National prevalence of atopic dermatitis in Korean adolescents from 2009 to 2022

Previous studies have examined the prevalence of allergic diseases in adolescents 1–2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the β difference (βdiff) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66–6.91) in 2009–2011 to 6.89% (95% CI 6.72–7.05) in 2018–2019, then decreased slightly to 5.82% (95% CI 5.60–6.04) in 2022. Across the 14 years, middle school student status, low parent’s highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic.


Statistical analysis
We included demographic characteristics of the study participants as covariates 30 .We analyzed secondary data from KYRBS spanning a total of 14 years, from 2009 to 2022.Only records with complete data were included in the study.Analysis was conducted using composite sampling linear and logistic regression models.The term "composite sampling linear regression" refers to a method of conducting linear regression analysis by amalgamating data obtained from multiple sampling sources 31 .To investigate the trends in prevalence before and during the COVID-19 pandemic, we utilized a weighted linear regression model, deriving a β coefficient along with a 95% confidence interval (CI) 32 .The β diff was used to emphasize the difference between the pre-pandemic (2009-2020) and the pandemic (2020 and 2022).This method was chosen to examine changes over time and to contrast the effects before and during the pandemic.We used a binary logistic regression model to calculate the odds ratio for the 2009-2019 and 2020-2022.We also employed this method to identify risk factors of AD and calculate the ratio of odds ratio (OR) by using odds ratios from before and during the pandemic.We further determined risk factors for the years 2020, 2021 and 2022, to deepen our understanding of the pandemic's impact [33][34][35] .Categorical data were presented as frequencies and percentages, whereas numerical data were presented as means along with their corresponding 95% CIs.All statistical analyses were performed using SAS version 9.4 software (SAS Institute, Cary, NC, USA) and GraphPad Prism version 9.5.0 (GraphPad, San Diego, CA, USA) [35][36][37] .

Ethics approval
The study protocol was approved by the Institutional Review Board of KDCA (2014-06EXP-02-P-A).

Informed consent
All participants provided written informed consent.
Table 2 and Fig. 2 shows the weighted prevalence of AD from 2009 to 2022, further stratified against socioeconomic factors.The weighted prevalence of AD increased from 6.79% (95% CI 6.66-6.91) in 2009-2011 to 7.22% (95% CI 7.06-7.38) in 2016-2017.However, there was a slight decrease immediately preceding the pandemic, from 2018-2019 (6.89%, 95% CI 6.72-7.05) to 2022 (5.82%, 95% CI 5.60-6.04).There was no significant difference between the pre-pandemic and pandemic in prevalence (β diff − 0.041, 95% CI − 0.124 to 0.042) showing that the prevalence decreased since the start of the pandemic.Table 3 was analyzed to more closely examine the changes in AD prevalence during the pandemic period.The prevalence consistently showed a decreasing trend.Notably, from 2021 to 2022, there was a significant decrease (weighted OR 0.93, 95% CI 0.88 to 0.98).Table 4 shows the odds ratios of the socioeconomic factors of AD.Overall, from 2009 to 2022, high school grade, female sex, urban, high BMI group, lower-middle school performance, university graduated or higher parent's highest educational level, middle household income, current alcohol consumption, smoker, severe stress, sadness and despair, suicidal thoughts, and suicidal attempts are observed as risk factor of AD.In addition, we calculated the ratio of OR for the pandemic/pre-pandemic period to analyze vulnerable groups during the pandemic.AD vulnerable groups during the pandemic were followed by; high school grade (ratio of OR 95% CI 1.07 [1.01 to 1.12]), middle household income (ratio of OR 95% CI 1.18 [1.09 to 1.27]), ≥ 10 days alcohol consumption (ratio of OR, 95% CI 1.25 [1.05 to 1.49]), and current smoker (ratio of OR 95% CI 1.10 [1.02 to 1.19]).
In Table S3, risk factors such as high school grade, female sex, high BMI group, low school performance, high school graduated parent's highest educational level, current alcohol consumption, smoker, severe stress, sadness and despair, suicidal thoughts, and suicidal attempts were identified during the pandemic in 2020-2022, respectively.

Key results
In this study we found the prevalence of AD to be 5.82% in 2022 among adolescents aged 13 to 18 years.Analyzing the prevalence of AD is important because this allergic disease has a significant impact on the quality of life, particularly among adolescents.The prevalence of AD continued to increase prior to the pandemic.However, the most significant decline in prevalence occurred after the COVID-19 pandemic began, with a smaller decline observed during the pandemic.Examining this prevalence contributes to understanding the scope of the COVID-19 pandemic and its influences on allergic disease trends.Additionally, current alcohol consumption, smoker, severe stress, sadness and despair, suicidal thoughts, and suicidal attempts are observed as risk factors of AD.These results could also provide a new perspective on coping with AD.

Global epidemiology and mechanism
In South Korea, the first cases of COVID-19 were discovered in January 2020, and the severity of the pandemic increased over time 37 .One hypothesis for this phenomenon could be the reduced exposure to allergens due to the changes during COVID-19.Several significant social and political changes occurred during this period, www.nature.com/scientificreports/which could have influenced the level of allergen exposure.Because the most drastic of measures included social distancing, lockdowns, closures of public places, decreased physical interaction, mask mandates, and other selfisolating actions [38][39][40] .Furthermore, during the COVID-19, there was a decrease in air pollution in South Korea 41 , which is consistent with decreased smoking and automobile traffic resulting from decreased socialization 42 .Air pollution has previously been linked to AD as air particulates can damage the skin barrier through oxidative stress, thus triggering immune dysregulation which can potentially increase inflammation of AD 43,44 .Heavy metals exposure (a factor of air pollution) has similarly been associated with allergic diseases, acting as a direct activator of Th2 cells as well as an adjuvant, increasing the effect of other allergens 42 .In addition, the use of face masks has further enhanced the protective effect as studies have shown that they reduce allergic diseases, particularly AD 45,46 .While face masks could have an inflammatory effect on facial dermatoses due to increased skin hydration, temperature, and sebum secretion, it has been found that in patients with AD, facial eczema is deceased due to covering sensitive areas 46 .In 2022, many COVID-19 regulations began to be rescinded, with South Korea removing the mask mandate and other social restrictions as the pandemic started to wind down.This return to pre-pandemic action could partially explain the decreased trend of AD during 2022 13 .However, although there is a decreasing trend, it is too early to determine the impact of reducing social restrictions in 2022, so future research is required.
In this study, we found that alcohol consumption and smoking are both associated with an increased risk of AD, which is consistent with the literature 9 .However, in Korean adolescents, we found a minor negative association between high BMI and AD, which is in contrasts with other sources, as overweight or obese individuals have been found to have an increased risk of AD through a small but important causal relationship 47 .Having suicidal thoughts was the only factor that demonstrated an increased risk of AD across the pandemic, 2020-2022.However, further research is necessary to fully understand the underlying mechanism behind this association.Falling rates of AD during COVID-19 may also be due to other factors.Firstly, the common allergens for AD have been  Vol:.(1234567890  www.nature.com/scientificreports/found to be changing as patients are less sensitized to them and new allergens emerge 48 .Secondly, in the United States, it has been postulated that falling rates of allergic disease could be due to the changes in measurements 49 , but the KYRBS has remained consistent in its measurement and questions.Finally, a study in Colombia found that leading up to 2019, there was an increasing utilization of healthcare resources and healthcare visits, which correlated with an increased in the incidence and prevalence of AD 50 .The COVID-19 pandemic saw a decrease in healthcare utilization, including for allergic disease, as fewer people reported to hospitals during COVID-19 for fear of contracting SARS-CoV-2 51 .Furthermore, many patients with AD are treated by specialists, and data from other countries data outpatient dermatological visits during the COVID-19 pandemic, with AD being the most common reason for visits 52,53 .However, specific studies conducted in South Korea found no decrease in incidence in adolescent AD from 2019 to 2020, so changes in incidence may not fully explain the decreasing trend of AD during this period 54 .

Strengths and limitations
We utilized the KYRBS, which serves as both the greatest strength and limitation of this study.The KYRBS is the only national database for the prevalence of allergic disease since the COVID-19 pandemic, with over one million Korean adolescents included in the study.The KYRBS is also integrated with the public school system in South Korea, as it is administered to most school-age adolescents via computers with anonymous online selfreporting 9 .However, this poses several limitations.First, the KYRBS excludes any student not in the Korean public education system, potentially excluding a segment of the adolescent population.Second, the KYRBS is a self-reporting questionnaire, which, although considered reliable based on a kappa coefficient of 0.78-0.80 55, still yields subjective data that lacks objective measures.Third, in our study, we analyzed the data without considering the sensitivity and specificity of AD.Therefore, there is a limitation that the numbers may change when considering this.However, even if we consider this limitation, it is unlikely to significantly alter the overall trend of the results.Fourth, this study has limitations due to the lack of use of validated questionnaires, impacting the reliability and accuracy of its results.This common issue in self-report studies necessitates caution in interpreting data and may restrict the generalizability of the findings.Fifth, while the results of this study show an overall decreasing trend in the number of AD patients, this may be attributed to a reduction in doctor visits during the pandemic.However, our dataset lacks information on doctor visits, making this difficult to ascertain.Finally, the data is confined to one country, South Korea.Primary healthcare is highly valued worldwide 56 .However, contrary to this, according to statistics from the World Health Organization, many countries suffer from poor access to primary healthcare 57,58 .On the other hand, South Korea boasts excellent accessibility to primary healthcare 59 .This disparity may be attributed to cultural differences, the presence or absence of social insurance, among other factors, which could result in the trends in other countries being different.

Conclusion
This study observed the prevalence of AD over a 14-year from 2009 to 2022, analyzing both the differences before and during the COVID-19 pandemic, as well as within the pandemic itself.The prevalence of AD increased before the pandemic, then decreased at the start of the pandemic and remained stable throughout the pandemic.This prevalence helps us understand the scope of the COVID-19 pandemic and its effects on allergic disease trends.In addition, risk factors of AD include alcohol consumption, smoking, severe stress, feelings of sadness and despair, suicidal ideation, and suicide attempts.Further research is necessary to understand whether these results are specific to the COVID-19 pandemic and whether the trend of AD will revert to pre-pandemic levels as the COVID-19 pandemic ends.

Table 3 .
Comparison with the previous year by the wORs for prevalence of AD and each socioeconomic factor, weighted % (95% CI).Significant values are in bold (p < 0.05).