Blood Eosinophils and Clinical Outcomes in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Propensity Score Matching Analysis of Real-World Data in China

Yanan Cui, Zijie Zhan, Zihang Zeng, Ke Huang, Chen Liang, Xihua Mao, Yaowen Zhang, Xiaoxia Ren, Ting Yang, Yan Chen, Yanan Cui, Zijie Zhan, Zihang Zeng, Ke Huang, Chen Liang, Xihua Mao, Yaowen Zhang, Xiaoxia Ren, Ting Yang, Yan Chen

Abstract

Background and Objective: Elevated eosinophils in chronic obstructive pulmonary disease (COPD) are recognized as a biomarker to guide inhaled corticosteroids use, but the value of blood eosinophils in hospitalized exacerbations of COPD remains controversial. This study aimed to evaluate the accuracy of eosinophils in predicting clinical outcomes in acute exacerbation of COPD (AECOPD). Methods: We analyzed data from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study, which is an ongoing nationwide multicenter, observational real-world study in patients admitted for AECOPD. Data collected between January 2018 and December 2019 in 163 centers were first reviewed. The eligible patients were divided into eosinophilic and non-eosinophilic groups, according to blood eosinophil with 2% of the total leukocyte count as the threshold. Propensity score (PS) matching was performed to adjust for confounders. Results: A total of 1,566 patients (median age: 69 years; 80.3% male) were included and 42.7% had an eosinophilic AECOPD. Eosinophil count <2% was associated with the development of respiratory failure and pneumonia. After PS matching, 650 pairs in overall patients, 468 pairs in patients with smoking history and 177 pairs in patients without smoking were selected, respectively. Only in patients with smoking history, the non-eosinophilic AECOPD was associated with longer median hospital stays (9 vs. 8 days, P = 0.034), higher dosage of corticosteroid use, higher economic burden of hospitalization, and poorer response to corticosteroid therapy compared to the eosinophilic AECOPD. No significant difference was found in patients without smoking. Eosinophil levels had no relationship with the change of COPD Assessment Test scores and readmissions or death after 30 days. Conclusion: Elevated eosinophils were associated with better short-term outcomes only in patients with a smoking history. Eosinophil levels cannot be confidently used as a predictor alone for estimating prognosis.

Keywords: AECOPD; corticosteroids; eosinophils; prediction; smoking.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Cui, Zhan, Zeng, Huang, Liang, Mao, Zhang, Ren, Yang and Chen.

Figures

Figure 1
Figure 1
Flowchart of patient enrollment process. AECOPD, acute exacerbations of chronic obstructive pulmonary disease; ACURE, acute exacerbation of chronic obstructive pulmonary disease inpatient registry study.
Figure 2
Figure 2
Length of hospital stay in patients with or without smoking history after matching. AECOPD, acute exacerbations of chronic obstructive pulmonary disease. The circles and asterisks are outliers.
Figure 3
Figure 3
Cumulative systemic corticosteroid dose and total cost during hospitalization in patients with or without smoking history after matching. Data are presented as median. AECOPD, acute exacerbations of chronic obstructive pulmonary disease.
Figure 4
Figure 4
Various cost during hospitalization in patients with or without smoking history after matching. Statistically significant differences between groups are indicated as *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001. Error bars show 95% confidence interval. AECOPD, acute exacerbations of chronic obstructive pulmonary disease.
Figure 5
Figure 5
CAT scores at baseline, discharge and day 30 in the three matched cohorts. Data are presented as mean (SEM). AECOPD, acute exacerbations of chronic obstructive pulmonary disease; CAT, COPD Assessment Test; SEM, standard error of mean.

References

    1. Gold Science Committee . Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (2020 REPORT). (2019). Available online at: (accessed November 5, 2019).
    1. Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications. Eur Respir J Suppl. (2003) 41:46s−53. 10.1183/09031936.03.00078002
    1. Zhang Y, Morgan RL, Alonso-Coello P, Wiercioch W, Bała MM, Jaeschke RR, et al. . A systematic review of how patients value COPD outcomes. Eur Respir J. (2018) 52:1800222. 10.1183/13993003.00222-2018
    1. Casanova C, Celli BR, de-Torres JP, Martínez-Gonzalez C, Cosio BG, Pinto-Plata V, et al. . Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD. Eur Respir J. (2017) 50:1701162. 10.1183/13993003.01162-2017
    1. Yun JH, Lamb A, Chase R, Singh D, Parker MM, Saferali A, et al. . Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. (2018) 141:2037–47.e10. 10.1016/j.jaci.2018.04.010
    1. Ko FWS, Chan KP, Ngai J, Ng SS, Yip WH, Ip A, et al. . Blood eosinophil count as a predictor of hospital length of stay in COPD exacerbations. Respirology. (2020) 25:259–66. 10.1111/resp.13660
    1. AE Bafadhel M, Greening NJ, Harvey-Dunstan TC, Williams JE, Morgan MD, Brightling CE, et al. . Blood eosinophils and outcomes in severe hospitalized exacerbations of COPD. Chest. (2016) 150:320–8. 10.1016/j.chest.2016.01.026
    1. Holland M, Alkhalil M, Chandromouli S, Janjua A, Babores M. Eosinopenia as a marker of mortality and length of stay in patients admitted with exacerbations of chronic obstructive pulmonary disease. Respirology. (2010) 15:165–7. 10.1111/j.1440-1843.2009.01651.x
    1. Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, 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. 10.1164/rccm.201108-1553OC
    1. Hegewald MJ, Horne BD, Trudo F, Kreindler JL, Chung Y, Rea S, et al. . Blood eosinophil count and hospital readmission in patients with acute exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. (2020) 15:2629–41. 10.2147/COPD.S251115
    1. Kwon N, Pizzichini E, Bansal AT, Albers FC, Barnes N, Rile JH, et al. . Factors that affect blood eosinophil counts in a non-asthmatic population: Post hoc analysis of data from Brazil. World Allergy Organ J. (2020) 13:100119. 10.1016/j.waojou.2020.100119
    1. Pei Z, Sun Y, Wang S, Chen Y, Yang T, Huang K, et al. . Estimating mortality among inpatients with acute exacerbation of chronic obstructive pulmonary disease using registry data. NPJ Prim Care Respir Med. (2020) 30:28. 10.1038/s41533-020-0186-y
    1. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, et al. . Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. (2011) 184:662–71. 10.1164/rccm.201104-0597OC
    1. Roussos C, Koutsoukou A. Respiratory failure. Eur Respir J Suppl. (2003) 47:3s−14. 10.1183/09031936.03.00038503
    1. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. . Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. (2007) 44(Suppl. 2):S27–72. 10.1086/511159
    1. Xue J, Cui YN, Chen P, Cai S, Chen L, Dai ZS, et al. . Blood eosinophils: a biomarker of response to glucocorticoids and increased readmissions in severe hospitalized exacerbations of COPD. Chin J Tuberc Respir Dis. (2019) 42:426–31. 10.3760/cma.j.issn.1001-0939.2019.06.005
    1. Wu HX, Zhuo KQ, Cheng DY. Peripheral blood eosinophil as a biomarker in outcomes of acute exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. (2019) 14:3003–15. 10.2147/COPD.S226783
    1. Kim VL, Coombs NA, Staples KJ, Ostridge KK, Williams NP, Wootton SA, et al. . Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort. Eur Respir J. (2017) 50:1700853. 10.1183/13993003.00853-2017
    1. MacDonald MI, Osadnik CR, Bulfin L, Hamza K, Leong P, Wong A, et al. . Low and high blood eosinophil counts as biomarkers in hospitalized acute exacerbations of COPD. Chest. (2019) 156:92–100. 10.1016/j.chest.2019.02.406
    1. Chis AF, Pop CM. Correlations between neutrophil to lymphocyte ratio, blood eosinophils and clinical characteristics in chronic obstructive pulmonary disease. Med Pharm Rep. (2020) 93:169–74. 10.15386/mpr-1412
    1. Li M, Yang T, He R, Li A, Dang W, Liu X, et al. . The value of inflammatory biomarkers in differentiating asthma-COPD Overlap from COPD. Int J Chron Obstruct Pulmon Dis. (2020) 15:3025–37. 10.2147/COPD.S273422
    1. Prins HJ, Duijkers R, Lutter R, Daniels JM, van der Valk P, Schoorl M, et al. . Blood eosinophilia as a marker of early and late treatment failure in severe acute exacerbations of COPD. Respir Med. (2017) 131:118–24. 10.1016/j.rmed.2017.07.064
    1. Serafino-Agrusa L, Scichilone N, Spatafora M, Battaglia S. Blood eosinophils and treatment response in hospitalized exacerbations of chronic obstructive pulmonary disease: a case-control study. Pulm Pharmacol Ther. (2016) 37:89–94. 10.1016/j.pupt.2016.03.004
    1. Zhang Y, Liang LR, Zhang S, Lu Y, Chen YY, Shi HZ, et al. . Blood eosinophilia and its stability in hospitalized COPD exacerbations are associated with lower risk of all-cause mortality. Int J Chron Obstruct Pulmon Dis. (2020) 15:1123–34. 10.2147/COPD.S245056
    1. Jabarkhil A, Moberg M, Janner J, Petersen MN, Jensen CB, Henrik Äangquist L, et al. . Elevated blood eosinophils in acute COPD exacerbations: better short- and long-term prognosis. Eur Clin Respir J. (2020) 7:1757274. 10.1080/20018525.2020.1757274
    1. Gonzalez-Barcala FJ, San-Jose ME, Nieto-Fontarigo JJ, Calvo-Alvarez U, Carreira JM, Garcia-Sanz MT, et al. . Blood eosinophils could be useful as a biomarker in chronic obstructive pulmonary disease exacerbations. Int J Clin Pract. (2019) 73:e13423. 10.1111/ijcp.13423
    1. Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, et al. . Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. (2018) 6:117–26. 10.1016/S2213-2600(18)30006-7
    1. Hinds DR, DiSantostefano RL, Le HV, Pascoe S. Identification of responders to inhaled corticosteroids in a chronic obstructive pulmonary disease population using cluster analysis. BMJ Open. (2016) 6:e010099. 10.1136/bmjopen-2015-010099
    1. Viinanen A, Lassenius MI, Toppila I, Karlsson A, Veijalainen L, Idänpään-Heikkilä JJ, et al. . The burden of chronic obstructive pulmonary disease (COPD) in Finland: impact of disease severity and eosinophil count on healthcare resource utilization. Int J Chron Obstruct Pulmon Dis. (2019) 14:2409–21. 10.2147/COPD.S222581
    1. Müllerová H, Hahn B, Simard EP, Mu G, Hatipoglu U. Exacerbations and health care resource use among patients with COPD in relation to blood eosinophil counts. Int J Chron Obstruct Pulmon Dis. (2019) 14:683–92. 10.2147/COPD.S194367
    1. Ortega H, Llanos JP, Lafeuille MH, Germain G, Duh MS, Bell CF, et al. . Burden of disease associated with a COPD eosinophilic phenotype. Int J Chron Obstruct Pulmon Dis. (2018) 13:2425–33. 10.2147/COPD.S170995
    1. Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, et al. . Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. (2019) 7:699–709. 10.1016/S2213-2600(19)30176-6

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