European Journal of Cardiovascular Medicine

Overview of Allergic Rhinitis

Allergic rhinitis is a long-standing inflammatory condition affecting the nasal passages and surrounding structures. It commonly presents with repetitive sneezing, nasal irritation, watery nasal discharge, and blockage of the nasal airway. The condition develops as a hypersensitivity response to airborne substances and can occur across all age groups. Although frequently regarded as a mild disorder, it has a notable impact on daily functioning, sleep quality, occupational efficiency, and academic activities. It is also frequently observed alongside other hypersensitivity-related conditions, including bronchial asthma, ocular allergies, and chronic skin inflammation [1].

Epidemiological data indicate a steady increase in the frequency of this condition over recent years, particularly in low- and middle-income regions. Contributing factors include rapid urban expansion, rising levels of air contaminants, altered living habits, and greater exposure to environmental triggers. In the Indian context, allergic rhinitis constitutes a significant public health issue, with many individuals remaining undiagnosed or receiving suboptimal management. The persistent nature of symptoms and recurrent exacerbations place a substantial strain on both healthcare services and affected individuals [2].

From a mechanistic standpoint, the disorder arises from the interaction between inherited susceptibility and external exposures. Contact with triggering substances leads to immune sensitization and subsequent activation of inflammatory pathways. This process involves immune cells that release biologically active substances responsible for vascular changes, mucus secretion, and tissue irritation. These mechanisms collectively contribute to the immediate and delayed responses that account for the characteristic clinical features of the condition [3].

Role of Immunoglobulin E in Allergic Rhinitis

Immunoglobulin E is central to the development and progression of allergic nasal inflammation. Following exposure to sensitizing agents, immune cells produce this antibody, which attaches to specific receptors located on effector cells within the nasal mucosa. Subsequent encounters with the same triggering agents result in antibody cross-linking, initiating cellular activation and the discharge of inflammatory substances. These mediators are responsible for mucosal swelling, irritation, and the onset of characteristic symptoms.

Elevated circulating levels of immunoglobulin E are commonly detected in individuals with allergic nasal disorders and are often used as an adjunctive laboratory indicator in clinical evaluation. Higher concentrations are generally associated with increased symptom burden and prolonged disease activity, although the extent of elevation can vary based on genetic background, environmental exposure, and the presence of concurrent allergic conditions [4]. Despite its importance, immunoglobulin E alone does not fully account for the variability observed in disease presentation or severity. This has encouraged exploration into additional regulatory influences, including nutritional and micronutrient-related factors that may modify immune responses and inflammatory activity.

Vitamin D and Immune Regulation

Vitamin D, long recognized for its involvement in skeletal health and mineral balance, has increasingly been recognized for its influence on immune system activity. Receptors for this nutrient are present on a wide range of immune-related cells, including various lymphocyte subsets, antigen-presenting cells, and phagocytic cells. Through receptor-mediated mechanisms, vitamin D participates in regulating both innate defense mechanisms and antigen-specific immune responses [5].

Insufficient vitamin D status has been linked to a higher likelihood of infectious conditions, immune-mediated disorders, and allergic manifestations. Several investigations suggest that reduced circulating vitamin D concentrations may amplify allergic inflammatory responses by facilitating immunoglobulin E–driven immune activity [6].

In the context of allergic rhinitis, inadequate vitamin D status may intensify inflammation of the nasal lining and worsen symptom burden due to impaired immune modulation. However, published findings on the association between vitamin D status and allergic rhinitis remain inconsistent, with some studies demonstrating an inverse relationship while others report minimal or no association. Such variability may stem from differences in study design, population characteristics, environmental exposure, dietary patterns, and methodological approaches [7].

Rationale for the Present Study

Both allergic rhinitis and suboptimal vitamin D status are widely observed within the Indian population, even in areas receiving substantial sunlight. Contributing factors include indoor-centered lifestyles, limited exposure to sunlight, skin pigmentation, and inadequate dietary intake, all of which promote low vitamin D levels. Despite this overlap, data exploring the link between vitamin D concentration, immunoglobulin E levels, and allergic rhinitis are limited, particularly in certain geographic regions of the country.

Clarifying the relationship between vitamin D status and immunoglobulin E–mediated immune responses may improve understanding of disease mechanisms and inform adjunctive management strategies. Comparing these parameters between individuals with allergic rhinitis and unaffected controls may help determine whether reduced vitamin D status is associated with elevated immunoglobulin E levels and increased allergic susceptibility. This hospital-based case–control investigation was carried out at Tripura Medical College and Dr. B.R.A.M. Teaching Hospital, Agartala.

Study Design and Setting

A hospital-based observational case–control study was conducted in the the Department of Biochemistry in collaboration with the Department of Otorhinolaryngology in Tripura Medical College & DR. BRAM Teaching Hospital,  Patients attending the outpatient department  of Otorhinolaryngology with symptoms suggestive of allergic rhinitis were screened and evaluated clinically. The diagnosis of allergic rhinitis was established based on a detailed clinical history and physical examination, with characteristic symptoms including sneezing, nasal itching, rhinorrhea, and nasal obstruction. The control group consisted of healthy volunteers and hospital staff without any history of allergic rhinitis or other atopic diseases.

Study Duration :The study was conducted for a period of six-month period (w.e.f 29.04.2025-28.10.2025)

Sample Size : The study included 100 participants, comprising 50 individuals with a confirmed diagnosis of allergic rhinitis (cases) and 50 healthy participants matched for age and sex (control).

Ethical approval : Ethical clearance was approved by The Institutional Ethics Committee, Tripura Medical College & Dr. BRAM Reaching Hospital with Ref. Sl. IEC/SFTMC/2025/1/001.

Inclusion and Exclusion Criteria

Inclusion criteria (Cases): Adults aged 18–60 years with a clinical diagnosis of allergic rhinitis based on history and physical examination were included. Only patients with active symptoms at the time of assessment and without any recent history of acute upper respiratory tract infection were enrolled.

Inclusion criteria (Controls): Age- and sex-matched healthy individuals without a history of allergic rhinitis, asthma, eczema, or other atopic conditions were included as controls.

Exclusion criteria (Both groups): Participants were excluded if they had bronchial asthma, chronic sinusitis, nasal polyposis, autoimmune disorders, or any chronic inflammatory or infectious disease. Individuals who had received systemic corticosteroids, antihistamines, immunotherapy, or vitamin D supplementation within the preceding four weeks were excluded due to their potential influence on serum IgE and vitamin D levels. Pregnant women, individuals with chronic medical illnesses affecting immune function or vitamin D metabolism, and those unwilling to participate were also excluded. All participants underwent a thorough general and systemic examination and provided informed consent prior to enrollment.

Sample Collection and Laboratory Analysis

Under standard aseptic precautions, approximately 5 mL of venous blood was collected from each participant into plain collection tubes. The samples were allowed to clot and were subsequently centrifuged to separate serum. The separated serum was stored under appropriate conditions until biochemical analysis.

Serum 25-hydroxy vitamin D levels were estimated using a chemiluminescent immunoassay (CLIA) method on CL-900i(mindray) Analyzer, in  Department of Biochemistry at Tripura Medical college . The assay is based on a competitive immunoassay principle, where serum 25-hydroxy vitamin D competes with labeled vitamin D for binding to specific antibodies, and the emitted chemiluminescent signal is inversely proportional to the vitamin D concentration in the sample.

Serum immunoglobulin E (IgE) levels were measured using nephelometry in mispa i3 analyzer, in Department of Biochemistry at Tripura Medical College.This method is based on antigen–antibody reactions, where immune complexes formed between IgE and specific antibodies cause light scattering proportional to the IgE concentration in the serum. Serum vitamin D levels were categorized as deficient (<20 ng/mL), insufficient (20–30 ng/mL), or sufficient (>30 ng/mL). Serum IgE levels were interpreted using age-specific laboratory reference ranges, and values exceeding the upper limit of normal were considered elevated.

Outcome Measures

The primary outcome measures were serum 25-hydroxy vitamin D levels and serum immunoglobulin E concentrations in patients with allergic rhinitis and healthy controls. Secondary analysis included comparison of these biochemical parameters between the two groups and assessment of the relationship between vitamin D status and IgE levels within the allergic rhinitis group. All data were recorded using structured data collection forms and entered into a secured database, ensuring participant confidentiality throughout the study.

Statistical Analysis

Statistical analysis was performed using appropriate statistical software. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Comparison of serum vitamin D and IgE levels between cases and controls was carried out using appropriate statistical tests based on data distribution. Correlation analysis was performed to assess the relationship between serum vitamin D levels and serum IgE concentrations among patients with allergic rhinitis. A p-value < 0.05 was considered statistically significant.

A total of 100 individuals participated in the study, including 50 participants diagnosed with allergic rhinitis who formed the case group and 50 participants without any documented allergic condition who served as controls. All recruited participants completed the study procedures, and none were excluded during the analysis phase. Baseline demographic variables were comparable between the two groups, with no meaningful differences observed in age or sex distribution.

Demographic Characteristics

Baseline demographic factors were similar between the two research groups. The control group was 33.9 ± 8.7 years old, whereas the average age of patients with allergic rhinitis was 34.6 ± 9.2 years. In both groups, there was a slight male majority: 56% (n = 28) of the cases and 54% (n = 27) of the controls were men. The fact that the age and sex distribution of the patients and controls did not differ statistically significantly (p > 0.05) suggests that the research groups were adequately matched.

Table 1: Demographic characteristics of study participants

Serum Vitamin D Levels

Serum 25-hydroxy vitamin D levels were substantially lower in allergic rhinitis patients than in healthy controls. The control group's mean serum vitamin D level was 24.9 ± 7.1 ng/mL, while the case group's was 18.2 ± 6.4 ng/mL. It was discovered that this difference was statistically significant (p < 0.001). When vitamin D status was categorized, a greater proportion of patients with allergic rhinitis fell into the insufficient and inadequate ranges, while more controls had appropriate levels. This distribution indicates a significant trend toward hypovitaminosis D in individuals with allergic rhinitis.

Figure 1: Comparison of mean serum 25-hydroxy vitamin D levels between allergic rhinitis patients and healthy controls.

Serum Immunoglobulin E Levels

Patients with allergic rhinitis had significantly higher serum levels of immunoglobulin E (IgE) than controls. The control group's mean serum IgE concentration was 126.4 ± 64.2 IU/mL, whereas the patients' mean was 412.6 ± 138.5 IU/mL. This difference was statistically significant (p < 0.001). Since allergic rhinitis is an atopic condition, several patients exhibited IgE levels that were greater than the age-specific laboratory reference range. Conversely, most controls had IgE levels that were within normal ranges, with only sporadic little increases.

Figure 2: Comparison of mean serum immunoglobulin E (IgE) levels between allergic rhinitis patients and controls.

Comparison of Biochemical Parameters Between Cases and Controls

A study of biochemical features found that patients with allergic rhinitis had higher serum IgE concentrations and lower serum vitamin D levels than healthy people. The two groups differed statistically significantly according to both metrics.

Table 2: Comparison of serum vitamin D and IgE levels between cases and controls

Figure 3: Scatter plot showing the inverse relationship between serum vitamin D and serum IgE levels among allergic rhinitis patients.

Relationship Between Serum Vitamin D and IgE Levels

Serum vitamin D and serum IgE levels were negatively correlated in patients with allergic rhinitis. Higher IgE levels were frequently linked to lower vitamin D concentrations, indicating a possible connection between vitamin D insufficiency and an increased IgE-mediated immunological response. There was a statistically significant correlation discovered. In the control group, where both metrics mostly stayed within normal ranges, no such correlation was seen.

Safety Observations

Since this was observational research with routine blood sample collection, no procedure-related adverse events were recorded. Every participant tolerated the blood sample well, and neither immediate nor long-term issues were observed.

Allergic rhinitis is a chronic inflammatory disorder of the upper airway characterized by immunoglobulin E–mediated hypersensitivity responses to environmental allergens. In the present case–control study, serum 25-hydroxyvitamin D and immunoglobulin E levels were evaluated in patients with allergic rhinitis and compared with healthy controls. The findings demonstrated significantly elevated serum IgE levels and significantly reduced serum vitamin D concentrations in allergic rhinitis patients compared to controls. Additionally, an inverse relationship between serum vitamin D and IgE levels was observed among affected individuals, suggesting a potential immunomodulatory role of vitamin D in the pathophysiology of allergic rhinitis.

Elevated IgE Levels in Allergic Rhinitis

The significantly higher serum IgE levels observed in patients with allergic rhinitis in this study are consistent with the established immunopathogenesis of the disease. Allergic rhinitis develops following allergen sensitization and subsequent activation of a Th2-dominant immune response, leading to increased production of IgE by B lymphocytes. IgE binds to high-affinity FcεRI receptors on mast cells and basophils, and upon re-exposure to the allergen, cross-linking of IgE results in degranulation and release of inflammatory mediators such as histamine, leukotrienes, and cytokines. These mediators are responsible for the hallmark symptoms of allergic rhinitis, including sneezing, rhinorrhea, nasal obstruction, and itching.

The present findings are in agreement with previous studies that have consistently demonstrated elevated serum IgE levels in patients with allergic rhinitis. Ciprandi et al. reported a positive association between serum IgE levels and disease persistence in allergic rhinitis, highlighting IgE as a marker of ongoing allergic inflammation [8]. Similarly, Erkan et al. observed significantly higher IgE concentrations in allergic rhinitis patients compared to non-allergic controls, reinforcing the role of IgE as a key mediator in disease expression [9]. Large-scale reviews and consensus documents, including those by Bousquet et al. and Pawankar et al., also emphasize IgE-mediated immune mechanisms as central to allergic rhinitis pathophysiology [1,2]. The consistently elevated IgE levels observed across studies support its relevance as a supportive laboratory marker in allergic rhinitis.

Vitamin D Deficiency and Allergic Rhinitis

In the present study, patients with allergic rhinitis exhibited significantly lower serum vitamin D levels compared to healthy controls. This finding is particularly relevant in the Indian context, where vitamin D deficiency is highly prevalent despite abundant sunlight. Factors such as limited sun exposure due to indoor lifestyles, air pollution, skin pigmentation, clothing practices, and inadequate dietary intake contribute to reduced cutaneous synthesis of vitamin D.

The association between low vitamin D levels and allergic rhinitis observed in this study aligns with findings reported by Arshi et al., who documented significantly lower vitamin D concentrations in patients with allergic rhinitis compared to healthy individuals [10]. Hyppönen et al. also reported an association between reduced serum vitamin D levels and increased allergic sensitization, suggesting a role for vitamin D in regulating allergic immune responses [11]. Beyond allergic rhinitis, Holick and Baeke et al. have highlighted the broader immunological functions of vitamin D, emphasizing its role in immune regulation and inflammation control [5,6]. These findings collectively suggest that vitamin D deficiency may contribute to immune dysregulation and increased susceptibility to allergic diseases.

Vitamin D exerts its biological effects through the vitamin D receptor, which is expressed on a wide range of immune cells, including dendritic cells, macrophages, T lymphocytes, and B lymphocytes. Through receptor-mediated pathways, vitamin D promotes immune tolerance, suppresses excessive inflammatory responses, and modulates cytokine production. Deficiency of vitamin D may therefore impair these regulatory mechanisms, predisposing individuals to exaggerated allergic inflammation.

Inverse Relationship Between Vitamin D and IgE

One of the key observations of the present study is the significant inverse relationship between serum vitamin D levels and IgE concentrations among patients with allergic rhinitis. Lower vitamin D levels were associated with higher IgE concentrations, suggesting that vitamin D deficiency may enhance IgE-mediated immune responses.

This finding is biologically plausible and supported by earlier research. Hyppönen et al. demonstrated a significant inverse, though nonlinear, relationship between serum 25-hydroxyvitamin D and IgE levels, proposing that vitamin D status may influence IgE synthesis [11]. Experimental studies have shown that activation of the vitamin D receptor can inhibit ε-germline gene transcription, thereby reducing IgE class switching in B cells. Milovanovic et al. and Yip et al. further demonstrated that vitamin D metabolites can suppress IgE-dependent mast cell activation, supporting its regulatory role in allergic inflammation [11,12]. The inverse association observed in the present study strengthens the hypothesis that vitamin D deficiency may contribute to immunological dysregulation and increased IgE production in allergic rhinitis.

Immunomodulatory Role of Vitamin D in Allergic Diseases

Vitamin D plays an essential role in maintaining immune homeostasis by influencing both innate and adaptive immune responses. It suppresses Th2-dominant immune pathways, reduces the production of pro-inflammatory cytokines, and enhances the development of regulatory T cells. These effects are particularly relevant in allergic conditions, where exaggerated Th2 responses and IgE-mediated pathways drive disease pathogenesis.

Deficiency of vitamin D may disrupt these immunoregulatory mechanisms, leading to heightened allergen sensitivity and sustained inflammatory responses. This may manifest clinically as persistent symptoms and chronicity of allergic rhinitis. Similar observations have been reported in studies examining allergic rhinitis and asthma severity, including those by Litonjua et al. and Brehm et al., which highlighted associations between low vitamin D levels and increased allergic disease severity [7,14]. The findings of the present study support the concept that vitamin D deficiency may act as a contributing factor in the immunopathogenesis of allergic rhinitis.

Comparison With Conflicting Evidence

Although an increasing body of evidence supports an association between vitamin D deficiency and allergic rhinitis, not all studies have reported consistent findings. Some investigations have observed higher vitamin D levels in individuals with allergic conditions, while others have found no significant association [13]. These discrepancies may be attributed to variations in study design, sample size, geographic location, seasonal timing of sample collection, dietary habits, sun exposure, and laboratory assay methods.

Despite these inconsistencies, the present study demonstrates a clear pattern of lower vitamin D levels and higher IgE concentrations in allergic rhinitis patients, along with a significant inverse relationship between the two parameters. This association is particularly relevant in populations with a high prevalence of vitamin D deficiency and supports the growing view that vitamin D status may influence allergic disease expression.

Limitations and Strengths

The present study has certain limitations that should be acknowledged. The relatively small sample size and single-center design may limit the generalizability of the findings to broader populations. Owing to the observational, case–control nature of the study, a causal relationship between vitamin D deficiency and allergic rhinitis cannot be established. Seasonal variations in serum vitamin D levels and fluctuations in environmental allergen exposure were not assessed, which may have influenced the biochemical measurements. Additionally, clinical severity grading of allergic rhinitis was not performed, which could have provided further insight into the relationship between serum vitamin D and IgE levels with disease severity.

Despite these limitations, the study has several notable strengths. It provides region-specific data from an Indian population, where both allergic rhinitis and vitamin D deficiency are highly prevalent. The inclusion of age- and sex-matched controls, along with the application of standardized and validated laboratory techniques, enhances the reliability of the findings. Furthermore, the demonstration of a significant inverse relationship between serum vitamin D and immunoglobulin E levels adds to the existing evidence supporting the immunoregulatory role of vitamin D in allergic disorders [14].

Overall, the findings of this study indicate that allergic rhinitis is associated with lower serum vitamin D levels and higher IgE concentrations, with an inverse relationship between these parameters. Although causality cannot be inferred, the results suggest that vitamin D status may represent a potentially modifiable factor in the immunological profile of allergic rhinitis. These observations underscore the need for larger, multicenter, and longitudinal studies to further clarify the role of vitamin D in allergic rhinitis and to evaluate the potential impact of vitamin D optimization on disease outcomes.

This investigation identifies a meaningful link between reduced vitamin D availability and elevated immunoglobulin E concentrations among individuals affected by allergic rhinitis. When compared with unaffected participants, those with allergic rhinitis showed lower vitamin D status alongside increased IgE levels, suggesting heightened immune reactivity. The inverse pattern observed between these two parameters indicates that vitamin D may influence immune mechanisms involved in allergic nasal disease. Given the widespread occurrence of suboptimal vitamin D levels in the general population, particularly within the Indian context, these observations carry clinical relevance. Reduced vitamin D status may contribute to exaggerated inflammatory responses and sustained symptoms in susceptible individuals. Evaluating vitamin D levels in patients presenting with allergic rhinitis may therefore aid in understanding disease activity and identifying individuals who could benefit from additional supportive measures. Although the present study does not establish a cause–effect relationship, the findings align with accumulating evidence that vitamin D participates in immune regulation and allergic response modulation. Integrating vitamin D evaluation into routine clinical assessment of allergic rhinitis could represent a practical and economical adjunct to standard treatment approaches. However, decisions regarding supplementation should be individualized and guided by further evidence from well-designed intervention trials. The results also emphasize the need for future research involving larger populations, multicenter participation, and longer follow-up durations to clarify the mechanistic role of vitamin D in allergic rhinitis. Further studies should explore the impact of vitamin D correction on symptom burden, immune markers, and long-term outcomes. In summary, individuals with allergic rhinitis tend to exhibit lower vitamin D levels alongside higher immunoglobulin E concentrations, highlighting a potential role for vitamin D in the disease process and its clinical management.

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