Peripheral Blood Eosinophilia and Asthma Severity

In This Article

Abstract and Introduction

Abstract

Background: Asthma is a diverse disease with various etiologic bases. Severe asthma can be associated with increased mortality, hospitalization, and decreased quality of life for asthma patients. High blood eosinophil counts were associated with severe asthma, but recent studies have failed to confirm this as a marker of severe asthma among adult asthma patients. As a result, the purpose of this study was to determine the association between the severity of asthma and high blood eosinophil count.

Methodology: A simple random sampling technique was used to select 291 asthmatic patients for an institution-based cross-sectional study. Socio-demographic, behavioral, and clinical characteristics were collected by using a pre-tested structured questionnaire. Four milliliters of venous blood were collected from asthmatic patients for complete blood count and peripheral morphology assessment. The eosinophil count was analyzed by the Unicel DxH 800 (Beckman Coulter, Ireland) analyzer. A statistical package for social science version 20 (SPSS) software was used to analyze the data. The non-parametric (Mann-Whitney U) test was used to compare the eosinophil count with different background variables. A binary logistic regression analysis was used to assess the factors associated with eosinophilia. A p-value less than 0.05 in multivariable logistic regression analysis was considered statistically significant.

Result: In this study, the overall magnitude of eosinophilia was 19.6% (95% CI = 14.8–24.1). Being admitted to the emergency department (AOR = 0.25; 95% CI: 0.09–0.69, p = 0.007) and being female (AOR = 0.49; 95% CI: 0.26–0.9, p = 0.025) were shown to have a statistically significant association with eosinophilia. Moreover, the absolute eosinophil count was significantly higher among asthmatic patients infected with intestinal parasitic infection (p < 0.045).

Conclusion: Being female and admission to the emergency department were negatively associated with eosinophilia. Lack of eosinophilia can be related to the low-T2 asthma phenotype. The absolute eosinophil counts were higher among intestinal parasite-infected patients. Therefore, different biomarkers will be considered for the proper diagnosis and management of adult asthma patients.

Introduction

Asthma is a diverse disease characterized by chronic airway inflammation.^[1] It is defined by a history of respiratory symptoms such as wheezing, chest tightness, shortness of breath, and cough that can fluctuate over time and in intensity along with variable expiratory airflow limitation.^[1,2] Asthma is a common disease of the airways that affects 339 million people worldwide.^[3] Asthma prevalence is still growing in various countries.^[4] In adults, the frequency of asthma ranges from 4 to 10%.^[4–6]

Asthma is a heterogenous disease with various etiologic bases.^[1,7] Asthma endotypes can be largely classified as type 2 (T2) high or T2-low.^[7] T2-high asthma is distinguished by fractional exhaled nitric oxide (FeNO) > 25 ppb, blood and airway eosinophilia (peripheral blood eosinophil levels > 300 or > 150 cells/μL, and sputum eosinophils > 2%), increased severity, and therapeutic responsiveness to Glucocorticoids and T2 inflammatory inhibitors.^[8,9] During exposure to allergens, T2 inflammation coexists with eosinophilic inflammation mediated by cytokines such as interleukin (IL) -4, IL-5, and IL-13.^[10,11] T2-low asthma is identified by increased neutrophils and a lack of airway and systemic eosinophilia.^[8,10]

The European Respiratory Society (ERS)/American Thoracic Society (ATS) task force defines severe asthma as "asthma that needs treatment with high-dose inhaled corticosteroids (ICS) plus additional controller and/or systemic corticosteroids to keep it from being "uncontrolled" or it remains "uncontrolled" despite maximally optimized Global Initiative for Asthma (GINA) step 4 or 5 therapy and treatment of contributing factors, or it worsens when optimized therapy is reduced". It is estimated that about 3 to 10% of asthma patients have severe asthma.^[1,11]

Severe asthma is associated with higher mortality, hospitalization, and a decreased quality of life. Also, it results in physical, mental, emotional, social, and occupational costs for individuals as well as a financial impact on health care systems.^[12,13]

Eosinophils are responsible for inflammatory effects when triggered by allergens. Persistent eosinophilic airway inflammation and airway remodeling lead to persistent airflow obstruction.^[14] A high blood eosinophil count causes immune-modulatory responses such as airway inflammation, airway hyperresponsiveness, damage to the epithelial lining, and increased mucus secretion.^[15] Nearly half of asthmatic patients have eosinophilic inflammation. Studies have shown that eosinophilia can be linked with increased disease severity, exacerbation frequency, and symptom burden, as well as impaired lung function.^[16–18]

Eosinophils are important predictors of disease severity and progression.^[19] As a result, eosinophils play a critical role in asthma diagnosis. Moreover, eosinophil counts have emerged as a promising and easily measurable marker in eosinophilic airway inflammation.^[20,21] Although allergic sensitization has been identified as a risk factor for asthma,^[22] non-allergic asthma is more common in adults. The prevalence of allergic asthma is higher during early childhood and gradually declines with advanced age. Especially after the age of 40 years, the new cases are non-allergic asthma.^[23,24]

The ERS/ATS task force considered sputum and blood eosinophilia as markers for severe asthma.^[11] However, GINA stated that the blood eosinophil count is not employed as a diagnostic biomarker for asthma. Instead, it can be utilized as a prognostic biomarker, predicting therapeutic responsiveness and a diagnostic biomarker for defining asthma phenotypes in patients with type 2 inflammation.^[25] Several cross-sectional and longitudinal studies have identified blood eosinophil counts as a risk factor for asthma exacerbation.^[26–28] Conversely, recent follow-up studies found that eosinophil counts are not linked to asthma exacerbations.^[29,30]

Many studies have revealed that eosinophil levels rise in cases of severe asthma. However, asthma is a diverse disease with different etiologies and phenotypes. Therefore, the main aim of this study was to determine the magnitude of the elevated peripheral eosinophil count and its association with the severity of asthma among adult asthmatic patients.

Table 1. Socio-demographic characteristics of the study participants (n = 291)
Variables	Category	Frequency	Percentage %
Age	≤ 40	103	35.4%
Age	> 40	188	64.6%
Sex	Male	127	43.6%
Sex	Female	164	56.4%
Residence	Urban	186	63.9%
Residence	Rural	105	36.1%
Marital status	Single	38	13.1%
	Married	192	66.0%
	Divorced	27	9.3%
	Widowed	34	11.7%
Education level	Unable to read and write	126	43.3%
	Primary school	64	22.0%
	Secondary school	49	16.8%
	College and above	52	17.9%
Occupation	House wife	101	34.7%
	Farmer	55	18.9%
	Employer	56	19.2%
	Private worker	57	19.6%
	Non-job, including students	22	7.6%
Family size	≤ 4	139	47.8%
	5–8	132	45.4%
	> 8	20	6.9%

Table 2. The clinical characteristics of adult asthmatic patients (n = 291)
Variables	Category	Frequency	Percentage %
Family history of asthma	Yes	88	30.2%
Family history of asthma	No	203	69.8%
Duration of asthma	≤ 5	121	41.6%
	6–10	79	27.1%
	> 10	91	71.3%
Severity of asthma	Mild	59	20.3%
	Moderate	176	60.5%
	Severe	56	19.2%
Stage of asthma	Intermittent	36	12.4%
	Mild persistent	19	6.5%
	Moderate persistent	186	63.9%
	Severe persistent	50	17.2%
Asthma medication	Yes	241	82.8%
Asthma medication	No	50	17.2%
History of taking drugs other than asthma	Yes	91	31.3%
History of taking drugs other than asthma	No	200	68.7%
Comorbidities	Yes	87	29.9%
Comorbidities	No	204	70.1%
ED admission	Yes	86	29.6%
ED admission	No	205	70.4%
Asthma drugs	ICS	7	3.1%
	ICS-SABA	110	49.1%
	SABA	91	40.6%
	Others	16	7.1%
Systemic corticosteroid use	Yes	17	7.1%
Systemic corticosteroid use	No	224	92.9%
Symptoms of asthma	Shortness of breath	118	40.5%
	Cough	88	30.2%
	Wheezing	13	4.5%
	≥ 2 symptoms	72	24.7%

Note: ICS: Inhaled Corticosteroids, SABA: Short-acting beta 2 antagonists, ICS-SABA: Inhaled Corticosteroids-Short acting beta 2 antagonists

Table 3. Comparison of eosinophilia with different background variables (Mann-Whitney test)
Variables	Category	Eosinophil count median (IQR)	p-value
Age	≤ 40	0.2(0.09–0.43	0.211
Age	> 40	0.18(0.07–0.4)	0.211
Family history of asthma	Yes	0.2(0.065–0.4)	0.134
Family history of asthma	No	0.16(0.07–0.4)	0.134
Asthma medication	Yes	0.2(0.075–0.4)	0.011*
Asthma medication	No	0.1(0.07–0.2)	0.011*
History of taking drugs other than asthma	Yes	0.12(0.04–0.4)	0.54
History of taking drugs other than asthma	No	0.2(0.1–0.4)	0.54
Comorbidities	Yes	0.19(0.1–0.4)	0.73
Comorbidities	No	0.2(0.06–0.4)	0.73
Admitted to ED	Yes	0.1(0.00–0.19)	0.0001*
Admitted to ED	No	0.2(0.1–0.4)	0.0001*
SC use	Yes	0.1(0.08–0.4)	0.47
SC use	No	0.2(0.035–0.36)	0.47
IP	Yes	0.3(0.1–0.4)	0.045*
IP	No	0.17(0.07–0.4)	0.045*

Note: IQR: Inter Quartile Range, ED: Emergency Department, SC: Systemic corticosteroids, IP: Intestinal parasite, * shows statistically significant association

Table 4. Bivariable and multivariable logistic analysis of factors associated with eosinophilia (n = 291)
Variables	Category	Eosinophilia		COR (95% CI)	P-value	AOR (95% CI)	P-value
Variables	Category	Yes	No	COR (95% CI)	P-value	AOR (95% CI)	P-value
Age	≤ 40	26(45.6%)	77(32.9%)	1^a	0.074	1^a	0.132
Age	> 40	31(54.4%)	157(67.1%)	0.58(0.32–1.05)		0.62(0.33–1.16)	0.132
Gender	Male	33(57.9%)	94(40.2%)	1^a	0.017	1^a	0.025*
Gender	Female	24(42.1%)	140(59.8%)	0.49(0.27–0.88)		0.49(0.26–0.9)	0.025*
Alcohol drinking habit	Yes	20(35.1%)	44(18.8%)	2.33(1.24–4.40)	0.009	1.81(0.9–3.54)	0.094
Alcohol drinking habit	No	37(64.9%)	190(81.2%)	1^a		1^a	0.094
Severity	Mild	9(15.8%)	50(21.4%)	1^a	0.078	1^a	0.102
	Moderate	31(54.4%)	145(62%)	1.19(0.53–2.67)		0.81(0.31–2.1)
	Severe	17(29.8%)	39(16.7%)	2.42(0.97–6.02)		1.79(0.63–5.1)
Asthmatic drug intake	Yes	51(89.5%)	190(81.2%)	1^a	0.14	1^a	0.9
Asthmatic drug intake	No	6(10.5%)	44(18.8%)	0.51(0.2–1.26)		1.08(0.32–3.59)	0.9
Emergency department admission	Yes	7(12.3%)	79(33.8%)	0.27(0.12–0.63)	0.002	0.25(0.09–0.69)	0.007*
Emergency department admission	No	50(87.7%)	155(66.2%)	1^a		1^a	0.007*