A retrospective analysis of eosinophilic disorder on poststroke pneumonia

Xin Huo; Wanchen Shi; Tianqi Zhang; Libin Guo; Ying Liu

doi:10.4103/VIT.VIT_3_19

ORIGINAL ARTICLE

Year : 2018 | Volume : 1 | Issue : 3 | Page : 98-102

A retrospective analysis of eosinophilic disorder on poststroke pneumonia

Xin Huo¹, Wanchen Shi², Tianqi Zhang³, Libin Guo⁴, Ying Liu⁵
¹ Department of Vascular Surgery, Zibo Central Hospital, Zibo, Shandong, China
² Department of Preventive Medicine, Jilin Medical University, Fengman District, Jilin, China
³ Department of Radiological Medicine, Jilin University, Chaoyang District, Jilin, China
⁴ Department of Neurology, Siping Central Hospital, Siping, Jilin, China
⁵ Science and Education Division, Siping Central Hospital, Siping, Jilin, China

Date of Web Publication

30-Apr-2019

Correspondence Address:
Ying Liu
Science and Education Division, Siping Central Hospital, Tiexi District, Siping, Jilin
China

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/VIT.VIT_3_19

Abstract

OBJECTIVE: The objective of the study was to evaluate the role of eosinophil on the outcome and prognosis in stroke patients with pneumonia.
PATIENTS AND METHODS: The study included 526 patients with ischemic stroke; the patients were divided into two groups according to whether the patients were complicated with pneumonia or not. All patients were supervised by the National Institutes of Health Stroke Scale (NIHSS) score in 2 weeks.
RESULTS: Stroke patients without pneumonia were observed a higher eosinophil count and lower platelet distribution width (PDW) compared to the patients with pneumonia (P < 0.05). Eosinophil counts continued to decrease in patients with pneumonia along with an increasing NIHSS score in 2 weeks. Logistic regression identified dysphagia, eosinophil count, and PDW as predictors of NIHSS scores in poststroke patients with pneumonia.
CONCLUSIONS: Our data suggested that eosinophil counts might have a significant role on outcomes in poststroke patients with pneumonia. The results underscored that the interaction between eosinophils and platelets might be a treatment target to improve the outcomes in stroke patients.

Keywords: Eosinophil, outcome, platelet, pneumonia, stroke

How to cite this article:
Huo X, Shi W, Zhang T, Guo L, Liu Y. A retrospective analysis of eosinophilic disorder on poststroke pneumonia. Vasc Invest Ther 2018;1:98-102

How to cite this URL:
Huo X, Shi W, Zhang T, Guo L, Liu Y. A retrospective analysis of eosinophilic disorder on poststroke pneumonia. Vasc Invest Ther [serial online] 2018 [cited 2022 Aug 19];1:98-102. Available from: https://www.vitonline.org/text.asp?2018/1/3/98/257417

Introduction

Poststroke pneumonia is one of the serious complications and a main cause of death after stroke,^[1],[2],[3] accounting for nearly 30% of all deaths.^[4] Growing studies have proved various factors that are related to poststroke pneumonia, such as older age, diabetes, dysarthria/aphasia, cognitive impairment, stroke severity, and dysphagia.^{[5],[6],[7],[8],[9],[10]} Moreover, following the biomolecular science literature constantly updated, biomarkers in stroke have received remarkable attention in the very recent years, including C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha, or IL-1 β, growth factor-like molecules, hormones, and microRNAs.^[11] However, no consensus has emerged as the data from previously reported studies were collected from different stroke units.

Eosinophils have been considered to play a crucial role in controlling parasitic infections, but increasing evidence suggested that they contribute to various physiological and pathological processes of inflammatory diseases as well as in thrombosis.^[12] In our previous study, we elaborated that eosinophil counts might have a significant impact on outcomes in stroke patients.^[13] To further illustrate the correlation between eosinophil and stroke complications, in the current study, we analyzed data of 526 acute ischemic stroke patients in 2 weeks who were newly developed pneumonia following stroke occurred after 24 h. The first purpose of this study was to demonstrate whether there was an eosinophil disorder in the patients with poststroke pneumonia. The second purpose was to determine whether eosinophil could be a predicted factor regarding the outcome of poststroke pneumonia patients.

Patients and Methods

Study population

A secondary analysis of a retrospective cohort study was performed on acute ischemic stroke patients. Cases were identified in the neurological department from October 1, 2010, to October 1, 2016. This study was approved by the Zibo Central Hospital Review Board.

All patients in the cohort were 18 years of age or older. “Acute” was defined as those patients who had neurological symptom onset within 2 days of hospital admission. Poststroke pneumonia was defined as those patients who were newly developed pneumonia following stroke occurred after 24 h. Patients were excluded from this study if (1) life-threatening conditions, (2) had missing stratification information, or (3) without standard care and rehabilitation. This exclusion criterion was chosen to ensure that all selected patients received a standard thrombolytic therapy and were treated according to the best medical practice. As it was a retrospective study, no informed consent was required.

For the data analysis, 526 patients were categorized into two groups according to stroke patients with pneumonia or not. The general characteristics of the patients were shown in [Table 1].

Table 1: General characteristics of stroke patients

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Definition

Stroke was diagnosed based on the World Health Organization criteria.^[14] The diagnosis of pneumonia requires chest X-ray along with other pathologic findings: cough, sputum, fever, chills, dyspnea, pleuritic chest pain, disturbance of consciousness, and crackles.^[15],[16]

Treatment

The antibacterial treatment was given in addition to standard stroke care, including thrombolysis and rehabilitation. Systematic use of antihypertensive, oral antithrombotic, and lipid-lowering agents was recommended for secondary prevention based on clinical symptoms and doctor's experience.

Data collection

Data were measured by documentation of a clinical diagnosis of stroke with/without pneumonia in the medical record. We included only documentation made by a physician.

Outcomes

The primary outcome included leukocytes and platelet parameters, infection, and dysphagia (categorized as present if there was dysphagia for liquids or solids or both). The secondary outcomes included pneumonia duration, neurological dysfunction, and brain infarct size at imaging assessment in the period 48 ± 24 h after stroke were followed up in 2 weeks.

Statistical analysis

Data were presented as mean ± standard deviation unless otherwise noted. P < 0.05 was considered statistically significant. Student's t-tests were used to compare continuous variables between the groups. Chi-square and Fisher's exact tests were used to compare proportional data between the groups. The multivariate logistic analysis was performed using a model including the following covariates: age, sex, the history of diabetes mellitus (DM) and hypertension, eosinophil count, and platelet distribution width (PDW), all of which are components of at least one of the proposed risk scores for neurological outcome in poststroke pneumonia patients. All analyses were performed by SPSS 19.0 (IBM SPSS Company, Chicago, IL, USA).

Results

General characteristics of stroke patients

For the data analysis, 526 patients were categorized into two groups. Group 1 consisted of 273 patients (156 males; average age = 63.2 ± 2.5) without pneumonia. Group 2 consisted of 253 patients (139 males; average age = 65.3 ± 3.2) with pneumonia. The general characteristics of the patients were shown in [Table 1]. Of these, 444 patients (84.4%) had a documented history of hypertension and 254 patients (48.3%) of DM.

Multiple factors predict outcomes

The baseline stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score. [Table 2] showed a comparison of unadjusted outcomes in patients of stroke with/without pneumonia. The data demonstrate that NIHSS score was better in patients who without pneumonia even their eosinophil counts were keeping a low level in 2 weeks. In addition, eosinophil counts continue to decrease in patients with pneumonia along with an increasing NIHSS score in 2 weeks. Dysphagia was observed in 65.8% of poststroke patients with pneumonia, so these data suggested that dysphagia was a risk factor for aggravated outcomes in these patients. Furthermore, more patients who had lower eosinophil counts experienced hypertension and DM. These data also included that 35 patients who had higher eosinophil counts got lower NIHSS score in 2 weeks, which were consistent with our previous results.^[13]

Table 2: Outcome data of the total population (G group)

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Analysis of the eosinophil count and platelet parameter on the National Institutes of Health Stroke Scale score

The relationship between leukocytes, platelet parameters, and pneumonia in the ischemic stroke patients is shown in [Table 3]. The data showed that patients in G1 showed a higher eosinophil count and lower PDW compared to G2. Next, we identified covariates that predicted NIHSS score by a forward stepwise regression [Table 4]. The base model derived by logistic regression identified dysphagia, eosinophil count, and PDW as predictors of NIHSS scores in poststroke patients with pneumonia.

Table 3: Leukocytes and platelet parameters of all patients

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Table 4: Analysis of related factors of the National Institutes of Health Stroke Scale score in 2 weeks

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Discussion

In the current study, we elaborated the changes of eosinophil count and analyzed the outcome of poststroke pneumonia patients in 2 weeks. Our data showed a lower level of eosinophil count in poststroke pneumonia patients compared to the participants without pneumonia. In addition, patients with lower eosinophil count usually combined with an increased platelet width and a higher NIHSS score [Table 2]. To our knowledge, this is the first report that eosinophil counts could be a biomarker and treatment target for the outcome of poststroke pneumonia.

Pneumonia is seen to be the most common infection after stroke.^[1],[17] The major cause for poststroke pneumonia was thought to aspiration and dysphagia that result from impaired swallowing function.^[3] In addition, the suppression of systemic immunity increased susceptibility to infection after stroke.^[18] Several immune cells were reported to infiltrate the brain from the periphery in a synchronized manner following acute focal ischemia.^[19] In this current study, we first investigated levels of peripheral leukocytes. We did not find any statistical difference in the count and percentage of neutrophils, monocytes, or lymphocytes between the patients with/without pneumonia poststroke. While, we observed a significant decrease in eosinophil count in poststroke pneumonia patients compared to patients without pneumonia [Table 3]. Although we did not make brain and lung tissue biopsy to confirm our inference, we supposed that lower eosinophil count level caused by their infiltration into the lesion tissue.

Next, we discuss the reasons of the lower eosinophil counts coherent increased NIHSS score in poststroke pneumonia patients. Eosinophils' role is classically focused on promoting allergic reactions against parasites. However, a series of recently studies demonstrated that eosinophils take part in fibrosis and vascular leakage by releasing mediators and repair/remodeling factors, such as nerve growth factors, neuropeptides, and cytokines such as IL-1β and IL-6.^[20] Moreover, using a large-scale epidemiological approach, Uderhardt et al. observed eosinophilic cationic protein, which serves as a potential eosinophilic activation marker associated with thrombotic events, such as stroke and myocardial infarction.^[21] Eosinophil infiltration/eosinophil degranulation was also discovered in fibrotic regions of endometriotic tissue.^[22] Other neurotoxic substances include eosinophil-derived neurotoxin.^[12] Hence, the activities of eosinophils are far more complex beyond previously appreciated and its role on stroke process needs to be further investigated.

On the other hand, we observed the synergistic changes in eosinophils and platelet-related parameters [Table 3]. In the current study, the second difference was the PDW between two groups, which is one of the indicators that reflect platelet activity.^{[23],[24],[25]} Platelets were demonstrated to communicate with other cells by direct cell-cell contact or by releasing bioactive compounds or microparticles. Platelet-derived chemokine (C-C motif) ligand 5 (CCL5) could enhance platelet-eosinophil interactions.^{[26],[27],[28]} Eosinophils could convey P-selectin granulocyte ligand 1 on the cell surface to promote its engagement on activated platelets. CD40 ligand/CD40 interactions were reported to accelerate the interactions among eosinophils, platelets, and the endothelium and then prolong inflammatory responses.^[29] Taken together, the cooperation between eosinophils and platelets might endow with a potentially enhanced thrombogenesis. Under this situation, the treatment regimen on the target to solve the interaction between eosinophils and platelets might improve the outcomes of poststroke pneumonia patients.

This study has some limitations. First, our study is the exclusion of patients who died within 14 days, which might lose the analysis of eosinophil changes in the most serious and final situation. Second, our study is a small and single-central study. Thus, the change of eosinophils should continue to be investigated in large samples in the future.

Conclusions

Our data demonstrated that the changes of eosinophil count participated in the pathophysiological process of stroke and its pulmonary complications. The continuous lower eosinophil count, in the current study, experienced a higher NIHSS score within two weeks [Table 4], which underscored that pneumonia poststroke was a serious pathophysiological situation and suggested a difficulty and/or extended recovery period of the disease. The interaction between eosinophils and platelets might be a treatment target to improve the outcomes of poststroke pneumonia patients in the future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Walter U, Knoblich R, Steinhagen V, Donat M, Benecke R, Kloth A, et al. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. J Neurol 2007;254:1323-9.
2.	Marciniak C, Korutz AW, Lin E, Roth E, Welty L, Lovell L, et al. Examination of selected clinical factors and medication use as risk factors for pneumonia during stroke rehabilitation: A case-control study. Am J Phys Med Rehabil 2009;88:30-8.
3.	Teramoto S. Novel preventive and therapuetic strategy for post-stroke pneumonia. Expert Rev Neurother 2009;9:1187-200.
4.	Heuschmann PU, Kolominsky-Rabas PL, Misselwitz B, Hermanek P, Leffmann C, Janzen RW, et al. Predictors of in-hospital mortality and attributable risks of death after ischemic stroke: The German Stroke Registers Study Group. Arch Intern Med 2004;164:1761-8.
5.	Hinchey JA, Shephard T, Furie K, Smith D, Wang D, Tonn S, et al. Formal dysphagia screening protocols prevent pneumonia. Stroke 2005;36:1972-6.
6.	Sellars C, Bowie L, Bagg J, Sweeney MP, Miller H, Tilston J, et al. Risk factors for chest infection in acute stroke: A prospective cohort study. Stroke 2007;38:2284-91.
7.	Aslanyan S, Weir CJ, Diener HC, Kaste M, Lees KR; GAIN International Steering Committee and Investigators. Pneumonia and urinary tract infection after acute ischaemic stroke: A tertiary analysis of the GAIN international trial. Eur J Neurol 2004;11:49-53.
8.	Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R, et al. Dysphagia after stroke: Incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-63.
9.	Ding R, Logemann JA. Pneumonia in stroke patients: A retrospective study. Dysphagia 2000;15:51-7.
10.	Mann G, Hankey GJ, Cameron D. Swallowing function after stroke: Prognosis and prognostic factors at 6 months. Stroke 1999;30:744-8.
11.	Ji Q, Ji Y, Peng J, Zhou X, Chen X, Zhao H, et al. Increased brain-specific MiR-9 and MiR-124 in the serum exosomes of acute ischemic stroke patients. PLoS One 2016;11:e0163645.
12.	Kita H. Eosinophils: Multifaceted biological properties and roles in health and disease. Immunol Rev 2011;242:161-77.
13.	Guo LB, Liu S, Zhang F, Mao GS, Sun LZ, Liu Y, et al. The role of eosinophils in stroke: A pilot study. Eur Rev Med Pharmacol Sci 2015;19:3643-8.
14.	Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T, et al. Cerebrovascular disease in the community: Results of a WHO collaborative study. Bull World Health Organ 1980;58:113-30.
15.	American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416.
16.	Carratalà J, Mykietiuk A, Fernández-Sabé N, Suárez C, Dorca J, Verdaguer R, et al. Health care-associated pneumonia requiring hospital admission: Epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med 2007;167:1393-9.
17.	Yeh SJ, Huang KY, Wang TG, Chen YC, Chen CH, Tang SC, et al. Dysphagia screening decreases pneumonia in acute stroke patients admitted to the stroke intensive care unit. J Neurol Sci 2011;306:38-41.
18.	Shim R, Wong CH. Ischemia, immunosuppression and infection – Tackling the predicaments of post-stroke complications. Int J Mol Sci 2016;17. pii: E64.
19.	Famakin BM. The immune response to acute focal cerebral ischemia and associated post-stroke immunodepression: A focused review. Aging Dis 2014;5:307-26.
20.	Jacobsen EA, Helmers RA, Lee JJ, Lee NA. The expanding role(s) of eosinophils in health and disease. Blood 2012;120:3882-90.
21.	Uderhardt S, Ackermann JA, Fillep T, Hammond VJ, Willeit J, Santer P, et al. Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease. J Exp Med 2017;214:2121-38.
22.	Blumenthal RD, Samoszuk M, Taylor AP, Brown G, Alisauskas R, Goldenberg DM, et al. Degranulating eosinophils in human endometriosis. Am J Pathol 2000;156:1581-8.
23.	Fujita S, Takeda Y, Kizawa S, Ito T, Sakane K, Ikemoto T, et al. Platelet volume indices are associated with systolic and diastolic cardiac dysfunction, and left ventricular hypertrophy. BMC Cardiovasc Disord 2015;15:52.
24.	Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, Labrianou I, et al. Platelet distribution width: A simple, practical and specific marker of activation of coagulation. Hippokratia 2010;14:28-32.
25.	Khandekar MM, Khurana AS, Deshmukh SD, Kakrani AL, Katdare AD, Inamdar AK, et al. Platelet volume indices in patients with coronary artery disease and acute myocardial infarction: An Indian scenario. J Clin Pathol 2006;59:146-9.
26.	Ojima-Uchiyama A, Masuzawa Y, Sugiura T, Waku K, Fukuda T, Makino S, et al. Production of platelet-activating factor by human normodense and hypodense eosinophils. Lipids 1991;26:1200-3.
27.	Shah SA, Page CP, Pitchford SC. Platelet-eosinophil interactions as a potential therapeutic target in allergic inflammation and asthma. Front Med (Lausanne) 2017;4:129.
28.	Rohrbach MS, Wheatley CL, Slifman NR, Gleich GJ. Activation of platelets by eosinophil granule proteins. J Exp Med 1990;172:1271-4.
29.	Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, et al. Eosinophils from physiology to disease: A comprehensive review. Biomed Res Int 2018;2018:9095275.