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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 16  |  Issue : 3  |  Page : 229-234

Blood eosinophilia in chronic obstructive pulmonary disease: is there a relation with airway eosinophilia?


Department of Chest Disease, Al-Azhar University, Faculty of Medicine, Cairo, Egypt

Date of Submission12-Mar-2018
Date of Acceptance04-Feb-2019
Date of Web Publication15-Apr-2019

Correspondence Address:
Atef W El Rifai
Department of Chest Disease, Al-Azhar University, Faculty of Medicine, Cairo, 35511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_10_18

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  Abstract 


Background Blood eosinophilia was considered an indicator of sputum eosinophilia in asthmatic patients. Nevertheless, its role in chronic obstructive pulmonary disease (COPD) was not completely examined.
Aim The aim was to investigate if peripheral blood eosinophilic cells represent an indicator (marker) of eosinophilia of the airway in stable cases.
Patients and methods The trial was held at Al-Azhar University Hospital (Damietta), between October 2015 and March 2017. It included 264 persons with stable COPD. All cases were assessed for demographic features, smoking history, history of exacerbation in the last year, dyspnea, associated comorbidities, quality of life, lung functions, sputum, and peripheral blood eosinophilic cell counts. The included participants were allocated into two sets: group with eosinophilia (n=76) and patients without eosinophilia (n=188).
Results There was proportional correlation between eosinophilia of the blood and sputum; and blood eosinophilia can differentiate between cases who had or had no sputum eosinophilia at a cutoff of 2.5%. In addition, eosinophil/lymphocyte ratio and eosinophil/neutrophil ratio were higher in eosinophilic COPD and are associated ELR with eosinophilia of the sputum ENR.
Conclusion There is correlation between eosinophils of the peripheral blood and sputum in stable cases. Thus, the count of blood eosinophil may act as a dependable marker for eosinophilic COPD

Keywords: bronchial asthma, chronic obstructive pulmonary disease, eosinophils, sputum


How to cite this article:
El Rifai AW, Hussein HA. Blood eosinophilia in chronic obstructive pulmonary disease: is there a relation with airway eosinophilia?. Al-Azhar Assiut Med J 2018;16:229-34

How to cite this URL:
El Rifai AW, Hussein HA. Blood eosinophilia in chronic obstructive pulmonary disease: is there a relation with airway eosinophilia?. Al-Azhar Assiut Med J [serial online] 2018 [cited 2020 Jul 10];16:229-34. Available from: http://www.azmj.eg.net/text.asp?2018/16/3/229/255849




  Introduction Top


Chronic obstructive pulmonary disease (COPD) is usually linked with significant morbidity. The proper management of these conditions consumes high health-care resources exceeding $29.5 billion in America every year [1].

It had obstructive airway as the sole characteristic, which is partially reversible. In addition, symptoms occur daily with decreased capacity of exercise and respiratory failure developed in advanced stages. Its exacerbations marked with deterioration of original symptoms often elicited by infection and these exacerbations increase the complications and the mortality of COPD [2].

Eosinophilic inflammation induced by allergy and the immune response mediated by T-helper (Th2) is the basic mechanism of inflamed airways in asthma. However, eosinophilic inflammation can happen without allergy and eosinophilic inflammation is neither essential nor adequate for the existence of asthma [3]. However, its associated Th1-mediated neutrophilic immune reaction is linked with bacterial infection. However, this represents only about half of the cases with COPD and in about 10–40% eosinophilic cases inflammation of the airway is a feature [4],[5]. Thus, eosinophilic inflammation can be evaluated as part of the routine assessment of airway diseases. This is vital when considering the probable role of inflammation linked with eosinophilia in disease as an indicator to direct therapies and for the upcoming progress of drugs. In addition, searching for disease biomarkers helps to understand COPD heterogeneity and to predict the treatment outcome [2].

By definition, eosinophilic COPD is considered if sputum eosinophils greater than or equal to 3% occur in up to 28% of cases during exacerbation [6], and 34–38% of patients during stable period [5],[7].

It needed the assessment of stimulated sputum production (induced sputum) [8]. The stimulation of sputum production seems to be a simple and reliable method for eosinophilic determination. However, it had some limitations. First, it is inappropriate for point-of-care testing. Second, it needs experience (failure rate around 30%) [9]. Thus, the search for minimally invasive and easily applicable diagnostic tools that can expect sputum eosinophilia in COPD is needed [10],[11],[12].

Peripheral counts of blood cells may be a suitable alternative due to its easy application in daily medical practice. In addition, the capacity of eosinophils of the blood to expect sputum eosinophilia in asthma had been described, with encouraging results. However, studies investigating the effectiveness of eosinophils of peripheral blood in identifying sputum eosinophilia in stable patients are deficient [13],[14],[15].

Thus, the current trial was planned to investigate if eosinophilia of the peripheral blood can be considered as an indicator of eosinophilia of the airway in stable COPD.


  Patients and methods Top


The study was a cross-sectional study, conducted at the Al-Azhar University Hospital (Damietta), from October 2015 to March 2017. The study protocol was approved by the local research and Ethics committee of Al-Azhar Faculty of Medicine (Damietta). It included 264 participants with stable COPD. Diagnosis of COPD was confirmed by an increase in postbronchodilator forced expiratory volume at the first second (FEV1) less than 12% predicted and FEV1 to forced vital capacity (FVC) ratio of less than 0.7. Stable COPD is defined as no increase in bronchodilator use, or use of systemic corticosteroids and antibiotics, and no hospital admission due to exacerbation in the last 90 days.

All participants were assessed for demographic features, smoking history, BMI, history of exacerbation in the last year, dyspnea (modified-Medical Research Council) [16], associated comorbidities (Charlson comorbidity index) [17], and health-related quality of life (Jones et al., 1992) [18] lung functions, sputum, and peripheral blood eosinophilic cell counts.

Induction and analysis of the sputum

Sputum was induced using nebulized 3.0% saline using the method described by Gupta and Garg [19]. The patient was pretreated with 200 mg of albuterol or equivalent β2-agonist by inhalation. Preinduction spirometry 10 min before and 10 min after β2-agonist is done. After putting a nasal clip, induction is initiated by 3% hypertonic saline (5–7 ml). Patient expectorate when he/she feels or every 5 min, FEV1 and PEF are checked every 5 min. Saline induction is sustained for 15 min (three times, 5 min each). If sputum is insufficient, induction is sustained for another 5 min. Procedure terminated after 20 min or if FEV1 decreased by 20%.

Sputum samples were prepared, stained, and a differential cell count was acquired from 400 nonsquamous cells as described by Fahy et al. [20]; eosinophilic COPD was defined as sputum eosinophil greater than or equal to 3% [21]. Patients were assigned into two sets: group with eosinophilia (n=76) and cases without eosinophilia (n=188).

Blood sampling and examination

A venous sample was drawn into the capillary tubes. Full cell counts were done by standardized approaches on a Beckman Coulter analyzer, USA.

Spirometry

Airflow limitation was evaluated by spirometry to measure prebronchodilator and postbronchodilator FEV1, FVC, and FEV1/FVC as defined by the American Thoracic Society [22].

Statistical analysis

SPSS computer software (SPSS Inc., Chicago, Illinois, USA), version 18 and MedCalc version 16.8 (MedCalc Software, Acacialaan 22, 8400 Ostend, Belgium) were used for analysis of data. Quantitative data were designated as mean±SD. Qualitative data were pronounced as number and percentage. Category variables were compared by Student’s t-test. For the categorical variables, we used χ2-tests for homogeneity or Fisher’s exact test if required by the sample size. Spearman’s rank correlation coefficient was calculated to determine the link between absolute blood cell counts/ratios and eosinophils of the sputum. Receiver operating characteristic curves were generated and the area under the curve (AUC) was calculated to evaluate the predictive relationship between eosinophils of the blood and sputum. All results were labeled as significant when the value of P is less than 0.05.


  Results Top


Patient characteristics are given in [Table 1]. It revealed that there was no significant difference between groups as regards age, sex, BMI, ex-smoking, packs/year or Charlson comorbidity index. The mean patient age was 63.5±5.7 and 65.9±6.2 years in eosinophilic and noneosinophilic groups, respectively. Men represented 60.5% of the eosinophilic group compared with 66.0% of the noneosinophilic group. The mean BMI was 28.8±2.8 and 28.5±3.1 kg/m2 in eosinophilic and noneosinophilic groups, respectively. In the eosinophilic group, 68.4% were exsmokers, compared with 74.5% of the noneosinophilic group. The mean packs/year were 29.9±6.0 and 32.1±7.5 in the eosinophilic and noneosinophilic groups, respectively, while there was significant increase of past history of asthma in eosinophilic when compared with the noneosinophilic groups (55.3 vs. 35.1%, respectively). Modified Medical Research Council score greater than or equal to 2 was significantly reduced in the eosinophilic group when compared with the noneosinophilic group (50.0 vs. 71.3%, respectively). Finally, St George Respiratory Questionnaire was significantly reduced in the eosinophilic group when compared with the noneosinophilic groups (45.5±2.9 vs. 47.0±3.8, respectively).
Table 1 Patient characteristics

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As regards disease characteristics, there was no statistically significant difference, as regards postbronchodilator FEV1% predicted, postbronchodilator FEV1/FVC% ratio; reversibility, frequent versus in-frequent exacerbations, and Global Initiative for COPD classifications (detailed results were presented in [Table 2]).
Table 2 Chronic obstructive pulmonary disease characteristics in the studied populations

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Regarding white blood cells total and differential count, the total leukocytic count showed nonsignificant difference between groups (7.69±1.04 vs. 7.71±0.99×103, respectively). In addition, lymphocytes had no significant difference between eosinophilic and noneosinophilic groups (1.78±0.054 vs. 1.79±0.055, respectively). However, there was statistically significant increase of eosinophil %, eosinophil/lymphocyte ratio (ELR) and eosinophil/neutrophil ratio (ENR) in the eosinophilic group when compared with the noneosinophilic group (3.73±0.59, 0.21±0.03 and 0.10±0.02 vs. 1.93±0.28, 0.11±0.02 and 0.05±0.01, respectively), while there was statistically significant decrease of neutrophils and neutrophil/lymphocyte ratio in the eosinophilic group when compared with the noneosinophilic groups (3.73±0.64, 2.09±0.34 vs. 4.41±0.72 and 2.50±0.41, respectively) ([Table 3]).
Table 3 Results of differential leukocytic count and ratios in the studied populations

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Searching the association (correlation) between sputum eosinophils % in the eosinophilic group and other variables discovered, there was moderate, proportional (positive), and statistically significant correlation between sputum eosinophils from one side and each of blood eosinophils, ELR, and ENR. However, the correlation was nonsignificant with neutrophil/lymphocyte ratio. In the noneosinophilic group, there was no significant correlation ([Table 4], [Figure 1]).
Table 4 Correlation between sputum eosinophils and each of blood eosinophils, neutrophil/lymphocyte, eosinophil/lymphocyte, and eosinophil/neutrophil ratios in eosinophilic and noneosinophilic groups

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Figure 1 Correlation between sputum and blood eosinophil %.

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In a trial to estimate the best cutoff point of blood eosinophils in the prediction of sputum eosinophilia, the receiver operating characteristic curve revealed that the AUC was 0.975 denoting an excellent power of blood eosinophilia in the prediction of sputum eosinophilia. The value of 2.5% was the best cutoff with a specificity of 97.4% and sensitivity of 100.0% ([Table 5], [Figure 2]).
Table 5 Sensitivity of blood eosinophils in the diagnosis of sputum eosinophilia

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Figure 2 Receiver operating characteristic for detection of sensitivity and specificity of blood eosinophils in the detection of sputum eosinophilia (>3.0%).

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  Discussion Top


The current trial aimed to examine the capacity of eosinophils in peripheral blood to identify sputum eosinophilia in stable cases. It revealed the following main findings: there was proportional correlation between eosinophils of the peripheral blood and sputum eosinophils; and blood eosinophilia can discriminate between those who had or had no sputum eosinophilia at a cutoff point of 2.5%. In addition, eosinophil counts of the blood and its ELR and ENR are high in eosinophilic COPD and correlate with sputum eosinophils. These findings are supported by those reported by Bafadhel et al. [6] who reported that peripheral eosinophils (>2%) can serve as a sensitive biomarker to determine sputum eosinophilia (≥3%) during attacks (exacerbations) (AUC: 0.85; 95% confidence interval=0.78–0.93, sensitivity=90%, specificity=60%). Fowler et al. [13] suggested that patients with blood eosinophilia equal or above the cutoff point may not need to be submitted to induction of sputum for the evaluation of airway eosinophilia.

However, in their study, Negewo et al. [23] observed that there was discordance between sputum and blood eosinophils in about 40% of the patients with eosinophilic COPD at a peripheral eosinophil count of (0.3×109/l). This is similar to the results of Schleich et al. [24] who observe that one-third of the participants exhibited discordance between blood and sputum eosinophils in uncontrolled asthma.

In the present trial, only 10 patients out of 188 participants (5.3%) had an eosinophilic count of greater than or equal to 2.5% and had no sputum eosinophilia, while all people with eosinophilia of the sputum had a value greater than or equal to 2.5% of blood eosinophilic count. This disagreement between sputum and blood eosinophilia can be explained by: (a) inequality between the manufacture and clearance of eosinophils by airway macrophages [25]; (b) disparities in the recruitment of eosinophils in the airways [24]. Also, Th2 cytokines may be accountable for inflammation in eosinophilic COPD [26]. However, eosinophilic airway inflammation in the absenteeism of higher values of Th2 has also been recognized in some cases [27].

Data of the present trial showed that blood eosinophils and ratios were increased in people with sputum eosinophilia when compared with those without. Blood eosinophil percentage correlated positively with eosinophil sputum percentage. These data are in accordance with those described by Khatry et al. [28].


  Conclusion Top


Our study showed that there is a predictive association between blood and sputum eosinophils in stable cases. Thus, the peripheral blood eosinophil count may potentially function as a dependable indicator (marker) for eosinophilic COPD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bach PB, Brown C, Gelfand SE, McCrory DC; American College of Physicians-American Society of Internal Medicine; American College of Chest Physicians. Management of acute exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence. Ann Intern Med 2001; 134:600–620.  Back to cited text no. 1
    
2.
George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther Adv Chronic Dis 2016; 7:34–51.  Back to cited text no. 2
    
3.
Eltboli O, Brightling C. Eosinophils as diagnostic tools in chronic lung disease. Expert Rev Respir Med 2013; 7:33–42.  Back to cited text no. 3
    
4.
Eltboli O, Bafadhel M, Hollins F, Wright A, Hargadon B, Kulkarni N, Brightling C. COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils. BMC Pulm Med 2014; 14:112.  Back to cited text no. 4
    
5.
Leigh R, Pizzichini M, Morris M, Maltais F, Hargreave FE, Pizzichini E. Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment. Eur Respir J 2006; 27:964–971.  Back to cited text no. 5
    
6.
Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med 2011; 184:662–671.  Back to cited text no. 6
    
7.
McDonald VM, Higgins I, Wood LG, Gibson PG. Multidimensional assessment and tailored interventions for COPD: respiratory utopia or common sense? Thorax 2013; 68:691–694.  Back to cited text no. 7
    
8.
Brightling CE. Clinical applications of induced sputum. Chest 2006; 129:1344–1348.  Back to cited text no. 8
    
9.
Baines KJ, Pavord ID, Gibson PG. The role of biomarkers in the management of airways disease. Int J Tuberc Lung Dis 2014; 18:1264–1268.  Back to cited text no. 9
    
10.
Korevaar DA, Westerhof GA, Wang J, Cohen JF, Spijker R, Sterk PJ et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med 2015; 3:290–300.  Back to cited text no. 10
    
11.
Pavord ID, Bafadhel M. Exhaled nitric oxide and blood eosinophilia: independent markers of preventable risk. J Allergy Clin Immunol 2013; 132:828–829.  Back to cited text no. 11
    
12.
Yap E, Chua WM, Jayaram L, Zeng I, Vandal AC, Garrett J. Can we predict sputum eosinophilia from clinical assessment in patients referred to an adult asthma clinic? Intern Med J 2013; 43:46–52.  Back to cited text no. 12
    
13.
Fowler SJ, Tavernier G, Niven R. High blood eosinophil counts predict sputum eosinophilia in patients with severe asthma. J Allergy Clin Immunol 2015; 135:822–824.e822.  Back to cited text no. 13
    
14.
Wagener AH, de Nijs SB, Lutter R, Sousa AR, Weersink EJ, Bel EH, Sterk PJ. External validation of blood eosinophils, FE (NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax 2015; 70:115–120.  Back to cited text no. 14
    
15.
Westerhof GA, Korevaar DA, Amelink M, Amelink M, de Nijs SB, de Groot JC. Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes. Eur Respir J 2015; 46:688–696.  Back to cited text no. 15
    
16.
Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999; 54:581–586.  Back to cited text no. 16
    
17.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40:373–383.  Back to cited text no. 17
    
18.
Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St George’s respiratory questionnaire. Am Rev Respir Dis 1992; 145:1321–1327.  Back to cited text no. 18
    
19.
Gupta KB, Garg S. Sputum induction − a useful tool in diagnosis of respiratory diseases. Lung India 2006; 23:82–86.  Back to cited text no. 19
    
20.
Fahy JV, Boushey HA, Lazarus SC, Mauger EA, Cherniack RM, Chinchilli VM. Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study. Am J Respir Crit Care Med 2001; 163:1470–1475.  Back to cited text no. 20
    
21.
Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet 1999; 353:2213–2214.  Back to cited text no. 21
    
22.
Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med 1995; 152:1107–1136.  Back to cited text no. 22
    
23.
Negewo NA, McDonald VM, Baines KJ, Wark PA, Simpson JL, Jones PW, Gibson PG. Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD. Int J COPD 2016; 11:1495–1504.  Back to cited text no. 23
    
24.
Schleich FN, Chevremont A, Paulus V, Henket M, Manise M, Seidel L, Louis R. Importance of concomitant local and systemic eosinophilia in uncontrolled asthma. Eur Respir J 2014; 44:97–108.  Back to cited text no. 24
    
25.
Kulkarni NS, Hollins F, Sutcliffe A, Saunders R, Shah S, Siddiqui S. Eosinophil protein in airway macrophages: a novel biomarker of eosinophilic inflammation in patients with asthma. J Allergy Clin Immunol 2010; 126:61–69.e63.  Back to cited text no. 25
    
26.
Woodruff PG, Agusti A, Roche N, Singh D, Martinez FJ. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management. Lancet 2015; 385:1789–1798.  Back to cited text no. 26
    
27.
Ghebre MA, Bafadhel M, Desai D, Cohen SE, Newbold P, Rapley L. Biological clustering supports both ‘Dutch’ and ‘British’ hypotheses of asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 2015; 135:63–72.e10.  Back to cited text no. 27
    
28.
Khatry DB, Gossage DL, Geba GP, Parker JM, Jarjour NN, Busse WW, Molfino NA. Discriminating sputum-eosinophilic asthma: accuracy of cutoffs in blood eosinophil measurements versus a composite index, ELEN. J Allergy Clin Immunol 2015; 136:812–814.e812.  Back to cited text no. 28
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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