proper financial system, especially in underdeveloped countries. Not only should significant additional resources be allocated for health, but there is also a need to reconsider and re-prioritize the use of existing resources, focusing them on primary health care. Only in this way may the money allocated to health reach the people who need it most. References: 1. th 2. Wonca. Final Program of the 19 Wonca World Conference. Cancun, Mexico, Shaikh BT. Marching toward the Millennium Development Goals: what about health systems, health-seeking behaviours and health service utilization in Pakistan? Healthc Q 2008;11: United Nations. The Millennium Development Goals Report The UN, New York, Sachs JD. Health in the developing World: achieving the Millennium Development Goals. Bull World Health Organisation 2004;82: Stuckler D, Basu S, McKee M. Drivers of inequality in Millennium Development Goal progress: a statistical analysis. PLoS Med 2010;7:e Bhutta ZA, Chopra M, Axelson H, Berman P, Boerma T, Bryce J, Bustreo F, Cavagnero E, Cometto G, Daelmans B, de Francisco A, Fogstad H, Gupta N, Laski L, Lawn J, Maliqi B, Mason E, Pitt C, Requejo J, Starrs A, Victora CG, Wardlaw T. Countdown to 2015 decade report ( ): taking stock of maternal, newborn and child survival. Lancet 2010;375: Sachs JD. Millennium Development Goals at 10. Sci Am 2010;02: Dodd R, Cassels A. Health, development and the Millennium Development Goals. Ann Trop Med Parasitol 2006;100: Sachs JD. Investing in development. A practical plan to achieve Millennium Development Goals. United Nations, New York, Kruk ME, Porignon D, Rockers PC, Van Lerberghe W. The contribution of primary care to health and health systems in low- and middle-income countries: a critical review of major primary care initiatives. Soc Sci Med 2010;70: World Health Organisation. The World Health Report 2008, Primary Health Care Now More Than Ever. WHO, New York, Shi L, Macinko J, Starfield B, Wulu J, Regan J, Politzer R. The relationship between primary care, income inequality and mortality in the United States, J Am Board Fam Pract 2003;16: Franks P, Fiscella K. Primary care physicians and specialist as personal physicians. Health care expenditures and mortality experience. J Fam Pract 1998;47: Weinberger M, Oddone EZ, Henderson WG. Does increased access to primary care reduce hospital readmissions? For the Veterans Affairs Cooperative Study Group on Primary Care and Hospital Readmission. N Engl J Med 1996;334: Gill JM, Mainous AGI, Nsereko M, The effect of continuity of care on emergency department use. Arch Fam Med 2000;9: Forrest CB, Starrfield B. The effect of first contact care with primary care clinicians on ambulatory health care expenditures. J Fam Pract 1996;43: Ross NP, Carriere KC, Friesen D. Factors influencing the frequency of visits by hypertensive patients to primary care physicians in Winnipeg. Can Med Ass J 1998;159: Starfield B, Lemke KW, Herbert R, Pavlovich WD, Anderson G. Comorbidity and the use of primary care and specialist care in the elderly. Ann Fam Med 2005;3: Starfield B. Primary Care/Specialty Care in the Era of Nultimorbidity, 19 Wonca World Conference, Cancun, Mexico, 19 th 23 rd May, 2010 ( 44

7 Review PAPERS Intracerebral haemorrhage risk factors, diagnostics and treatment Krwotok śródmózgowy czynniki ryzyka, diagnostyka i leczenie Joanna Tarasiuk, Alina Kułakowska, Wiesław Drozdowski Key words: stroke, intracerebral haemorrhage, hypertension Słowa kluczowe: udar mózgu, krwotok śródmózgowy, nadciśnienie tętnicze Abstract: Intracerebral haemorrhage accounts for 10 15% of strokes and is characterized by a severe clinical course with high early mortality, which is 35 52%. The outcome after intracerebral haemorrhage is influenced by: the patient s age, clinical state at the admission to hospital and localization of haemorrhagic focus. The main risk factor for intracerebral haemorrhage is hypertension, present in 70 80% of patients. Other less common risk factors are: amyloid angiopathy, tumors, coagulation disorders, arterio-venous malformations, cavernous angiomas, aneurysms, trauma. The onset of symptoms in intracerebral haemorrhage is abrupt. It commonly starts during the day, frequently after physical exercise or with emotions. The character of neurological symptoms depends on the site and extensiveness of haemorrhagic lesion. In the diagnosis the basic role play neuroimaging investigations mainly computer tomography. The management depends on the cause of bleeding, is aimed at maintaining the basic vital functions and also the important role plays the patients complex rehabilitation. Streszczenie: Krwotok śródmózgowy stanowi 10 15% wszystkich udarów mózgu oraz cechuje się ciężkim przebiegiem klinicznym z wysoką śmiertelnością wczesną, która sięga 35 52%. Na przeżycie chorych z krwotokiem śródmózgowym istotny wpływ mają: wiek chorego, stan kliniczny przy przyjęciu oraz lokalizacja ogniska krwotocznego. Najczęstszym czynnikiem ryzyka krwotoku śródmózgowego jest nadciśnienie tętnicze, które występuje u około 70 80% chorych. Inne rzadsze czynniki ryzyka to: angiopatia amyloidowa, guzy, zaburzenia krzepnięcia, malformacje tętniczo-żylne, naczyniaki jamiste, tętniaki, urazy. Początek objawów w krwotoku śródmózgowym jest nagły. Do zachorowania dochodzi najczęściej w ciągu dnia, często w trakcie wysiłku fizycznego lub pod wpływem emocji. Charakter objawów neurologicznych zależy od lokalizacji oraz rozległości ogniska krwotocznego. W diagnostyce podstawowe znaczenie mają badania neuroobrazowe przede wszystkim tomografia komputerowa. Leczenie zależy od przyczyny krwawienia, ma na celu podtrzymanie podstawowych funkcji życiowych, istotną rolę odgrywa też kompleksowa rehabilitacja chorych. Clinic of Neurology, Medical University in Białystok Lek. Joanna Tarasiuk Asystent dr n. med. Alina Kułakowska Adiunkt prof. dr hab. Wiesław Drozdowski Kierownik Kliniki CORRESPONDENCE ADDRESS: Lek. Joanna Tarasiuk, Klinika Neurologii, Uniwersytecki Szpital Kliniczny w Białymstoku ul. Skłodowskiej-Curie 24a Białystok tel.: (+48) fax: (+48) amirtarasiuk@wp.pl RECEIVED: ACCEPTED: Wstęp Badania epidemiologiczne wskazują, iż udar mózgu jest istotnym społecznie problemem zdrowotnym i stanowi trzecią co do częstości, po chorobie niedokrwiennej serca i nowotworach, przyczynę zgonów na świecie oraz główną przyczynę długotrwałej niesprawności u osób dorosłych. Według definicji WHO udarem mózgu nazywamy zespół kliniczny charakteryzujący się nagłym pojawieniem się ogniskowych lub uogólnionych zaburzeń funkcji mózgu, które utrzymują się powyżej 24 godzin i nie mają innej przyczyny niż naczyniowa. Krwotoki śródmózgowe (ang. intracerebral haemorrhage ICH) stanowią 10 15% wszystkich udarów mózgu w populacji rasy białej. Proporcja ta jest wyższa w populacjach rasy żółtej oraz czarnej (Probl Med Rodz 2010;2(31):45 49) i wynosi 30 40% udarów 1. Stwierdzono, iż roczna zapadalność na krwotok śródmózgowy wynosi od 20 do 60 przypadków na 100 tysięcy dorosłych w wieku od 45 do 84 lat 2, ze szczytem zachorowań około 60 roku życia nieco wcześniej niż w przypadku udarów niedokrwiennych. Krwotoki śródmózgowe mogą również występować u osób przed 45 rokiem życia. Najbardziej narażoną grupę stanowią chorzy z wieloletnim, nieleczonym nadciśnieniem tętniczym 3. Unaczynienie mózgowia Krew doprowadzana jest do mózgu przez parzyste tętnice: szyjne wewnętrzne i kręgowe. Tętnica szyjna wewnętrzna oddaje w jamie czaszki tętnicę przednią i środkową mózgu oraz tętnicę łączącą tylną. Tętnice kręgowe, prawa i lewa, łączą się w jamie czaszki tworząc tętnicę podstawną, która 45

8 review PAPERS rozgałęzia się na prawą i lewą tętnicę tylną mózgu. Tętnice szyjne wewnętrzne unaczyniają większą część przodomózgowia, natomiast tętnice kręgowe wraz z tętnicą podstawną tworzą układ podstawno-kręgowy, unaczyniający pień mózgu i móżdżek oraz tylno-dolną część przodomózgowia. Tętnice mózgowe tworzą na podstawie mózgowia tzw. koło tętnicze mózgu Willysa. Ośrodkowy Układ Nerwowy (oun) cechuje się bardzo intensywną przemianą materii, stąd konieczność jego bogatego unaczynienia i bardzo duża wrażliwość na niedotlenienie. Mózg nie ma zdolności gromadzenia i przechowywania energii, z czego wynika konieczność stałego dopływu tlenu i glukozy. Ustanie dopływu krwi do mózgu powoduje utratę świadomości po 10 s. W warunkach prawidłowych przepływ krwi przez mózgowie wynosi 50 ml/100 g/min (15 20% pojemności minutowej serca) 4. Udar mózgu Ze względu na etiologię, udary mózgu dzielimy na: udary niedokrwienne 80% krwotoki śródmózgowe 15% krwotoki podpajęczynówkowe 5% Krwotok śródmózgowy polega na nagłym wylewie krwi z pękniętego naczynia, co powoduje mechaniczne zniszczenie tkanki nerwowej mózgu. W wyniku krwotoku powstaje krwiak śródmózgowy, który w ciągu kilku tygodni ulega hemolizie i wchłonięciu, pozostawiając jamę pokrwotoczną lub bliznę 5. Udar krwotoczny cechuje się zwykle ciężkim przebiegiem klinicznym, co wynika ze zniszczenia poszczególnych ośrodków i szlaków nerwowych w ośrodkowym układzie nerwowym (oun) oraz z towarzyszącego krwawieniu wzrostu ciśnienia śródczaszkowego. Czynniki ryzyka krwotoku śródmózgowego Do najczęstszych czynników ryzyka krwotoku śródmózgowego zalicza się: nadciśnienie tętnicze, które występuje u około 70 80% chorych i zwiększa ryzyko zachorowania ponad 4-krotnie 2, malformacje naczyniowe, a wśród nich drobne tętniaki, malformacje tętniczo-żylne, naczyniaki jamiste, angiopatię amyloidową. Rzadziej występujące czynniki ryzyka to: pierwotny (glejak wielopostaciowy) lub przerzutowy nowotwór wewnątrzczaszkowy (najczęściej przerzuty czerniaka, raka oskrzeli, gruczołu tarczowego, kosmówczaka i raka jasnokomórkowego nerki) 6, choroby krwi, a zwłaszcza koagulopatie (hemofilia typu A, zakrzepowa plamica małopłytkowa, ostra białaczka zwłaszcza szpikowa i promielocytowa), leki i narkotyki sympatykomimetyczne (amfetamina, efedryna, pseudoefedryna, kokaina), leki przeciwzakrzepowe, urazy czaszkowo-mózgowe, choroba moya-moya, ukrwotocznienie udaru niedokrwiennego, palenie papierosów, nadużywanie alkoholu, niskie stężenie cholesterolu we krwi. Obraz kliniczny krwotoku śródmózgowego Objawy kliniczne krwotoku mózgowego pojawiają się nagle i narastają gwałtownie w ciągu 1 2 godzin. Charakter objawów neurologicznych jest zależny od wielkości i topografii krwawienia 3. Można je podzielić na dwie grupy: objawy ogólne związane ze wzrostem ciśnienia śród- 1. czaszkowego: silny ból głowy, nudności, wymioty, zaburzenia świadomości, tarcza zastoinowa na dnie oka, objawy ogniskowe wynikające z lokalizacji ogniska 2. krwotocznego. Krwotoki śródmózgowe spowodowane nadciśnieniem tętniczym zlokalizowane są najczęściej w okolicy jąder podstawy, wzgórza, pnia mózgu lub móżdżku 7. Natomiast wywołane innymi czynnikami są zazwyczaj zlokalizowane w obrębie półkul mózgu (krwotoki płatowe). Krwotok zlokalizowany w okolicy jąder podstawy objawia się niedowładem połowiczym oraz połowiczym zaburzeniem czucia, niedowładem nerwu twarzowego typu ośrodkowego, skojarzonym zwrotem gałek ocznych w stronę ogniska (Rycina 1). Krwotok ten przebiega przeważnie bez zaburzeń przytomności. Krwotok do wzgórza stanowi drugą co do częstości występowania lokalizację, objawia się zaburzeniami czucia, czasem też deficytem ruchowym, zespołem pozapiramidowym, zaburzeniami poznawczymi oraz świadomości. Krwotok do mostu powoduje porażenie czterokończynowe, z porażeniem skojarzonego patrzenia do boku, obustronnie szpilkowate źrenice, zespół opuszkowy, szybko dochodzi do zaburzeń świadomości, niedomogi pnia mózgu oraz śpiączki. W krwotoku do móżdżku dominują bóle i zawroty głowy, wymioty, dyzartryczne zaburzenia mowy, ataksja kończyn i tułowia. Przy ucisku na pień mózgu szybko dochodzi do zaburzeń świadomości. W krwotokach do półkul mózgo- 46

9 REVIEW PAPERS prace poglądowe Postępowanie terapeutyczne powinno być rozpoczęte jak najwcześniej i być prowadzone wspólnie z procesem diagnostycznym. Nie została udowodniona wyższość leczenia neurochirurgicznego nad leczeniem zachowawczym 3,10,11. Postępowanie powinno być ukierunkowane na podtrzymanie podstawowych funkcji życiowych, leczenie objawowe oraz zapobieganie powikłaniom krwotoku. Istotne znaczerycina 1. Krwawienie zlokalizowane w strukturach głębokich po stronie prawej z przebiciem do układu komorowego krew w komorach bocznych, komorze iii, wodociągu i komorze iv wych (płatowych) krwiaki płata czołowego często mają przebieg z utratą przytomności, zaburzeniami mowy, zaburzeniami czucia oraz niedowładami połowiczymi. Krwiaki płata skroniowego objawiają się bólami głowy, nadpobudliwością, zaburzeniami behawioralnymi, może dojść także do niedowładów połowiczych oraz napadów padaczkowych. Krwiaki płata potylicznego charakteryzują się niedowidzeniem połowiczym jednoimiennym, mogą wystąpić także napady padaczkowe. Krwiaki płata ciemieniowego powodują ból okolicy ciemieniowo-skroniowej oraz przeciwstronne zaburzenia czucia. Objawy kliniczne oraz przebieg krwotoku mózgowego zależą od objętości wynaczynionej krwi oraz lokalizacji krwawienia. Na skutek wynaczynienia krwi spada przepływ we wszystkich naczyniach mózgu, co powoduje niedokrwienie całego mózgu i obrzęk mózgu z zespołem ciasnoty śródczaszkowej, co może prowadzić do wgłobienia z objawami niedomogi pnia mózgu 8. Powikłania Najpoważniejszymi powikłaniami krwotoku śródmózgowego są: ponowne krwawienie, niedomoga pnia mózgu wskutek wklinowania migdałków móżdżku do otworu wielkiego oraz przebicie się krwi do układu komorowego, co powoduje podrażnienie ośrodków oddychania i krążenia położonych pod dnem komory IV i często prowadzi do zgonu w mechanizmie ostrej neurogennej niewydolności oddechowo-krążeniowej oraz do powstania wodogłowia (Rycina 2). Powikłaniem internistycznym krwotoku śródmózgowego może być neurogenny obrzęk płuc, infekcje układu oddechowego, odleżyny, zakrzepica żylna w kończynach dolnych oraz infekcje układu moczowego spowodowane cewnikowaniem pęcherza moczowego. Badania diagnostyczne W rozpoznaniu i różnicowaniu krwotoku śródmózgowego istotne są dane z wywiadu, badania przedmiotowego i badań neuroobrazowych, z których najistotniejszą rolę odgrywa tomografia komputerowa (TK) głowy wykonywana w celu wykrycia krwawienia. W przypadku podejrzenia krwawienia na tle malformacji naczyniowej lub tętniaka wskazane jest wykonanie badań naczyniowych, tj. angiografii tomografii komputerowej lub rezonansu magnetycznego (MRI), czy też cyfrowej angiografii substrakcyjnej (DSA). W przypadku podejrzenia naczyniaka jamistego należy wykonać badanie MRI9. Wszyscy chorzy z rozpoznanym krwotokiem śródmózgowym wymagają intensywnego nadzoru i monitorowania podstawowych funkcji życiowych, tj. ciśnienia tętniczego krwi, częstości pracy serca i temperatury. Należy wykonać podstawowe badania laboratoryjne, takie jak: morfologia, OB, elektrolity, cukier, kreatynina, aminotransferazy, układ krzepnięcia. Leczenie PROBLEmY medycyny RODZINNEj, september 2010, VOL. Xii, No. 2 47

10 review PAPERS Rycina 2. Krwawienie do układu komorowego nie ma obniżenie ciśnienia śródczaszkowego lub zapobieganie jego narastaniu. Jednak gwałtowne obniżanie ciśnienia śródczaszkowego może nasilać krwawienie. Leczenie diuretykami osmotycznymi powinno być wdrożone w wypadku wyraźnych objawów wzmożonego ciśnienia śródczaszkowego z zaburzeniami świadomości. Należy pamiętać o zapobieganiu powikłaniom krwotoku śródmózgowego, takim jak: zakrzepica żył głębokich, zator tętnicy płucnej, odleżyny, zapalenie płuc, zakażenie układu moczowego. Zaleca się rozważenie podskórnego podawania małych dawek heparyny niefrakcjonowanej lub drobnocząsteczkowej w celu zapobieżenia zakrzepicy żył głębokich w drugim dniu od wystąpienia ICH u pacjentów w stanie neurologicznym stabilnym, obciążonych dużym ryzykiem zakrzepicy żył głębokich i zatorowości płucnej. Odleżynom zapobiega częste zmienianie pozycji ciała chorego oraz użycie materacy przeciwodleżynowych. Zakażenia dróg oddechowych czy układu moczowego należy leczyć odpowiednimi antybiotykami. U wszystkich pacjentów zaleca się wczesną rehabilitację, natomiast wczesne uruchamianie tych chorych, u których nie stwierdza się nadciśnienia śródczaszkowego. Wczesne usprawnianie zapobiega powikłaniom, takim jak zachłystowe zapalenie płuc, zakrzepica żył głębokich i odleżyny. W celu leczenia drgawek i zapobiegania ich nawrotom zaleca się stosowanie leków przeciwdrgawkowych. Chirurgiczna ewakuacja krwiaka wskazana jest u pacjentów, u których zmiana jest zlokalizowana powierzchownie, a ich stan stopniowo pogarsza się z powodu efektu masy. Leczenie chirurgiczne jest najczęściej wdrażane w przypadku krwotoków zlokalizowanych w tylnym dole czaszkowym w istocie białej półkul móżdżku. Ewakuacja krwiaka z jąder podstawy lub pnia mózgu nie daje dobrych efektów 2. Ze względu na obecność deficytów neurologicznych ważną rolę w leczeniu chorych z krwotokiem śródmózgowym odgrywa kompleksowa rehabilitacja. Rokowanie Krwotok śródmózgowy jest chorobą obarczoną ryzykiem dużej niesprawności i wysoką śmiertelnością 1. Śmiertelność w ciągu pierwszych 30 dni jest bardzo wysoka wynosi 35 52%, z czego połowa zgonów następuje w ciągu pierwszych 2 dni 15. Rokowanie odległe w większości przypadków jest niepomyślne, jedynie 10% chorych odzyskuje samodzielność po miesiącu, 20% chorych w ciągu 6 miesięcy, a śmiertelność roczna wynosi 42 65% 16. Wpływ na rokowanie mają: wielkość, lokalizacja oraz szybkość powiększania się ogniska krwotocznego. Wskaźniki złego rokowania to: rozległe i głębokie zmiany zlokalizowane w jądrach podkorowych i wzgórzu, krwotok z przebiciem do układu komorowego, zaburzenia świadomości, starszy wiek chorych i obecność schorzeń ogólnoustrojowych 17. Wskaźniki dobrego rokowania to: małe, powierzchownie zlokalizowane ogniska krwotoczne oraz wysoka punktacja w Skali Glasgow przy przyjęciu. Chorzy z krwotokami do pnia mózgu umierają najczęściej natychmiast lub w ciągu kilku, kilkunastu godzin na skutek zatrzymania oddechu i czynności serca. Również 48

11 review PAPERS niepomyślnie rokują krwotoki do móżdżku, które często powodują niedomogę pnia mózgu. U chorych, którzy przeżyli krwotok śródmózgowy, po roku od krwawienia stwierdza się zazwyczaj obecność ubytków neurologicznych. U pacjentów z amyloidozą naczyń mózgowych często ponownie dochodzi do krwawienia. Reasumując należy podkreślić, że krwotok śródmózgowy jest ciężką postacią udaru mózgu, obarczoną wysoką śmiertelnością wczesną oraz prowadzącą zazwyczaj do wystąpienia istotnej niesprawności psychofizycznej u tych chorych, którzy przeżyją. W codziennej praktyce klinicznej trzeba pamiętać przede wszystkim o prawidłowym leczeniu nadciśnienia tętniczego, które jest głównym czynnikiem ryzyka choroby. Natomiast każdy pacjent, u którego nagle wystąpi deficyt neurologiczny, powinien być jak najszybciej skierowany do oddziału neurologicznego z podejrzeniem udaru mózgu. References: 1. Gąsecki D, Kozera G, Chwojnicki K, Nyka W. Krwotok wewnątrzmózgowy obraz kliniczny i aktualności w leczeniu. Choroby Serca i Naczyń 2006;3(3): Ferro JM. Update on intracerebral haemorrhage. J Neurol 2006;253: Karwacka M, Siemiński M, Nyka W. Krwotok śródmózgowy. Forum Medycyny Rodzinnej 2008;2(1): Gołąb B. Anatomia czynnościowa ośrodkowego układu nerwowego. PZWL: Warszawa, Gorelick P. Alter M. Deekker M. Handbook of Neuroepidemiology. New York, Basel, Hong Kong, Minutoli F, Angileri FF, Cosentiono S i wsp. 99m Tc-MIBI SPECT in distuinguishing neoplastic from nonneoplastic intracerebral hematoma. J Nucl Med 2003;44: Brott T, Broderick J, Kothari R i wsp. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28: Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med 2001;344: Lehmann-Horn F, Ludolph A. Neurologia diagnostyka i leczenie. Urban & Partner: Wrocław, Tung GA, Julius BD, Rogg JM. MRI of intracerebral hematoma: value of vasogenic edema ratio for predicting the cause. Neuroradiology 2003;45: Zuccarello M, Brott T, Derex L i wsp. Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study. Stroke 1999;30: Broderick J, Connolly S, Feldmann E et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update. Circulation 2007;116:e391-e Steiner T, Kaste M, Forsting M et al. Recommendations for the management of intracerebral hemorrhage part I: spontaneous intracerebral hemorrhage. Cerebrovasc Dis 2006;22: Jüttler E, Steiner T. Treatment and prevention of spontaneous intracerebral hemorrhage: comparison of EUSI and AHA/ASA recommendations. Expert Rev Neurother 2007;7: Anderson CS, Chakera TM, Stewart-Wynne EG i wsp. Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, : incidence and outcome. J Neurol Neurosurg Psychiatry 1994;57: Castellanos M, Leira R, Tejada J i wsp. Predictors of good outcome in medium to large spontaneous supratentorial intracerebral haemorrhages. J Neurol Neurosurg Psychiatry 2005;7: Godlewski B, Zagórski J, Błaszczyk B, Staszek D. Samoistny krwiak śródmózgowy leczenie chirurgiczne czy zachowawcze. Lekarz Wojskowy 2006;82(3):

12 Review PAPERS Vitamin D today and tomorrow prophylactic and therapeutic road map for family physicians Witamina D dziś i jutro profilaktyczna i terapeutyczna mapa dla lekarzy rodzinnych Katarzyna Anna Rygiel Key words: vitamin D, calcidiol 25-hydroxycholecalciferol; [25(OH)D], calcitriol 1.25 dihydroxycholecalciferol; [1.25(OH)2D], deficiency, recommendations Słowa kluczowe: witamina D, kalcydiol 25-hydroxycholekalciferol; [25(OH)D], kalcytriol 1,25 dihydroxycholekalciferol; [1,25(OH)2D], niedobór, zalecenia Abstract: Vitamin D is essential for optimal skeletal development, maintenance of bone health, and neuromuscular function not only in childhood, but also during the entire life cycle. It plays an important role in proper functioning of cardiovascular and immune system, being protective against cardiovascular disease, different types of cancer and autoimmune diseases. The diagnosis of vitamin D deficiency can be difficult, since its clinical symptoms are often nonspecific. This article discusses the most common risk factors for vitamin D deficiency (e.g.: age >65 years, insufficient exposure to sunlight, sedentary lifestyle, obesity body mass index BMI >30 kg/m 2, breast-feeding, dark skin pigmentation, excessive use of sunscreens, and iatrogenic causes). It presents current recommendations for vitamin D supplementation in different age groups (such as infants, children, adolescents, elderly, and women in reproductive or menopausal age). The article focuses on selected topics, related to the link between vitamin D and certain endocrine, neoplastic and autoimmune diseases (e.g.: type 1 diabetes mellitus, breast, prostate or colon cancer, and multiple sclerosis). Potential toxicity of vitamin D metabolites is described. The article also summarizes the recent research findings, including some methodological limitations, and indicates new directions for studies in this area. Streszczenie: Witamina D ma kluczowe znaczenie dla optymalnego rozwoju i funkcjonowania układu kostno-szkieletowego i nerwowo-mięśniowego nie tylko w dzieciństwie, ale również w ciągu całego cyklu życiowego. Odgrywa ona również istotną rolę w prawidłowej pracy układu sercowo-naczyniowego i odpornościowego, działając protekcyjnie przeciwko wielu chorobom sercowo-naczyniowym, nowotworowym i autoimmunologicznym. Diagnoza niedoboru witaminy D może być trudna, ponieważ objawy kliniczne są często niespecyficzne. Artykuł omawia najczęstsze czynniki ryzyka niedoboru witaminy D (np.: wiek >65 lat, niewystarczająca ekspozycja na promieniowanie słoneczne, siedzący tryb życia, otyłość BMI >30 kg/m 2, okres laktacji, ciemna pigmentacja skóry, nadmierne używanie filtrów przeciwsłonecznych oraz przyczyny jatrogenne). Przedstawiono w nim obecne zalecenia dotyczące suplementacji witaminy D w różnych grupach wiekowych (niemowlęta, dzieci, młodzież, osoby starsze oraz kobiety w wieku reprodukcyjnym i menopauzalnym). Artykuł koncentruje się na wybranych zagadnieniach, które dotyczą powiązań pomiędzy niedoborem witaminy D a chorobami endokrynologicznymi, nowotworowymi i autoimmunologicznymi (np.: cukrzyca typu 1, nowotwór piersi, prostaty lub okrężnicy i stwardnienie rozsiane). Opisano także potencjalną toksyczność metabolitów witaminy D i podsumowano rezultaty szeregu obecnych badań klinicznych, wraz z ich ograniczeniami metodologicznymi, wskazując nowe kierunki badawcze w tej dziedzinie. Department of Family Medicine, Medical University of Silesia in Zabrze Katarzyna Anna Rygiel, MD Member of research and education team CORRESPONDENCE ADDRESS: dr Katarzyna Anna Rygiel Katedra i Zakład Medycyny Rodzinnej, Śląski Uniwersytet Medyczny ul. 3 Maja 13/ Zabrze redakcja.pmr@wp.pl RECEIVED: ACCEPTED: Introduction Vitamin D deficiency causes impaired mineralization of the collagen matrix in young children s bones leading to growth retardation and bone deformities known as rickets 1. In adults, and in elderly, vitamin D deficiency induces secondary hyperparathyroidism and increases the risk of osteomalacia, muscle weakness, falls, osteoporosis and bone fractures 2. Although, the rickets epi- (Probl Med Rodz 2010;2(31):50 56) demic that was common in children in the past, has subsided, vitamin D deficiency and insufficiency have recently been more prevalent globally, affecting persons of all ages, in various forms of pathologic conditions 3. There is growing evidence implicating that vitamin D deficiency is associated with increased risk of many chronic diseases, including type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, 50

13 review PAPERS arterial hypertension, cardiovascular disease, and many types of malignancy 3,5. Brief summary of synthesis and metabolism of vitamin D Vitamin D (representing D 2 and D 3 forms) plays a key role in metabolism and cellular communication 3. During exposure to sunlight, vitamin D precursor 7-dehydrocholesterol (7-DHC) in the skin undergoes conversion to previtamin D 3, and then to vitamin D 3. Vitamin D that is made in the skin or ingested with food is subsequently converted in the liver, by the enzyme 25-hydroxylase, to 25-hydroxyvitamin D [25(OH)D] calcidiol, which in turn is converted in the kidneys, by the enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (1-OH-ase) to its metabolically active form 1.25-dihydroxyvitamin D [1.25(OH)2D] calcitriol. 1.25(OH)2D as an active hormonal compound goes to the circulation, binds to proteins and travels to its major target tissues, including the intestine and bone, where it acts upon vitamin D receptors, increasing calcium absorption, stimulating osteoclastic functions, and regulating, in collaboration with other hormones, calcium phosphorus (Ca-P) balance in the body 3,5. In addition, calcitriol is being locally produced in different extrarenal tissues (e.g.: colon, prostate, and breast), where it regulates genetic expression, and in consequence improves control mechanisms of cellular growth and differentiation. In this way, calcitriol potentially decreases the risk of malignancy, inhibits renin production in the kidney, and modulates activities of immune system cells monocytes and T and B lymphocytes 3,5. Endogenous and exogenous sources of vitamin D An adequate level of vitamin D is difficult to maintain, since approximately 90% of this vitamin is usually obtained as a result of its synthesis in the skin, in response to sunlight, and only about 10% from dietary sources that are relatively limited. They include vitamin D 2 (ergocalciferol), found in some plants and vitamin D 3 (cholecalciferol), found in oily fish (e.g.: salmon, mackerel, herring, and cod liver oil) and some foods that are fortified with vitamin D (e.g.: milk or soft margarines) 1,4. Determination of vitamin D status of a patient The measurement of the serum level of major circulating metabolite of vitamin D, calcidiol 25(OH)D, is the gold standard for determining the vitamin D status of a patient 6. Many studies indicate that the PTH levels plateau and are at the physiologic concentration when the serum level of 25(OH)D is in the range of ng/ml ( mmol/l) in children, and in the range of ng/ml ( nmol/l) in adults (1 ng/ml=2.5 nmol/l) 7. The measurement of serum level of the most hormonally active metabolite of vitamin D, calcitriol 1.25(OH)2D provides no insight about the vitamin D status of a patient, since it may be normal or elevated even in vitamin D deficient patients. This is because the 1.25(OH)2D levels are 1000 times lower than 25(OH)D levels, and the secondary hyperparathyroidism causes an increase of the renal production of 1.25(OH)2D 8,9. A way to accomplish physiologic production of vitamin D and provide skin cancer protection Although it appears counterintuitive, some studies have suggested that controlled exposure to sunlight decreases the risk of morbidity and mortality of the most severe form of skin cancer, melanoma malignant 10,11. It has been estimated that exposure to sunlight (UVB) for approximately 5 15 min/d (between 10 AM and 3 PM), including approximately 18% of the uncovered skin surface (on arms, legs, hands, or face), during the spring, summer, or fall (from April to September), but not winter (from October to March), without using sunscreens with sun protection factors (SPF) provides the body with its required daily amount of approximately 1000 IU of cholecalciferol 12,13. According to a simple strategy, after a short sunlight exposure (about 15 min), a sunscreen with SPF (of at least 15) should be applied to prevent sun burning or damaging effects of the excessive exposure to UV radiation. In this way, both skin cancer protection and physiologic production of vitamin D can be accomplished. General recommendations for prevention of vitamin D deficiency in different age groups, according to the American Academy of Family Physicians (with levels of evidence A, B, C) 14 : To prevent vitamin D deficiency, infants and children with inadequate sun exposure should have vitamin D intake of 400 IU/day (level of evidence, C). To prevent vitamin D deficiency, adults with inad- equate sun exposure should have vitamin D intake of 400 to 600 IU per day (level of evidence, C). Adults with vitamin D deficiency, except for those with malabsorption syndromes, should receive maintenance dosages of 800 to 1000 IU of vitamin D per day (level of evidence, C). In older adults, vitamin D supplementation of 700 to 800 IU per day is associated with a lower risk for falls (level of evidence, B), and with a lower risk for fractures (level of evidence, A). 51

14 review PAPERS The American Academy of Pediatrics recommends that infants and children have vitamin D intake of at least 400 IU/day from diet and supplements in order to prevent vitamin D deficiency 14. In particular, supplementation of 400 IU/day is recommended for all: breast-fed infants until they are ingesting at least 1 l/ day of vitamin D-fortified formula or milk, and for all infants who are not breast-fed, but who are consuming less than 1 l/day of vitamin D-fortified formula or milk, and children and adolescents who do not get regular sunlight exposure, who do not consume at least 1 l/day of vitamin D-fortified formula or milk, or who do not take a daily multivitamin supplement containing at least 400 IU of vitamin D 14. Translating these guidelines into a daily practice, it should be emphasized that in the absence of sufficient exposure to sunlight, approximately IU/d of cholecalciferol should be obtained from dietary sources and supplements of vitamin D (IU International Unit; 1 microgram [mcg] =40 IU). Vitamin D 2 and D 3 have comparable biological activity. Vitamin D deficiency or insufficiency treatment goals, doses and duration According to the recently published article by Bordelon 14, when vitamin D deficiency or insufficiency has been diagnosed, the therapy goal should be to normalize its serum levels, in order to alleviate clinical symptoms and decrease the risk for bone fractures or other adverse events 14. For this purpose, an oral preparation of vitamin D 2 (ergocalciferol), 50,000 IU per week, for 8 weeks has been recommended. As a diagnostic marker, serum 25(OH)D level should be rechecked after completion of the 8-weeks therapy. If values of 25(OH)D are still below the target level, this 8-week treatment course should be repeated. After normalization of vitamin D levels, patients should receive maintenance dose of vitamin D 3 (cholecalciferol), equal to 800 to 1000 IU daily, from both diet and/or supplements 14. Based on recommendations of Holick, Misra, and Heaney that are concurrent with the most recent recommendations (2009) of the Polish Panel of Experts from the Children s Memorial Health Institute, the following management strategy of severe vitamin D deficiency (when serum level of 25(OH)D is <10 ng/ml) in children and adults has been recommend 7,15,16 : Therapeutic doses of vitamin D, for 1 3 months, applied according to the following schedule: neonates <1 month of age 1000 IU/d, infants 1 12 months of age IU/d, children >12 months of age 5000 IU/d, adults up to 7000 IU/d. During this therapy, it is required to monitor serum concentration of 25(OH)D, alkaline phosphatase, calcium, and calcuria, every 1 3 months, and adjust a dose, if necessary. The main contraindications to vitamin D supplementation include granulomatous diseases, tuberculosis, sarcoidosis, metastatic bone disease, or Williams syndrome 14,16. The most probable reasons for lack of therapeutic effect may include patient s nonadherence (that should be individually addressed) or malabsorption such as Crohn s disease, Whipple s disease, cystic fibrosis, or sprue. Such cases would require a gastroenterology consultation 17. In addition, in obese individuals (BMI>30), vitamin D can be partially sequestered in the adipose tissue that causes reduction of its bioavailability 16. Also, it should be kept in mind that iatrogenic causes of vitamin D deficiency include therapy with anticonvulsants, glucocorticoids, or with other medications that affect vitamin D metabolism 16. Balancing benefits of vitamin D against the risk of its toxicity From a clinical point of view, signs and symptoms of vitamin D toxicity, characterized mostly by hypercalcemia and hypercalciuria, occur relatively infrequently, and may include headache, metallic taste, nausea, vomiting, renal stones, vascular calcinosis, or pancreatitis. Despite the fact that the fat-soluble vitamin D was identified almost a 100 years ago, and that some recent studies have explained to some degree the genetic, molecular and cellular mechanisms of action of its active hormonal metabolite calcitriol, there is still a paucity of knowledge about specific mechanisms of vitamin D toxicity 18. The lipophilic affinity of vitamin D explains its adipose tissue distribution and its slow turnover (about 2 months) in the body. Its main metabolite, calcidiol [25(OH)D] that represents the functional status indicator (marker) for safety and efficacy of vitamin D, has a half-life of approximately 15 days and its serum concentration typically ranges from 25 to 200 nmol/l. However, its active metabolite, calcitriol D [1.25(OH)2D], has a half-life of only about 15 hours. The elevation of 25(OH)D is accompanied by rise of its precursor, vitamin D and by rises in many of its dihydroxy- metabolites, except from calcitriol. Vitamin D intoxication that includes hypercalcemia is not usually observed, until the 25(OH)D reach levels of approximately 375 nmol/l (150 ng/ ml). According to some other studies, the serum 25(OH)D concentration of 250 nmol/l has been considered as safe

15 review PAPERS According to Heaney, efficacy for several health outcomes requires the levels of calcidiol to be at least 80 nmol/l, while toxicity occurs at levels of 500 nmol/l or higher. The vitamin D intake, necessary for its efficacy, should be about 1000 IU/day. Based on Heaney s report, vitamin D toxicity is associated only with its excessive supplemental intake (above 20,000 IU/day) 19. In another report, high doses of vitamin D may cause hypercalcemia once the 25(OH)D level is well above the upper physiologic range. The natural buffer for vitamin D safety is the capacity of plasma vitamin D-binding protein to bind the total amount of circulating 25(OH)D and 1.25(OH)2D. Based on this concept, hypercalcemia occurs only when vitamin D and its other metabolites have displaced 1.25(OH)2D from vitamin D-binding protein. Evidence from clinical trials presented by Vieth showed that a prolonged intake of 10,000 IU/d of vitamin D poses no risk of adverse effects for adults 20. In general, it appears that there is a wide margin of confidence that allows balancing benefits of vitamin D against the risk of its potential toxicity, which should be individually assessed for each patient. The role of vitamin D in cancer prevention An observation that people who lived in northern latitudes in the United States were more likely to die of cancer than those living in southern states was very intriguing 21. However, very little attention was paid to it. Subsequently, it was noted that people living in southern states were more likely to develop non-life-threatening skin cancer, but they have lower prevalence of more serious cancers, such as breast, colon, and prostate. Finally, the report by Garland et al revealed that colon cancer mortality was much higher in the northeastern U.S. compared with the southern states 22. Since then, it has been well documented that the risk of morbidity and mortality of colon, prostate, breast, ovarian, esophageal, non-hodgkin s lymphoma, and many other lethal cancers is related to living at higher geographical latitudes and being more at risk of vitamin D deficiency 22,23. Another milestone in this direction was a discovery of the vitamin D receptor (VDR) that exists in most calls and tissues of the body, and finding that calcitriol 1.25(OH)2D is a potent inhibitor of both physiologic and malignant cell growth 23. These findings have been important in explaining the fact that the increased renal production of 1.25(OH)2D could downregulate malignant cell growth, and potentially decrease cancer morbidity and mortality. However, the renal production of 1.25(OH)2D was tightly controlled, and an increased intake of vitamin D or exposure to sunlight did not result in an increase of renal production of 1.25(OH)2D 23. The fact is, that the increased intake of vitamin D (from diet or increased production of cholecalciferol in the skin) results in a higher level of circulating 25(OH)D. The skin not only makes cholecalciferol, but it also has the enzymatic capability to convert 25(OH)D to 1.25(OH)2D 23. A discovery that cells in different tissues and organs of the body are able to metabolize 25(OH)D to 1.25(OH)2D was essential to advance understanding of the vital role of vitamin D in cancer prevention 23. In particular, in the case of prostate gland, higher levels of 25(OH)D are used by the prostate cells to make 1.25(OH)2D, which in turn helps in keeping prostate cell proliferation under control, reducing the risk of malignancy 23. In addition, it has been observed that many other cells in the body, especially in the breast, colon, lung, and brain, have the enzymatic ability to make 1.25(OH)2D 23. Based on these observations, it has been suggested that elevating blood levels of 25(OH)D provides tissues, organs and systems with sufficient amount of 25(OH)D as a precursor, enabling the body to make sufficient amount of 1.25(OH)2D in many local areas. In this way, the adequate control of cellular growth and maturation as well as reducing the risk of malignancy can be assured 23. Many subsequent prospective and retrospective studies supported this theory and have revealed that, if the 25(OH)D level was at least 20 ng/ml, then there was a 30 50% decreased risk of morbidity and mortality of colon, prostate and breast cancers 22,23. Vitamin D as a potent immunomodulator in autoimmune disease prevention Activated immune system cells, such as monocytes, macrophages, B and T lymphocytes, display VDRs that interact with 1.25(OH)2D, modulating monocyte maturation, macrophage activity, lymphocyte function, and cytokine production 23. Preclinical research, including numerous animal studies, substantiated the important effect of vitamin D on the prevention of various autoimmune diseases. For instance, in nonobese diabetic mice that typically develop type 1 diabetes mellitus (T1DM) by 200 day of age, the risk of developing T1DM was reduced by 80%, after they were given a physiologic daily dose of 1.25(OH)2D 24. Similarly, mice that were pretreated with 1.25(OH)2D, before they were injected with a compound that induces a multiple-sclerosislike disease, displayed immunity to it 25. Beneficial results were also noted upon pretreatment with 1.25(OH)2D in an experimental mouse model of Crohn s disease 26. In human trials, related to autoimmune diseases, it was shown that women taking 400 IU of vitamin D decreased their risk of rheumatoid arthritis by 40% 27. Also, it is worth noticing that in an observational study conducted in Finland, 53

16 review PAPERS children who received 2000 IU/d of vitamin D from their first year of age on, and who were subsequently followed for the next 25 years, had approximately 80% decreased risk of developing T1DM. In contrast, children who were vitamin D deficient had a 4-fold increased risk of developing T1DM later in their life 28. Vitamin D in prevention of cardiovascular disease It appears that patients with cardiovascular disease are more prone to develop arterial hypertension and heart failure if they have vitamin D deficiency 29. Vitamin D can display its cardioprotective properties by variety of mechanisms. In particular, 1.25(OH)2D is one of the most potent hormonal mediators, downregulating the level of renin, produced by the kidneys. Also, vascular smooth muscle cells that have VDRs, can relax in the presence of 1.25(OH)2D. According to the observation by Teng et al, the patients suffering from end-stage renal disease, undergoing hemodialysis, who received the 1.25(OH)2D-3 analog, paracalcitol, were less likely to die of cardiovascular complications 31. Deficiency of vitamin D in hospitalized patients In a recent study by Thomas et al, it was reported that inadequate vitamin D intake, winter season, and housebound status represented independent predictors of hypovitaminosis D in a small subgroup of in-patients, <65 years of age, without known risk factors for vitamin D deficiency. Interestingly, the results of this study indicated that undiagnosed hypovitaminosis D is very common in general medical inpatients, including those, who take the recommended daily doses of vitamin D, and those without apparent risk factors for vitamin D deficiency 32. Association between serum 25(OH)D level and Upper Respiratory Tract Infection In a recent study by Ginde et al, it was reported that serum 25(OH)D levels revealed an independent, inverse association with recent Upper Respiratory Tract Infection (URTI) 33. Despite the fact that the 25(OH)D levels <30 ng/ml and URTI were higher in winter, this inverse association was present across the entire year. In addition, it was noted that individuals with respiratory tract diseases, such as asthma, who have low serum 25(OH)D levels, may even be more susceptible to URTI. The authors concluded that vitamin D supplementation may reduce the incidence of URTI and exacerbations of respiratory tract diseases. However, randomized controlled trials are necessary to further explore the direct effect of vitamin D supplementation on URTI, and to establish optimal levels of serum 25(OH)D in the prevention of URTI 33. A meta-analysis related to fracture prevention and vitamin D supplementation A meta-analysis by Bischoff-Ferrari et al examined the role and dosage range of oral vitamin D supplementation in bone fracture prevention, estimating the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older patient population. Its results have revealed that oral vitamin D supplementation of IU/d appears to reduce the risk of hip and nonvertebral fractures in ambulatory or institutionalized elderly persons. In contrast, previously recommended oral vitamin D dose of 400 IU/d was shown to be insufficient for fracture prevention 34. Evidence-based review of vitamin D efficacy and safety in relation to bone health A current review of the literature related to association of specific circulating 25(OH)D levels with bone health outcomes, among different age groups has revealed that there is fair evidence of an association between circulating 25(OH) D levels with some specific bone health outcomes, such as rickets, falls, parathormone (PTH) values, and bone mineral density (BMD) scores 35. In contrast, the evidence for this association was inconsistent for some other outcomes, such as fractures in adults or bone mineral content (BMC) in infants. In addition, due to the imprecision of different 25(OH)D assays, it was difficult to define specific thresholds of circulating 25(OH)D for determining an optimal bone health. There is a need to create standard reference preparations for more accurate and reliable measurement of serum 25(OH)D. Also, it is important to underline that in most trials, the effects of vitamin D and calcium could not be separated. For example, vitamin D 3 in a dose >700 IU/day, with calcium supplementation compared to placebo had a small beneficial effect on BMD, but reduced the risk of fractures and falls in specific subgroups of adults. It is encouraging that the vitamin D intake above currently recommended dietary references was not reported to be associated with an increased risk of adverse events. The results of this systematic review underscore the need for additional well designed research trials, especially in populations of infants, children, premenopausal women, and in various ethnic groups

17 review PAPERS Another evidence based review, focused on the effectiveness and safety of nutritional and ultraviolet (UVB) radiation sources of vitamin D, with relation to bone health outcomes, across the human lifespan was conducted by Cranney 36. The main purpose of this review was to identify knowledge gaps existing in the research community, and to indicate areas that require further studies. The authors found inconsistent evidence of an association between serum 25(OH)D levels and BMC in infants and fair evidence of this association with BMC or BMD in older children and older adults. They also reported that evidence of an association between serum 25(OH)D levels and bone fractures and performance measures of functional status among postmenopausal women and older men were inconsistent. In addition, they noted a good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D serum levels. However, the evidence for a benefit of vitamin D on falls and fractures varied in their report, as in some other systematic studies 36. Research questions, limitations, and further directions Although, a considerable progress in understanding of the relation of 25(OH)D to bone health outcomes in the elderly and postmenopausal women has been made, still a little is known about these relations in other stages of life, and in certain high risk groups. Due to these limitations, it is difficult to establish a specific threshold of 25(OH)D in serum, as a marker for vitamin D status, in relation to bone and other health outcomes 37. In particular, the following limitations in current research have been identified: Few studies have assessed the effects of vitamin D independently of calcium magnesium, phosphate or other nutrients, Many studies were not adequately controlled for confounders such as diet, physical activity, baseline vitamin D status, patients compliance, age, developmental stage, preexisting diseases and seasons of the year, Currently used 25(OH)D assays may be variable, The relations between 25(OH)D, its extra renal hydroxylation, and tissue (paracrine) functional outcomes are still not well understood, There is a paucity of evidence related to the nonskeletal functional outcomes of vitamin D, including the role of vitamin D in preventing chronic diseases, such as diabetes mellitus, cardiovascular disease, immune system dysfunctions, and various types of cancer. Conclusions Since the diagnosis of vitamin D deficiency may often be missed, as the signs and symptoms of this condition are nonspecific or develop slowly, primary care and family physicians need to be vigilant, because both early diagnosis and correct treatment can significantly improve the patients outcome. It should be emphasized that: Diagnosis of suspected vitamin D deficiency or insuf- ficiency should be confirmed with measurement of serum 25(OH)D levels, and is defined as vitamin D deficiency when a 25(OH)D level is <20 ng/ml (50 nmol/l), and insufficiency when it is in a range from 20 to 30 ng/ml (50 75 nmol/l). Studies have shown that in older adults, vitamin D supplementation of 700 to 800 IU per day is associated with a lower risk for falls and fractures, and therefore, it is recommended that adults with vitamin D deficiency should receive a maintenance daily dose of 800 to 1000 IU of vitamin D per day. This is reflected in the new Polish guidelines related to the prophylaxis of vitamin D deficiency, released in 2009, by Polish Panel of Experts. Risk factors for vitamin D deficiency include age >65 years, insufficient exposure to sunlight, sedentary lifestyle, obesity (BMI>30 kg/m 2 ), breast-feeding without vitamin D supplementation, dark skin, excessive use of sun protectors, and iatrogenic therapeutic causes. Vitamin D plays an important role in modulation of the immune system functions, control of malignant cells growth, and regulation of the hormone renin. Due to its pleiotropic properties, vitamin D active metabolite calcitriol contributes to prevention of many chronic illnesses among both children and adults. There is a need for further research to investigate sev- eral issues related to vitamin D deficiency, especially in vulnerable populations, such as infants, children, adolescents, women in reproductive age, elderly, dark-skinned persons, and different ethnic groups. Education of both medical personnel and general population about the beneficial effects of appropriate sun exposure and adequate daily intake of vitamin D should be promoted to enable assessment of vitamin D status, and to provide adequate dose of vitamin D for health maintenance, disease prevention, and successful therapy across the human lifespan. 55

18 review PAPERS References: 1. Holick MF. Vitamin D: a millenium perspective. J Cell Biochem 2003;88: Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging 2007;24(12): Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med 2008;29(6): Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. An evaluation of the vitamin D 3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? J Steroid Biochem Mol Biol 2007;103(3 5): Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008;87(4):1080S 1086S. 6. Holick MF. The vitamin D epidemic and its health consequences. J Nutr 2005;135(11):2739S 2748S. 7. Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults. Am J Med 2002;112: Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22: Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002;9: Kennedy C, Bajdik CD, Willemze R, de Gruijl FR, Bavinck JN. The influence of painful sunburns and lifetime of sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi and skin cancer. J Invest Dermatol 2003;120: Berwick M, Armstrong B, Ben-Porat L, Fine J, Kricker A, Eberle C, Barnhill R. Sun exposure and mortality from melanoma. J Natl Cancer Inst 2005;97: Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int 1998;8: Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D 3 : exposure to winter sunlight in Boston and Edmonton will not promote vitamin D 3 synthesis in human skin. J Clin Endocrinol Metab 1988;67: Bordelon P, Ghetu MV, Langan RC. Recognition and management of vitamin D deficiency. Am Fam Physician 2009;80(8): Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr 1985;42: Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72: Heaney RP. The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 2005;97: Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008;88(2):582S 586S. 19. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr Rev 2008;66(10 Suppl 2):S178 S Vieth R. Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Ann Epidemiol 2009;19(7): Apperley FL. The relation of solar radiation to cancer mortality in North America. Cancer Res 1941;1: Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Oglesby P. Dietary vitamin D and calcium and risk of colorectal cancer: A 19-year prospective study in men. Lancet 1985;9: Holick MF. Vitamin D. Importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004;79: Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1.25 dihydroxyvitamin D 3. Diabetologia 1994;37: Cantorna MT, Hayes CE, DeLuca HF Dihydroxyvitamin D 3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 1996;93: Cantorna MT, Munsick C, Bemiss C, Mahon BD dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. 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N Engl J Med 1998;338(12): Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 2009;169(4): Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005;293(18): Cranney A, Horsley T, O Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 2007;(158): Cranney A, Weiler HA, O Donnell S, Puil L. Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr 2008;88(2):513S 519S. 37. Brannon PM, Yetley E A, Bailey RL, Picciano MF. 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19 Review PAPERS Exercise-induced asthma and bronchospasm Astma powysiłkowa i powysiłkowy skurcz oskrzeli Elżbieta Kryj-Radziszewska, Adam Windak, Janusz Krzysztoń Key words: asthma, bronchoconstriction, physical exercise, diagnosis, treatment, prophylaxis Słowa kluczowe: astma, skurcz oskrzeli, wysiłek fizyczny, diagnostyka, leczenie, zapobieganie Abstract: Exercise-induced asthma (EIA) and exercise-induced bronchoconstriction (EIB) are a temporary narrowing of the airways that occurs 5 15 minutes after physical exertion. The cooling and drying of airways stimulate the mast cells to produce mediators, which cause spasms of the muscles. In EIA and EIB diagnosis is based on the results of a detailed history, including symptoms and assessment of asthma triggers. An objective diagnosis of EIB requires performing spirometry prior and after physical activity. In both conditions treatment consists of the use of short-acting inhaled bronchodilators prior to planned physical activity. In asthma patients symptoms may be the result of poorly controlled disease and may require the intensification of antiinflammatory treatment. In both conditions nonpharmacologic measures such as increasing physical capacity, warm-up exercises, nasal breathing and use of facial mask, should be instituted. Although this condition is highly preventable it is still underdiagnosed and diminishes one s aerobic fitness and quality of life. Streszczenie: Astma powysiłkowa (EIA) i powysiłkowy skurcz oskrzeli (EIB) stanowią okresowe zwężenie dróg oddechowych, które występuje 5 15 minut po wysiłku fizycznym. Ochładzanie i wysuszenie dróg oddechowych stymuluje komórki tuczne do produkcji mediatorów, które wywołują skurcz mięśni gładkich oskrzeli. W przypadku EIA i EIB rozpoznanie opiera się na dokładnie zebranym wywiadzie lekarskim, który uwzględnia objawy i ich związek z czynnikami je wywołującymi. EIB wymaga obiektywizacji diagnozy przez wykonanie spirometrii przed i po wysiłku fizycznym. W obydwu stanach leczenie polega na inhalowaniu krótko działających leków rozszerzających oskrzela przed planowanym wysiłkiem. U chorych z astmą objawy EIA mogą wynikać ze złej kontroli choroby i wskazywać na konieczność zintensyfikowania leczenia przeciwzapalnego. W obu stanach powinno się również wprowadzać działania niefarmakologiczne, jak zwiększanie wydolności wysiłkowej, stosowanie rozgrzewki, nauka wdychania powietrza przez nos, stosowanie masek na nos i usta. Mimo dobrych metod zapobiegania zaburzenie to nadal jest rzadko rozpoznawane i prowadzi do upośledzenia jakości życia. Department of Family Medicine, Chair of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow Elżbieta Kryj-Radziszewska, MD, PhD Senior assistant Adam Windak, MD, PhD Chair of the Department Janusz Krzysztoń, MD Lecturer CORRESPONDENCE ADDRESS: Zakład Medycyny Rodzinnej UJCM ul Bocheńska Kraków mmradzis@cyf-kr.edu.pl RECEIVED: ACCEPTED: Introduction Regular physical activity as part of a healthy lifestyle is important to the health and well-being of everyone. The physical, social, emotional and cognitive benefits of sports and physical activity are well researched, including the possibility of preventing chronic diseases such as: cardiovascular disease, diabetes, cancer, hypertension, obesity, depression and osteoporosis 1,2,3. Additionally, moderate exercise has been shown to stimulate the immune system 4. Unfortunately sports may lead among other complications (EIrhinitis, EI-anaphylaxis and EI-urticaria) to exercise induced respiratory disorders: asthma and bronchoconstriction, worsen one s quality of life and may result in limitations and unnecessary avoidance of physical activity. This problem affects healthy people and those with respiratory diseases, particularly in patients with asthma. Recognition, (Probl Med Rodz 2010;1(30):57 61) education and proper treatment using pharmacotherapy and nonpharmacologic methods allow individuals to practice a chosen sport. Such people can participate in physical activities to the same extent as their healthy peers. Exercise-induced respiratory disorders should not be the cause of limiting one s physical activity, especially in the case of children 4. Patients who exercise regularly have fewer exacerbations, use less medication, and miss less time from school and work. EIA and EIB was given special prominence in the context of increasing amount of athletes who are dependent on drugs (as seen with participants of the Winter Olympics 2010 in Vancouver). In conjunction with that sporting event raises the question: if medically treated patients with EIA/EIB should be permitted to participate in the Olympics and other sports competitions. Exercise induced asthma (EIA) and exercise induced bronchoconstriction (EIB) are clinically 57

20 review PAPERS important and are prevalent clinical conditions affecting young children teenagers and adults. They are characterized by transient airway narrowing induced by sustained aerobic exercise or exertion. Much confusion concerning the understanding of EI hypersensitivity is due to the fact that EIA and EIB are usually used interchangeably 5. It is certain that EIA and EIB are not the same but the differences are not clearly defined due to their similarity and sharing a common pathophysiological mechanism 6. Well-known experts have been working on these issues for some time now. To correct these inconsistencies in 2007 a consensus report known as PRACTALL was developed concerning the pathogenesis of these disorders and how to diagnose and treat them 7. The group who prepared the report consisted of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology. The report presents the approach to the issue and a logical and noncomplicated definition of the two states. Thanks to this the fate of many patients with previously undiagnosed and undertreated EIA/ EIB has changed. Pathophysiology of exercise-induced respiratory disorders The pathogenesis of EIA and EIB can be explained by both the osmotic and thermal hypothesis. The first one proposes that the narrowing of airways seen in exercise is due to dehydration of the airways during inhalation of large amounts of dry, cold air. Loss of water results in hyperosmolarity of the airway surface liquid with subsequent water loss from the airway cells in order to keep an osmotic balance. In patients with EIA this is accompanied by the release of mediators (histamine, leukotrienes, prostaglandins), causing bronchoconstriction, increased permeability of blood vessels and mucus hypersecretion 8,9. An inflammatory basis for EIB has not yet been established 10. Inflammatory changes may be secondary to damage of the airways by physical factors during hyperventilation which heals with rest 7. The thermal hypothesis proposes that changes in airway temperature result in airway narrowing and obstruction. Hyperventilation as result of exercise leads to a loss of heat in the airways. Thermal losses magnify as airways cool with an increasing amount ventilation. The rewarming of the airways immediately following exercise results in reactive hyperaemia of the bronchial circulation. The vascular engorgement, vasodilatation and edema contribute to airway narrowing. EIA and EIB are modulated by the baseline condition of the patient any coexisting atopy, ambient conditions (temperature, humidity, air quality, aeroallergen exposure) and the type of training being done. The most potent stimulus for EIA/EIB is exercise in cold and dry air rather than warm, wet environments 11. Athletes who train in environments in which there may be environmental pollutants are at increased risk for the development of EIB. An example would be chlorine compounds in swimming pools and gases such as carbon monoxide and nitrogen dioxide, which are abundant in indoor ice arenas. The prevalence of EIB in cross-country skiers is estimated to be around 50% 12. Asthma is more common in competitive athletes because of airway dehydration from hyperpnoea, increased exposure to aeroallergens and airway injury from irritant chemicals and environmental factors. Exercise-induced asthma EIA concern for individuals with known asthma who have bronchoconstriction associated with exercise. EIA applies to patients with asthma at all levels of severity. This applies to nearly all uncontrolled asthma patients and in the majority of children with asthma 7. The reported incidence of EIA varies between 70 90% of the general asthma patients 7. This is primarily, because exercise is a common trigger for asthmatic symptoms after viral upper respiratory infections. EIA symptoms can be progressed by other asthma triggers, such as sensitivity to cold dry air, air pollution/ exhaust fumes or pollen/mold spores in the air. Warm and humid air may lessen the symptoms. Unfortunately since pollens and molds are present at the times of the year when the air is warm and humid, these substances in the air may also trigger attacks of asthma. EIA is most frequently seen in children and young adults because of their high levels of physical activity 7. In patients with asthma, having detailed information about the type of effort, time of onset of symptoms and their duration, EIA can be identified solely by one s history. In well controlled asthma, patients should not have exacerbations during recreational exercising. Optimal control of underlying asthma minimizes airway narrowing during exercise. Asthma patients with symptoms characteristic of the EIA should be evaluated for poorly controlled asthma that is exacerbated by exercise or, by the type of physical activity which is inappropriate for them. However one must keep in mind the diagnosis of obscure cases of asthma, in which physical activity is the sole factor concerning the exacerbation of asthma. In this situation diagnosis requires carrying out examination including pre and post exercise spirometry and reversibility tests after short-β 2 mimetic (SABA) application. For the asthma diagnosis is a necessary FEV 1 (forced expiratory volume in one second) improves after SABA inhalation more than 12% and 58