Eosinophil-guided treatment of COPD exacerbations: unfinished business

As a community of respirologists, we are far from achieving success in the management of acute exacerbations of chronic obstructive pulmonary disease (COPD), particularly severe events requiring admission to hospital that drive most of the disease-related health-care costs, morbidity, and mortality. The availability, efficacy, and convenience of maintenance treatments for stable COPD disease have advanced substantially, but the pharmacological management of exacerbations for patients admitted to hospital has not materially changed in the past 20 years. Findings from a study published in 1999 1 Niewoehner DE Erbland ML Deupree RH et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999; 340: 1941-1947 Crossref PubMed Scopus (788) Google Scholar validated long-standing practice by showing that the addition of systemic corticosteroids to usual care reduced the frequency of treatment failure and that 8 weeks of steroid treatment offered no advantage over 2 weeks. Yet, despite evidence that even 2 weeks of steroids was associated with a higher risk of side-effects, it was 14 years until the findings from the REDUCE trial 2 Leuppi JD Schuetz P Bingisser R et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013; 309: 2223-2231 Crossref PubMed Scopus (309) Google Scholar showed that a short course of systemic corticosteroids (40 mg prednisone for 5 days) was non-inferior to 2 weeks of treatment and uptake of this approach has been variable, with many patients continuing to receive prolonged courses of high-dose steroids. 3 Gulati S Zouk AN Kalehoff JP et al. The use of a standardized order set reduces systemic corticosteroid dose and length of stay for individuals hospitalized with acute exacerbations of COPD: a cohort study. Int J Chron Obstruct Pulmon Dis. 2018; 13: 2271-2278 Crossref PubMed Scopus (8) Google Scholar Not only is this practice associated with a higher risk for hyperglycaemia, adrenal suppression, infection, osteoporosis, and fracture, but it is also increasingly evident that exacerbations are biologically heterogeneous and that a subset of patients might derive no respiratory benefit, and perhaps be harmed, from systemic corticosteroids. 4 Walters JA Gibson PG Wood-Baker R Hannay M Walters EH Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2009; 1 (CD001288.) Crossref Scopus (172) Google Scholar , 5 Bafadhel M McKenna S Terry S et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012; 186: 48-55 Crossref PubMed Scopus (433) Google Scholar , 6 Bafadhel M McKenna S Terry S et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011; 184: 662-671 Crossref PubMed Scopus (727) Google Scholar Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trialEosinophil-guided therapy was non-inferior compared with standard care for the number of days alive and out of hospital, and reduced the duration of systemic corticosteroid exposure, although we could not entirely exclude harm on some secondary outcome measures. Larger studies will help to determine the full safety profile of this strategy and its role in the management of COPD exacerbations. Full-Text PDF