Das RR, Panigrahi MK, Mahapatro S, John J. Clinical and functional correlates of blood eosinophilia in pediatric asthma: A retrospective cohort study. World J Clin Pediatr 2026; 15(4): 122880 [DOI: 10.5409/wjcp.122880]
Corresponding Author of This Article
Rashmi Ranjan Das, MD, FCCP, Professor, Department of Pediatrics, All India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar 751019, Odisha, India. ped_rashmi@aiimsbhubaneswar.edu.in
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Das RR, Panigrahi MK, Mahapatro S, John J. Clinical and functional correlates of blood eosinophilia in pediatric asthma: A retrospective cohort study. World J Clin Pediatr 2026; 15(4): 122880 [DOI: 10.5409/wjcp.122880]
Rashmi Ranjan Das, Samarendra Mahapatro, Joseph John, Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar 751019, Odisha, India
Manoj Kumar Panigrahi, Department of Pulmonary Medicine and Critical Care, All India Institute of Medical Sciences, Bhubaneswar 751019, Odisha, India
Author contributions: Das RR, Mahapatro S, and John J contributed to the conceptualization and design; Das RR, Panigrahi MK, and John J contributed to material preparation, and data acquisition; Das RR, Panigrahi MK, and Mahapatro S, contributed to data analysis; and all authors contributed to writing-draft manuscript and writing-revision and approved to submit the final version.
AI contribution statement: AI tool (ChatGPT) was used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Institutional review board statement: The study was reviewed and approved by the Institutional Ethics Committee, All India Institute of Medical Sciences, Bhubaneswar (Approval No. T/IM-NF/Paedia/20/179; dated: February 8, 2021).
Informed consent statement: The requirement for informed consent was waived by the Institutional Ethics Committee owing to the retrospective nature of the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: There is no additional data available.
Corresponding author: Rashmi Ranjan Das, MD, FCCP, Professor, Department of Pediatrics, All India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar 751019, Odisha, India. ped_rashmi@aiimsbhubaneswar.edu.in
Received: May 7, 2026 Revised: June 13, 2026 Accepted: June 26, 2026 Published online: December 9, 2026 Processing time: 161 Days and 22.2 Hours
Abstract
BACKGROUND
Pediatric asthma is a heterogeneous disease with distinct inflammatory phenotypes. Asthma with blood eosinophilia (driven by type 2 inflammation) is associated with increased asthma severity and poor asthma control. However, pediatric data including that from resource-limited settings [low-and-middle-income country (LMIC)] remains limited.
AIM
To evaluate the clinical characteristics, asthma severity, and lung function in children with asthma and blood eosinophilia from a LMIC setting.
METHODS
This retrospective cohort study included children aged 5-14 years with asthma evaluated at a tertiary care center in Eastern India between March 1, 2017 and February 29, 2020. Blood eosinophilia was defined as an absolute eosinophil count (AEC) of ≥ 400 cells/mm3. The primary outcome was the association between blood eosinophilia and asthma control. Secondary outcomes included asthma severity, spirometry parameters, serum immunoglobulin E (IgE) levels, and factors independently associated with eosinophilia. Clinical characteristics, asthma control test scores, lung function parameters, and serum IgE levels were compared between children with and without eosinophilia. Multivariate analysis was performed to identify factors independently associated with blood eosinophilia.
RESULTS
Among 176 children included in the analysis, 84 (47.8%) had blood eosinophilia. Poor asthma control was more common in children with eosinophilia than in those without eosinophilia (51.2% vs 34.8%, P = 0.027). Eosinophilia was significantly associated with moderate and severe asthma and with greater airway obstruction, reflected by a lower mean forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (65.5% vs 69.7%, P = 0.006). Median serum IgE levels were significantly increased in the eosinophilic group (295 vs 98 kIU/L, P < 0.001). On multivariate analysis, age > 8 years, elevated serum IgE (> 300 kIU/L), poor asthma control, and reduced FEV1/FVC ratio were independently associated with blood eosinophilia.
CONCLUSION
Childhood asthma with blood eosinophilia (an AEC of ≥ 400 cells/mm3) is associated with poor control, greater disease severity, and increased airflow limitation. Peripheral eosinophil count may serve as an important biomarker for risk stratification and personalized asthma management in a LMIC setting.
Core Tip: Asthma with blood eosinophilia (driven by type 2 inflammation) is associated with increased asthma severity and poor asthma control. In this retrospective cohort study, we included 176 children with asthma, of which 84 had eosinophilic asthma. Asthma with blood eosinophilia (asthma with an absolute eosinophil count of ≥ 400 cells/mm3) was associated with poor asthma control, greater disease severity, and increased airflow limitation. Peripheral eosinophil count may serve as a practical biomarker for risk stratification and personalized asthma management in a low-and-middle-income country setting.
Citation: Das RR, Panigrahi MK, Mahapatro S, John J. Clinical and functional correlates of blood eosinophilia in pediatric asthma: A retrospective cohort study. World J Clin Pediatr 2026; 15(4): 122880
Asthma affects nearly 14% of children and young people worldwide, with a mean prevalence in the Indian subcontinent being around 8%[1-3]. There is persistent airway inflammation in asthma leading to variable respiratory symptoms, reversible airflow limitation, airway hyperresponsiveness, and airway remodeling. Asthma has multiple phenotypes and endotypes with distinct pathologic mechanisms[3-5]. Eosinophilic asthma is the most common phenotype driven primarily by type 2 helper T-cell (Th2)-mediated responses[6,7]. In this phenotype, in addition to the Th2 lymphocytes other innate immune cells including mast cells, basophils, and type 2 innate lymphoid cells are also involved. These contribute to cytokine production and eosinophilic airway inflammation[8,9]. Eosinophilic asthma phenotype is associated with increased severity, frequent exacerbations, reduced lung function, and poor asthma control[10,11]. Furthermore, eosinophilic asthma is particularly relevant in children, where allergic sensitization and type 2 inflammation are more common compared with adult-onset asthma[11].
Direct measurement of airway eosinophilia using induced sputum analysis or bronchial biopsy is considered the gold standard for assessment of airway inflammation; however, these methods are invasive, technically demanding, and often impractical in children[10-12]. Blood eosinophil count has emerged as a convenient, minimally invasive surrogate biomarker for airway eosinophilia[13]. Several studies have demonstrated a significant association between blood eosinophilia and airway inflammation, asthma severity, and risk of exacerbations[14,15]. Blood eosinophil count is also increasingly used to guide therapeutic decisions, particularly in identifying patients who may benefit from corticosteroids or biologic therapies targeting eosinophilic pathways[14,15]. In a recent trial including adults with asthma exacerbation, blood eosinophil-guided asthma management safely reduced systemic corticosteroid use in non-eosinophilic exacerbations[16]. In a recent meta-analysis on blood eosinophil count as a marker of asthma exacerbation, of the 23 studies included, only three were pediatric studies, and the other three included children and adults[17]. In addition, no study was from any low-and-middle-income country (LMIC) setting[18-23].
The present study aimed to evaluate the clinical characteristics, asthma severity, and lung function impairment in children with asthma and blood eosinophilia and to identify factors independently associated with eosinophilia.
MATERIALS AND METHODS
Study design and setting
This retrospective cohort study was conducted in the pediatrics department of a tertiary care teaching institute from Eastern India over a three-year period (between March 1, 2017 and February 29, 2020). The study protocol was reviewed and approved by the Institutional Ethics Committee, All India Institute of Medical Sciences, Bhubaneswar (Approval No. T/IM-NF/Paedia/20/179; dated: February 8, 2021). Patient confidentiality was maintained throughout the study. Due to the retrospective nature of the study, the requirement for informed consent was waived.
Study population
Children aged 5-14 years with asthma were eligible for inclusion. A diagnosis of asthma was made as per the Global Initiative for Asthma (GINA) guideline[24]. Only children with complete demographic data, blood eosinophil count, spirometry, and asthma control assessment were included. Serum immunoglobulin E (IgE) measurements were available for a subset of patients and were analyzed separately. Exclusion criteria included the presence of chronic lung diseases (e.g., bronchiectasis, cystic fibrosis, or interstitial lung disease), congenital heart disease, primary or secondary immunodeficiency, parasitic infections, hematological disorders affecting eosinophil counts, and recent use of systemic corticosteroids within 4 weeks prior to evaluation. Patients with incomplete medical records were also excluded.
Definition of blood eosinophilia
Blood eosinophil count was measured as part of a routine complete blood count using an automated hematology analyzer. Blood eosinophilia in asthma has variably been defined as an absolute eosinophil count (AEC) of either ≥ 300 cells/mm3 or ≥ 400 cells/mm3 in children and adults with asthma[13,17-27]. In a developing country like India, where the worm infestations are very common, many healthy children have peripheral blood eosinophilia[28]. Accordingly, we defined asthma with blood eosinophilia taking an AEC cut-off of ≥ 400 cells/mm3. So, patients were categorized into two groups: (1) Asthma with eosinophilia (≥ 400 cells/mm3); and (2) Asthma without eosinophilia (< 400 cells/mm3).
Data collection
A structured data collection form was prepared to extract the data from medical records. The following variables were recorded: Age and sex, anthropometric measurements (height, weight, and body mass index), duration of asthma symptoms, family history of asthma or allergic diseases, presence of allergic comorbidities such as allergic rhinitis, eczema, or food allergy, and history of asthma exacerbations and hospitalizations. Asthma severity was classified according to GINA guidelines into intermittent, mild, moderate, and severe asthma based on symptom frequency, nighttime awakenings, and lung function parameters[24].
Assessment of asthma control
Asthma control was evaluated using the standard asthma control test (ACT)[29]. Standard ACT consists of five questions with scores ranging from 5 to 25. It is used in children aged ≥ 12 years. An ACT score ≥ 20 indicates well-controlled asthma, while a score < 20 indicates poorly controlled asthma. Childhood ACT (cACT) is a validated questionnaire widely used in children aged 4-11 years and uses seven questions to assess asthma control[30]. The score ranges from 0 to 27 with a score ≤ 19 suggesting poorly controlled asthma, and a score ≥ 20 indicating well-controlled asthma.
Spirometry assessment
Spirometry was performed with HELIOS 702 spirometer according to American Thoracic Society and European Respiratory Society guidelines[31]. Children were instructed and supervised by trained technicians to ensure proper technique. The following parameters were recorded: Forced expiratory volume in one second (FEV1), Forced vital capacity (FVC), and FEV1/FVC ratio. Results were expressed as percentages of predicted values based on age, sex, height, and ethnicity. Airflow limitation was defined as reduced FEV1/FVC ratio or FEV1 below the lower limit of normal, consistent with obstructive airway disease[32].
Measurement of serum immunoglobulin E
Serum total IgE levels were measured using enzyme-linked immunosorbent assay or chemiluminescent immunoassay, depending on laboratory availability. Studies of severe asthma frequently use IgE > 100 kIU/L combined with blood AEC level > 300 cells/mm3 to define overlapping allergic-eosinophilic phenotypes. We defined elevated IgE levels using clinically relevant cutoff values (> 100 kIU/L and higher thresholds such as ≥ 300 kIU/L), which have been widely used in previous studies to identify allergic and eosinophilic asthma phenotypes in conjunction with blood AEC[33-38].
Case management
At the time of assessment, all included children were managed as per the GINA guidelines and were receiving inhaled corticosteroid therapy (budesonide) as the primary controller medication[24]. Because the study relied on retrospective records, information regarding adherence to treatment and specific dose adjustments could not be tracked consistently.
Post-hoc sample size adequacy assessment
A total of 176 children were included based on complete availability of key variables. A post hoc adequacy assessment was performed considering the primary comparison between children with and without eosinophilia. Assuming a difference in poor asthma control of 51.2% vs 34.8% between groups, with α = 0.05 and power of 80%, the minimum required sample size was estimated to be approximately 160 participants. Therefore, the final sample size of 176 was considered adequate to detect clinically meaningful differences.
Statistical analysis
Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software version 20.0 (IBM Corp., Armonk, NY, United States). Continuous variables were expressed as mean ± SD or median with interquartile range, depending on data distribution. Categorical variables were presented as frequencies and percentages. Comparisons between the groups were performed using Student’s t-test or Mann-Whitney U test for continuous variables, and χ2 test or Fisher’s exact test for categorical variables, as appropriate. Variables with a P value < 0.1 in univariate analysis were entered into the multivariate logistic regression model to identify factors associated with asthma and blood eosinophilia. Adjusted odds ratios (OR) with 95% confidence intervals (CIs) were calculated. Age was analyzed both as a continuous variable and as a categorical variable (> 8 years vs ≤ 8 years). The threshold of 8 years approximated the median age of the study population and was selected to facilitate clinical interpretation while allowing exploration of potential age-related threshold effects. A P value < 0.05 was considered statistically significant.
RESULTS
Study population and baseline characteristics
A total of 214 medical records were screened during the study period, of which 176 consecutive children aged 5-14 years with asthma fulfilled the eligibility criteria and were included in the analysis (Table 1, Figure 1). Among these, 84 (47.8%) children had blood eosinophilia (AEC ≥ 400 cells/mm3), while 92 (52.2%) did not. The mean (± SD) age of the study population was 8.2 (± 1.1) years and showed a slight male preponderance. Baseline demographic and clinical characteristics were broadly comparable between children with and without eosinophilia (Table 1). There were no significant differences in age, sex distribution, body mass index, duration of asthma symptoms, family history of atopy, or prevalence of allergic comorbidities including allergic rhinitis and atopic dermatitis. Although allergic rhinitis and family history of atopy were numerically more common among children with eosinophilia, these differences did not reach statistical significance. None of the children had received biologic therapy. No substantial differences in baseline demographic or clinical characteristics were observed between the two groups.
Asthma control and severity differed significantly according to blood eosinophilia status (Table 2). Children with asthma and blood eosinophilia demonstrated a significantly higher frequency of poorly controlled asthma (51.2% vs 34.8%) (P = 0.027) as indicated by lower ACT/cACT scores. Similarly, asthma with blood eosinophilia demonstrated a greater severity of asthma with moderate and severe asthma being significantly more common in children with eosinophilia. The odds of severe asthma were four times higher in the eosinophilic group (OR = 4.01; P = 0.02). These findings support the role of blood eosinophilia as a marker of increased disease burden in pediatric asthma.
Table 2 Severity of asthma based on blood eosinophilia, n (%).
Spirometry revealed evidence of greater airflow limitation (obstructive airway impairment) among children with asthma and blood eosinophilia (Table 2). This was suggested by a significantly lower mean FEV1/FVC ratio in the eosinophilic group (65.5 vs 69.7, P = 0.006). Although mean FEV1 values were also lower among children with asthma and eosinophilia, the difference did not achieve statistical significance (P = 0.18). Similarly, FVC values were comparable between the two groups (P = 0.58). Taken together, these findings indicate that asthma with blood eosinophilia is associated primarily with greater airflow obstruction rather than reduced lung volumes.
Serum IgE levels and association with asthma
Serum IgE testing was performed in selected children based on clinician discretion and affordability considerations. Analyses involving serum IgE were therefore performed using available-case data in 93 (52.8%) children. Among those tested, children with asthma and eosinophilia exhibited substantially higher median IgE concentrations (295 vs 98 kIU/L, P < 0.001) (Table 3). Notably, the proportion of children with IgE levels exceeding 300 kIU/L was more than two-fold higher among those with eosinophilia (40% vs 18.6%, P = 0.024). These findings demonstrate a close association between blood eosinophilia and markers of allergic sensitization, further supporting the contribution of type 2 inflammatory pathways in pediatric asthma.
Table 3 Serum total immunoglobulin E level (kIU/L), n (%).
Variables showing associations in univariate analyses, together with clinically relevant covariates, were entered into a multivariate logistic regression model (Table 4). After adjustment, age > 8 years (OR 2.34, P = 0.034), increased serum IgE levels (> 300 kIU/L) (OR 1.98, P = 0.031), poor asthma control (OR 2.15, P = 0.037), and reduced FEV1/FVC ratio (< 70% of predicted) (OR 1.78, P = 0.012) remained independently associated with blood eosinophilia. Among these factors, poor asthma control and older age demonstrated particularly strong associations with eosinophilia.
Table 4 Multivariate analysis of factors for asthma with blood eosinophilia.
This study from a LMIC setting provides critical data on the clinical and functional characteristics of pediatric asthma with blood eosinophilia. Approximately 50% of the patients demonstrated blood eosinophilia, underscoring the high prevalence of a type 2 inflammatory phenotype. The findings of the study highlight significant associations between blood eosinophilia and poor asthma control, increased asthma severity, airflow limitation, and elevated serum IgE, reinforcing the clinical significance of this phenotype.
Defining pediatric asthma with eosinophilia requires careful selection of the blood eosinophil threshold, as no universal standard exists. Studies have reported values ranging from 150 cells/mm3 to 500 cells/mm3. To improve specificity in a helminth-endemic setting where background eosinophilia is common, we utilized an eosinophil cut-off of ≥ 400 cells/mm3. While lowering the cut-off to ≥ 300 cells/mm3 increases sensitivity for type 2 inflammation, it also increases the risk of misclassification due to repeated parasitic infections. Our cut-off aligns with previous pediatric studies as well as reference data from a healthy Indian population (median: 4%; interquartile range: 3%-6%)[28]. Given that optimal cut-offs vary according to geographic and epidemiological context, future studies evaluating eosinophil counts as continuous variables are essential to enhance risk stratification and improve pediatric asthma phenotyping.
A key finding of this study is the significant association between blood eosinophilia and poor asthma control. Children with eosinophilia were more likely to have lower ACT scores indicating poorly controlled asthma. This observation is consistent with previous adults and pediatric studies demonstrating that eosinophilic inflammation may contribute to persistent airway inflammation and increased bronchial hyperresponsiveness, leading to suboptimal disease control[12,13,18-23,25-27]. In a randomized controlled trial (n = 170) including children aged 1 year to 5 years from the United States, the daily inhaled corticosteroid use was associated with more asthma control days and fewer exacerbations compared with the other treatments in children with both aeroallergen sensitization and blood eosinophil counts of ≥ 300/μL[27]. In a retrospective study including 589 children from the United States, elevated blood eosinophils were associated with increased odds and shorter time to first acute visit[16]. In a large retrospective cohort study including 376 children aged 5-12 years from the United Kingdom, an eosinophil count of > 400/μL was associated with an increase in odds of an asthma attack[20].
Additionally, eosinophilia was significantly associated with moderate and severe asthma. Children with eosinophilia had nearly a two-fold higher odds of moderate asthma and a four-fold higher odds of severe asthma. This is consistent with previous studies suggesting that eosinophilic inflammation is linked to more severe disease phenotypes[11,18-21,23]. In a large database analysis of 3162 patients (children = 54%) from the United States, higher blood eosinophil levels were associated with increased asthma severity and healthcare utilization in children but not in adults[22]. Other pediatric studies have also shown that eosinophilic asthma is often characterized by frequent exacerbations and an increased need for controller therapy[18-20,27]. These findings suggest that peripheral eosinophilia may serve as a useful marker for identifying children at risk of more severe disease.
Another key finding is the marked decline in the FEV1/FVC ratio in children with eosinophilia, which points to more severe airflow limitation. This is consistent with the known pathophysiological effects of eosinophilic inflammation, which include airway remodeling, epithelial damage, and mucus hypersecretion. Previous studies have demonstrated that eosinophilic airway inflammation is associated with structural airway changes and persistent airflow obstruction[39,40].
The association between elevated serum IgE levels and eosinophilia observed in this study further supports the role of type 2 inflammation in pediatric asthma. Children with eosinophilia had significantly higher median IgE levels and a greater proportion exceeding clinically relevant thresholds (> 300 kIU/L). This finding agrees with previous studies demonstrating a strong relationship between IgE-mediated allergic sensitization and eosinophilic inflammation. In a retrospective study including 227 children aged 3-17 years from the United States, 57% had an IgE level of > 200 IU/mL, and 33% had an IgE level of > 500 IU/mL. An elevated baseline IgE level was correlated with higher asthma symptom severity with increased hospitalization[37]. In a retrospective cohort study including 313 children aged 2-18 years from the United States, elevated baseline IgE level was correlated with higher asthma symptom severity when hospitalized and with longer hospital stay[38]. The interplay between IgE and eosinophils is well established in the Th2 inflammatory pathway, where cytokines such as interleukin-4 and interleukin-13 promote IgE production, while interleukin-5 drives eosinophil proliferation and survival.
A notable finding of this study is the role of age as an independent predictor of eosinophilia when analyzed categorically. Although age as a continuous variable did not differ significantly between groups, children older than 8 years had higher odds of eosinophilia in the multivariate analysis. Consistent with earlier findings, the prevalence of atopy and eosinophilic inflammation appears to increase throughout childhood, potentially driven by cumulative environmental factors[41]. The association between eosinophilia and age > 8 years likely illustrates age-dependent increases in atopic sensitization and type 2 inflammatory pathways, which result from immune system maturation and cumulative environmental exposures. Nonetheless, this finding should be interpreted cautiously, given that the age cut-off was chosen primarily for clinical and analytical clarity.
The identification of independent factors like elevated IgE, poor asthma control, and reduced FEV1/FVC ratio underscores the multifactorial nature of asthma with blood eosinophilia. Consequently, integrating clinical, functional, and laboratory data may enhance the diagnostic accuracy of this phenotype in clinical practice. In resource-limited settings, where advanced diagnostic tools such as sputum eosinophil analysis and fractional exhaled nitric oxide (FeNO) are not readily available, the peripheral blood eosinophil count offers a simple and cost-effective alternative. Its integration into routine clinical assessment may facilitate early identification of high-risk patients and guide personalized treatment strategies.
Unlike previous pediatric studies from high-income countries, our study provides data from a helminth-endemic LMIC setting and evaluates a clinically pragmatic eosinophil threshold (≥ 400 cells/mm3), potentially improving identification of high-risk children in similar environments. However, certain limitations must be acknowledged. The retrospective design limits causal inference and may introduce selection bias. Selection bias may have occurred because only children with complete datasets were included. The single-center design limits external validity. The study defined eosinophilia using a single threshold of ≥ 400 cells/mm3. Consequently, the present findings may not be directly comparable with studies employing lower eosinophil cut-offs. Serum IgE measurements were unavailable in nearly half of participants, because testing was performed based on clinical indication and affordability constraints. This may have introduced selection bias and limited the precision of IgE-related analyses. While all children were prescribed inhaled budesonide therapy, details were missing on their exact dose, duration, and compliance. This precluded a comprehensive evaluation of how varying levels of corticosteroid exposure impact asthma outcomes and eosinophil counts. Age-stratified analysis (young vs old) was not conducted due to limited statistical power. Additionally, lack of FeNO, sputum eosinophils, medication adherence data, and longitudinal outcomes limited comprehensive phenotyping.
Future research should focus on prospective studies evaluating the role of blood eosinophilia in predicting clinical outcomes and response to targeted therapies in pediatric asthma. The integration of blood eosinophil count with other biomarkers, such as FeNO and periostin, may further enhance phenotypic characterization. Moreover, the role of biologic therapies targeting eosinophilic pathways in children from resource-limited settings warrants further exploration.
CONCLUSION
In this retrospective cohort study, blood eosinophilia (AEC ≥ 400 cells/mm3) was significantly associated with poor asthma control, greater disease severity, increased airflow limitation, and elevated serum IgE levels in childhood asthma with blood eosinophilia. Importantly, our study provides evidence from a helminth-endemic LMIC population, where interpretation of peripheral eosinophil counts may differ from that in high-income settings. The use of a pragmatic eosinophil threshold of ≥ 400 cells/mm3 may improve identification of children at increased risk of uncontrolled and more severe disease in such environments. Importantly, peripheral blood eosinophil count is an inexpensive, widely available, and minimally invasive biomarker that may aid risk stratification and individualized management, particularly in resource-limited settings where advanced inflammatory biomarkers are not readily available. Prospective multicenter studies are needed to validate these findings.
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