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\begin{document}

\title{Changes in sensitization rates in patients with asthma and/or rhinitis
in China between 2008 and 2018: a national cross-sectional study}



\author[1]{wanjun wang}%
\author[2]{Jianhong Wang}%
\author[3]{Guihua Song}%
\author[4]{Hua Xie}%
\author[4]{Xiaoping Lin}%
\author[4]{Ruonan Chai}%
\author[5]{Rongfei Zhu}%
\author[6]{Yong He}%
\author[7]{Juan Tang}%
\author[8]{Junge Wang}%
\author[9]{Jinghua Yang}%
\author[10]{Lili Zhi}%
\author[11]{Lin Wu}%
\author[12]{Yan Jiang}%
\author[13]{Xiaoqin Zhou}%
\author[14]{Dongming Huang}%
\author[15]{Ning Wang}%
\author[16]{Rui Xu}%
\author[17]{Yuan Gao}%
\author[18]{Zhimin Chen}%
\author[18]{Jinling Liu}%
\author[19]{Xiaoli Han}%
\author[20]{Guolin Tan}%
\author[21]{Jinzhun Wu}%
\author[22]{De-Yu Zhao}%
\author[23]{Jianjun Chen}%
\author[24]{Xiwei Zhang}%
\author[24]{Mengrong Li}%
\author[25]{Yuemei Sun}%
\author[26]{Yi Jiang}%
\author[27]{Wei-Tian  Zhang}%
\author[28]{Qianhui  Qiu}%
\author[29]{Chuanhe Liu}%
\author[30]{Jie Yin}%
\author[31]{Guodong Hao}%
\author[32]{Huabin Li}%
\author[33]{Yongsheng Xu}%
\author[34]{Shaohua Chen}%
\author[35]{Hua Zhang}%
\author[36]{Shi Chen}%
\author[37]{Juan Meng}%
\author[38]{Dan Zeng}%
\author[39]{Wei Tang}%
\author[40]{Chuangli Hao}%
\author[1]{Jing Li}%
\author[1]{Nanshan Zhong}%
\affil[1]{State Key Laboratory of Respiratory Disease}%
\affil[2]{Sichuan Academy of Medical Sciences and Sichuan People's Hospital}%
\affil[3]{Yunnan Provincial Hospital of Chinese Medicine}%
\affil[4]{General Hospital of Northern Theatre command}%
\affil[5]{Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology}%
\affil[6]{Ningbo Chinese Medical Hospital}%
\affil[7]{First People's Hospital of Foshan}%
\affil[8]{Beijing Hospital of Traditional Chinese Medicine}%
\affil[9]{Guangdong Provincial Academy of Traditional Chinese Medicine}%
\affil[10]{Shandong Cancer Hospital and Institute}%
\affil[11]{Hangzhou Hospital of Traditional Chinese Medicine}%
\affil[12]{The Affiliated Hospital of Qingdao University}%
\affil[13]{Hubei Province Women and Children Hospital}%
\affil[14]{Third People's Hospital of Zhongshan}%
\affil[15]{NYU Winthrop Hospital Children's Medical Center}%
\affil[16]{Sun Yat-Sen Memorial Hospital}%
\affil[17]{Zhengzhou First People Hospital}%
\affil[18]{Zhejiang University School of Medicine Children's Hospital}%
\affil[19]{Hebei Sixth People's Hospital}%
\affil[20]{Central South University Third Xiangya Hospital}%
\affil[21]{Qingdao Women and Children's Hospital}%
\affil[22]{Children's Hospital of Nanjing Medical University}%
\affil[23]{Tongji Hospital Department of Hematology}%
\affil[24]{The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University}%
\affil[25]{Jiading District Central Hospital Affiliated Shanghai University of Medicine \& Health Sciences}%
\affil[26]{First Hospital of Shanxi Medical University}%
\affil[27]{Shanghai Jiao Tong University Affiliated Chest Hospital}%
\affil[28]{Zhujiang Hospital}%
\affil[29]{Capital Medical University Beijing Children's Hospital Imaging Centre}%
\affil[30]{Chengdu First People's Hospital}%
\affil[31]{Tangshan Gongren Hospital}%
\affil[32]{Vikram ENT Hospital and Research Institute}%
\affil[33]{Tianjin Children's Hospital}%
\affil[34]{Guangdong Second Provincial General Hospital}%
\affil[35]{Xinjiang Medical University Affiliated First Hospital}%
\affil[36]{Hainan Provincial Nongken Hospital}%
\affil[37]{Sichuan University West China Hospital}%
\affil[38]{Chongqing City Hospital of Traditional Chinese Medicine}%
\affil[39]{Shanghai Jiaotong University First People's Hospital Department of Orthopaedics}%
\affil[40]{First Affiliated Hospital of Soochow University}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\sloppy


Changes in sensitization rates in patients with asthma and/or rhinitis
in China between 2008 and 2018: a national cross-sectional study

Wanjun Wang\textsuperscript{1}*, Jianhong Wang\textsuperscript{2}*,
Guihua Song\textsuperscript{3}*, Hua Xie\textsuperscript{4}*, Xiaoping
Lin\textsuperscript{4}*, Ruonan Chai\textsuperscript{4}*, Rongfei
Zhu\textsuperscript{5}*, Yong He\textsuperscript{6}*, Jun
Tang\textsuperscript{7}*, Junge Wang\textsuperscript{8}*, Jinghua
Yang\textsuperscript{9}*, Lili Zhi\textsuperscript{10}*, Lin
Wu\textsuperscript{11}*, Yan Jiang\textsuperscript{12}*, Xiaoqin
Zhou\textsuperscript{13}*, Dongming Huang\textsuperscript{14}*, Ning
Wang\textsuperscript{15}*, Rui Xu\textsuperscript{16}*, Yuan
Gao\textsuperscript{17}*, Zhimin Chen\textsuperscript{18}*, Jinling
Liu\textsuperscript{18}*, Xiaoli Han\textsuperscript{19}*, Guolin
Tan\textsuperscript{20}*, Jinzhun Wu\textsuperscript{21}*, Deyu
Zhao\textsuperscript{22}*, Jianjun Chen\textsuperscript{23}*, Xiwei
Zhang\textsuperscript{24}*, Mengrong Li\textsuperscript{24}*, Yuemei
Sun\textsuperscript{25}*, Yi Jiang\textsuperscript{26}*, Weitian
Zhang\textsuperscript{27}*, Qianhui Qiu\textsuperscript{28}*, Chuanhe
Liu\textsuperscript{29}*, Jie Yin\textsuperscript{30}*, Guodong
Hao\textsuperscript{31}*, Huabin Li\textsuperscript{32}*, Yongsheng
Xu\textsuperscript{33}*, Shaohua Chen\textsuperscript{34}*, Hua
Zhang\textsuperscript{35}, Shi Chen\textsuperscript{36}, Juan
Meng\textsuperscript{37}, Dan Zeng\textsuperscript{38}, Wei
Tang\textsuperscript{39}, Chuangli Hao\textsuperscript{40}, Jing
Li\textsuperscript{1}+, Nanshan Zhong\textsuperscript{1}+, for the China
Alliance of Research on Respiratory Allergic Disease

*Contributed equally

+Joint corresponding authors

1 National Clinical Research Center for Respiratory Disease, State Key
Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory
Health, The First Affiliated Hospital of Guangzhou Medical University;

2 The First People's Hospital of Yibin, Sichuan;

3 The First Affiliated Hospital of Henan University of Traditional
Chinese Medicine;

4 General Hospital of Northern Theater Command;

5 Tongji Hospital, Tongji Medical College, Huazhong University of
Science\&Technology;

6 The Affiliated Hospital of Medical School, Ningbo University;

7 Foshan First people's hospital;

8 Beijing Hospital of Traditional Chinese Medicine;

9 GuangDong Provincial Hospital of Chinese Medicine;

10 The First Affiliated Hospital of Shandong First Medical University,
Shandong Institute of Respiratory Diseases;

11 Hangzhou Hospital of Traditional Chinese;

12 The Affiliated Hospital of Qingdao University;

13 Hubei Province Maternal and Child Health Hospital;

14 Boai Hospital of Zhongshan City;

15 Xi'an Children's Hospital;

16 The First Affiliated Hospital of Sun-Yat University;

17 The First Affiliated Hospital of Zhengzhou University;

18 Children's Hospital of Zhejiang University School of Medicine,
National Clinical Research Center for Child Health;

19 Hebei General Hospital;

20 Third Xiangya Hospital of Central South University;

21 The Women and Children's Hospital affiliated to Xiamen University;

22 Children's Hospital of Nanjing Medical University;

23 Union hospital of Tongji medical college;

24 The Second Affiliated Hospital and Yuying Children's Hospital of
Wenzhou Medical University;

25 Yu Huang Ding Hospital;

26 The First Hospital of Shanxi Medical University;

27 Shanghai Jiao Tong University Affiliated Sixth People's Hospital;

28 Zhujiang Hospital of Southern Medical University;

29 Children's Hospital Capital Institute of Pediatrics;

30 Chengdu First People's Hospital;

31 Tangshan Gongren Hospital;

32 ENT Institute and Department of Otorhinolaryngology, Eye \& ENT
Hospital, Fudan University;

33 Children's Hospital of Tianjin University;

34 Guangdong Provincial People's Hospital;

35 The First Affiliated Hospital of Xinjiang Medical University;

36 Hainan provincial people's Hospital;

37 West China Hospital of Sichuan University;

38 Chongqing General Hospital, University of Chinese Academy of
Sciences;

39 Ruijin Hospital of Shanghai Jiaotong University;

40 Children's Hospital of Soochow University.

\textbf{Correspondence}

Jing Li, Nanshan Zhong

National Clinical Research Center for Respiratory Disease

State Key Laboratory of Respiratory Disease

Guangzhou Institute of Respiratory Health

The First Affiliated Hospital of Guangzhou Medical University,
Guangzhou, Guangdong, 510120, P.R. China

E-mail: lijing@gird.cn

To the Editor,

Recent epidemiological studies revealed that the prevalence of allergic
rhinitis and asthma dramatically increased in
China\textsuperscript{\textbf{{[}1, 2{]}}} . In 2008, to better
represent sensitization rates in rhinitis and asthma, the China Alliance
of Research on Respiratory Allergic Disease (CARRAD) conducted a
national cross-sectional study on allergen sensitization in outpatients
with asthma and rhinitis. The study demonstrated that house dust mites
were the most prevalent allergens in China. The allergen sensitization
rates varied by geographic location\textsuperscript{\textbf{{[}3{]}}} .
One decade has passed since our last national multi-center epidemiologic
survey in 2008. Tremendous transformations have been taken place in
economy status, e.g. people's living and working styles, urbanizations
and the environment variations in China. Especially in the northern
part, the regional governments have made great efforts to plant a large
scale of \emph{Artemisia desertorum} in order to control the impact of
sandstorms on the big cities. Little is known about the impact of social
and environmental changes on temperature and humidity as well as
sensitizations in the general population or in patients with rhinitis
and/or asthmas. Given the needs in providing important evidences for the
national developmental strategies and clinical managements to reduce the
burden and morbidity of allergic airway diseases, CARRAD decided to
conduct the second national survey in 2018 with the same study protocol
used in 2008 to understand the trends of sensitizations of patients with
rhinitis and asthma in the past 10 years.

The 2008 survey was conducted from January 2008 to December 2008 in 17
cities with 24 participating centers. Expanding on this, the 2018 study
was conducted from January 2018 to December 2018 in 26 cities with 36
centers from the northern, eastern, central, and southern coastal
regions of China. A total of 6304 patients and 5532 patients, aged 5--65
years, in outpatient clinics at the study sites were enrolled in 2008
and 2018, respectively. After finishing the questionnaire, participants
underwent serum specific IgE measurement. A total of 2322 and 2798
patients were enrolled in 2008 and 2018, respectively. The study
protocol was approved by the ethics review board of each study center.
Details about the methods were in the Appendix S1.

As shown in Table 1, the general sensitization rates to mites were
significantly higher in 2018 than in 2008 (\emph{Dermatophagoides
pteronyssinus, Dermatophagoides farinae, Blomia tropicalis} : 52.1\% vs
45.4\%, 51.7\% vs 44.5\%, 30.7\% vs 24.1\%, respectively; all
P\textless{}0.01). Likewise, sensitization rates to pollens
(\emph{Populus nigra} , \emph{Ambrosia artemisifolia} ,
and\emph{Artemisia vulgaris} ) (4.2\% vs 2.9\%, 5.2\% vs 1.7\%, 10.5\%
vs 7.4\%, respectively; all P \textless{}0.05) and dog fur (5.9\% vs
3.7\%, P\textless{}0.01) was increased in 2018 compared with 2008. No
significant differences in sensitization rates to cat dander, timothy
grass, and \emph{Alternaria alternata} were observed between the 2018
and 2008 cohorts. Adults showed a greater increase in sensitization rate
to mites (all P\textless{}0.01), while children had a greater increase
in sensitization rates to dog dander, \emph{Populus nigra} ,
\emph{Ambrosia artemisifolia} , and \emph{Artemisia vulgaris} (all
P\textless{}0.01). Sensitivity to \emph{Alternaria alternata} was
significantly higher in children than in adults in both cohorts (both
P\textless{}0.01). Among four regions, individuals from the southern
coast showed the highest and the north the lowest prevalence of
sensitization to\emph{Dermatophagoides pteronyssinus} in 2008 and 2018.
Except for the east region, the other three regions showed a significant
increase in sensitization rates to \emph{Dermatophagoides pteronyssinus}
and\emph{Dermatophagoides farinae} in 2018. Sensitization to cat
and\emph{Alternaria alternata} was higher in children than in adults in
both cohorts. The northern region showed a dramatic increase in
sensitization rates to \emph{Ambrosia artemisifolia} and \emph{Artemisia
vulgaris} in 2018 compared with those in 2008, and it showed the highest
sensitization rate among the four regions in both surveys.

Compared to 2008 data, results from 2018 found that in northern China,
high-degree pollen sensitization (IgE grade 4-6) and low-degree
sensitization to dog dander increased in both children and adults,
whereas high-degree mite sensitization increased only in adults (all
P\textless{}0.05). In eastern China, grade 6 sIgE levels to mites
(\emph{Dermatophagoides pteronyssinus} and \emph{Dermatophagoides
farinae} ) sIgE were observed in greater numbers of children (both
P\textless{}0.05). High-level sIgE sensitization to dog dander declined
in adults (P\textless{}0.001). In central China, mites
(\emph{Dermatophagoides pteronyssinus} and \emph{Dermatophagoides
farinae} ) sIgE levels (grades 4--6) were increased in adults (both
P\textless{}0.05). In the southern coast, high-degree sensitization to
mites increased, whearas to Art v decreased in both children and adults
(all P\textless{}0.05). All degrees of sensitization to \emph{Alternaria
alternata} significantly decreased in children (P\textless{}0.01)
(Figure S1).

As in 2008, mites were still the most important allergen in 2018,
especially for the youngest group. Sensitization to mite increased in
nearly all age groups among individuals with rhinitis alone as well as
in those with rhinitis and asthma (all P\textless{}0.05) (Figure
1A\textbf{)} . Patients with rhinitis had significantly higher positive
rates of pollen sensitization in 2018, peaking between 25 and 44 years
(P\textless{}0.05) (Figure 1C\textbf{)} . In 2018, the positive rate of
animal sensitization was twofold higher in the 15--24-year-old rhinitis
group (P\textless{}0.05). In addition, the fungus sensitization was
increased in children with rhinitis and asthma (P\textless{}0.05)
(Figure 1B and 1D\textbf{)} .

Using nationwide epidemiological study data, we found that the
prevalence of sensitization to house dust mites (\emph{Dermatophagoides
pteronyssinus} , \emph{Dermatophagoides farinae and Blomia tropicalis}
), pollens (\emph{Populus nigra, Ambrosia artemisifolia} ,
and\emph{Artemisia vulgaris} ), and animals (dog dander) in individuals
with asthma and/or rhinitis significantly increased in China over the
last decade. We noted that sensitization to pollens, especially those
of\emph{Artemisia vulgaris} , showed the greatest increase in the north,
with sIgE grades 4--6. This may attributed to the allergenic properties
of the pollen changing with climate across the northern hemisphere and
sand dust control planting with \emph{Artemisia desertorum} in our
country\textsuperscript{\textbf{{[}4,5{]}}} . These findings suggest
that policies need to be adjusted to mitigate human-induced climate
change and conduct further studies on the allergen testing for
\emph{Artemisia desertorum.}

\textbf{Figure S1. Comparison of allergen sensitization grades in
children and adults in four geographic regions of China.} Allergen
abbreviations: Der p=\emph{Dermatophagoides pteronyssinus} , Der
f=\emph{Dermatophagoides farinae} , Blo t=\emph{Blomia tropicalis} , Phl
p=\emph{Phleum pretense} , Pop n=\emph{Populus nigra} , Amb
a=\emph{Ambrosia artemisifolia} , Art v=\emph{Artemisia vulgaris} , Alt
a=\emph{Alternaria alternata} . *P\textless{}0\selectlanguage{ngerman}·05, **P\textless{}0·01,
***P\textless{}0·001.

\textbf{Figure 1. Distribution of sensitizations to different groups of
allergens in patients with rhinitis, asthma, and asthma with rhinitis by
stratification to age groups between 2008 and 2018.} *P\textless{}0·05,
**P\textless{}0·01.

\textbf{Conflicts of interest}

The authors declare that they have no conflicts of interest.

\textbf{Acknowledgments}

This study was supported by the Precision Medicine Research of the
National Key Research and Development Plan of China (grant no
2016YFC0905800). We thank the study participants of the China Alliance
of Research on Respiratory Allergic Disease who made this analysis
possible. We would like to thank Professor Yiwu Zheng and Professor
Xuxin Lai for their cooperation and suggestions to the manuscript;
Professor Mei Jiang (Guangzhou Institute of Respiratory Health) for
assistance in statistical considerations; Professor Zhaowei Yang
(Guangzhou Medical University) for help in editing the figures.
Professor Ming Liao (Guangdong Academy of Agricultural Sciences) for
assistance in Artemisia desertorum data collection.

\textbf{References}

1. Huang K, Yang T, Xu J, et al. Prevalence, risk factors, and
management of asthma in China: a national cross-sectional study. Lancet
2019; 394: 407-418. 2. Wang X, Zheng M, Lou H, et al. An increased
prevalence of self-reported allergic rhinitis in major Chinese cities
from 2005 to 2011. Allergy 2016; 71: 1170-1180. 3. Li J, Sun B, Huang Y,
et al. A multicentre study assessing the prevalence of sensitizations in
patients with asthma and/or rhinitis in China. Allergy 2009; 64:
1083-1092.

4. Lewis HZ, László M, Susan KH, et al. Temperature-related changes in
airborne allergenic pollen abundance and seasonality across the northern
hemisphere: a retrospective data analysis. Lancet Planet Health
2019;3:e124-e131

5. Lu K, He Y, Mao W, et al. Potential geographical distribution and
changes of Artemisia ordosica in China under future climate change.
Chinese Journal of Applied Ecology 2020;31:3758\selectlanguage{english}-3766\selectlanguage{english}
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