Background: Difficult-to-treat asthma afflicts a small percentage of the asthma population. However, these patients remain refractory to treat, and account for 40% to 50% of the health costs of asthma treatment, incurring significant morbidity. We conducted a multi-center cross-sectional study to characterize difficult-to-treat asthma in Korea. Methods: Subjects with difficult-to-treat asthma and subjects with controlled asthma were recruited from 5 outpatient clinics of referral hospitals. We reviewed medical records of previous 6 months and obtained patient-reported questionnaires composed of treatment compliance, asthma control, and instruments for stress, anxiety, and depression. Results: We recruited 21 subjects with difficult-to-treat asthma and 110 subjects with controlled asthma into the study. The subjects with difficult-to-treat asthma were associated with longer treatment periods, more increased health care utilization, more medication (oral corticosteroids, number of medication), and more anxiety disorder compared to those of well-controlled asthmatics. There was no difference in age, gender, history of allergy, serum IgE, blood eosinophil count, or body mass index between the 2 groups. Conclusion: Difficult-to-treat asthma is characterized by increased health care utilization and more co-morbidity of anxiety.
1. Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States. N Engl J Med 1992;326:862-6.
2. Godard P, Chanez P, Siraudin L, Nicoloyannis N, Duru G. Costs of asthma are correlated with severity: a 1-yr prospective study. Eur Respir J 2002;19:61-7.
3. Antonicelli L, Bucca C, Neri M, De Benedetto F,Sabbatani P, Bonifazi F, et al. Asthma severity and medical resource utilisation. Eur Respir J 2004;23:723-9.
4. Sullivan SD, Rasouliyan L, Russo PA, Kamath T, Chipps BE; TENOR Study Group. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy 2007;62:126-33.
5. Miller MK, Lee JH, Miller DP, Wenzel SE; TENOR Study Group. Recent asthma exacerbations: a key predictor of future exacerbations. Respir Med 2007;101:481-9.
6. Haselkorn T, Fish JE, Zeiger RS, Szefler SJ, Miller DP,Chipps BE, et al. Consistently very poorly controlled asthma, as defined by the impairment domain of the Expert Panel Report 3 guidelines, increases risk for future severe asthma exacerbations in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. J Allergy Clin Immunol 2009;124:895-902.e1-4.
7. O'Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW; START Investigators Group. Severe exacerbations and decline in lung function in asthma. Am J Respir Crit Care Med 2009;179:19-24.
8. Proceedings of the ATS workshop on refractory asthma:current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med 2000;162:2341-51.
9. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma.European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J 2003;22:470-7.
10. Dolan CM, Fraher KE, Bleecker ER, Borish L, Chipps B, Hayden ML, et al. Design and baseline characteristics of the epidemiology and natural history of asthma:Outcomes and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficultto-treat asthma. Ann Allergy Asthma Immunol 2004;92: 32-9.
11. Frank SH, Zyzanski SJ. Stress in the clinical setting: the Brief Encounter Psychosocial Instrument. J Fam Pract 1988;26:533-9.
12. Yim JH, Bae JM, Choi SS, Kim SW, Hwang HS, Huh BY. The validity of modified Korean-translated BEPSI (brief encounter psychosocial instrument) as instrument of stress measurement in outpatient clinic. J Korean Acad Fam Med 1996;17:42-53.
13. Yook SP, Kim ZS. A clinical study on the Korean version of beck anxiety inventory: comparative study of patient and non-patient. Korean J Clin Psychol 1997;16:185-97.
14. Cho Y, Kim J. Confirmatory factor analysis of the Korean version of the beck depression inventory: testing configural and metric invariance across undergraduate and clinical samples. Korean J Clin Psychol 2002;21:843-57.
15. Partridge MR, van der Molen T, Myrseth SE, Busse WW. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med 2006;6:13.
16. Bateman ED, Boushey HA, Bousquet J, Busse WW,Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004;170:836-44.
17. Chung KF, Godard P, Adelroth E, Ayres J, Barnes N,Barnes P, et al. Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes,evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma. European Respiratory Society. Eur Respir J 1999;13:1198-208.
18. Osborne M, Deffebach M. The epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study. Ann Allergy Asthma Immunol 2004;92:3-4.
19. Reddel HK, Taylor DR, Bateman ED, Boulet LP,Boushey HA, Busse WW, et al. An official American Thoracic Society/European Respiratory Society statement:asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice.Am J Respir Crit Care Med 2009;180:59-99.
20. Bousquet J, Mantzouranis E, Cruz AA, Ait-Khaled N,Baena-Cagnani C, Bleecker ER. WHO definition of asthma severity, control and exacerbations. A draft for WHO consultation on severe asthma, April 6-7, 2009 geneva, WHO headquarters (personal communication).
21. National Heart Lung and Blood Institute, National Institutes of Health (USA), World Health Organization.The Global Initiative for Asthma (GINA) [Internet].[place unknown]: GINA; c2009 [cited 2010 Oct 30].Available from: http://www.ginasthma.com.
22. Schatz M, Li JT, Sorkness CA. Responsiveness of the asthma control tes (ACT) to changes in specialist ratings of asthma control and FEV1. Am J Respir Crit Care Med 2004;169:A319.
23. Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT,Marcus P, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol 2004;113:59-65.
24. Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ,Nathan RA, et al. Asthma Control Test: reliability, validity,and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol 2006;117:549-56.
25. Zhou X, Ding FM, Lin JT, Yin KS, Chen P, He QY,et al. Validity of asthma control test in Chinese patients.Chin Med J (Engl) 2007;120:1037-41.
26. Lai CK, Kuo SH, Guia T de, Lloyd A, Williams AE,Spencer MD. Asthma control and its direct healthcare costs: findings using a derived Asthma Control TestTM score in eight Asia-Pacific areas. Eur Respir Rev 2006;15:24-9.
27. Gaga M, Papageorgiou N, Yiourgioti G, Karydi P,Liapikou A, Bitsakou H, et al. Risk factors and charac teristics associated with severe and difficult to treat asthma phenotype: an analysis of the ENFUMOSA group of patients based on the ECRHS questionnaire.Clin Exp Allergy 2005;35:954-9.
28. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC,Ameredes BT, Bacharier L, 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;119:405-13.
29. Wenzel SE, Busse WW; National Heart, Lung, and Blood Institute's Severe Asthma Research Program.Severe asthma: lessons from the Severe Asthma Research Program. J Allergy Clin Immunol 2007;119:14-21.
30. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H,Li X, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program.Am J Respir Crit Care Med 2010;181:315-23.
31. Hartert TV, Speroff T, Togias A, Mitchel EF Jr, Snowden MS, Dittus RS, et al. Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma. Ann Allergy Asthma Immunol 2002;89:467-73.
32. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment:meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 2000;160:2101-7.
33. Ministry of Health and Welfare, Korea. The epidemiological survey of psychiatric illnesses in Korea, 2006.Seoul: Ministry of Health and Welfare; 2007.
34. Scott KM, Von Korff M, Ormel J, Zhang MY, Bruffaerts R, Alonso J, et al. Mental disorders among adults with asthma: results from the World Mental Health Survey.Gen Hosp Psychiatry 2007;29:123-33.
35. ten Brinke A, Ouwerkerk ME, Zwinderman AH,Spinhoven P, Bel EH. Psychopathology in patients with severe asthma is associated with increased health care utilization. Am J Respir Crit Care Med 2001;163:1093-6.
36. Campbell DA, Yellowlees PM, McLennan G, Coates JR,Frith PA, Gluyas PA, et al. Psychiatric and medical features of near fatal asthma. Thorax 1995;50:254-9.