Role of IgE cells in the exacerbation and management of asthma: An experimental study

Abstract

BACKGROUND

IgE plays a critical role in allergic inflammation and asthma pathogenesis. This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.

AIM

To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes. Specifically, the study investigates changes in serum IgE levels, lung function, asthma control scores, and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.

METHODS

A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025. Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents. IgE levels and asthma control parameters were monitored.

RESULTS

Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels (P < 0.001), improved Forced expiratory volume in one second scores, and fewer exacerbation episodes compared to the control group.

CONCLUSION

IgE cells significantly contribute to asthma severity, and targeted therapy against IgE can improve disease outcomes. These findings underscore the importance of immunomodulatory strategies in asthma management.

Key Words: Asthma; IgE; Allergic inflammation; Anti-IgE therapy; Experimental study

Core Tip: Asthma is a chronic respiratory disease driven in part by immune mechanisms involving IgE. This experimental study highlights the significant role of IgE in asthma exacerbation and demonstrates that anti-IgE therapy—specifically with omalizumab—can markedly reduce IgE levels, improve lung function, enhance asthma control, and decrease the frequency of exacerbations. These findings emphasize the clinical value of incorporating immunomodulatory strategies, particularly targeted anti-IgE interventions, into the treatment of moderate to severe allergic asthma.

INTRODUCTION

Asthma is a multifactorial chronic respiratory condition affecting more than 300 million individuals globally, characterized by recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning hours[1]. It is marked by airway inflammation, bronchial hyperresponsiveness, mucus hypersecretion, and reversible airflow limitation. The immunopathogenesis of asthma involves complex interactions between structural cells of the airway and immune cells, including mast cells, eosinophils, T-helper 2 (Th2) lymphocytes, and dendritic cells[2].

Among the immune mediators, IgE plays a central role in allergic asthma, the most prevalent asthma phenotype. IgE is produced in response to allergens and subsequently binds to its specific high-affinity receptor, the high-affinity IgE receptor, located on the surface of mast cells and basophils, leading to the release of pro-inflammatory mediators such as histamine, leukotrienes, and prostaglandins upon allergen re-exposure[3]. This IgE-mediated degranulation not only triggers acute bronchoconstriction but also contributes to chronic inflammation and airway remodeling over time[4]. Numerous studies have demonstrated that elevated serum IgE levels are strongly correlated with disease severity, frequency of exacerbations, and reduced pulmonary function[5].

Given the central role of IgE in allergic asthma, recent immunological advances have focused on targeting IgE as a therapeutic strategy. Monoclonal antibodies that neutralize circulating IgE or block its receptor interactions have emerged as effective tools in asthma management. Omalizumab, the first biologic agent approved for asthma, binds to free IgE and prevents its interaction with the high-affinity IgE receptor, thereby reducing receptor expression and subsequent cell activation[6]. Clinical trials have shown that omalizumab significantly reduces asthma exacerbations, improves quality of life, and decreases the need for inhaled corticosteroids in patients with moderate to severe allergic asthma[7,8].

Despite these advancements, challenges remain. The precise molecular mechanisms by which IgE contributes to chronic inflammation and airway remodeling are still being elucidated[9]. Furthermore, not all patients respond equally to anti-IgE therapy, and the identification of biomarkers predicting therapeutic response remains an active area of research[10]. In addition, the cost and accessibility of biologic therapies pose practical limitations in many healthcare settings[11].

Therefore, further investigation into the immunological role of IgE and the clinical efficacy of anti-IgE interventions is warranted. This study aims to evaluate the contribution of IgE cells to asthma pathogenesis and determine the impact of anti-IgE therapy on disease outcomes. By exploring these aspects, the study seeks to provide insights into the broader applicability of immunomodulatory treatments in managing asthma and potentially reducing the long-term disease burden.

MATERIALS AND METHODS

Study design

This study was designed as a prospective, randomized experimental trial conducted over a 12-month period from April 2024 to April 2025. The research was carried out at a tertiary healthcare facility with specialized asthma clinics and pulmonology units. All procedures were conducted in accordance with the Declaration of Helsinki. Ethical approval for the study protocol was obtained from the Health Research Ethics Committee of Poltekkes Kemenkes Makassar (Approval No. EC/2785/2024). Written informed consent was obtained from all participants prior to enrollment.

Participants

A total of 200 individuals with physician-diagnosed asthma were recruited through outpatient screening. Inclusion criteria were: Age between 18 and 60 years, diagnosis of moderate to severe persistent asthma based on Global Initiative for Asthma (GINA) 2023 guidelines, and evidence of elevated serum IgE levels (> 100 IU/mL). Exclusion criteria included non-allergic asthma phenotypes, current pregnancy or lactation, concurrent autoimmune disorders, recent respiratory tract infections, and prior treatment with biologics or immunotherapy within the past 6 months. A detailed medical history, physical examination, and baseline spirometry were performed prior to randomization.

Randomization and intervention

Participants were randomly allocated using a computer-generated block randomization scheme into two equal groups (n = 100 each). Group A served as the control group and received standard asthma therapy comprising inhaled corticosteroids and long-acting β2-agonists adjusted according to GINA stepwise treatment. Group B, the intervention arm, received standard therapy along with subcutaneous omalizumab (anti-IgE monoclonal antibody), administered bi-weekly at a dosage determined by baseline IgE level and body weight in accordance with manufacturer guidelines[12]. Treatment adherence was monitored at every visit using patient self-reports and pharmacy refill records.

Data collection and monitoring

Clinical assessments were performed at baseline and every three months for 12 months. Key outcome measures included:

Serum IgE levels: Quantified using enzyme-linked immunosorbent assay.

Lung function: Assessed using spirometry [forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio] following American Thoracic Society/European Respiratory Society guidelines[13].

Asthma control: Measured using the validated asthma control test (ACT), with a score ≥ 20 indicating well-controlled asthma.

Exacerbations: Defined as worsening of symptoms requiring systemic corticosteroids, unscheduled clinic visits, or hospitalization. All assessments were conducted by trained clinicians blinded to group allocation.

Statistical analysis

Data were analyzed using SPSS version 26 (IBM Corp., Armonk, NY, United States). Continuous variables were presented as means ± SD, while categorical variables were expressed as frequencies and percentages. Within-group differences were assessed using paired t-tests, and between-group comparisons were performed using independent t-tests and ANOVA, as appropriate. A P-value of < 0.05 was considered statistically significant. Missing data were handled using multiple imputation techniques. Subgroup analysis was also performed to assess response variations based on age, baseline IgE levels, and disease duration. Effect sizes were reported with 95%CI. Sensitivity analysis was conducted to test the robustness of the findings.

RESULTS

Participant flow and baseline characteristics

Of the 230 patients screened, 200 met the eligibility criteria and were randomized into Group A (standard therapy) and Group B (standard therapy plus anti-IgE treatment). There were no significant differences in age, sex distribution, asthma duration, or baseline lung function between the two groups, indicating successful randomization and homogeneity of study populations (Table 1).

Table 1 Baseline characteristics of participants, n (%)/mean ± SD.

Characteristic	Group A (n = 100)	Group B (n = 100)	P value
Age (years)	39.6 ± 12.4	38.9 ± 11.8	0.74
Female	58 (58)	55 (55)	0.68
Duration of asthma (years)	7.1 ± 4.3	7.3 ± 4.0	0.81
Baseline IgE (IU/mL)	239.1 ± 49.7	240.6 ± 52.1	0.89
FEV1 (L)	1.91 ± 0.52	1.93 ± 0.49	0.84
ACT score	14.3 ± 2.6	14.2 ± 2.4	0.92

FEV1: Forced expiratory volume in one second; ACT: Asthma control test.

Changes in immunologic and clinical parameters

After 12 months of treatment, Group B exhibited substantial improvements in multiple clinical outcomes compared to Group A. The mean serum IgE levels in Group B decreased by 40% from baseline (240 IU/mL to 144 IU/mL; P < 0.001), while no statistically significant change was noted in Group A (P = 0.12). This reduction in circulating IgE was associated with better asthma control, consistent with previous studies emphasizing the role of IgE in allergic inflammation[14].

Lung function, as measured by FEV1, showed a 25% improvement in Group B (mean increase from 1.9 L to 2.4 L) vs a 10% increase in Group A (1.9 L to 2.1 L; P = 0.003). Improvement in FEV1 suggests enhanced airway patency resulting from decreased airway inflammation and remodeling, aligning with the established effects of omalizumab on airway physiology[15].

ACT scores increased by 6 points in Group B (from a mean of 14 to 20) and by 3 points in Group A (from 14 to 17). ACT scores of ≥ 20 denote well-controlled asthma; thus, more patients in Group B reached optimal disease control compared to those on standard therapy alone[16].

The frequency of acute exacerbations requiring systemic corticosteroids, emergency department visits, or hospitalization decreased by 65% in Group B, significantly greater than the 28% reduction observed in Group A (P = 0.001). This finding aligns with prior research demonstrating the efficacy of anti-IgE agents in reducing asthma morbidity[17]. In addition, specific data on adverse reactions were collected to assess treatment safety. Mild injection-site reactions occurred in 8% of Group B patients, and transient headache in 5%, with no serious adverse events reported. Group A reported no adverse drug-related effects. These findings support a favorable safety profile for anti-IgE therapy.

Table 1 presents the baseline demographic and clinical characteristics of participants in both study groups prior to the initiation of treatment. The objective of this table is to demonstrate the comparability between Group A (standard therapy) and Group B (anti-IgE therapy + standard therapy), thereby confirming the effectiveness of the randomization process.

The mean age of participants in Group A was 39.6 years (± 12.4), while in Group B it was 38.9 years (± 11.8), with no statistically significant difference (P = 0.74). Similarly, the gender distribution was nearly identical, with 58% females in Group A and 55% in Group B (P = 0.68), indicating a balanced representation of sexes in both groups.

Regarding disease profile, the mean duration of asthma was 7.1 years (± 4.3) in Group A and 7.3 years (± 4.0) in Group B (P = 0.81), suggesting that participants had comparable experience living with the disease.

The baseline serum IgE levels, a critical inclusion criterion, were similar between the two groups (239.1 IU/mL in Group A vs 240.6 IU/mL in Group B; P = 0.89), supporting the homogeneity of immunological status at the outset of the study.

Lung function, assessed by FEV1, showed comparable baseline values (1.91 L vs 1.93 L; P = 0.84), indicating that both groups had similar respiratory impairment at enrollment. Finally, asthma control, as measured by the ACT, showed nearly identical scores (14.3 vs 14.2; P = 0.92), further confirming the lack of any significant baseline differences.

Table 2 presents the comparative outcomes between the two study groups—Group A (standard therapy) and Group B (anti-IgE therapy combined with standard therapy)—after 12 months of treatment. The data highlight significant differences in the clinical and immunologic responses between both groups.

Table 2 Changes in key outcomes after 12 months.

Outcome	Group A (standard therapy)	Group B (Anti-IgE + Standard)	P value
IgE reduction (%)	4.5	40.0	< 0.001
FEV1 improvement (%)	10.2	25.1	0.003
ACT score increase (points)	+3	+6	0.004
Exacerbation frequency change	-28	-65	0.001

FEV1: Forced expiratory volume in one second; ACT: Asthma control test.

IgE reduction: Group B demonstrated a 40% reduction in serum IgE levels, compared to only a 4.5% reduction in Group A. This substantial decline in Group B indicates that the addition of anti-IgE therapy (omalizumab) effectively neutralizes circulating IgE, which is a critical step in disrupting the allergic cascade that contributes to asthma severity. The difference was statistically significant (P < 0.001).

FEV1 improvement: FEV1—a key indicator of lung function—improved by 25.1% in Group B, compared to 10.2% in Group A. This suggests that anti-IgE therapy contributes to enhanced airway function and reduced bronchial obstruction. The between-group difference in FEV1 improvement was statistically significant (P = 0.003), supporting the superior efficacy of the combination treatment.

ACT score increase (points): The ACT scores increased by an average of 6 points in Group B, compared to a 3-point increase in Group A. An ACT score improvement of 3 or more points is considered clinically meaningful, and the greater improvement in Group B reflects better overall asthma control. The difference was statistically significant (P = 0.004).

Exacerbation frequency change: Group B experienced a 65% reduction in the frequency of acute asthma exacerbations, while Group A showed a 28% reduction. This indicates that anti-IgE therapy not only improves day-to-day asthma control but also significantly reduces severe episodes requiring urgent medical attention. The difference between groups was highly significant (P = 0.001).

These data confirm that the addition of anti-IgE therapy to standard asthma management provides clinically and statistically significant benefits across multiple domains. The reduction in serum IgE levels appears to be a critical mechanism underlying these improvements. Previous studies have also supported the correlation between lowered IgE levels and decreased Th2-driven airway inflammation[18].

DISCUSSION

This study supports the pivotal role of IgE in the immunopathogenesis of asthma and reinforces the therapeutic potential of anti-IgE interventions in disease management. The observed improvement in pulmonary function (FEV1), reduction in serum IgE levels, enhanced asthma control scores (ACT), and significant decrease in exacerbation rates collectively affirm the immunologic and clinical impact of targeted IgE suppression. These outcomes align with earlier findings demonstrating that neutralizing IgE can attenuate allergic inflammation and improve patient outcomes in moderate to severe asthma[19].

Mechanistically, IgE contributes to asthma by sensitizing mast cells and basophils, triggering degranulation upon allergen exposure, and amplifying the release of histamines, prostaglandins, and leukotrienes. Furthermore, IgE promotes the recruitment and survival of eosinophils and activates dendritic cells, thus sustaining a chronic Th2-mediated inflammatory environment in the airways[20]. This network of cellular interactions not only contributes to bronchial hyperresponsiveness and mucus hypersecretion but also fosters airway remodeling—a hallmark of persistent asthma. Anti-IgE therapies such as omalizumab interrupt this cascade by binding to free IgE, preventing its attachment to the high-affinity IgE receptors, and downregulating receptor expression on effector cells[21].

The immunologic benefits of anti-IgE therapy extend beyond IgE neutralization. Recent findings suggest that omalizumab may also suppress the expression of pro-inflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-13, which are central to the perpetuation of eosinophilic inflammation[22]. In a controlled study published in the World Journal of Immunology, treatment with omalizumab significantly reduced biomarkers associated with airway remodeling, including periostin and matrix metalloproteinases, suggesting a potential role in preventing long-term structural damage in the lungs[23]. These effects could explain the sustained improvements in FEV1 and reduction in exacerbation frequency observed in this study.

However, despite these promising results, several limitations to anti-IgE therapy remain. One major concern is the high cost of biologics, which may limit access in low- and middle-income countries. Additionally, response to therapy varies significantly among individuals, and its efficacy appears to be limited in patients with non-atopic or intrinsic asthma phenotypes[24]. This underscores the importance of precise phenotyping and biomarker identification before initiating treatment.

To overcome such limitations, ongoing research has shifted toward combination biologic therapies. Dual-target strategies that simultaneously inhibit IgE and IL-5 or the IL-4 receptor alpha pathway have demonstrated synergistic benefits in refractory asthma patients[25]. These biologics aim to address both upstream IgE sensitization and downstream eosinophilic inflammation, offering broader control over complex inflammatory pathways. Furthermore, advances in genomic and proteomic profiling may soon enable the personalization of asthma treatment based on individual immunological signatures[26].

This study contributes to the growing body of evidence supporting the role of IgE in allergic asthma and the clinical utility of anti-IgE monoclonal antibodies. While current therapies offer substantial benefits for many patients, the development of more cost-effective and personalized strategies remains a critical direction for future research and clinical practice.

CONCLUSION

IgE plays a central and critical role in the pathogenesis and exacerbation of allergic asthma. By facilitating the activation of mast cells, basophils, and other inflammatory mediators, IgE contributes to airway hyperresponsiveness, chronic inflammation, and structural remodeling—key features associated with disease progression and poor clinical outcomes. The findings of this study reinforce the pathogenic relevance of IgE by demonstrating that targeted anti-IgE therapy leads to substantial improvements in multiple clinical parameters, including lung function (FEV1), asthma control, and a marked reduction in the frequency of exacerbations.

The therapeutic use of monoclonal antibodies against IgE, such as omalizumab, offers a precise and effective strategy for interrupting the allergic cascade at its origin. Patients receiving anti-IgE therapy experienced better symptom relief, improved spirometric performance, and fewer acute episodes requiring hospitalization or emergency intervention compared to those receiving standard treatment alone. These results highlight the substantial clinical benefits of immunomodulation in managing moderate to severe allergic asthma.

Given its ability to address both the immunological and physiological components of the disease, IgE-targeted intervention should be integrated as a core element of asthma management, particularly for patients with an allergic phenotype. Future asthma treatment protocols should prioritize individualized, biomarker-driven approaches that incorporate immunomodulatory agents alongside standard therapies to achieve optimal and sustained disease control.

ACKNOWLEDGEMENTS

The author acknowledges the support of the research team at Poltekkes Kemenkes Makassar and the participating patients.