Yazd?r

ARIA (allerjik rinit ve ast?m ?zerine etkisi)
10 y?ldaki kazan?mlar ve gelecekteki gereksinimler

A. YORGANCIO?LU1, C. ?ZDEM?R2, ?. KALAYCI3, A.F. KALYONCU4, C. BACHERT5,
C.E. BAENA-CAGNANI6, T.B. CASALE7, Y.Z. CHEN8, A.A. CRUZ9, P. DEMOLY10,
W.J. FOKKENS11,? K.C. LODRUP CARLSEN12, Y. MOHAMMAD13, J. MULLOL14, K. OHTA15,
N.G. PAPADOPOULOS16, R. PAWANKAR17, B. SAMOLINSKI18, H.J. SCH?NEMANN19,
O.M. YUSUF20, T. ZUBERBIER21, J. BOUSQUET22
(D?nya Sa?l?k ?rg?t? Ast?m ve Rinit ??birli?i Merkezi ile birlikte)

1 Celal Bayar ?niversitesi T?p Fak?ltesi, G???s Hastal?klar? Anabilim Dal?, Manisa,

2 Memorial Ata?ehir Hastanesi, ?ocuk Allerjisi B?l?m?, ?stanbul,

3 Hacettepe ?niversitesi T?p Fak?ltesi, Pediatrik Allerji Bilim Dal?, Ankara,

4 Hacettepe ?niversitesi T?p Fak?ltesi, G???s Hastal?klar? Anabilim Dal?, Ankara,

5 Ghent ?niversitesi, Kulak Burun Bo?az B?l?m?, ?st Solunum Yollar? Ara?t?rma Laboratuvar?, Bel?ika,

6 Katolik ?niversitesi T?p Fak?ltesi, Solunum T?p Ara?t?rma Merkezi, Kordoba, Arjantin,

Cenova ?niversitesi Solunum Hastal?klar? Uzmanl?k Okulu, ?talya,

7 Creighton ?niversitesi T?p B?l?m?,? Allerji ve ?mm?noloji B?l?m?, Omaha, Nebraska, Amerika Birle?ik Devletleri,

8 Pediatri Sermaye Enstit?s? Ast?m Klini?i ve E?itim Merkezi, Pekin, ?in, Ast?m Ara?t?rma ve

E?itim Merkezi, Beijing, ?in,

9 Bahia Federal ?niversitesi, ProAR-Nucleo de Excelencia em Asma, and CNPq, Salvador, Brezilya,

10 Hopital Arnaud De Villeneuve ?niversite Hastanesi, Solunum Hastal?klar? B?l?m?, Montpellier, Fransa,

11 Amsterdam ?niversitesi, Kulak Burun Bo?az B?l?m?, Amsterdam, Hollanda,

Akademik T?p Merkezi, Kulak Burun Bo?az B?l?m?, Amsterdam, Hollanda,

12 Oslo ?niversitesi Hastanesi, Pediatri B?l?m?, Oslo, Norve?,

13 Tishreen ?niversitesi T?p Fak?ltesi, ?? Hastal?klar? B?l?m?, D?nya Sa?l?k ?rg?t?,

EMRO Kronik Solunum Yolu Hastal?klar? E?itim ve Ara?t?rma ??in ??birli?i Merkezi, Lattakia, Suriye,

14 IDIBAPS, Hastane Klini?i, Rinoloji ?nitesi ve Koku Klini?i, ENT B?l?m?. CIBERES, Barselona,

Katalonya, ?spanya,

15 Tokyo ?niversitesi T?p Fak?ltesi, T?p B?l?m?, Solunum T?bb? ve Allerji Birimi, Tokyo, Japonya,

16 Atina ?niversitesi, Allerji B?l?m?, 2. Pediatri Klini?i, Atina, Yunanistan,

17 Nippon T?p Okulu, Bunkyo-ku, Tokyo, Japonya,

18 Var?ova T?p ?niversitesi, ?evresel Tehlikeler ve Allerji ?nleme B?l?m?, Polonya,

19 McMaster ?niversitesi, Klinik Epidemiyoloji ve Biyoistatistik ve T?p B?l?m?, Hamilton, Kanada,

20 Allerji ve Ast?m Enstit?s?, ?slamabad, Pakistan,

21 Berlin T?p ?niversitesi, Dermatoloji B?l?m?, Charite, Berlin, Almanya,

GA2LEN Genel Sekreteri, Uzmanl?k A??, Charite, Berlin, Almanya,

22 Hopital Arnaud De Villeneuve ?niversite Hastanesi, Solunum Hastal?klar? B?l?m?, Montpellier, Fransa,

INSERM, CESP Epidemiyoloji ve Halk Sa?l??? Ara?t?rma Merkezi, Solunum ve ?evre Epidemiyolojisi Ekibi,

Villejuif, Fransa.

?ZET

ARIA (allerjik rinit ve ast?m ?zerine etkisi) 10 y?ldaki kazan?mlar ve gelecekteki gereksinimler

Allerjik rinit ve ast?m t?m ya? gruplar? i?in k?resel sa?l?k sorunlar?d?r. Ast?m ve rinit s?kl?kla bir arada bulunur. Allerjjik rinit ve ast?m ?zerine etkisi (ARIA), D?nya Sa?l?k ?rg?t?n?n 1999 y?l?ndaki bir ?al??tay?nda ba?lat?lm?? ve 2001 y?l?nda yay?nlanm??t?r. ARIA, allerjik riniti hafif/orta-a??r ve intermittan/persistan olarak yeniden s?n?fland?rm??t?r. Bu s?n?fland?rma allerjik rinitin hastalar ?zerindeki etkisini daha yak?n yans?tmaktad?r. 2010 y?l? revizyonunda ARIA, allerjik rinit/ast?m birlikteli?inin y?netiminde, GRADE [Grading of Recommendation, Assessment, Development and Evaluation (?nerme, Saptama, Geli?tirme ve De?erlendirme Derecelendirmesi)] sistemine dayanan klinik ve pratik bir rehber geli?tirmi?tir. ARIA d?nyada 50'nin ?zerinde ?lkeye yay?lm?? ve y?r?t?lmektedir. T?rkiye'de de ARIA kazan?mlar?n? raporlamak ve klinik, ara?t?rma ve y?r?tmede halen var olan gereksinimleri belirlemek,? 2011 Avrupa Birli?i ?ocuk Ast?m ve Allerji ?nceliklerini g??lendirmek ad?na ?ok ?nemlidir.

Anahtar Kelimeler: Rinit, ast?m, ARIA, allerjik rinit ve ast?m ?zerine etkisi, allerji, GRADE.

SUMMARY

ARIA (Allergic rhinitis and its impact on asthma) Achievements in 10 years and future needs

A. YORGANCIO?LU1, C. ?ZDEM?R2, ?. KALAYCI3, A.F. KALYONCU4, C. BACHERT5,
C.E. BAENA-CAGNANI6, T.B. CASALE7, Y.Z. CHEN8, A.A. CRUZ9, P. DEMOLY10,
W.J. FOKKENS11,? K.C. LODRUP CARLSEN12, Y. MOHAMMAD13, J. MULLOL14, K. OHTA15,
N.G. PAPADOPOULOS16, R. PAWANKAR17, B. SAMOLINSKI18, H.J. SCH?NEMANN19,
O.M. YUSUF20, T. ZUBERBIER21, J. BOUSQUET22 (WHO Collaborating Center on Asthma and Rhinitis)

1 Department of Chest Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey,

2 Department of Pediatric Allergy, Memorial Atasehir Hospital, Istanbul, Turkey,

3 Division of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Ankara, Turkey,

4 Department of Chest Diseases, Faculty of Medicine, Hacettepe University, Ankara, Turkey,

5 Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Belgium,

6 Research Centre in Respiratory Medicine (CIMER). Faculty of Medicine, Catholic University,

Cordoba, Argentina,

School of Specialization, Respiratory Medicine, University of Genoa, Italy,

7 Division of Allergy and Immunology, Department of Medicine, Creighton University,

Omaha, Nebraska, USA,

8 National Cooperative Group of Pediatric Research on Asthma. Asthma Clinic and Education Center of the

Capital Institute of Pediatrics, Peking, China Center for Asthma Research and Education, Beijing, China,

9 ProAR-Nucleo de Excelencia em Asma, Federal University of Bahia and CNPq, Salvador, Brazil,

10 University Hospital, H?pital Arnaud de Villeneuve, Department of Respiratory Diseases, Montpellier, France,?

11 Department of Otorhinolaryngology, University of Amsterdam, The Netherlands

Department of Otorhinolaryngology, Academic Medical Centre, Amsterdam, The Netherlands,

12 University of Oslo; Oslo University Hospital, Department of Paediatrics, Oslo, Norway,

13 Tishreen University School of Medicine, Department of Internal Medicine, WHO,

EMRO Collaborating Center for Training and Research in Chronic Respiratory Diseases, Lattakia, Syria,

14 Rhinology Unit & Smell Clinic, ENT Department, Hospital Clinic, IDIBAPS. CIBERES,

Barcelona, Catalonia, Spain,

15 Division of Respiratory Medicine and Allergology, Department of Medicine,

Tokyo University School of Medicine, Tokyo, Japan,

16 Allergy Department, 2nd Pediatric Clinic, University of Athens, Greece,

17 Nippon Medical School, Bunkyo-ku, Tokyo, Japan,

18 Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland,

19 Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University,

Hamilton, Canada,

20 The Allergy and Asthma Institute, Islamabad, Pakistan,?

21 Allergy-Centre-Charit? at the Department of Dermatology, Charit? - Universit?tsmedizin Berlin,

Berlin, Germany,

Secretary General of the Global Allergy and Asthma European Network (GA2LEN),

Network of Excellence, Charit?- Universit?tsmedizin Berlin, Berlin, Germany,

22 University Hospital, Hopital Arnaud de Villeneuve, Department of Respiratory Diseases, Montpellier, France,

INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018, Respiratory and

Environmental Epidemiology Team, Villejuif, France.

Allergic rhinitis and asthma represent global health problems for all age groups. Asthma and rhinitis frequently co-exist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization (WHO) workshop in 1999 and was published in 2001. ARIA has reclassified allergic rhinitis as mild/moderate-severe and intermittent/persistent. This classification schema closely reflects the impact of allergic rhinitis on patients. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of allergic rhinitis and asthma co-morbidities based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation). ARIA has been disseminated and implemented in over 50 countries of the world. In Turkey,? it is important to make a record of ARIA achievements and to identify the still unmet clinical, research and implementation needs in order to strengthen the 2011 EU Priority on allergy and asthma in children.

Key Words: Rhinitis, asthma, ARIA, allergic rhinitis and its impact on asthma, allergy, GRADE.

Geli? Tarihi/Received: 13/01/2012 - Kabul Edili? Tarihi/Accepted: 19/01/2012

ARIA, KANITA DAYALI K?RESELB?RREHBER

Allerjik rinit t?m ya? gruplar? i?in k?resel bir sa?l?k sorunudur. Ast?m ve rinit s?k g?r?len komorbid durumlard?r. ARIA (Allerjik Rinit ve Ast?m ?zerine Etkisi), D?nya Sa?l?k ?rg?t? (DS?)'n?n 1999 y?l?ndaki bir uzmanl?k ?al??tay? s?ras?nda olu?turulmu?tur (1).

ARIA ?al??tay raporu ?u konularda yenilik getirmi?tir (1):

? "Persistans" ve "A??rl?k" kavramlar?n? kullanarak yeni bir s?n?fland?rma ?nerisi getirilmesi.

Bu yeni s?n?flama daha ?nceki mevsimsel ve y?l boyu rinit ?eklindeki ay?r?ma k?yasla hastan?n gereksinimlerine daha yak?n bulunmu?tur (2). Mevsimsel ve y?l boyu rinit fenotipleriyle "intermittan" ve "persistan" ARIA s?n?fland?rmas? birbirinin yerine kullan?lamaz, ??nk? hastal???n ayn? ?zelli?ini yans?tmazlar.

? Hastalar?n y?netiminde, ast?m ve rinit birlikteli?inin tan?nmas?n?n anahtar nokta olarak ?nerilmesi.

Ast?ml? hastalar?n (allerjik, mesleksel ya da nonallerjik) b?y?k ?o?unlu?unun riniti vard?r ve allerjik rinit hastalar?nda %10-40 oranlar?nda ast?m birlikteli?i g?r?l?r (3). Baz? b?y?k kapsaml? ?al??malarda her iki hastal???n a??rl??? ve/veya kontrol? aras?nda ba?lant?lar g?sterilmi?tir (4,5,6,7).

? Hastalar da dahil olmak ?zere t?m payda?larla i?birli?i yaparak rehberler geli?tirilmesi.

? ARIA'y? k?resel bir giri?im yapabilmek i?in geli?mi? ve geli?mekte olan ?lkelerde uzmanlar?n giri?ime dahil edilmesi.

Bu a?amada "The International Union Against Tuberculosis and Lung Diseases (T?berk?loz ve Akci?er Hastal?klar?na Kar?? Uluslararas? Birlik)" ile i?birli?i yap?lm??t?r.

? Rinit ve ast?m rehberlerinde ilk kez kan?ta dayal? bir yakla??m?n uygulanmas? (8).

? Sa?l?k ?al??anlar? ve hastalar aras?nda k?resel bir giri?im ba?lat?lmas?.

? "The International Primary Care Respiratory Group (Uluslararas? Birinci Basamak Solunum Grubu) (IPCRG)" allerjik rinit rehberi, ARIA temel al?narak haz?rlanm??t?r (9).

ARIA G?ncellemesi (2)

? Daha ?nceki ARIA belgelerinde i?lenmemi? olan tamamlay?c? ve alternatif t?p, spor konular?n? i?leyen; rinit ile ast?m aras?ndaki ba?lant?, koruma ve tedavi konular?nda ise g?ncel bilgileri i?eren bir literat?r taramas? ile ba?layan kesintisiz bir s?re?ti (3,10,11,12,13,14).

? Ayn? kan?ta dayal? model kullan?larak geli?tirildi (8).

? Yeni ARIA revizyonunda koruma ve tedavi konusundaki sorular? belirlemek i?in kullan?ld? (15).

ARIA 2010 revizyonu, GRADE yakla??m?n? kullanarak daha ?nce yay?nlanm?? olan bir y?ntemle geli?tirildi (16,17). Yeni ARIA 2010'un yenilik?i ?zellikleri vard?r, ??nk?;

? Neredeyse her ?neriyi destekleyen kan?tlarla ilgili olarak k?sa ve ?z kan?t ?zetleri (kan?t profilleri) sunan ilk rehberlerden birisidir (18).

? ?nerilerle ilgili olas? yarar ve zararlarla birlikte, ?nerilerin hem g?c?n? hem de y?n?n? etkileyen de?erler ve tercihler konusundaki varsay?mlar? ?zetler.

? Eri?kin ve ?ocuklar i?in farkl? ?neriler getirir: Koruma i?in 11, ila? tedavisi i?in 31, allerjen spesifik imm?noterapi i?in 11, tamamlay?c? ve alternatif t?p i?in be? ve biyolojik tedavi (omalizumab) i?in bir ?neri (Tablo 1).


Tablo 1

ARIA G?r??leri, Rehberler ve ?neriler

ARIA uzman paneli, temelde di?er kurulu?larla ve/veya D?nya Sa?l?k ?rg?t? (WHO CC) Ast?m ve Rinit ??birli?i Merkezi (Montpellier) ile birlikte ?al??arak ?e?itli ?neriler, g?r??ler ve rehberler olu?turmu?tur (Tablo 2)(19,20,21,22,23,24).


Tablo 2

ARIA'NIN K?RESELANLAMDA UYGULANAB?L?RL??? ve EKS?KL?KLER?

1. Allerjik Rinit Fenotipleri

Allerjik rinitin alt tiplerinin belirlenmesi: Fenotiplerin belirlenmesi, hastal?k a??rl???n?n tahmin edilmesi ve tan?mlanmas?n?, hastal?k seyrinin ve tedaviye yan?t?n de?erlendirilmesini ve tedavi hedeflerinin belirlenmesini kolayla?t?rabilir. Fenotipik ?zellikleri de?erlendirme konusunda g?zetimsiz istatistiksel analiz y?ntemleri (k?me analizi ya da fakt?r analizi gibi) g?n ge?tik?e daha s?k kullan?lmaktad?r (25). Ancak, allerjik rinit i?in b?yle bir fenotipleme hen?z yap?lmam??t?r.

Hastal???n kontrol?: SCUAD (A??r Kronik ?st Hava Yolu Hastal???) terimi, rehberlere g?re d?zenlenen yeterli farmakolojik tedaviye ra?men semptomlar? istenilen d?zeyde kontrol alt?na al?namayan hastalar? tan?mlar (20). Bu hastalar?n, ya?am kaliteleri (QOL), i? ve okul performanslar? azalm??t?r (26). Bu ?ekilde, kontrol ve a??rl???n hasta bazl? tan?m?n?n yap?lmas? art?k t?m allerjik hastal?klar i?in ge?erlidir (27). Allerjik rinit kontrol ?l?ekleri, semptom skorlar?, g?rsel analog skalalar? (VAS), ya?am kalitesi (QOL) gibi hastan?n rapor etti?i ?l?ekleri ya da birka? de?i?kenli puanlamalar? i?erir (28,29,30,31). Allerjik rinitte VAS gibi kolay bir ?l??m hastalar?n kontrol?n? de?erlendirmek ve takibini yapmak i?in yeterli olabilir (32). ?al??malar, allerjik rinit i?in en uygun kontrol testini belirlemelidir.

Pediatri: ARIA dok?manlar? her zaman i?in pediatrik sorunlara de?inmi?tir ancak, ?zellikle okul ?ncesi ?ocuklarda allerjik rinit ?ok s?kl?kla g?zden ka?makta ve beklenenin alt?nda tan? almaktad?r. ?zellikle bu ya? grubunda ?al??malara ihtiya? vard?r.

Ya?l?lar: Bir?ok hasta 65 ya? ?st?ndedir ancak, bu ya? grubu i?in veri yoktur.?

2. Allerjik Rinitin Y?netimi

Rehberlerin s?rekli g?ncellenmesi gerekir. Yeni sorular ileri s?r?lebilir. Hastalar?n ?o?u birinci basamakta g?r?lmektedir ve rehberler bu kurumlara adapte edilmelidir. Bir?ok ?lkede, allerjik riniti tedavi etmek i?in kullan?lan ila?lar re?etesiz (OTC) sat?lmaktad?r. Bu nedenle, hastalara ?neride bulunan eczac?lara yard?mc? olmak ?nemlidir.

Hastalar kendi bak?mlar?yla ilgili s?z sahibi olmak isterler. Bu nedenle hastalar?n cesaretlendirilmesi hayati ?nem ta??r. Bu da hasta e?itimi ve kendi kendini y?netim planlar? arac?l???yla olabilir. ARIA olu?turulmas?, yayg?nla?t?r?lmas? ve y?r?t?lmesinde hasta ?rg?tleri yer alm??t?r.

3. Klinik ?al??malar ve Ara?t?rma

Randomize kontroll? ?al??ma ve ara?t?rmalarda hastal???n tan?m?, ?iddeti ve kontrol?n?n net olarak tariflenmesi gereklidir. Komorbiditeler ve katk?s? olan durumlar (?rn. sigara kullan?m?) da dikkate al?nmal?d?r. Allerjik rinit ile ilgili randomize kontroll? ?al??ma yay?nlar? ortak bir yap?da bulunmal?d?r. A??r allerjik hastal?klarda daha fazla ara?t?rmaya acilen gereksinim duyulmaktad?r. Standardize tan?mlar epidemiyolojik toplumsal ara?t?rmalarda, risk fakt?rlerinin anla??lmas?nda ve ?al??malar?n kar??la?t?r?labilirli?ini sa?lamada ?ok ?nemlidir.

4. Geli?mekte Olan ?lkeler

Ortak bir allerjik rinit tan?m?, t?m d?nyada farkl?l?klar g?sterecek ?ekilde ?lkelerin y?resel ve co?rafi ko?ullar?na, fenotiplere, risk fakt?rlerine g?re uygulanabilmelidir. Geli?mekte olan ?lkelerde ARIA'n?n uygulanmas?, etkin t?bbi tedaviye eri?ilebilmeyi ve uygulanabilirli?i art?rmal?d?r.

5. Halk Sa?l??? Planlamas?

Halk Sa?l??? a??s?ndan ortak bir allerjik rinit ve a??rl?k tan?m?, prevalans, y?k ve maliyet, bak?m kalitesi ve sa?l?k bak?m planlanmas? ve politikalar?n iyile?tirilmesi i?in gereklidir.

6. Yeni Tedavilerin Geli?tirilmesi

Tedaviye diren?li a??r allerjik ve nonallerjik rinitte, yeni tedavilerin geli?tirilmesi, yeni hedeflerin belirlenmesi ve maliyet etkin bir ?ekilde mevcut tedavilerin daha da geli?tirilmesi i?in, daha ayr?nt?l? h?cresel ve molek?ler fenotipleme gereklidir.

7. ARIA ?yeli?ine A??k Eri?im

ARIA k?resel anlamda t?m payda?lara a??kt?r ve ?yelik talepleri DS? Ast?m ve Rinit ??birli?i Merkezine y?nlendirilmelidir (anna.bedbrook@inserm.fr).

?ZELSEKT?RLE ETK?LE??MLER

ARIA'da ?zel sekt?r, DS? kronik solunum hastal?klar?na kar?? K?resel Birle?im'inde belirtildi?i gibi g?zlemci stat?s? ile yer almaktad?r (http://www.who.int/gard GARD).

S?YAS?G?NDEMDE ARIA

ARIA bir DS? ?al??tay? s?ras?nda (1999) ba?lat?ld? ve DS? i?birli?i ile yay?nland?. Daha sonra DS? Ast?m ve Rinit ??birli?i Merkezinde aktif olarak faaliyetlere dahil oldu (Montpellier). 2008 g?ncelle?tirmesi DS?, GA2LEN (FP6) ve AllerGen (Kanada allerji a??) ile i?birli?i i?inde y?r?t?ld?.

ARIA baz? kamu sa?l?k kurulu?lar? (?rn. Brezilya ve Singapur, Finlandiya Allerji Plan?) ya da bilimsel topluluklar taraf?ndan ?nerilen rehberlerde kullan?lm??t?r (33).

2011 y?l?nda Polonya Ba?kanl???ndaki Avrupa Birli?i Konseyinin temel ?nceli?i Avrupa toplumlar? aras?nda sa?l?k e?itsizliklerinin azalt?lmas?, bu ?er?evede ?ocuklarda solunum hastal?klar?n?n ?nlenmesi ve kontrol?n? te?vik etmektir (34). ARIA ara?t?rmalar? aktif ve sa?l?kl? ya?lanman?n geli?tirilmesi i?in ?ocuklarda allerji ve ast?m y?k?n? azaltma ?nceli?inin sonu?lar?n? g??lendirecektir.

T?RK?YE'DE ARIA

Yay?nlar

1. Kalayci O, Yorgancioglu A, Kalyoncu F, Khaltaev AN, Bousquet J. Allergic rhinitis and its impact on asthma update (ARIA 2008): the Turkish perspective. Turk J Pediatr 2008; 50: 307-12.

2- Yorgancioglu A, Kalayci O, Kalyoncu AF, Khaltaev N, Bousquet J. Allergic rhinitis and its impact on asthma update (ARIA 2008): the Turkish perspective. Tuberk Toraks 2008; 56: 224-31.

ARIA T?rkiye ?al??ma Grubu

Arzu Yorganc?o?lu (ARIA T?rkiye Sorumlusu)

Celal Bayar ?niversitesi T?p Fak?ltesi, G???s Hastal?klar? Anabilim Dal?, Manisa.

A. Fuat Kalyoncu

Hacettepe ?niversitesi T?p Fak?ltesi, G???s Hastal?klar? Anabilim Dal?, Ankara.

?mer Kalayc?

Hacettepe ?niversitesi T?p Fak?ltesi, Pediatrik Allerji Bilim Dal?, Ankara.

Cevdet ?zdemir

Memorial Ata?ehir Hastanesi, ?ocuk Allerjisi B?l?m?, ?stanbul.

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Yaz??ma Adresi (Address for Correspondence):

Dr. Arzu YORGANCIO?LU,

Celal Bayar ?niversitesi T?p Fak?ltesi,

G???s Hastal?klar? Anabilim Dal?,

MAN?SA - TURKEY

e-mail: arzuyo@hotmail.com

Yazd?r