INTRODUCTION
Rhinitis is a common chronic disease worldwide. Rhinitis can be categorized into several types, including allergic rhinitis (AR), infectious rhinitis, hormonal rhinitis, drug-induced rhinitis, occupational rhinitis, and idiopathic rhinitis. Among these, AR is the most common. The prevalence of AR is steadily increasing, posing a significant global socioeconomic burden [1]. There are four main symptoms of AR: nasal obstruction, sneezing, rhinorrhea, and itching; some patients also experience post-nasal drip, eye redness, eye itching, and hyposmia [2,3]. AR is a chronic condition that can significantly impact patients’ quality of life, causing issues such as mood disorders, sleep disorders, and decreased social performance [3].
AR is an immunoglobulin E (IgE)-mediated hypersensitivity disease; thus, skin and immunological tests targeting IgE-mediated reactions are useful tools for confirming AR [4]. However, due to the high cost and limited practicality of these tests, medical history-taking and physical examinations remain the preferred methods for obtaining critical diagnostic information regarding AR [5].
Nasal endoscopy is an important procedure utilized by otolaryngologists. It is cost-effective, easy to perform, and provides direct visualization of the nasal cavity. Several endoscopic findings have been associated with AR, including pale mucosal swelling, watery secretion (WS) or mucoid discharge (MD), post-nasal drip, and inferior turbinate hypertrophy, among others. Several studies have investigated the role of nasal endoscopy in assessing AR and have attempted to establish universally accepted definitions of AR-related nasal endoscopic findings [6-10]. However, no consensus currently exists regarding objective evaluations of AR via physical examination, and other factors may influence endoscopic findings.
Therefore, we investigated nasal endoscopic findings associated with AR and identified factors influencing these findings.
METHODS
Study population
The Korean Centers for Disease Control and Prevention and the Korean Society of Otorhinolaryngology-Head and Neck Surgery collected medical histories and clinical examination data from representative samples of Korean individuals through the Korean National Health and Nutrition Examination Survey (KNHANES).
Our study used the KNHANES 2010 dataset, which included ear, nose, and throat (ENT) physical examination results, related questionnaires, and ENT disease prevalence. Also, the combined measurement of allergen levels in blood and nasal endoscopy was only done in 2010; this allows us to better understand how allergen test results relate to what we see in endoscopy. A total of 8,958 individuals were invited to participate in the KNHANES 2010. These individuals were randomly selected as representative of the South Korean population. The surveys evaluated data from a civilian, non-institutionalized South Korean population, using a stratified, multistage, clustered sampling method based on national census data. An analysis was conducted with 7,636 participants who underwent endoscopic examination by ENT doctors. Written informed consent was obtained from all participants before the survey and physical examination. The Institutional Review Boards of the Korea Centers for Disease Control and Prevention (2010-02CON-21-C) and Kyung Hee University Hospital at Gangdong (KHNMC 2024-11-013) approved the study protocol.
AR and nasal endoscopic findings
In this study, AR was diagnosed if any immunoradiometric assay (ImmunoCAP) results for Dermatophagoides farinae (D.f), cockroach, or dog dander-specific IgE (sIgE) showed a level of 1+ or higher. Nasal endoscopic examinations were conducted by trained ENT residents. The residents performed physical examinations, including nasal endoscopy, and recorded six intranasal endoscopic findings (pale mucosal swelling, WS, MD, pus drainage in the middle meatus, nasal polyp, nasal cavity neoplasm, and septal deviation) according to the standardized examination criteria established by the KNHANES, using a 4-mm 0° endoscope. The recorded endoscopic findings were subsequently verified by professors from the ENT department to enhance reliability. Prior to the study, nasal endoscopic findings suggestive of AR were selected (Table 1).
Demographic characteristics and serum laboratory tests
Trained interviewers from the Korean Centers for Disease Control and Prevention collected basic demographic information and medical histories of the participants. Personal information (age, sex, marital status, and body mass index), socioeconomic status (type of residence, occupation), and social behaviors (smoking and alcohol consumption) were collected and categorized according to predefined standards. Participants were categorized as male or female. Marital status was classified as married or unmarried. Residence type was categorized as apartment or house, where “house” included all forms of housing other than apartments. Occupations were classified according to the Korean Standard Classification of Occupations into white-collar workers (managers, professionals, clerks, service workers, students, and housewives) and blue-collar workers (agriculture, forestry, fishery workers, craft workers, machine operators, and laborers). Smoking status was classified as smoker or non-smoker. Alcohol consumption was categorized by drinking frequency into two groups: less than once a week or more than once a week (Table 2).
Blood tests were conducted by a team of four specialized investigators, including nurses and medical laboratory scientists. Laboratory tests included allergen-specific tests, total cholesterol, triglycerides, hemoglobin, and vitamin D measurements. Allergy-related tests measured serum sIgE levels for D.f, cockroach, and dog dander, as well as total IgE (tIgE) levels. Serum sIgE samples were collected over one year, specifically during the 2010 survey. Continuous variables were evaluated for multicollinearity, and strongly correlated variables were excluded. All collected samples were transported to a designated laboratory (Neodin Medical Institute) and analyzed according to the manufacturer’s protocol. Before conducting analyses, dichotomous variables were created based on laboratory test results using normal laboratory ranges for hemoglobin, hypercholesterolemia, hypertriglyceridemia, and vitamin D deficiency. SIgE was converted into a dichotomous variable based on the positive diagnostic threshold (≥0.35 kU/L) of the ImmunoCAP test, while tIgE was categorized based on a clinically significant cutoff value (100 kU/L) (Table 3).
Evaluation of AR symptoms and comorbid disease
Typical AR symptoms, including sneezing, nasal obstruction, itchy nose without upper respiratory infection, and anosmia, were investigated by trained researchers. Additionally, the duration of allergic symptoms was assessed. Each participant’s medical history was recorded using an open-ended question: “Have you ever had this disease?.” This study examined the presence of comorbidities, including hypertension, diabetes mellitus, dyslipidemia, asthma, and atopic dermatitis. ENT conditions, such as benign laryngeal diseases affected by allergic status, and nasal septal deviation (identified through endoscopic examination), were also investigated (Table 4).
Statistical analysis
Data were analyzed using SPSS software (version 18.0; IBM Corp.). SPSS enables complex sample analyses by assigning appropriate weights. The KNHANES sampling weight variables, along with masked variance primary sampling unit and stratum variables, allowed for the estimation of findings representative of the entire non-institutionalized Korean population. Categorical variables are presented as proportions and standard errors, while continuous variables are reported as mean±standard deviation. Differences between groups were evaluated using the chi-square test for categorical variables and general linear models for continuous variables. Multivariable logistic regression analysis was performed to identify factors influencing each endoscopic finding, with adjustments for covariates. Variables with p-values <0.20 in preliminary analyses were included in the logistic regression model, and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Statistical significance was set at p<0.05.
RESULTS
Nasal endoscopic findings related to AR
Six nasal endoscopic findings were analyzed in relation to AR, and among these, WS and MD were significantly associated with AR. WS was the finding most significantly indicative of AR, with the highest OR (OR, 1.799; 95% CI, 1.374–2.357), followed by MD (OR, 1.484; 95% CI, 1.050–2.097) (Table 1).
Demographic data of the study population and analysis of factors influencing endoscopic findings
In total, 7,636 participants were available for analysis. Among this population, 1,045 individuals were diagnosed with AR, representing a proportion of 13.6%. Within the AR group, 22.2% (232/1,045) and 9.6% (101/1,045) of the individuals showed WS and MD, respectively. Mean age and marital status showed significant correlations with WS, whereas other demographic factors did not (Table 2). In the multivariate logistic regression analysis, each variable’s effect was adjusted for all other variables. WS was significantly associated with age (OR, 0.980; 95% CI, 0.962–0.999), nasal septal deviation (OR, 1.839; 95% CI, 1.238–2.731), and sensitization to dog allergens (OR, 2.000; 95% CI, 1.202–3.329) (Table 5). MD was significantly associated only with nasal septal deviation (OR, 1.980; 95% CI, 1.070–3.663) (Table 6). Furthermore, the proportion of WS increased with higher levels of dog allergen sensitization, consistent with the findings of this study (Fig. 1).
Association between typical AR symptoms and nasal endoscopic findings
WS was significantly associated with all durations of AR symptoms. Both WS and MD were related to the symptom of anosmia, but MD was not associated with symptom duration (Supplementary Table 1 in the online-only Data Supplement).
DISCUSSION
AR is a chronic atopic disorder characterized by diverse symptoms and clinical findings, with an increasing incidence worldwide [1]. Nasal endoscopy is a valuable diagnostic tool due to its low cost, short duration, and ease of performance. Clinically, many physicians diagnose AR based on a combination of patient symptoms, endoscopic findings, and therapeutic responses [5]. Numerous endoscopic findings are associated with suspected AR, and various studies have attempted to assess the reliability of these intranasal findings [6-8]. Traditionally, pale mucosal swelling, inferior turbinate hypertrophy, or watery rhinorrhea have been key indicators used to evaluate AR. However, other findings have recently gained attention [9,10]. A recent meta-analysis identified middle turbinate edema or watery discharge as crucial findings for diagnosing AR [9]. Another study investigated several middle turbinate appearances in AR and identified middle turbinate edema as the most significant feature predicting inhalant allergy [10]. Despite these efforts, there is still no consensus on definitive endoscopic findings that reliably represent AR, and most prior studies involved relatively small sample sizes.
This study has several strengths. First, it is a large-scale, population-based study that identifies factors influencing nasal endoscopic findings suggestive of AR. Because the survey involved a nationally representative sample, not limited to a specific condition, the reliability of the results is high. Second, the relationship between serum laboratory results and nasal endoscopic findings has not previously been thoroughly explored. Importantly, this study uniquely presents the association between sIgE levels and endoscopic findings.
In this study population, WS and MD were identified as representative nasal endoscopic findings suggestive of AR, with WS being more prevalent than MD. Furthermore, WS was more closely correlated with typical AR symptoms (sneezing, itching, nasal obstruction, rhinorrhea, etc.), making it the most definitive endoscopic finding of AR. The nasal mucosa is covered by mucus consisting of two layers: the gel and sol layers. Submucosal glands and goblet cells regulate mucus secretion, facilitating mucociliary clearance. Fluid hypersecretion leads to thickening and reduced viscosity of the sol layer, while mucin hypersecretion results in thickening and increased viscosity of the gel layer. Thus, WS corresponds to fluid hypersecretion, whereas MD is associated with mucin hypersecretion [11]. Allergens trigger inflammatory mediators such as histamine and leukotrienes, causing fluid hypersecretion and increased cellular permeability, leading to watery discharge. Therefore, WS may better reflect AR conditions compared to MD. Notably, in this study, pale mucosal swelling was not significantly associated with AR. This finding likely reflects the fact that nasal mucosal swelling can result from various other conditions. According to previous studies, nasal mucosal swelling can occur in asthma patients [12], autoimmune disorders such as rheumatoid disease, and even due to hormonal fluctuations during the menstrual cycle [13,14]. Consequently, mucosal swelling may be considered a nonspecific finding.
Nasal septal deviation was a common influencing factor for both WS and MD. A deviated nasal septum refers to a misalignment of the septum from the midline, leading to persistent rhinorrhea and nasal obstruction. Septal deviation can be congenital or acquired through trauma. Previous studies have indicated that rhinorrhea and mucosal swelling associated with septal deviation result from prolonged mucociliary clearance time [15]. The concave side of a deviated septum experiences increased infiltration by inflammatory cells and ciliary loss compared to the convex side, impairing mucociliary function. Chronic dysfunction of mucociliary clearance can transform nasal discharge from watery to mucoid, further compromising nasal mucosa physiology [16]. Thus, septal deviation appears to be linked to chronic impairment of the nasal mucosa, with WS and MD emerging as manifestations of this pathophysiology.
Age was identified as a factor inversely correlated with WS (OR<1). It is well-known that the prevalence of AR decreases with age. A single-center study conducted in South Korea showed that allergen sensitization prevalence gradually declined with age after peaking between 20 and 29 years [17]. Another study indicated that AR in children tends to be more intermittent, severe, and accompanied by more comorbidities compared to adults [18]. Therefore, our findings align with those of previous studies. Although the precise reasons for a higher prevalence of allergic symptoms in children remain unclear, factors such as immune system immaturity and poorer medication adherence might contribute to this phenomenon.
The most notable finding of this study was that certain sIgE may be related to specific nasal endoscopic findings. According to our results, sensitization to dog allergens was associated with WS, and increased levels of sensitization correlated with more frequent occurrences of WS. As no prior studies have reported associations between sIgE levels and endoscopic findings in AR, this represents a unique discovery. Typically, allergen sensitization arises from direct allergen exposure, and pet allergies are often linked to pet ownership. However, some studies have reported that pet allergies are not necessarily connected to pet ownership [19,20]. Furthermore, research indicates that sensitization to pet allergens can occur not only through direct exposure to the specific pet allergen but also through cross-reactivity with similar epitopes from other allergens [21]. Therefore, these study results should not be interpreted as limited exclusively to dog ownership but as broadly relevant to all AR patients, regardless of pet ownership.
The specific impact of dog allergens on WS has not been extensively studied. However, dog allergens are generally recognized to have relatively low antigenicity, potentially explaining their limited effect on WS findings. Dog allergens Can f 1, Can f 2, Can f 4, and Can f 6 belong to the lipocalin protein family and are commonly associated with respiratory allergies. The lipocalin family, which includes many mammalian allergens, is characterized by weak cellular immunity responses and promotes proliferation of Th2-mediated responses [22]. Although the exact mechanism remains unclear, Pierre et al. demonstrated that gene silencing of the mannose receptor on dendritic cells derived from human peripheral blood monocytes inhibits recognition and uptake of Can f 1 [23]. This mechanism suggests that dog allergens may exhibit lower allergenic potency. As described earlier, MD may arise due to prolonged accumulation of WS. Hence, the lower antigenicity of dog allergens might result in relatively mild symptoms, such as WS. Additionally, a dose-response trend between dog allergen sensitization and WS is depicted in Fig. 1, further supporting the association between sIgE levels and endoscopic findings.
This study has several limitations. First, seasonal allergen levels were not assessed in the national survey, meaning the impact of outdoor allergens on AR was not considered. However, indoor allergens typically involve greater exposure opportunities and longer exposure durations than outdoor allergens, making them particularly relevant in AR research. Second, the exact relationship between low antigenicity and specific endoscopic findings remains unclear, warranting further follow-up studies to elucidate this association. Third, although the observed endoscopic findings were verified by experts, observer bias cannot be completely excluded. Fourth, as this study employed a cross-sectional design, it inherently has limitations in inferring causal relationships. Temporal changes in allergen exposure and sensitization were not evaluable. Therefore, longitudinal studies are needed to clarify potential interactions and eliminate confounding effects among the various investigated variables.
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