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MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ

Yıl 2008, Cilt: 71 Sayı: 3, 65 - 72, 14.11.2011

Öz

Amaç: Bu çalışma allerjik rinit (AR) tedavisinde nispeten yeni uygulanmaya başlanmış olan mevsim öncesi immünoterapinin (IT) mevsim sonundaki klinik ve laboratuar etkinliğini değerlendirmek amacı ile tasarlandı. Gereç ve yöntem: Çalışma Kocaeli Üniversitesi Tıp Fakültesi İç Hastalıkları AD Allerji Polikliniği’nde Eylül 2005-Eylül 2006 tarihleri arasında yapıldı. Çalışmaya anamnez, fizik muayene ve farklı laboratuvar yöntemleriyle mevsimsel AR tanısı konulan 20-60 yaşları arasında 27’si kadın, 13’ü erkek toplam 40 hasta alındı. Bu hastalardan rastgele seçilen 20’si kontrol grubuna dahil edildi. Diğer 20 kişiye de mevsim öncesi IT uygulandı. Astım ve kronik metabolik hastalıkları olanlar çalışmaya alınmadı. Bulgular: Mevsim öncesi IT alan hastalarda polen mevsimi boyunca görülen semptomlarda ve buna bağlı olarak ilaç kullanma ihtiyacında azalma gözlendi. Allerjen spesifik IgE düzeylerindeki mevsimsel artış engellendi. Polen allerjenlerine ve histamine olan deri testi duyarlılığında, serum allerjen spesifik IgG6 düzeylerinde, serum ECP ve eozinofil değerlerinde azalma saptandı. Nazal sürüntüdeki eozinofil yüzdesinde ve serum triptaz düzeylerinde artış olduğu görüldü. Sonuç: Sonuç olarak mevsim öncesi uygulanan IT’nin mevsimsel AR tedavisinde güvenilir ve etkili bir yöntem olduğu söylenebilir. Deri testi duyarlılığının azalması, allerjen spesifik IgE’lerin mevsimsel artışının baskılanması ve serum ECP düzeylerindeki azalma klinik etkinlik ile uyumlu bulundu. Mevsim öncesi IT’nin immünolojik etkilerinin erken dönemde ortaya çıktığı gösterildi. Serum allerjen spesifik IgG6 , nazal eozinofil ve serum triptaz sonuçlarının klinik etkinlik ile uyumsuz olduğu görüldü. Kesin yargıya varabilmek için immünizasyonun ilerleyen dönemlerinde de IT’nin etkinliğini değerlendirecek daha ayrıntılı çalışmalara ihtiyaç vardır.

Kaynakça

  • Bentley AM, Jacobson MR, Cumberworth V. Immunohistology of the nasal mucosa in seasonal allergic rhinitis: Grass pollen im- munotherapy increases in activated eosinophils and epithelial mast cells. J Allergy Clin Immunol 1992;89:877-883.
  • Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. WHO position paper. J Allergy Clin Immunol 1998;102:558–562.
  • Bousquet J. Allergic rhinitis and its impact on asthma (ARIA). J Allergy Clin Immunol 2001;108:147-336.
  • Bousquet J, Cauwenberge P, Khaltaev N. ARIA in the pharmacy: management of allergic rhinitis symptoms in the pharmacy. Al- lergy 2004;59:373–387.
  • Can D, Tanaç R, Demir E, Gülen F, Veral A. Efficacy of pollen immunotherapy in seasonal allergic rhinitis. Pediatrics Internati- onal 2007;49:64–69.
  • Casanovas M, Fernandez-Caldas E, Alamar R, Basomba A. Comparative study of tolerance between unmodified and high doses of chemically modified allergen vaccines of Dermatopha- goides pteronyssinus. Int Arch Allergy Immunol 2005;137:211–218.
  • Chen ST, Sun HL, Lu KH, Lue KH, Chou MC. Correlation of immunoglobulin E, eosinophil cationic protein, and eosinophil count with severity of childhood perennial allergic rhinitis. J Microbiol Immunol Infect 2006;39:212-218.
  • Ciprandi G, Vizzaccaro A, Cirillo I, Tosca M, Massolo A, Passa- lacqua G. Nasal eosinophils display the best correlation with symptoms, pulmonary function and inflammation in allergic rhi- nitis. Int Arch Allergy Immunol 2005;136:266-272.
  • Consensus statement on the treatment of allergic rhinitis. Euro- pean Academy of Allergology and Clinical Immunology. Al- lergy 2000;55:116-134.
  • Corrigan CJ for the Study Group, Kettner J, Doemer C, Crom- well O, Narkus A. Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid. Allergy 2005;60:801–807.
  • Durham SR, Till SJ. Immunologic changes associated with aller- gen immunotherapy. J Allergy Clin Immunol 1998;102:157- 164.
  • Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Nobel W. Long-term clinical efficacy of grass pollen immunot- herapy. N Engl J Med 1999;341:468-475.
  • Durham SR. Allergen immunotherapy (desensitisation) for aller- gic diseases. Clin Med 2006;6:348-351.
  • Erel F, Karaayvaz M, Çalıflkaner AZ. Effects of allergen immu- notherapy on the nasal mucosa in patients with allergic rhinitis. J Invest Allergol Clin Immunol 2000;10:14–19.
  • Frew AJ, Powell RJ, Corrigan CJ, Durham SR. Efficacy and sa- fety of specific immunotherapy with SQ allergen extract in tre- atment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:319-25.
  • International Consensus Report on diagnosis and management of rhinitis. International Rhinitis Management Working Group. Allergy 1994;49:1–34.
  • Kelly V, Bomer and Robert M. Naclerio. Embriology, Anatomy, and Physiology of The Upper Airway. Chapter 41. Allergy: Prin- ciples and Practice.
  • Keskin O, Tuncer A, Adalioglu G, Sekerel BE, Saçkesen C, Ka- laycı O. The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis. Pediatr Allergy Immunol 2006;17:396–407.
  • King HC, Mabry RL, Mabry CS. Allergy in ENT Practice-A Ba- sic Guide. 1st ed. New York and Stuttgart: Thieme 1998; 103-54.
  • Klimek L, Dormann D, Jarman ER, Cromwell O, Riechelmann H, Reske-Kunz AB. Short-term preseasonal birch pollen allergo- id immunotherapy influences symptoms, specific nasal provoca- tion and cytokine levels in nasal secretions, but not peripheral T- cell responses, in patients with allergic rhinitis. Clin Exp Allergy 1999;29:1326–1335.
  • Lim MC, Taylor RM, Naclerio RM. The histology of allergic rhinitis and its comparison to cellular changes in nasal lavage. Am J Respir Crit Care Med 1995;151:136–144.
  • Masuyama K, Till SJ, Jacobson MR. Nasal eosinophilia and IL- 5 mRNA expression in seasonal allergic rhinitis induced by na- tural allergen exposure: effect of topical corticosteroids. J Al- lergy Clin Immunol 1998;102:610-617.
  • Naclerio RM, Proud D, Moylan B, Balcer S, Freidhoff L, Kage- yo-Sobotka A. A double blind study of the discontinuation of ragweed immunotherapy. J Allergy Clin Immunol 1997;100:293-300.
  • Nakamoto S, Ukai K, Sakakura Y. Effect of allergen immunot- herapy on nasal responses in guinea-pigs with allergic rhinitis. Clin Exp Allergy 1997;27:1103–1108.
  • Nelson HS. Immunotherapy for inhalant allergens. Chapter 74. Allergy: Principles and Practice.
  • Nivenka PJ, Tudor PT, Williams A, Rajakulasingam K. Mecha- nisms of immunotherapy in allergic rhinitis. Biomedicine & Pharmacotherapy 2007;29-33.
  • Ohashi Y, Nakai Y, Kakinoki Y, Ohno Y, Okomato H, Sakamato H, Kato A, Tanaka A. The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allerjic rhinitis. Clin Otolaryngol 1997;22:100-105.
  • Ohashi Y, Nakai Y, Tanaka A, Kakinoki Y, Masamoto T, Kato A, Sakamoto H. The Clinical role of spesific IgE and IgG4 antibo- dies in patients having immunotherapy for seasonal allergic rhi- nitis. Clin Otolaryngol 1998;23:128-135.
  • Pastarello EA, Pravettoni V, Incorvaia C. Clinical and immuno- logical effects of immunotherapy with aluminium-absorbed grass allergoid in grass pollen- induced hay fever. Allergy 1992;47:281–290.
  • Rossi RE, Monasterolo G. Evaluation of Recombinant and Na- tive Timothy Pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- Specific IgG4 Antibodies Induced by Subcutaneous Immunot- herapy with Timothy Pollen Extract in Allergic Patients. Int Arch Allergy Immunol 2004;135:44–53.
  • Sin A, Terzioglu E, Kokuludag A. Immunology and Infection eosinophil cationic protein (ECP) levels in patients with seaso- nal allergic rhinitis and allergic asthma. Allergy Asthma Proc 1998;19:69-73.
  • Sin B, Mısırlıgil Z, Aybay C, Gürbüz L, İmir T. Effect of aller- gen specific immunotherapy (IT) on natural killer cell activity (NK), IgE, IFN-_ levels and clinical response in patients with al- lergic rhinitis and asthma. J Invest Allergol Clin Immunol 1996;6:341-347.
  • Tari MG, Mancino M, Ghezzi E, Frank E, Cromwell O. Immu- notherapy with an alum-adsorbed Parietaria pollen allergoid: a 2 year, double-blind, placebo controlled study. Allergy 1997;52:65–74.
  • Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. J Allergy Clin Immunol 2004;113:1025–1034.
  • Van Cauwenberger P, De Belder T, Vermeiren J, Kaplan A. Glo- bal resources in allergy (GLORIA): allergic rhinitis and allergic conjunctivitis. Clin Exp All Rev 2003;3:46-50.
  • Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR. Grass polen immunotherapy for seasonal rhinitis and asthma: randomized, controlled trial. J Allergy Clin Immunol 2001;107:87–93.
  • Wheeler AW, Woroniecki SR. Allergy vaccines: new approaches to an old concept. Expert Opin Biol Ther 2004;9:1473-1481.
  • Wilson DR, Nouri-Aria KT, Walker SM. Grass pollen immunot- herapy: symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa du- ring the pollen season. J Allergy Clin Immunol 2001;107:971–976.
  • Wilson DR, Irani A, Walker SM, Jacobson MR, Mackay IS, Schwartz LB and Durham SR. Grass pollen immunotherapy in- hibits seasonal increases in basophils and eosinophils in the na- sal epithelium. Clinical and Experimental Allergy 2001;Volume 31:1705-1713.
  • Wimther L, Moseholm L, Reimert CM, Stahl Skov P, Kaergaard Poulsen L. Basophil histamine release, IgE, eosinophil counts, ECP and EPX are related to the severity of symptoms in seaso- nal allergic rhinitis. Allergy 1999;54:436-445.
Yıl 2008, Cilt: 71 Sayı: 3, 65 - 72, 14.11.2011

Öz

Kaynakça

  • Bentley AM, Jacobson MR, Cumberworth V. Immunohistology of the nasal mucosa in seasonal allergic rhinitis: Grass pollen im- munotherapy increases in activated eosinophils and epithelial mast cells. J Allergy Clin Immunol 1992;89:877-883.
  • Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. WHO position paper. J Allergy Clin Immunol 1998;102:558–562.
  • Bousquet J. Allergic rhinitis and its impact on asthma (ARIA). J Allergy Clin Immunol 2001;108:147-336.
  • Bousquet J, Cauwenberge P, Khaltaev N. ARIA in the pharmacy: management of allergic rhinitis symptoms in the pharmacy. Al- lergy 2004;59:373–387.
  • Can D, Tanaç R, Demir E, Gülen F, Veral A. Efficacy of pollen immunotherapy in seasonal allergic rhinitis. Pediatrics Internati- onal 2007;49:64–69.
  • Casanovas M, Fernandez-Caldas E, Alamar R, Basomba A. Comparative study of tolerance between unmodified and high doses of chemically modified allergen vaccines of Dermatopha- goides pteronyssinus. Int Arch Allergy Immunol 2005;137:211–218.
  • Chen ST, Sun HL, Lu KH, Lue KH, Chou MC. Correlation of immunoglobulin E, eosinophil cationic protein, and eosinophil count with severity of childhood perennial allergic rhinitis. J Microbiol Immunol Infect 2006;39:212-218.
  • Ciprandi G, Vizzaccaro A, Cirillo I, Tosca M, Massolo A, Passa- lacqua G. Nasal eosinophils display the best correlation with symptoms, pulmonary function and inflammation in allergic rhi- nitis. Int Arch Allergy Immunol 2005;136:266-272.
  • Consensus statement on the treatment of allergic rhinitis. Euro- pean Academy of Allergology and Clinical Immunology. Al- lergy 2000;55:116-134.
  • Corrigan CJ for the Study Group, Kettner J, Doemer C, Crom- well O, Narkus A. Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid. Allergy 2005;60:801–807.
  • Durham SR, Till SJ. Immunologic changes associated with aller- gen immunotherapy. J Allergy Clin Immunol 1998;102:157- 164.
  • Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Nobel W. Long-term clinical efficacy of grass pollen immunot- herapy. N Engl J Med 1999;341:468-475.
  • Durham SR. Allergen immunotherapy (desensitisation) for aller- gic diseases. Clin Med 2006;6:348-351.
  • Erel F, Karaayvaz M, Çalıflkaner AZ. Effects of allergen immu- notherapy on the nasal mucosa in patients with allergic rhinitis. J Invest Allergol Clin Immunol 2000;10:14–19.
  • Frew AJ, Powell RJ, Corrigan CJ, Durham SR. Efficacy and sa- fety of specific immunotherapy with SQ allergen extract in tre- atment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:319-25.
  • International Consensus Report on diagnosis and management of rhinitis. International Rhinitis Management Working Group. Allergy 1994;49:1–34.
  • Kelly V, Bomer and Robert M. Naclerio. Embriology, Anatomy, and Physiology of The Upper Airway. Chapter 41. Allergy: Prin- ciples and Practice.
  • Keskin O, Tuncer A, Adalioglu G, Sekerel BE, Saçkesen C, Ka- laycı O. The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis. Pediatr Allergy Immunol 2006;17:396–407.
  • King HC, Mabry RL, Mabry CS. Allergy in ENT Practice-A Ba- sic Guide. 1st ed. New York and Stuttgart: Thieme 1998; 103-54.
  • Klimek L, Dormann D, Jarman ER, Cromwell O, Riechelmann H, Reske-Kunz AB. Short-term preseasonal birch pollen allergo- id immunotherapy influences symptoms, specific nasal provoca- tion and cytokine levels in nasal secretions, but not peripheral T- cell responses, in patients with allergic rhinitis. Clin Exp Allergy 1999;29:1326–1335.
  • Lim MC, Taylor RM, Naclerio RM. The histology of allergic rhinitis and its comparison to cellular changes in nasal lavage. Am J Respir Crit Care Med 1995;151:136–144.
  • Masuyama K, Till SJ, Jacobson MR. Nasal eosinophilia and IL- 5 mRNA expression in seasonal allergic rhinitis induced by na- tural allergen exposure: effect of topical corticosteroids. J Al- lergy Clin Immunol 1998;102:610-617.
  • Naclerio RM, Proud D, Moylan B, Balcer S, Freidhoff L, Kage- yo-Sobotka A. A double blind study of the discontinuation of ragweed immunotherapy. J Allergy Clin Immunol 1997;100:293-300.
  • Nakamoto S, Ukai K, Sakakura Y. Effect of allergen immunot- herapy on nasal responses in guinea-pigs with allergic rhinitis. Clin Exp Allergy 1997;27:1103–1108.
  • Nelson HS. Immunotherapy for inhalant allergens. Chapter 74. Allergy: Principles and Practice.
  • Nivenka PJ, Tudor PT, Williams A, Rajakulasingam K. Mecha- nisms of immunotherapy in allergic rhinitis. Biomedicine & Pharmacotherapy 2007;29-33.
  • Ohashi Y, Nakai Y, Kakinoki Y, Ohno Y, Okomato H, Sakamato H, Kato A, Tanaka A. The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allerjic rhinitis. Clin Otolaryngol 1997;22:100-105.
  • Ohashi Y, Nakai Y, Tanaka A, Kakinoki Y, Masamoto T, Kato A, Sakamoto H. The Clinical role of spesific IgE and IgG4 antibo- dies in patients having immunotherapy for seasonal allergic rhi- nitis. Clin Otolaryngol 1998;23:128-135.
  • Pastarello EA, Pravettoni V, Incorvaia C. Clinical and immuno- logical effects of immunotherapy with aluminium-absorbed grass allergoid in grass pollen- induced hay fever. Allergy 1992;47:281–290.
  • Rossi RE, Monasterolo G. Evaluation of Recombinant and Na- tive Timothy Pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- Specific IgG4 Antibodies Induced by Subcutaneous Immunot- herapy with Timothy Pollen Extract in Allergic Patients. Int Arch Allergy Immunol 2004;135:44–53.
  • Sin A, Terzioglu E, Kokuludag A. Immunology and Infection eosinophil cationic protein (ECP) levels in patients with seaso- nal allergic rhinitis and allergic asthma. Allergy Asthma Proc 1998;19:69-73.
  • Sin B, Mısırlıgil Z, Aybay C, Gürbüz L, İmir T. Effect of aller- gen specific immunotherapy (IT) on natural killer cell activity (NK), IgE, IFN-_ levels and clinical response in patients with al- lergic rhinitis and asthma. J Invest Allergol Clin Immunol 1996;6:341-347.
  • Tari MG, Mancino M, Ghezzi E, Frank E, Cromwell O. Immu- notherapy with an alum-adsorbed Parietaria pollen allergoid: a 2 year, double-blind, placebo controlled study. Allergy 1997;52:65–74.
  • Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. J Allergy Clin Immunol 2004;113:1025–1034.
  • Van Cauwenberger P, De Belder T, Vermeiren J, Kaplan A. Glo- bal resources in allergy (GLORIA): allergic rhinitis and allergic conjunctivitis. Clin Exp All Rev 2003;3:46-50.
  • Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR. Grass polen immunotherapy for seasonal rhinitis and asthma: randomized, controlled trial. J Allergy Clin Immunol 2001;107:87–93.
  • Wheeler AW, Woroniecki SR. Allergy vaccines: new approaches to an old concept. Expert Opin Biol Ther 2004;9:1473-1481.
  • Wilson DR, Nouri-Aria KT, Walker SM. Grass pollen immunot- herapy: symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa du- ring the pollen season. J Allergy Clin Immunol 2001;107:971–976.
  • Wilson DR, Irani A, Walker SM, Jacobson MR, Mackay IS, Schwartz LB and Durham SR. Grass pollen immunotherapy in- hibits seasonal increases in basophils and eosinophils in the na- sal epithelium. Clinical and Experimental Allergy 2001;Volume 31:1705-1713.
  • Wimther L, Moseholm L, Reimert CM, Stahl Skov P, Kaergaard Poulsen L. Basophil histamine release, IgE, eosinophil counts, ECP and EPX are related to the severity of symptoms in seaso- nal allergic rhinitis. Allergy 1999;54:436-445.
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Klinik Araştırma
Yazarlar

Gülfinar Çağlar Kılıç Bu kişi benim

Bülent Kardeş Bu kişi benim

Ayşe Çefle Bu kişi benim

Ayten Yazıcı Bu kişi benim

Gülfinar Kılıç Bu kişi benim

At All. Bu kişi benim

Yayımlanma Tarihi 14 Kasım 2011
Gönderilme Tarihi 14 Kasım 2011
Yayımlandığı Sayı Yıl 2008 Cilt: 71 Sayı: 3

Kaynak Göster

APA Kılıç, G. Ç., Kardeş, B., Çefle, A., Yazıcı, A., vd. (2011). MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ. Journal of Istanbul Faculty of Medicine, 71(3), 65-72.
AMA Kılıç GÇ, Kardeş B, Çefle A, Yazıcı A, Kılıç G, All. A. MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ. İst Tıp Fak Derg. Kasım 2011;71(3):65-72.
Chicago Kılıç, Gülfinar Çağlar, Bülent Kardeş, Ayşe Çefle, Ayten Yazıcı, Gülfinar Kılıç, ve At All. “MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ”. Journal of Istanbul Faculty of Medicine 71, sy. 3 (Kasım 2011): 65-72.
EndNote Kılıç GÇ, Kardeş B, Çefle A, Yazıcı A, Kılıç G, All. A (01 Kasım 2011) MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ. Journal of Istanbul Faculty of Medicine 71 3 65–72.
IEEE G. Ç. Kılıç, B. Kardeş, A. Çefle, A. Yazıcı, G. Kılıç, ve A. All., “MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ”, İst Tıp Fak Derg, c. 71, sy. 3, ss. 65–72, 2011.
ISNAD Kılıç, Gülfinar Çağlar vd. “MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ”. Journal of Istanbul Faculty of Medicine 71/3 (Kasım 2011), 65-72.
JAMA Kılıç GÇ, Kardeş B, Çefle A, Yazıcı A, Kılıç G, All. A. MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ. İst Tıp Fak Derg. 2011;71:65–72.
MLA Kılıç, Gülfinar Çağlar vd. “MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ”. Journal of Istanbul Faculty of Medicine, c. 71, sy. 3, 2011, ss. 65-72.
Vancouver Kılıç GÇ, Kardeş B, Çefle A, Yazıcı A, Kılıç G, All. A. MEVSİMSEL ALLERJİK RİNİTLİ HASTALARDAMEVSİM ÖNCESİ İMMÜNOTERAPİNİN ETKİNLİĞİ. İst Tıp Fak Derg. 2011;71(3):65-72.

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