Sanya climatic-treatment cohort profile: objectives, design, and baseline characteristics

Background The prevalence of allergic diseases has increased globally, climate and environment also have important effects on respiratory or allergic diseases. However, population-based studies investigating the impact of tropical climates and environments on migratory-bird old people (MBOP) are lacking. Methods/Design For this prospective cohort study, we recruited 756 participants from the community in Sanya City, Hainan Province, China. In addition to the completed baseline survey, a follow-up survey will be conducted during the periods of October–December and March–April for the next 3 years of MBEPs from northern China who spend the winter in Sanya. We will continue to record the height, weight, and blood pressure of all participants, as well as lung function for those with asthma and chronic obstructive pulmonary disease (COPD). Venous blood at baseline and urine samples will be collected during follow-up. Results A total of 756 volunteers were recruited. Their average age is 66.1 years; 32.1% of them have high-school educations, while 37.3% have graduated from college or done undergraduate studies. The top five diseases in this cohort are allergic rhinitis (57.9%); eczema, urticaria, or dermatitis (35.6%); bronchitis and bronchiectasis (35.6%); asthma (14.7%); and emphysema (11.7%). Compared with their symptoms while at their summer places of residence, rates of remission reported by participants while living in Sanya were 80.4% for allergic rhinitis, 82.3% for bronchitis and emphysema, 85.2% for asthma, 96.0% for COPD (P < 0.001). Conclusions The baseline survey has been completed. The preliminary findings support that a tropical climate may relieve the symptoms of allergic diseases in migratory-bird old people.


Introduction
The prevalence of allergic diseases has increased globally in recent decades (1,2).According to the World Health Organization's (WHO) 2019 report, approximately 262 million people worldwide suffered from asthma at the time, resulting in 455,000 deaths.Allergic diseases, including allergic rhinitis and eczema, together constitute a major global public-health burden (3).China is also facing this issue: according to epidemiological surveys, the prevalence of allergic diseases (4,5) such as asthma (6,7), allergic rhinitis (8), and eczema are increasing in China.Influencing factors include climate change (9), air pollution (10), environmental temperature (11), meteorological factors (12), and allergens (13).
Current studies on allergic diseases mainly focus on the effects of climate and environmental factors.There are reports on the treatment and relief of asthma in alpine environments (14, 15).However, population-based research is lacking on the effect of tropical climate and environment on migratorybird old people (MBOP).Sanya, China has a unique tropical climate, with a minimum temperature of >15 • C in winter; by contrast, the minimum winter temperature in northern China is below −40 • C (16).Therefore, many MBEPs relocate from northern China to Sanya for the winter.It is reported that more than 1 million people spend the winter in Sanya every year (17).
In addition to drug treatment, climate, and environment also have important effects on respiratory or allergic diseases.In Europe, cave therapy is widely used to treat chronic airway diseases.Some studies have shown that exercise in winter combined with cave therapy can improve the quality of life (QoL) and allergic symptoms of adults with allergic rhinitis and/or asthma (18,19).A systematic review showed that high-altitude climate therapy improved the lung function of adult asthma patients (15, 20).However, there is no relevant evidence that symptoms and climate-related factors of allergic diseases improve in MBEPs who move from high latitudes to low ones.The establishment of this cohort will help us better study the effect of Sanya's tropical climate on respiratory or allergic diseases, clarify risk factors related to these diseases, and determine whether such a climate effectively mitigates these diseases in MBEPs.

Cohort description Study design, setting, and participants
This is a prospective cohort study whose subjects were recruited from the community in Sanya City, Hainan, the southernmost province in China from 2022 to 2025.We will conduct a followup survey focused on allergic diseases in MBEPs from northern China who move to Sanya for the winter (Figure 1).Northern China includes three northeastern provinces (Heilongjiang, Jilin, Abbreviations: WHO, World Health Organization; MBOP, Migratory bird's old people; FEV , Forced expiratory volume in s; COPD, Chronic obstructive pulmonary disease; FVC, Forced vital capacity; AQLQ, Asthma quality of life questionnaire; SGRQ, Saint George respiratory questionnaire. and Liaoning), five northern provinces (Beijing, Tianjin, Hebei, Shanxi, and the Inner Mongolia Autonomous Region), and five northwestern provinces (Xinjiang Uygur Autonomous Region; Ningxia Hui Autonomous Region; and Qinghai, Gansu, and Shaanxi Provinces).The subjects of this study are MBEPs who travel from northern China to Sanya in autumn, stay for the winter, and return to northern China in spring.The sample size was estimated by forced expiratory volume in 1 s (FEV 1 ) (15), which was 92.8% ± 23.1 and 86.5 ± 26.2 for the trial and control groups, respectively.A type I error α = 0.05, β = 0.10, and loss of follow-up rate of 20% for 3 years, requiring 775 participants.
For easier follow-up, we recruited participants from communities of mainly MBEPs, who own apartments in Sanya and spend the winter there for many years.Inclusion criteria were as follows: (a) age 50-80 years; (b) suffering from allergic rhinitis, asthma, eczema, urticaria, or chronic obstructive pulmonary disease (COPD); (c) previous or winter residence in northern China; (d) willingness to participate in the study and be followed up on at the designated location for the subsequent 3 years; and (e) no difficulty in communication.Exclusion criteria were (a) other respiratory diseases and (b) communication barriers or unwillingness to cooperate with the requirements of the study.
Diagnosis of allergic rhinitis, asthma, eczema, urticaria, or COPD was based on self-reported disease history in face-toface interviews at recruitment.Allergic rhinitis was defined as an affirmative response to the question "Do you have any nasal allergies, including hay fever?" according to the Allergic Rhinitis and Its Impact on Asthma guidelines (8).Asthma was defined as a self-reported history of asthma, diagnosis by a physician, or wheezing during the preceding 12 months (6).Eczema or urticaria was defined as self-reported history and/or diagnosis by a physician (21,22).Atopic dermatitis was diagnosed by an affirmative response to the question "Have you had an itchy rash at any time in the past 12 months?"(8).COPD was defined as postbronchodilator FEV 1 /forced vital capacity (FVC) < 0.7 according to the 2017 Global Initiative for Chronic Obstructive Lung Disease guidelines (23).Chronic bronchitis was defined as self-reported phlegm production for at least 3 months each year over 3 successive years (24).

Data collection Demography and outcomes
A paper questionnaire was used to collect a range of basic information in march 2022.After obtaining informed consent, trained investigators collected relevant information in faceto-face interviews.The questionnaire covered demographic data, socioeconomic status, clinical disease characteristics, living habits, and past medical history (Table 1).Participants with asthma and COPD were evaluated using the Asthma Quality of Life Questionnaire (AQLQ) (25) and Saint George Respiratory Questionnaire (SGRQ) (26), respectively; SGRQ assesses the quality of life of participants with COPD.The primary outcome was the effect of Sanya's tropical climate

Physical examination
We used a unified measuring tool for physical examination.After calibration, we measured the height, weight, and blood pressure of all participants, and in those with asthma and COPD, we also measured lung function.Participants were asked to take off their shoes and coats before their heights and weights were measured.

Collection and measurement of biological samples
Nurses from local hospitals traveled to the community, collected 5-10 mL of patients' venous blood, and then transferred the samples to the laboratory at Sanya Women and Children's Hospital (SWCH) for centrifugation and subpackaging.Whole blood was used for routine blood tests; serum was used to test for liver and kidney function, blood sugar, blood lipids, and allergen.Some samples were stored in a freezer at −80 • C. Table 2 lists the types of samples and main tests using these samples.

Quality control
All investigators received unified training.Two investigators independently input the results of all questionnaires into database using EpiData 3.0 software (EpiData, Copenhagen, Demark).A Portion of the data underwent double entry, and in cases where inconsistencies arose, a third researcher reviewed and resolved them to guarantee data accuracy.We adopted various policies to retain participants in the cohort.Health consultation was and will be provided during recruitment and follow-up, and free health examinations were and will be provided during baseline and follow-up.We are following up on participants in the spring (March-April) and autumn (October-December) every year for the next 3 years and providing them with timely reminders to take advantage of the free health examinations.

Statistical analysis
Baseline characteristics of participants who stayed in or withdrew from the cohort, and loss of follow-up, were described.All missing data were noted.We analyzed classification data using a χ 2 test and continuous data using Student's t test.All analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA).P < 0.05 was considered to indicate a statistically significant difference.

Ethical approval
The research protocol and informed-consent form of this study were reviewed and approved by the Ethics Committee of Sanya Women and Children's Hospital (Approval No. SYFYIRB2022009).All participants signed their informed consent before participating.

FIGURE
FIGUREGeographical location of the Sanya migratory cohort.The shaded regions represent participants' original places of residence, red indicates the northwest China, blue represents the north China, and green signifies the northeast China.
TABLE Data collected from participants in the Sanya migratory cohort.
TABLE Collection of biological samples from participants in the Sanya migratory cohort.
TABLE Baseline characteristics of the Sanya migratory cohort.TABLE Data collected from participants in the Sanya migratory cohort.The author(s) declare financial support was received for the research, authorship, and/or publication of this article.The study was supported by the Unveiling the Top Project of Sanya Women and Children's Special Program for Women and Children health (2020YJZX0212), Cultivation Project of Clinical Research from SCMC (LY-SCMC2020-06).