Allergic rhinitis, allergic conjunctivitis, and allergic asthma are representative diseases caused by aeroallergens that have a high prevalence worldwide [1,2]. In South Korea (hereafter, Korea), the prevalence of respiratory allergic diseases is gradually increasing [3,4]. Allergic diseases are caused by a combination of genetic and environmental factors [2,5]. Considering that the number of multicultural households in Korea was less than 2% in 2020 [6], this increase is likely due to environmental factors rather than a change in genetic factors. Air pollution and the westernization of diet and lifestyle are typical environmental factors [5]. With the proliferation of new plant species due to climate warming and the introduction of various pets, the types of allergens causing respiratory allergies are estimated to become very diverse [7,8].

Many studies have been conducted on the status of aeroallergen sensitization in Koreans [9-20]. However, many of these studies are old, and it is difficult to consider them representative of the national situation as only a limited number of aeroallergens were investigated, or relatively few patients were enrolled at a single institution. Furthermore, the recently used aeroallergen panel is somewhat different from that determined in 2001 [21].

In this study, data regarding more than 360,000 multiple allergosorbent tests (MASTs) stored by a domestic medical diagnosis company over the past 3 years were analyzed. These data were collected all over the country, and the MAST kit used for the test was also produced in 2017, enabling the detection of new aeroallergens. In this study, we investigated the status of aeroallergen sensitization in Koreans.

The total number of cases was 368,156; from these, 347,996 cases were analyzed, with the exclusion of 18,889 cases corresponding to those aged 0 or ≥90 years and 1,271 cases with missing data. This figure is equivalent to approximately 0.66% of the total population of Korea in 2020, and the regional distribution varied from 0.40% to 1.21% (Fig. 1). The study included 159,561 male patients (45.9%) and 188,433 female patients (54.1%). The distribution of cases by age groups is presented in Table 1. The percentage of positive cases relative to total cases was 56.7%; this percentage was highest in adolescents (74.1%) and lowest in the elderly (47.0%).

The rates and types of common aeroallergen sensitization vary widely across countries, and studies conducted in the same country have reported different results [1,2,22]. Studies on sensitization to aeroallergens in Koreans have also shown very different results depending on the test method, type of aeroallergen, region, and subject selection (Table 4) [9-20]. DP and DF showed an overwhelmingly high sensitization rate compared to other antigens, but the reported frequency of sensitization to other aeroallergens had varied from study to study. Common causes include cat, dog, birch, alder, oak, mugwort, and cockroach. However, it was difficult to understand changes in the prevalence of aeroallergens over time by comparing these studies. One study found that the sensitization rate to tree pollen such as oak, birch, alder, and pine increased by 2010 compared to the 1980s, while sensitization to weed and grass pollens decreased. However, DP and DF did not significantly change, and sensitization to dogs and cockroaches slightly decreased [23].

A skin prick test or a specific IgE measurement was performed to identify the causative aeroallergen [5,24]. Although the skin prick test is highly sensitive, it requires specialized personnel and the results are affected by several factors. The ImmunoCAP (ThermoFisher Scientific, Waltham, MA, US) and MAST systems were used for specific IgE measurements [24]. They are not affected by medication, have high specificity, and provide objective results. Although the ImmunoCAP system can quantitatively measure IgE levels for individual allergens, it is expensive and difficult to test multiple allergens simultaneously [5]. In contrast, MAST is the most useful method for studying sensitization to a large number of allergens in a large number of people because it can test more than 60 allergens simultaneously and is relatively inexpensive [24]. Previous studies have shown that the MAST is less accurate than the ImmunoCAP system, but recent studies have shown no significant difference between the two methods [24]. In the early 1990s, the Korean aeroallergen panel was first introduced for MAST [25], and the currently used panel includes about 50 aeroallergens, based on data from patients in three hospitals in Seoul, Suwon, and Jeju around 2001 [21]. Subsequently, many companies have introduced various types of MAST products. Compared with the panel developed in 2001, the MAST aeroallergen panel used in this study has added A. siro, olive, white ash, acacia, white pine, reed, plantain, Russian thistle, goldenrod, pigweed, horse, guinea pig, mouse, sheep, rabbit, hamster, and others. According to the manufacturer, the new aeroallergen panel was created by excluding allergens with a low detection rate in the past MAST and adding allergens that are currently known to be newly detected in Korea. It is estimated that the new panel will be more useful in diagnosing allergies in Koreans than the past panel, but no study has compared the two panels directly.

Similar to previous studies, the most commonly detected aeroallergens in this study were DP and DF. The PRs for both allergens were approximately the same, but the PR of DF was approximately 0.01 higher. The actual distribution of DF and DP is 65.3% and 20.6%, respectively, with DF showing an overwhelming predominance [26]. However, the cross-reactivity between DP and DF is high [27]; therefore, the PR of DP was also high. In addition, sensitization to A. siro and T. putrescentiae, storage mites inhabiting hay and granaries, was detected at a significant frequency [27]. However, it was unclear whether there was cross-reactivity between mites or sensitization to storage mites. Further studies are required to determine the clinical significance of sensitization against these storage mites.

Five types of molds were investigated; only Alternaria species (sp.) had a PR exceeding 0.05, and the remaining molds had PRs of less than 0.05. However, another recently published study reported that the PR of molds among Koreans was highest for A. fumigatus (11.6%) and lowest for Alternaria sp. (4.1%) [23]. This difference may be due to the difficulty in standardizing fungal antigens. Therefore, the results may vary greatly depending on the antigen used and may not reflect actual sensitization.

In Korea, the wind begins to carry grass pollen around in spring, tree pollen in summer, and weed pollen in autumn [28]. However, it is difficult to accurately distinguish each pollen season because they overlap significantly and differ between regions. In particular, pollen allergies have increased due to the warming of the Korean Peninsula. In the case of Jeju, compared to 1970, the annual average temperature had increased by 2°C in 2011, resulting in a 2.5-fold increase in cedar allergies in 15 years [29]. Additionally, an increase in exotic plants is likely to be a factor. Grass has an overall higher PR than trees or weeds. For trees, there was a significant difference between the types. The PR of willow was 0.141, whereas that of alder was only 0.079. For weeds, most PRs were approximately 0.10.

Among animals, cats (0.231) and dogs (0.183) showed very high PRs. However, the PRs were less than 0.1 for horses, rodents, sheep, and rabbits. Further investigation is needed to determine whether there is actual sensitization or cross-reactivity with other common pets like cats and dogs. Cockroaches also showed a high PR of 0.211. According to a study analyzing changes in the aeroallergen sensitization rate of Koreans over the past 30 years, there was little change in the sensitization rate to other indoor antigens, such as mites, molds, and animals [23]. However, the proportion of sensitization against cockroaches decreased from 25.3% in the 1980s to the 1990s to 12.3% in the 2010s [23]. This is thought to have resulted from improved sanitary conditions, but is still considered to be high.

Only one type of positive aeroallergen was found in 44.4% of patients, and 85.1% had three types or fewer. Conversely, about 15% of patients were poly-sensitized (i.e., sensitized to four or more types). On average, one person was sensitized to 2.07 types of aeroallergens; adolescents had the highest average number, at 2.31, while the rest were similar. It has been reported that poly-sensitization causes more severe symptoms, such as nasal congestion and sneezing, and that conjunctivitis and eczema are more common in poly-sensitized patients than in mono-sensitized patients [30]. Although information on the correlation between the number of sensitizing aeroallergens and the severity of symptoms was not available in this study, it is presumed that poly-sensitization is high during adolescence and gradually decreases with age. This is also consistent with the high prevalence of asthma, allergic rhinitis, and atopic dermatitis in adolescents, which decreases with age [1-4].

The distribution of PRs by age differed according to the type of aeroallergen. Most mold PRs in children were very low, changing to very high in adolescents, and decreasing again in adults. In the elderly, the PRs for grass, trees, and weeds were very high. Sensitization to cats and dogs was very high in adolescents and low in the elderly population. For cockroaches, the number of sensitized adolescents was very low, while that for the elderly was very high. An accurate explanation for these differences in the PRs, depending on the aeroallergen, is lacking. It is presumed that the PRs were high for molds and pets (the indoor aeroallergens) and low for pollen because of the decrease in outdoor activities among adolescents [13]. However, it is not well understood why the PR for cockroaches, also an indoor aeroallergen, was high in the elderly. Korea’s rapid urbanization, the increase in the number of companion animals, and improved sanitary conditions are suspected to be reasons underlying this difference [23].

The aeroallergen PRs also varied by region. The differences were greater for pollen than for indoor allergens, such as mites, molds, and animals. This is presumed to be because the eastern part of the country is mainly mountainous, and the flora changes depending on the latitude [28]. Jeju is an island away from the mainland and is covered with granite; therefore, the sensitization rate to pollen is quite different from other regions [29]. Although the PR for all pollen was very low, Japanese cedars native to this area showed an overwhelmingly high sensitization ratio, with a PR was 0.222 (5.8 times the national average).

Although this study has the strength of analyzing large-scale data from over 360,000 MASTs collected across Korea, it has the following limitations. First, clinical information regarding the patients was unavailable. However, MASTs would have probably been performed for patients suspected of having a respiratory allergy. Second, although the data were collected from all over the country, the sample was not systematically selected and lacked representativeness. However, since the data were collected from 3,735 hospitals across the country, various patient groups were selected; therefore, we believe that there would be little specific bias. Third, class 1 (0.35–0.69 IU/mL) was used as the positivity criterion, and the results may vary upon changing this criterion. Class 1 was selected as the positivity criterion in this study because the MAST has recently become very accurate, and the measurement level is very similar to that of ImmunoCAP, which has a positivity criterion of 0.35 IU/mL [24]. Fourth, there may have been cases where one person received multiple MASTs, but this possibility could not be confirmed because there was no personally identifiable information in the data. However, it is thought that there would not have been many cases of repeating allergy tests within a short period of 2 and a half years.

From this study, we learned several lessons. First, since Koreans are sensitized to a wide variety of aeroallergens, we do not think it is appropriate to test for allergies with only a small number of aeroallergens. Second, since common aeroallergens were different for each region, the region should be considered when composing an aeroallergen panel. Third, since adolescents are often simultaneously sensitized to various aeroallergens, it is necessary to test them using a sufficient number of items.