Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions

doi:10.1016/j.chest.2016.10.003

Chest

Volume 151, Issue 2, February 2017, Pages 366-373

https://doi.org/10.1016/j.chest.2016.10.003 Get rights and content

Background

A subset of patients with COPD demonstrates eosinophilic inflammation either in their sputum or blood. Previous studies regarding the association between increased blood eosinophil levels and poor readmission outcomes are conflicting. The goal of this study was to investigate outcomes following severe COPD exacerbations in patients with higher blood eosinophil levels.

Methods

With an observational study design, data on hospitalizations for severe COPD exacerbation were retrospectively gathered. Patient health data previous to and up to 1 year following the index hospitalization were included. Patients were stratified into the eosinophilic group if the blood eosinophil level on admission was ≥ 200 cells/μL and/or ≥ 2% of the total WBC count. Clinical outcomes were 12-month COPD-related readmission, 12-month all-cause readmission, length of stay, and time to COPD-related readmission. These outcomes were analyzed by using logistic, negative binomial, and Cox regression models.

Results

A total of 167 patients were included; 55 had eosinophilia. Eosinophilia was associated with an increased risk of 12-month COPD-related readmission (OR, 3.59 [95% CI, 1.65-7.82]; P = .0013), an increased risk of 12-month all-cause readmission (2.32 [95% CI, 1.10-4.92]; P = .0277), and a shorter time to first COPD-related readmission (hazard ratio, 2.74 [1.56-4.83]; P = .0005). The length of stay was not statistically different between eosinophilic and noneosinophilic patients. Sensitivity analyses using different eosinophilia definitions revealed a proportional increase in effect size with increasing eosinophil cell count definitions for predicting 12-month readmissions.

Conclusions

Blood eosinophil levels can be used as a biomarker in severe COPD exacerbations for predicting higher readmission rates.

Section snippets

Study Design

With an observational study design, all severe exacerbations of COPD in the hospital health centers of Sherbrooke, Quebec, Canada, between April 1, 2012, and March 31, 2013, were retrospectively screened through electronic medical records. The main diagnosis of hospitalization had to be registered as “acute exacerbation of COPD,” with no mention of decompensated asthma in this field and no comorbid bronchiectasis elsewhere. Patients had to have survived the index hospitalization. The

Results

A total of 447 candidate hospitalizations were included, and 236 were retained after applying exclusion criteria. From these, 167 patients had a corticosteroid-free CBC count available (Fig 1). Patient characteristics are presented in Table 1. Fifty-five patients had eosinophilia as defined by the cutoff of ≥ 200 cells/μL and/or ≥ 2%. Except for eosinophil counts, none of the differences between eosinophilic and noneosinophilic patients was statistically significant.

Discussion

The main finding of the present study was that an increased eosinophil count at admission, when defined by using a cutoff of ≥ 200 cells/μL and/or ≥ 2% of the WBC count, can predict a more than threefold increase in 12-month readmission for COPD, a more than double increase in 12-month all-cause readmission, and a shorter time to first COPD-related readmission. The influence of eosinophil cell counts on readmissions was consistent throughout the sensitivity analyses conducted on our data.

Conclusions

We found that higher blood eosinophil counts at admission for severe exacerbation of COPD, when assessed in a corticosteroid-free time frame, was associated with a more than threefold increase in 12-month readmission for COPD, a more than double 12-month all-cause readmission, and a shorter time to first COPD-related readmission. These findings reaffirm that adequately phenotyping specific COPD inflammatory profiles is worthwhile and of clinical importance.

Acknowledgments

Author contributions: A. V. is the guarantor of this study; he developed the initial questions; and contributed to the development of the protocol, validated the collected data, and reviewed and approved the manuscript. S. C. contributed to collection, analysis and interpretation of data, and preparation of the manuscript. P. L. contributed to conceiving the study, validating collected data, and reviewing the manuscript. J. C. contributed to conceiving the study, collecting data, performing

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Acute exacerbations (AE) are severe complications of chronic obstructive pulmonary disease (COPD); however, the need for biomarkers which predict them is still unmet. High platelet count (PLC) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in patients with COPD. We investigated if PLC and PLR at the onset of a severe AE could predict the time of the next relapse.
In a prospective observational cohort study, data of 152 patients hospitalized with AECOPD were collected, and patients were divided into PLC-low (<239 × 10⁹/L, n = 51), PLC-medium (239-297 × 10⁹/L, n = 51) and PLC-high (>297 × 10⁹/L, n = 50) or PLR-low (<147, N = 51), PLR-medium (147–295, n = 51) and PLR high (>295, n = 50) groups based on PLC and PLR tertiles using admission laboratory results. Clinical characteristics and the time to the next severe or moderate AE within 52 weeks were compared among subgroups using log-rank test.
PLC and PLR tertiles did not differ in clinical characteristics or the time till the next AE (p > 0.05). PLC and PLR showed a direct weak correlation to neutrophil count (Pearson r = 0.26, p < 0.01 and r = 0.20, p = 0.01) and PLC also demonstrated a weak relationship to white blood cell counts (Pearson r = 0.29, p < 0.001). However, PLR presented an inverse relationship to monocyte and eosinophil counts (r = −0.32, p < 0.001 and r = −0.17, p = 0.03).
PLC and PLR do not predict the time till the next relapse; however, they may reflect on neutrophilic inflammatory response during an exacerbation of COPD.
The association between blood eosinophils and clinical outcome of acute exacerbations of chronic obstructive pulmonary disease: A systematic review and meta-analysis
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Studies have shown an association between eosinophilia and clinical outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, contradictory findings exist. Our study aims to systematically evaluate the association between elevated peripheral blood eosinophils and clinical outcome of patients with AECOPD.
An electronic search was conducted for relevant studies published from database inception to February 28, 2023, on PubMed, EMBASE, Cochrane Library, and Web of Science. The analysis covered studies on the correlation between EOS AECOPD and mortality, hospital stay duration, readmission and hospitalization rates, and invasive mechanical ventilation. Where applicable, relative risk (RR) and weighted mean difference (WMD) were extracted, pooled, and assessed using meta-analysis. Sensitivity analysis was performed to explore the source of heterogeneity.
Fifteen high-quality studies including 14 cohort studies and one case-control study were included in the meta-analysis. Compared with non-eosinophilic AECOPD patients, those with eosinophilic AECOPD had a lower risk of mortality (RR = 0.65, 95 % confidence interval [CI] 0.54, 0.77, P < 0.001), shorter length of hospital stay (WMD = −1.56, 95%CI -2.16, −0.96, P < 0.001), and higher readmission rate (RR = 1.07, 95%CI 1.01,1.13, P = 0.029). No difference was found concerning the rate of hospitalization and invasive mechanical ventilation between the two groups.
Individuals diagnosed with eosinophilic AECOPD had a reduced mortality rate, a truncated period of hospitalization, and an insubstantial increase in the probability of readmission relative to their non-eosinophilic AECOPD counterparts. The level of eosinophils in blood has been shown to serve as a potential predictive biomarker for AECOPD patients.
Toward a Predict and Prevent Approach in Obstructive Airway Diseases
2023, Journal of Allergy and Clinical Immunology: In Practice
Asthma and chronic obstructive pulmonary disease are currently diagnosed and treated after the demonstration of variable airflow limitation and symptoms. Under this framework, undiagnosed and unchecked airway inflammation is associated with recurrent acute attacks, airway remodeling, airflow limitation, adverse effects of corticosteroids, and impaired quality of life, ultimately leading to the collection of side effects termed “people remodeling.” This one-size-fits-all damage control approach aims to control symptoms and treat exacerbations rather than modify the underlying disease process. The advent of highly effective therapies targeting proximal drivers of airway inflammation calls for a paradigm shift; upstream-acting therapies offer potential to alter the disease course and achieve clinical remission. We propose moving away from downstream firefighting and toward a “predict and prevent” model, measuring inflammation and providing anti-inflammatory therapy early, without waiting for further clinical deterioration. Much in the same way that high blood pressure and cholesterol are used to predict and prevent heart attacks, in asthma, elevated blood eosinophils and/or exhaled nitric oxide can be used to predict and prevent asthma attacks. We also advocate moving research further upstream by identifying patients with subclinical airway inflammation or disease who may be at risk of progressing to airflow limitation and associated morbidities and intervening early to prevent them. In summary, we call for a predict and prevent approach in obstructive airway disease.
Predictive value of neutrophil-to-lymphocyte ratio and bilirubin levels in the readmission of acute exacerbation of chronic obstructive pulmonary disease
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Th aim of this study was to analyze acute exacerbation of chronic obstructive pulmonary disease (AECOPD) readmission events and to determine whether neutrophil-to-lymphocyte ratio (NLR) and bilirubin levels were associated with readmission after discharge due to AECOPD.
A total of 170 patients with AECOPD were included. Patients were stratified into the readmission group if patients had two or more readmissions within 2 years of the previous discharge, and the non-readmission group with one readmission or none within 2 years of the last discharge. Data were collected and compared between groups. The patients were separated by the cutoffs of NLR and bilirubin level. The number of all-cause readmissions within 2 years, time to first COPD-related readmission, 1-year/2-year COPD-related readmission, 1-year/2-year all-cause mortality were compared between groups, respectively.
Compared with the readmission group, patients of the non-readmission group had a shorter length of hospital stay, more systemic corticosteroid use, higher NLR, higher bilirubin levels, and lower eosinophils counts (p < 0.05). NLR and bilirubin levels on admission had significant association with the number of all-cause readmissions (p < 0.05). Lower bilirubin was associated with an increased risk of 1-year COPD-related readmission (OR 5.063) and 2-year COPD-related readmission (OR 4.699).
For patients with AECOPD, longer hospital stay, and less use of systemic corticosteroids may be associated with a higher risk of readmission. NLR and bilirubin levels on admission may be related to the number of all-cause readmissions. Bilirubin can be regarded as a biomarker to predict readmission rates within 2 years after discharged throughout the course of the disease.
Readmission rate for acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis
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Citation Excerpt :
The selection procedure is illustrated in Fig. 1. A total of 46 studies [16–61] were included, of which 21, 9, 13, 2, and 1 were conducted in European region, Western Pacific region, Americas region, Eastern Mediterranean region, and Non-member observer country or region, respectively, based on the WHO regions. The included studies were published from 2001 to 2022, with 19 prospective and 27 retrospective studies.
The readmission rate following hospitalization for chronic obstructive pulmonary disease (COPD) exacerbations is extremely high and has become a common and challenging clinical problem. This study aimed to systematically summarize COPD readmission rates for acute exacerbations and their underlying risk factors.
A comprehensive search was performed using PubMed, Embase, Cochrane Library, and Web of Science, published from database inception to April 2, 2022. Methodological quality was evaluated using the Newcastle-Ottawa Scale (NOS). We used a random-effects model or a fixed-effects model to estimate the pooled COPD readmission rate for acute exacerbations and underlying risk factors.
A total of 46 studies were included, of which 24, 7, 17, 7, and 20 summarized the COPD readmission rates for acute exacerbations within 30, 60, 90, 180, and 365 days, respectively. The pooled 30-, 60-, 90-, 180-, and 365-day readmission rates were 11%, 17%, 17%, 30%, and 37%, respectively. The study design type, age stage, WHO region, and length of stay (LOS) were initially considered to be sources of heterogeneity. We also identified potential risk factors for COPD readmission, including male sex, number of hospitalizations in the previous year, LOS, and comorbidities such as heart failure, tumor or cancer, and diabetes, whereas obesity was a protective factor.
Patients with COPD had a high readmission rate for acute exacerbations, and potential risk factors were identified. Therefore, we should propose clinical interventions and adjust or targeted the control of avoidable risk factors to prevent and reduce the negative impact of COPD readmission.
PROSPERO, identifier CRD42022333581.
Factors affecting length of hospital stay in chronic obstructive pulmonary disease patients in a tertiary hospital of Nepal: A retrospective cross-sectional study
2022, Annals of Medicine and Surgery
Despite the increasing burden of chronic obstructive pulmonary disease in Nepal, studies analyzing the factors associated with inpatient length of hospital stay are lacking.
This is a retrospective, cross-sectional hospital-based study conducted between July 2020 and July 2021 on patients admitted to the inpatient ward of Pulmonary and Critical Care Medicine of Tribhuvan University Teaching Hospital with a primary diagnosis of acute exacerbation of chronic obstructive pulmonary disease. The sample size of our study was 90. Clinical and demographic factors, blood investigation parameters, and treatment received were analyzed via univariate and multivariate analysis to find the factors associated with length of stay.
The mean age of chronic obstructive pulmonary disease patients was 68.84 ± 10.22 years, with 42.2% of males and 43.3% of current smokers. The length of hospital stay ranged from 2 to 25 days, with an average stay of 6.69 ± 4.02 days. Factors associated with length of stay are the number of comorbidities (p = 0.007), blood eosinophils at admission (p = 0.022), and use of mechanical ventilatory support (p < 0.001).
Proper management of comorbidities and eosinophilic exacerbations as well as careful use of mechanical ventilatory support are required to further reduce the duration of hospital stay in chronic obstructive pulmonary disease patients.

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: FUNDING/SUPPORT: This work was supported by local funds and the Fonds de Recherche en Santé du Québec.

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Chest

Original Research: COPDEosinophils in COPD Exacerbations Are Associated With Increased Readmissions

Background

Methods

Results

Conclusions

Section snippets

Study Design

Results

Discussion

Conclusions

Acknowledgments

Lancet

Lancet

Chest

Lancet Respir Med

Blood

2015 condition-specific measures updates and specifications report hospital-level 30-day risk-standardized readmission measures

Centers Medicare Medicaid Serv

Hospital cardiovascular outcome measures in federal pay-for-reporting and pay-for-performance programs: a brief overview of current efforts

Circ Cardiovasc Qual Outcomes

Immunology of asthma and chronic obstructive pulmonary disease

Nat Rev Immunol

Eosinophilic airway inflammation in chronic obstructive pulmonary disease and asthma

J Physiol Pharmacol

Biomarkers that predict and guide therapy for exacerbations of chronic obstructive pulmonary disease

Ann Am Thorac Soc

Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers

Am J Respir Crit Care Med

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment

Eur Respir J

Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease

Thorax

Original Research: COPD
Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions