ktd

Kocatepe Tıp Dergisi

3061-9904

Afyonkarahisar Sağlık Bilimleri Üniversitesi

10.18229/kocatepetip.475027

SEVERE ASTHMA

ZOR ASTIM

Sağmen

Seda Beyhan

Ceyhan

Berrin

10 26 2018

19 4 157 163 01 10 2017 02 01 2018

1999

Kocatepe Tıp Dergisi

Asthma is a common inflammatory disease that has wideclinical characteristics of the airway of the lungs. Asthmasymptoms can be prevented by avoiding triggers likeallergens and by the effective inhaled treatment. Themajority of asthma patients can be treated effectivelyby current medications. Difficult asthma is a distinctentity of asthma, comprising approximately %5-10 ofasthmatic patients. Despite the high effective treatment,the patients with asthma have disease that is poorlycontrolled. Severe asthmatics account for up to half ofthe cost for asthma. It will include asthma uncontrolledby new standard therapy, steroid dependent, steroidresistant asthma patients. Asthma related deathsare seen especially in severe asthma group. Asthmais a heterogeneous disease, consisting of differentphenotypes. It requires multidisciplinary approach fortreatment management. Severe asthma may suddenlydevelop in early time in disease or overtime. There was anevidence that severe asthma related to genetic factors,environmental factors, age, inflammation, duration ofdisease The genetic and environmental factors mayplay a role in severe asthma management. Phenotypetargetedtherapy has an important role in severe asthma,but it is associated with high treatment costs. At firstdiagnosis of asthma must be confirmed COPD and vocalcord dysfunction is needed to be particular interest indifferential diagnosis. Triggering factors such as smoking,atopy, work place condition and aspirin hypersensitivityshould be evaluated. Comorbidities that may affectasthma should be considered. This review examinesthe definition of asthma, its differential diagnosis,phenotypes and available treatment options.

Astım havayolu inflamasyonu ile seyreden çeşitli kliniközelliklere sahip bir hastalıktır. Dünyada yaklaşık 300milyon insanı etkileyen bir inflamatuvar hastalıktır. Astımsemptomları alerjenler gibi risk faktörlerinden kaçınarakve etkili inhaler tedavi ile kontrol altına alınmaktadır.Astımlı hastaların büyük bir çoğunluğu uygun tedaviile kontrol altına alınmaktadır. Astımlı hastaların %5-10’unu oluşturan zor astım klinisyenler için tanımıve tedavisi hala zor bir grubu oluşturmaktadır. İş gücükaybı ve ekonomik maliyet açısından yüksektir. Uyguntedaviye rağmen bazı olguların kontrolü zorlaşmaktadır.Standart tedavi ile kontrol edilemeyen, steroide bağımlıveya dirençli astım olgularını içermektedir. Astıma bağlıölümlerin çoğu ağır olan veya stabil olmayan gruptagörülmektedir. Heterojen bir hastalık olan astımda farklıfenotipler vardır ve net olarak anlaşılmamıştır. Tedaviyönetimi için multidisipliner yaklaşım gerekmektedir. Ağırastım hastalığın ilk yıllarında veya yıllar sonra gelişebilir.Ağır astımda fenotipe özgü tedaviler günümüzde önemkazanmıştır ve tedavi maliyeti yüksektir. Genetik, çevreselfaktörler, yaş ve hastalık süresinin ağır astımda rolüolduğuna dair kanıtlar vardır. Özellikle genetik ve çevreselfaktörler ağır astımda önemli rol oynamaktadır. Ağır astımolduğu düşünülen hastalar dikkatle değerlendirilmelidir.Birçok hastalık astımı taklit edebilir. Bu hastalardaöncelikle astım tanısı doğrulanmalıdır. KOAH ve vokalkord disfonksiyonu ayırıcı tanıda özellikle dikkat edilmesigerekli hastalıklardır. İkinci olarak hastanın tedaviyeuyumu gözden geçirilmelidir. Ardından sigara içimi,atopik durum, çalışma ortamı ve aspirin aşırı duyarlılığıgibi faktörler araştırılmalıdır. Aynı zamanda ek hastalıklargibi astım kontrolünü etkileyebilen durumlar gözdengeçirilmelidir. Astımı zorlaştıran durumlar tek tekaraştırılmalıdır. Bu derlemede ağır astım tanımı, ayırıcıtanıların dışlanması, fenotipleri ve tedavi yaklaşımları ele alınmıştır.

Asthma phenotypes asthma control corticosteroid

Astım fenotipleri astım kontrolü kortikosteroid

1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Revised 2017 available from http://www.ginasthma.org

2. Bavbek S, Misirligil Z; Study Group. A breath for health: an exploratory study in severe asthma patients in Turkey. Allergy 2008;63(9): 1218-27.

3. Chung KF , Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43(2):343-73.

4. Bousquet J, Jeffery PK, Busse WW, et al. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000;161:1720-45.

5. Miller AL, Lukacs NW. Chemokine receptors: understanding their role in asthmatic disease. Immunol Allergy Clin North Am 2004;24:667-83, vii.

6. Simpson JL, Scott RJ, Boyle MJ, et al. Differential proteolytic enzyme activity in eosinophillic and neutrophillic asthma. Am J Respir Crit Care Med 2005;172:559-65.

7. Hastie AT, Moore WC, Meyers DA, et al. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol 2010; 125: 1028–1036

8. Kharitonov SA. Exhaled nitric oxide and carbon monoxide in asthma. Eur Respir Rev 1999;68:212-18.

9. Turktas H, Oguzulgen K, Kokturk N, et al. Correlation of exhaled nitric oxide levels and airway inflammation markers in stable asthmatic patients. J Asthma 2003;40:425-30.

10. Vignola AM, Mirabella F, Costanzo G, et al. Airway remodeling in asthma. Chest 2003;123(3 Suppl):417S-22S

11. Robinson DS, Campbell DA, Durham SR, et al. Systematic assessment of difficult-to-treat asthma. Eur Respir J 2003; 22: 478–483.

12. Aaron SD, Vandemheen KL, Boulet LP, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ 2008; 179: 1121–1131.

13. Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol 2007; 119:405–413.

14. The ENFUMOSA cross-sectional Europe an multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J 2003;22(3):470-7.

15. Ten Brinke A, Grootendorst DC, Schmidt JT, et al. Chronic sinusitis in severe asthma is related to sputum eosinophilia. J Allergy Clin Immunol 2002; 109: 621–626.

16. Chaudhuri R, Livingston E, McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med 2006; 174: 127–133

17. Good JT Jr, Kolakowski CA, Groshong SD, et al. Refractory asthma: importance of bronchoscopy to identify phenotypes and direct therapy. Chest 2012; 141: 599–606.

18. Mastronarde JG, Anthonisen NR, Castro M, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med 2009; 360: 1487–1499.

19. Holguin F, Bleecker ER, Busse WW, et al. Obesity and asthma: an association modified by age of asthma onset. J Allergy Clin Immunol 2011;127(6):148693

20. Peters-Golden M, Swern A, Bird SS, et al. Influence of body mass index on the response to asthma controller agents. Eur Respir J 2006; 27: 495–503

21. Vamos M, Kolbe J. Psychological factors in severe chronic asthma. Aust NZ J Psychiatry 1999; 33: 538–544

22. Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010; 181: 315– 323. 163

23. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178: 218–224.

24. Sutherland ER, Goleva E, Strand M, et al. Body mass and glucocorticoid response in asthma. Am J Respir Crit Care Med 2008; 178: 682–687.

25. Berry M, Morgan A, Shaw DE, et al. Pathological features and inhaled corticosteroid response of eosinophilic and noneosinophilic asthma. Thorax 2007; 62: 1043–1049

26. Rabe KF, Atienza T, Magyar P, et al. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet 2006;368(9537):74453.

27. Scicchitano R, Aalbers R, Ukena D, et al. Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma. Curr Med Res Opin 2004;20(9):140318.

28. ten Brinke A, Zwinderman AH, Sterk PJ, et al. ‘‘Refractory’’ eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am J Respir Crit Care Med 2004; 170: 601–605.

29. Ogirala RG, Aldrich TK, Prezant DJ, et al. High-dose intramuscular triamcinolone in severe, chronic, life-threatening asthma. N Engl J Med 1991; 324: 585–589

30. Ducharme FM, Lasserson TJ, Cates CJ. Longacting beta2agonists versus antileukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev 2006(4):CD003137.

31. Evans DJ, Taylor DA, Zetterstrom O, et al. A comparison of lowdose inhaled budesonide plus theophylline and highdose inhaled budesonide for moderate asthma. N Engl J Med1997;337(20):14128

32. Spears M, Donnelly I, Jolly L, et al. Effect of lowdose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study. Eur Respir J 2009;33(5):10107.

33. Barnes PJ. Theophylline. Am J Respir Crti Care Med 2013:188;9016

34. Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012;367(13):1198207.

35. Bousquet J, Siergiejko Z, Swiebocka E, et al. Persistency of response to omalizumab therapy in severe allergic (Ig- Emediated) asthma. Allergy 2011;66(5):6718.

36. Bousquet J, Cabrera P, Berkman N, et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy 2005;60(3):3028.

37. Schumann C, Kropf C, Wibmer T, et al. Omalizumab in patients with severe asthma: the XCLUSIVE study. Clin Respir J 2012;6(4):21527.

38. Reiter J, Demirel N, Mendy A, et al. Macrolides for the longterm management of asthma a metaanalysis of randomized clinical trials. Allergy 2013;68(8):10409.

39. Brusselle GG, Vanderstichele C, Jordens P, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 2013 Apr;68(4):3229.

40. Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factoralpha in refractory asthma. N Engl J Med 2006;354(7):697708.

41. Morjaria JB, Chauhan AJ, Babu KS, et al. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 2008;63(7):58491.

42. Holgate ST, Noonan M, Chanez P, et al. Efficacy and safety of etanercept in moderatetosevere asthma: a randomised, controlled trial. Eur Respir J 2011;37(6):13529

43. Castro M , Rubin AS , Laviolette M, et al ; AIR2 Trial Study Group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial . Am J Respir Crit Care Med . 2010 ; 181 ( 2 ): 116 - 124

44. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380(9842):651-9.

45. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365(12):1088-98.

46. Rodrigo GJ, Castro-Rodríguez JA What is the role of tiotropium in asthma?: a systematic review with meta-analysis. Chest. 2015 Feb;147(2):388-39

47. Castro, M, Zangrilli, J, Wechsler, ME. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015; 3: 355–366