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Difficult Asthma and its Treatment

Year 2017, Volume: 9 Issue: 2, 39 - 47, 15.03.2017

Abstract

Abstract

Difficult asthma accounts for 5-10% of asthmatic patients but a great deal of mor-bidity and expenditures due to asthma belongs to this group of patients. The definition is still contraversial; patients with poor asthma control or frequent exacerbations with high-dose anti-asthma drugs are defined as ‘difficult asthma’. It may be difficult to assess this complex and mixed patient group under standard outpatient conditions. These patients should be evaluated systematically in centers special for asthma. There are well defined phenotypes according to history, pathophysiology, clinical features and treatment response. Knowing these phenotypes makes targeted treatment possible. In the treatment plan, firstly, we must be sure of asthma diagnosisand exclude the alternative diseases. Secondly, all the triggerinf factors that may disrupt asthma control should be removed, and comorbid diseases such as rhinosinusitis and gastroesophageal reflux should be treated. In addition to conventional asthma drugs, monoclonal antibodies such as omalizumab, macrolides, bronchial thermoplasty and newly developed biological agents can be used for treatment.

References

  • Kaynaklar 1.Masoli M, Fabian D, Holt S, Beasley R, Global Initiative forAsthma P. The global burden of asthma: executive summaryof the GINA Dissemination Committee report. Allergy.2004;59(5):469-78. 2.Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, SterkPJ, et al. International ERS/ATS guidelines on definition, eva-luation and treatment of severe asthma. The European respi-ratory journal. 2014;43(2):343-73. 3.Lopez-Vina A, Aguero-Balbin R, Aller-Alvarez JL, Bazus-Gon-zalez T, Cosio BG, de Diego-Damia A, et al. [Guidelines forthe diagnosis and management of difficult-to-control asthma].Archivos de bronconeumologia. 2005;41(9):513-23. 4.Radhakrishna N, Tay TR, Hore-Lacy F, Hoy R, Dabscheck E,Hew M. Profile of difficult to treat asthma patients referredfor systematic assessment. Respiratory medicine.2016;117:166-73. 5.Robinson DS, Campbell DA, Durham SR, Pfeffer J, Barnes PJ,Chung KF, et al. Systematic assessment of difficult-to-treat asth-ma. The European respiratory journal. 2003;22(3):478-83. 6.Gibeon D, Heaney LG, Brightling CE, Niven R, Mansur AH, Cha-udhuri R, et al. Dedicated severe asthma services improve he-alth-care use and quality of life. Chest. 2015;148(4):870-6. 7.Cisneros Serrano C, Melero Moreno C, Almonacid SanchezC, Perpina Tordera M, Picado Valles C, Martinez MoragonE, et al. Guidelines for severe uncontrolled asthma. Archivosde bronconeumologia. 2015;51(5):235-46. 8.Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML,Bel EH. The prevalence of severe refractory asthma. The Jour-nal of allergy and clinical immunology. 2015;135(4):896-902. 9.Wenzel SE, Balzar S, Ampleford E, Hawkins GA, Busse WW,Calhoun WJ, et al. IL4R alpha mutations are associated withasthma exacerbations and mast cell/IgE expression. Ameri-can journal of respiratory and critical care medicine.2007;175(6):570-6. 10.Hawkins GA, Robinson MB, Hastie AT, Li X, Li H, Moore WC,et al. The IL6R variation Asp(358)Ala is a potential modifi-er of lung function in subjects with asthma. The Journal of al-lergy and clinical immunology. 2012;130(2):510-5 e1. 11.Li X, Howard TD, Zheng SL, Haselkorn T, Peters SP, MeyersDA, et al. Genome-wide association study of asthma identi-fies RAD50-IL13 and HLA-DR/DQ regions. The Journal ofallergy and clinical immunology. 2010;125(2):328-35 e11. 12.Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthmaphenotypes and endotypes. Allergy. 2012;67(7):835-46. 13.Hastie AT, Moore WC, Meyers DA, Vestal PL, Li H, PetersSP, et al. Analyses of asthma severity phenotypes and inflam-matory proteins in subjects stratified by sputum granulocytes.The Journal of allergy and clinical immunology.2010;125(5):1028-36 e13. 14.Wenzel SE. Complex phenotypes in asthma: current definitions.Pulmonary pharmacology & therapeutics. 2013;26(6):710-5. 15.Sutherland ER. Linking obesity and asthma. Annals of the NewYork Academy of Sciences. 2014;1311:31-41. 16.Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C,Bush A, et al. Relationship between serum vitamin D, disea-se severity, and airway remodeling in children with asthma.American journal of respiratory and critical care medicine.2011;184(12):1342-9. 17.Bel EH, Sousa A, Fleming L, Bush A, Chung KF, Versnel J,et al. Diagnosis and definition of severe refractory asthma:an international consensus statement from the Innovative Me-dicine Initiative (IMI). Thorax. 2011;66(10):910-7. 18.Williams LK, Joseph CL, Peterson EL, Wells K, Wang M,Chowdhry VK, et al. Patients with asthma who do not fill the-ir inhaled corticosteroids: a study of primary nonadherence.The Journal of allergy and clinical immunology.2007;120(5):1153-9. 19.Tay TR, Radhakrishna N, Hore-Lacy F, Smith C, Hoy R, Dabsc-heck E, et al. Comorbidities in difficult asthma are indepen-dent risk factors for frequent exacerbations, poor control anddiminished quality of life. Respirology. 2016;21(8):1384-90. 20.Schleich F, Sophie D, Renaud L. Biomarkers in the Manage-ment of Difficult Asthma. Current topics in medicinal chemistry.2016;16(14):1561-73. 21.Zaihra T, Walsh CJ, Ahmed S, Fugere C, Hamid QA, Olivens-tein R, et al. Phenotyping of difficult asthma using longitudi-nal physiological and biomarker measurements reveals sig-nificant differences in stability between clusters. BMC pulmo-nary medicine. 2016;16(1):74. 22.Thomson NC, Chaudhuri R, Livingston E. Asthma and ciga-rette smoking. The European respiratory journal.2004;24(5):822-33. 23.Reddy D, Little FF. Glucocorticoid-resistant asthma: more thanmeets the eye. The Journal of asthma : official journal of theAssociation for the Care of Asthma. 2013;50(10):1036-44. 24.Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Bright-ling CE, et al. Cluster analysis and clinical asthma phenoty-pes. American journal of respiratory and critical care medi-cine. 2008;178(3):218-24. 25.Adams NP, Bestall JC, Jones P, Lasserson TJ, Griffiths B, Ca-tes CJ. Fluticasone at different doses for chronic asthma inadults and children. The Cochrane database of systematic re-views. 2008(4):CD003534. 26.Bateman ED, Cheung D, Lapa e Silva J, Gohring UM, Scha-fer M, Engelstatter R. Randomized comparison of ciclesoni-de 160 and 640 microg/day in severe asthma. Pulmonary phar-macology & therapeutics. 2008;21(3):489-98. 27.De Bosscher K, Haegeman G, Elewaut D. Targeting inflam-mation using selective glucocorticoid receptor modulators. Cur-rent opinion in pharmacology. 2010;10(4):497-504. 28.Ogirala RG, Aldrich TK, Prezant DJ, Sinnett MJ, Enden JB,Williams MH, Jr. High-dose intramuscular triamcinolone insevere, chronic, life-threatening asthma. The New England jo-urnal of medicine. 1991;324(9):585-9. 29.ten Brinke A, Zwinderman AH, Sterk PJ, Rabe KF, Bel EH. "Ref-ractory" eosinophilic airway inflammation in severe asthma:effect of parenteral corticosteroids. American journal of res-piratory and critical care medicine. 2004;170(6):601-5. 30.Hanania NA, Dickey BF, Bond RA. Clinical implications ofthe intrinsic efficacy of beta-adrenoceptor drugs in asthma:full, partial and inverse agonism. Current opinion in pulmo-nary medicine. 2010;16(1):1-5. 31.Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vande-walker M, et al. Tiotropium in asthma poorly controlled withstandard combination therapy. The New England journal ofmedicine. 2012;367(13):1198-207. 32.Iwamoto H, Yokoyama A, Shiota N, Shoda H, Haruta Y, Hat-tori N, et al. Tiotropium bromide is effective for severe asth-ma with noneosinophilic phenotype. The European respira-tory journal. 2008;31(6):1379-80. 33.Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R,Ameredes BT, et al. Tiotropium bromide step-up therapy foradults with uncontrolled asthma. The New England journalof medicine. 2010;363(18):1715-26. 34.Park JS, Jang AS, Park SW, Lee YM, Uh ST, Kim YH, et al.Protection of leukotriene receptor antagonist against aspirin-induced bronchospasm in asthmatics. Allergy, asthma & im-munology research. 2010;2(1):48-54. 35.Gao JM, Cai F, Peng M, Ma Y, Wang B. Montelukast impro-ves air trapping, not airway remodeling, in patients with mo-derate-to-severe asthma: a pilot study. Chinese medical jo-urnal. 2013;126(12):2229-34. 36.Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharryC, et al. Effect of low-dose theophylline plus beclometasoneon lung function in smokers with asthma: a pilot study. TheEuropean respiratory journal. 2009;33(5):1010-7. 37.Barnes PJ. Theophylline: new perspectives for an old drug.American journal of respiratory and critical care medicine.2003;167(6):813-8. 38.Miravitlles M, Soler-Cataluna JJ, Calle M, Molina J, Almag-ro P, Quintano JA, et al. Spanish guideline for COPD (Ge-sEPOC). Update 2014. Archivos de bronconeumologia.2014;50 Suppl 1:1-16. 39.Bateman ED, Izquierdo JL, Harnest U, Hofbauer P, MagyarP, Schmid-Wirlitsch C, et al. Efficacy and safety of roflumi-last in the treatment of asthma. Annals of allergy, asthma &immunology : official publication of the American College ofAllergy, Asthma, & Immunology. 2006;96(5):679-86. 40.Paul G, Brehm JM, Alcorn JF, Holguin F, Aujla SJ, CeledonJC. Vitamin D and asthma. American journal of respiratoryand critical care medicine. 2012;185(2):124-32. 41.Wong EH, Porter JD, Edwards MR, Johnston SL. The role ofmacrolides in asthma: current evidence and future directions.The Lancet Respiratory medicine. 2014;2(8):657-70. 42.Brusselle GG, Vanderstichele C, Jordens P, Deman R,Slabbynck H, Ringoet V, et al. Azithromycin for prevention ofexacerbations in severe asthma (AZISAST): a multicentre ran-domised double-blind placebo-controlled trial. Thorax.2013;68(4):322-9. 43.Lin CH, Cheng SL. A review of omalizumab for the manage-ment of severe asthma. Drug design, development and therapy.2016;10:2369-78. 44.Aubier M, Thabut G, Hamidi F, Guillou N, Brard J, DombretMC, et al. Airway smooth muscle enlargement is associated withprotease-activated receptor 2/ligand overexpression in patientswith difficult-to-control severe asthma. The Journal of allergyand clinical immunology. 2016;138(3):729-39 e11. 45.Castro M, Rubin AS, Laviolette M, Fiterman J, De AndradeLima M, Shah PL, et al. Effectiveness and safety of bronchi-al thermoplasty in the treatment of severe asthma: a multicen-ter, randomized, double-blind, sham-controlled clinical trial.American journal of respiratory and critical care medicine.2010;181(2):116-24. 46.Pretolani M, Bergqvist A, Thabut G, Dombret MC, Knapp D,Hamidi F, et al. Effectiveness of bronchial thermoplasty in pa-tients with severe refractory asthma: Clinical and histopat-hologic correlations. The Journal of allergy and clinical im-munology. 2016. 47.Liu Y, Zhang S, Li DW, Jiang SJ. Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PloS one.2013;8(3):e59872. 48.Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM,Chetta A, et al. Mepolizumab treatment in patients with seve-re eosinophilic asthma. The New England journal of medici-ne. 2014;371(13):1198-207. 49.Corren J, Lemanske RF, Hanania NA, Korenblat PE, ParseyMV, Arron JR, et al. Lebrikizumab treatment in adults withasthma. The New England journal of medicine.2011;365(12):1088-98. 50.Busse WW, Israel E, Nelson HS, Baker JW, Charous BL, Yo-ung DY, et al. Daclizumab improves asthma control in pati-ents with moderate to severe persistent asthma: a randomi-zed, controlled trial. American journal of respiratory and cri-tical care medicine. 2008;178(10):1002-8.

Zor Astım ve Tedavisi

Year 2017, Volume: 9 Issue: 2, 39 - 47, 15.03.2017

Abstract

Öz

Zor astım, astımlı hastaların %5-10 ‘unu oluşturmakla birlikte astıma bağlı morbidite ve harcamaların büyük bir kısmı bu gruba aittir. Zor astım tanımı tartışmalıdır, yüksek doz astım tedavisine rağmen semptom kontrolü sağlanamayan, sık alevlenme yaşayan hastalar bu gruba girmektedir. Bu en kompleks ve karışık hasta grubunu standart poliklinik koşullarında değerlendirmek zor olabilir, hastalar astıma özelmerkezlerde sistematik bir şekilde değerlendirilmelidir. Öykü, patofizyoloji, kliniközellikler ve tedavi cevaplarına göre iyi tanımlanmış zor astım fenotipleri vardır, bu fenotiplerin bilinmesi hedeflenmiş tedaviyi mümkün kılabilir. Zor astım tedavi planında öncelikle astım tanısından emin olunmalı, ayırıcı tanı yapılmalıdır. Astım kont-rolünü bozabilecek olan tüm tetikleyici faktörler ortadan kaldırılmalı, rinosinüzit, gastroözefageal reflü gibi komorbid hastalıklar tedavi edilmelidir. Zor astımda konvansiyonel astım ilaçlarının yanı sıra omalizumab gibi monoklonal antikorlar, makrolidler,  bronşial termoplasti ve yeni geliştirilen biyolojik ajanlar kullanılabilir.

References

  • Kaynaklar 1.Masoli M, Fabian D, Holt S, Beasley R, Global Initiative forAsthma P. The global burden of asthma: executive summaryof the GINA Dissemination Committee report. Allergy.2004;59(5):469-78. 2.Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, SterkPJ, et al. International ERS/ATS guidelines on definition, eva-luation and treatment of severe asthma. The European respi-ratory journal. 2014;43(2):343-73. 3.Lopez-Vina A, Aguero-Balbin R, Aller-Alvarez JL, Bazus-Gon-zalez T, Cosio BG, de Diego-Damia A, et al. [Guidelines forthe diagnosis and management of difficult-to-control asthma].Archivos de bronconeumologia. 2005;41(9):513-23. 4.Radhakrishna N, Tay TR, Hore-Lacy F, Hoy R, Dabscheck E,Hew M. Profile of difficult to treat asthma patients referredfor systematic assessment. Respiratory medicine.2016;117:166-73. 5.Robinson DS, Campbell DA, Durham SR, Pfeffer J, Barnes PJ,Chung KF, et al. Systematic assessment of difficult-to-treat asth-ma. The European respiratory journal. 2003;22(3):478-83. 6.Gibeon D, Heaney LG, Brightling CE, Niven R, Mansur AH, Cha-udhuri R, et al. Dedicated severe asthma services improve he-alth-care use and quality of life. Chest. 2015;148(4):870-6. 7.Cisneros Serrano C, Melero Moreno C, Almonacid SanchezC, Perpina Tordera M, Picado Valles C, Martinez MoragonE, et al. Guidelines for severe uncontrolled asthma. Archivosde bronconeumologia. 2015;51(5):235-46. 8.Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML,Bel EH. The prevalence of severe refractory asthma. The Jour-nal of allergy and clinical immunology. 2015;135(4):896-902. 9.Wenzel SE, Balzar S, Ampleford E, Hawkins GA, Busse WW,Calhoun WJ, et al. IL4R alpha mutations are associated withasthma exacerbations and mast cell/IgE expression. Ameri-can journal of respiratory and critical care medicine.2007;175(6):570-6. 10.Hawkins GA, Robinson MB, Hastie AT, Li X, Li H, Moore WC,et al. The IL6R variation Asp(358)Ala is a potential modifi-er of lung function in subjects with asthma. The Journal of al-lergy and clinical immunology. 2012;130(2):510-5 e1. 11.Li X, Howard TD, Zheng SL, Haselkorn T, Peters SP, MeyersDA, et al. Genome-wide association study of asthma identi-fies RAD50-IL13 and HLA-DR/DQ regions. The Journal ofallergy and clinical immunology. 2010;125(2):328-35 e11. 12.Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthmaphenotypes and endotypes. Allergy. 2012;67(7):835-46. 13.Hastie AT, Moore WC, Meyers DA, Vestal PL, Li H, PetersSP, et al. Analyses of asthma severity phenotypes and inflam-matory proteins in subjects stratified by sputum granulocytes.The Journal of allergy and clinical immunology.2010;125(5):1028-36 e13. 14.Wenzel SE. Complex phenotypes in asthma: current definitions.Pulmonary pharmacology & therapeutics. 2013;26(6):710-5. 15.Sutherland ER. Linking obesity and asthma. Annals of the NewYork Academy of Sciences. 2014;1311:31-41. 16.Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C,Bush A, et al. Relationship between serum vitamin D, disea-se severity, and airway remodeling in children with asthma.American journal of respiratory and critical care medicine.2011;184(12):1342-9. 17.Bel EH, Sousa A, Fleming L, Bush A, Chung KF, Versnel J,et al. Diagnosis and definition of severe refractory asthma:an international consensus statement from the Innovative Me-dicine Initiative (IMI). Thorax. 2011;66(10):910-7. 18.Williams LK, Joseph CL, Peterson EL, Wells K, Wang M,Chowdhry VK, et al. Patients with asthma who do not fill the-ir inhaled corticosteroids: a study of primary nonadherence.The Journal of allergy and clinical immunology.2007;120(5):1153-9. 19.Tay TR, Radhakrishna N, Hore-Lacy F, Smith C, Hoy R, Dabsc-heck E, et al. Comorbidities in difficult asthma are indepen-dent risk factors for frequent exacerbations, poor control anddiminished quality of life. Respirology. 2016;21(8):1384-90. 20.Schleich F, Sophie D, Renaud L. Biomarkers in the Manage-ment of Difficult Asthma. Current topics in medicinal chemistry.2016;16(14):1561-73. 21.Zaihra T, Walsh CJ, Ahmed S, Fugere C, Hamid QA, Olivens-tein R, et al. Phenotyping of difficult asthma using longitudi-nal physiological and biomarker measurements reveals sig-nificant differences in stability between clusters. BMC pulmo-nary medicine. 2016;16(1):74. 22.Thomson NC, Chaudhuri R, Livingston E. Asthma and ciga-rette smoking. The European respiratory journal.2004;24(5):822-33. 23.Reddy D, Little FF. Glucocorticoid-resistant asthma: more thanmeets the eye. The Journal of asthma : official journal of theAssociation for the Care of Asthma. 2013;50(10):1036-44. 24.Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Bright-ling CE, et al. Cluster analysis and clinical asthma phenoty-pes. American journal of respiratory and critical care medi-cine. 2008;178(3):218-24. 25.Adams NP, Bestall JC, Jones P, Lasserson TJ, Griffiths B, Ca-tes CJ. Fluticasone at different doses for chronic asthma inadults and children. The Cochrane database of systematic re-views. 2008(4):CD003534. 26.Bateman ED, Cheung D, Lapa e Silva J, Gohring UM, Scha-fer M, Engelstatter R. Randomized comparison of ciclesoni-de 160 and 640 microg/day in severe asthma. Pulmonary phar-macology & therapeutics. 2008;21(3):489-98. 27.De Bosscher K, Haegeman G, Elewaut D. Targeting inflam-mation using selective glucocorticoid receptor modulators. Cur-rent opinion in pharmacology. 2010;10(4):497-504. 28.Ogirala RG, Aldrich TK, Prezant DJ, Sinnett MJ, Enden JB,Williams MH, Jr. High-dose intramuscular triamcinolone insevere, chronic, life-threatening asthma. The New England jo-urnal of medicine. 1991;324(9):585-9. 29.ten Brinke A, Zwinderman AH, Sterk PJ, Rabe KF, Bel EH. "Ref-ractory" eosinophilic airway inflammation in severe asthma:effect of parenteral corticosteroids. American journal of res-piratory and critical care medicine. 2004;170(6):601-5. 30.Hanania NA, Dickey BF, Bond RA. Clinical implications ofthe intrinsic efficacy of beta-adrenoceptor drugs in asthma:full, partial and inverse agonism. Current opinion in pulmo-nary medicine. 2010;16(1):1-5. 31.Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vande-walker M, et al. Tiotropium in asthma poorly controlled withstandard combination therapy. The New England journal ofmedicine. 2012;367(13):1198-207. 32.Iwamoto H, Yokoyama A, Shiota N, Shoda H, Haruta Y, Hat-tori N, et al. Tiotropium bromide is effective for severe asth-ma with noneosinophilic phenotype. The European respira-tory journal. 2008;31(6):1379-80. 33.Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R,Ameredes BT, et al. Tiotropium bromide step-up therapy foradults with uncontrolled asthma. The New England journalof medicine. 2010;363(18):1715-26. 34.Park JS, Jang AS, Park SW, Lee YM, Uh ST, Kim YH, et al.Protection of leukotriene receptor antagonist against aspirin-induced bronchospasm in asthmatics. Allergy, asthma & im-munology research. 2010;2(1):48-54. 35.Gao JM, Cai F, Peng M, Ma Y, Wang B. Montelukast impro-ves air trapping, not airway remodeling, in patients with mo-derate-to-severe asthma: a pilot study. Chinese medical jo-urnal. 2013;126(12):2229-34. 36.Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharryC, et al. Effect of low-dose theophylline plus beclometasoneon lung function in smokers with asthma: a pilot study. TheEuropean respiratory journal. 2009;33(5):1010-7. 37.Barnes PJ. Theophylline: new perspectives for an old drug.American journal of respiratory and critical care medicine.2003;167(6):813-8. 38.Miravitlles M, Soler-Cataluna JJ, Calle M, Molina J, Almag-ro P, Quintano JA, et al. Spanish guideline for COPD (Ge-sEPOC). Update 2014. Archivos de bronconeumologia.2014;50 Suppl 1:1-16. 39.Bateman ED, Izquierdo JL, Harnest U, Hofbauer P, MagyarP, Schmid-Wirlitsch C, et al. Efficacy and safety of roflumi-last in the treatment of asthma. Annals of allergy, asthma &immunology : official publication of the American College ofAllergy, Asthma, & Immunology. 2006;96(5):679-86. 40.Paul G, Brehm JM, Alcorn JF, Holguin F, Aujla SJ, CeledonJC. Vitamin D and asthma. American journal of respiratoryand critical care medicine. 2012;185(2):124-32. 41.Wong EH, Porter JD, Edwards MR, Johnston SL. The role ofmacrolides in asthma: current evidence and future directions.The Lancet Respiratory medicine. 2014;2(8):657-70. 42.Brusselle GG, Vanderstichele C, Jordens P, Deman R,Slabbynck H, Ringoet V, et al. Azithromycin for prevention ofexacerbations in severe asthma (AZISAST): a multicentre ran-domised double-blind placebo-controlled trial. Thorax.2013;68(4):322-9. 43.Lin CH, Cheng SL. A review of omalizumab for the manage-ment of severe asthma. Drug design, development and therapy.2016;10:2369-78. 44.Aubier M, Thabut G, Hamidi F, Guillou N, Brard J, DombretMC, et al. Airway smooth muscle enlargement is associated withprotease-activated receptor 2/ligand overexpression in patientswith difficult-to-control severe asthma. The Journal of allergyand clinical immunology. 2016;138(3):729-39 e11. 45.Castro M, Rubin AS, Laviolette M, Fiterman J, De AndradeLima M, Shah PL, et al. Effectiveness and safety of bronchi-al thermoplasty in the treatment of severe asthma: a multicen-ter, randomized, double-blind, sham-controlled clinical trial.American journal of respiratory and critical care medicine.2010;181(2):116-24. 46.Pretolani M, Bergqvist A, Thabut G, Dombret MC, Knapp D,Hamidi F, et al. Effectiveness of bronchial thermoplasty in pa-tients with severe refractory asthma: Clinical and histopat-hologic correlations. The Journal of allergy and clinical im-munology. 2016. 47.Liu Y, Zhang S, Li DW, Jiang SJ. Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PloS one.2013;8(3):e59872. 48.Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM,Chetta A, et al. Mepolizumab treatment in patients with seve-re eosinophilic asthma. The New England journal of medici-ne. 2014;371(13):1198-207. 49.Corren J, Lemanske RF, Hanania NA, Korenblat PE, ParseyMV, Arron JR, et al. Lebrikizumab treatment in adults withasthma. The New England journal of medicine.2011;365(12):1088-98. 50.Busse WW, Israel E, Nelson HS, Baker JW, Charous BL, Yo-ung DY, et al. Daclizumab improves asthma control in pati-ents with moderate to severe persistent asthma: a randomi-zed, controlled trial. American journal of respiratory and cri-tical care medicine. 2008;178(10):1002-8.
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Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section makale
Authors

Prof. Dr. Bülent Enis Şekerel This is me

Publication Date March 15, 2017
Published in Issue Year 2017 Volume: 9 Issue: 2

Cite

APA Şekerel, P. D. B. E. (2017). Zor Astım ve Tedavisi. Klinik Tıp Pediatri Dergisi, 9(2), 39-47.
AMA Şekerel PDBE. Zor Astım ve Tedavisi. Pediatri. March 2017;9(2):39-47.
Chicago Şekerel, Prof. Dr. Bülent Enis. “Zor Astım Ve Tedavisi”. Klinik Tıp Pediatri Dergisi 9, no. 2 (March 2017): 39-47.
EndNote Şekerel PDBE (March 1, 2017) Zor Astım ve Tedavisi. Klinik Tıp Pediatri Dergisi 9 2 39–47.
IEEE P. D. B. E. Şekerel, “Zor Astım ve Tedavisi”, Pediatri, vol. 9, no. 2, pp. 39–47, 2017.
ISNAD Şekerel, Prof. Dr. Bülent Enis. “Zor Astım Ve Tedavisi”. Klinik Tıp Pediatri Dergisi 9/2 (March 2017), 39-47.
JAMA Şekerel PDBE. Zor Astım ve Tedavisi. Pediatri. 2017;9:39–47.
MLA Şekerel, Prof. Dr. Bülent Enis. “Zor Astım Ve Tedavisi”. Klinik Tıp Pediatri Dergisi, vol. 9, no. 2, 2017, pp. 39-47.
Vancouver Şekerel PDBE. Zor Astım ve Tedavisi. Pediatri. 2017;9(2):39-47.