[en] BACKGROUND: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. METHODS: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. RESULTS: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. CONCLUSION: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Graff, Sophie ; Université de Liège - ULiège > I3-Pneumology
Vanwynsberghe, S.; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
Brusselle, G.; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-73.
Accordini S, Corsico A, Cerveri I, Gislason D, Gulsvik A, Janson C, et al. The socio-economic burden of asthma is substantial in Europe: the burden of asthma in Europe. Allergy. 2007;63:116-24.
Chen W, Safari A, FitzGerald JM, Sin DD, Tavakoli H, Sadatsafavi M. Economic burden of multimorbidity in patients with severe asthma: a 20-year population-based study. Thorax. 2019;74:1113-9.
van Bragt JJMH, Adcock IM, Bel EHD, Braunstahl G-J, ten Brinke A, Busby J, et al. Characteristics and treatment regimens across ERS SHARP severe asthma registries. Eur Respir J. 2020;55:1901163.
Casan Clarà P, Martínez González C. Accumulated Dose of Systemic Corticosteroids: Significant Medical Information. Arch Bronconeumol. 2020.
Chen W, Lynd LD, FitzGerald JM, Marra CA, Balshaw R, To T, et al. Excess medical costs in patients with asthma and the role of comorbidity. Eur Respir J. 2016;48:1584-92.
Ramsahai JM, Wark PA. Appropriate use of oral corticosteroids for severe asthma. Med J Aust. 2018;209:18-21.
Barnes PJ, Adcock IM. How do corticosteroids work in asthma? Ann Intern Med. 2003;139:359.
James A, Gyllfors P, Henriksson E, Dahlén SE, Adner M, Nilsson G, et al. Corticosteroid treatment selectively decreases mast cells in the smooth muscle and epithelium of asthmatic bronchi. Allergy. 2012;67:958-61.
Schleich F, Brusselle G, Louis R, Vandenplas O, Michils A, Pilette C, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian severe asthma registry (BSAR). Respir Med. 2014;108:1723-32.
Fahy J. Proceedings of the ATS workshop on refractory asthma. Am J Respir Crit Care Med. 2000;162:2341-51.
GINA-Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org.
Louis R, Sele J, Henket M, Cataldo D, Bettiol J, Seiden L, et al. Sputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness. Allergy. 2002;57:907-12.
Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax. 1992;47:76-83.
Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999;14:902-7.
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.
Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Olin A-C, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184:602-15.
Guiot J, Demarche S, Henket M, Paulus V, Graff S, Schleich F, et al. Methodology for Sputum Induction and Laboratory Processing. J Vis Exp. 2017; [cited 2019 Dec 9]; Available from: https://www.jove.com/video/56612/methodology-for-sputum-induction-and-laboratory-processing.
Louis R, Godinas L, Schleich F. Induced sputum - towards normal values, non invasive assessment of airways inflammation in asthma and COPD. 14th, tetrapoleos street, Athens, 115 27. Greece: Paschalidis Medical Publications; 2011.
Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and depression scale: an update d literature review. J Psychosom Res. 2002;52:69-77.
Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral glucocorticoid-sparing effect of Benralizumab in severe asthma. N Engl J Med. 2017;376:2448-58.
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-97.
Cataldo D, Louis R, Michils A, Peché R, Pilette C, Schleich F, et al. Severe asthma: oral corticosteroid alternatives and the need for optimal referral pathways. J Asthma Off J Assoc Care Asthma. 2020:1-11.
Schleich FN, Manise M, Sele J, Henket M, Seidel L, Louis R. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm Med. 2013;13:11.
Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178:218-24.
Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360:1715-21.
Berthon BS, Gibson PG, Wood LG, MacDonald-Wicks LK, Baines KJ. A sputum gene expression signature predicts oral corticosteroid response in asthma. Eur Respir J. 2017;49:170-80.
Demarche S, Schleich F, Henket M, Paulus V, Louis R, Van Hees T. Step-down of inhaled corticosteroids in non-eosinophilic asthma: a prospective trial in real life. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2018;48:525-35.
Schleich FN, Chevremont A, Paulus V, Henket M, Manise M, Seidel L, et al. Importance of concomitant local and systemic eosinophilia in uncontrolled asthma. Eur Respir J. 2014;44:97-108.
Price D, Wilson AM, Chisholm A, Rigazio A, Burden A, Thomas M, et al. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice. J Asthma Allergy. 2016;9:1-12.
Kerkhof M, Tran TN, van den Berge M, Brusselle GG, Gopalan G, Jones RCM, et al. Association between blood eosinophil count and risk of readmission for patients with asthma: historical cohort study. PLoS One. 2018;13:e0201143.
Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe Eosinophilic asthma. N Engl J Med. 2014;371:1198-207.
Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet Lond Engl. 2012;380:651-9.
Bjerrum AS, Skjold T, Schmidt J. Baseline characteristics of 36 mepolizumab-patients. Experiences from the clinical practice. Eur Respir J. 2017;50:PA3588.
Hassan M, Davies SE, Trethewey SP, Mansur AH. Prevalence and predictors of adherence to controller therapy in adult patients with severe/difficult-to-treat asthma: a systematic review and meta-analysis. J Asthma Off J Assoc Care Asthma. 2019:1-10.
Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2017;9:CD010834.
