The target population for this trial will be recruited from the respiratory clinic of Shanghai Children's Medical Center. Shanghai Children's Medical Center is a tertiary first-class pediatric hospital with a large number of outpatient with asthma and rhinitis and a professional respiratory medical team.
- Age 3 -12 years, male or female.
- Children diagnosed with AR in accordance with the 2019 guidelines for diagnosis and treatment of allergic rhinitis. At the same time, the diagnosis will conform to the diagnostic criteria for childhood asthma formulated by the National Children's Asthma Prevention and Treatment Cooperation Group in 2016 .
- Maintained use of guide-based rhinitis and asthma control drugs for the past 1 month. Inhaled drugs such as budesonide suspension, fluticasone aerosol, salmeterol dry powder inhalation and budesonide formoterol dry powder inhalation can be chosen to control the condition according to age characteristics.
- Performance of the serum-specific allergen test, with the level of dust mite allergen sIgE > 0.35 IU/mL considered positive.
- Informed consent signed by the guardians of all subjects (approved by the Ethics Committee of Shanghai Children's Medical Center affiliated with Shanghai Jiao Tong University School of Medicine).
- Agreement to collect dust mites from indoor mattresses.
- Basic diseases such as congenital heart disease, immune deficiency, gastroesophageal reflux, bronchopulmonary dysplasia, and obliterative bronchiolitis.
- Inability to sleep in a separate bed.
- Participation in other clinical studies within the past 3 months.
Who will take informed consent?
Before the implementation of the trial, we will inform the parents of children under the age of eight about the specific process of the trial, obtain their consent and sign the informed consent form. If the child is older than 8 years old, both the child and the parents will be required to sign the informed consent after learning about the trial process.
Explanation for the choice of comparators
We will compare Hestelia Mite Bait, containing 0.1% emamectin with the placebo that has a consistent appearance and odor but no acaricidal effect to investigate the change of dust mite exposure and the improvement in asthma and rhinitis symptoms after using mite bait indoors.
After recruitment (V0), the baseline medical characteristics of name, age, gender, diagnosis of asthma and rhinitis and allergen test report need to be collected. The subjects will be randomly grouped. We stipulate that the children randomly assigned to Group 1 are first placed with package A for an 8-week intervention. All HDM species reach adulthood within 3 to 4 weeks. Once mature, adult mites have a life expectancy of between 4 and 6 weeks . To avoid the impact of the previous intervention on the second intervention, we have established a 4-week washout period according to the growth cycle of dust mites. Then, package B will be placed for an 8-week intervention after a 4-week washout period. In Group 2, package B will be placed for an 8-week intervention, followed by a 4-week washout period, and then package A placed for an 8-week intervention. Each child will undergo a total intervention period of 16 weeks, a washout period of 4 weeks, and a follow-up period of 4 weeks after the end of the second intervention. The flow chart of the study is shown in Figure 1.
At V1, V3, V4 and V6, the staff will collect indoor samples from mattresses with a glass fibre membrane mite-clearing vacuum cleaner. The components of dust mite antigens in the collected samples will be detected by ELISA. Parents will be asked to evaluate the AR and asthma symptom scores and clinical event records at V1-V7 (see the outcome indicators for details), as shown in Table 1.
Criteria for discontinuing or modifying allocated interventions
If the research physician feels that it is not in the child’s best interest to continue participating in the study, for example, there is an allergic reaction to the mite bait or placebo used, he/she may decide to withdraw the child from the study at any time.If the subjects’ parents fail to complete the questionnaire after 3 reminders or fail to cooperate with the indoor sample collections, the subjects will be considered poorly compliant and will be excluded from the study.
Strategies to improve adherence to interventions
First, we will explain our study to each child’s parents as follows: The enrolled children can receive regular follow-up, a questionnaire evaluation and standardized treatment by respiratory specialists at Shanghai Children's Medical Center. The detection of the HDM antigen concentration in the bedroom mattress is free of charge, and the mite bait and placebo package are safe. If a child is randomly assigned to the placebo group, he/she may not be able to benefit from the intervention but not to aggravate the original symptoms. During the study, professional staff will enter the room four times to clean the mattress with a mite-removing vacuum cleaner and collect attractors. The whole process requires the cooperation of the subjects' family members, and the subjects' parents will be able to complete the questionnaires in 10-20 minutes.
Secondly, during the implementation process, we will regularly remind parents to fill out the questionnaire via WeChat. The research team will also provide detailed answers and help to parents' questions during the trial.
Relevant concomitant care permitted or prohibited during the trial
The original asthma medication can be maintained during the trial. When acute asthma attack symptoms occur, β2 agonists will be used to relieve bronchospasm, and oral or intravenous corticosteroids will be used, depending on the clinical severity, until the symptoms are relieved.
However, during the test, the children went out for a long time or could not guarantee the indoor living in a room with mite bait or placebo will not be allowed.
- VAS of clinical symptoms of AR
- In 1988, Linder first applied VAS to the assessment of AR symptoms, demonstrating its sensitivity and specificity . Patients will be scored with a VAS score for symptoms occurring in the past week, including sneezing, rhinorrhoea, nasal itching, nasal congestion, itchy eyes, teary eyes, foreign body sensation and red eyes, for a total of eight symptoms. The VAS uses a 10 cm long ruler, 0 ~ 10, to show the severity of the patient symptoms ("0" for no such symptoms and "10" representing the heaviest of such symptoms), instructs the patients according to the symptoms, and directs the patients to mark the symptom scores on the scale.
- Change in RCAT
- The RCAT demonstrated adequate reliability, validity, and responsiveness and was deemed acceptable and appropriate by the patients. This tool can facilitate the detection of AR symptom-control problems, and its brevity supports its usefulness in clinical care. The RCAT has 6 items that include nasal congestion, sneezing, watery eyes, sleep problems caused by rhinitis, activity avoidance, and rhinitis symptom control. Responses are measured on 5-point Likert-type scales. RCAT scores range from 6 to 30, with higher scores indicating better rhinitis control. 
- Change in ACQ-5
- ACQ-5 is a scale composed of 5 simple multiple choice questions. The results are obtained by adding the total points and averaging them. It plays a significant role in evaluating whether asthma is controlled and can rapidly assess asthma control. The child will be asked to evaluate the level of asthma control asthma in the past 1 week. The lower the score, the better the control level.
- RQLQ for children with AR 
- In this study, children with rhinitis in the past 1-2 weeks will be evaluated on their own symptoms, psychological status, mental status, social communication and other aspects of 14 problems caused by rhinitis, 0 points: normal; 1 point: slight; 2 points: mild; 3 points: serious; 4 points: very serious. The higher the score, the more severe the rhinitis effect on quality of life.
- Changes in levels of dust mite antigen in children's beds.
- Three sampling points will be randomly selected for each mattress, and each sampling point will have a range of 30 cm2. Each sampling point needs to be vacuumed 10 times repeatedly with a glass fibre membrane mite-clearing vacuum cleaner (and the bed area will be recorded at the same time). Dust on the glass fibre membrane in the vacuum cleaner will be put into a plastic bag and stored at -20℃ (killing the dust mites). Allergens will be extracted from samples from each family after weighing. The ELISA method (Indoor Biotechnologies, Charlottesville, VA, USA) will be adopted to detect dust mite antigen Der p2 (Dermatophagoides pteronyssinus) and Der f2 ( farinae) in the extracted solution.
- Use of medicines for children's AR and asthma
- For children who over the past 4 weeks have used anti-asthma drugs frequently for the control of rhinitis, the percentages are as follows: no use ever: 0%; a total of 1 week of use: 25%; and use every day: 100%. Specific drugs include physiological saline, nasal spray hormone (Mometasone Furoate Aqueous Nasal Spray, Fluticasone Propionate Nasal Spray, Budesonide Nasal Spray, etc.), oral allergy drugs (cetirizine, loratadine, levocetirizine, desloratadine, etc), Sinupret Drops, montelukast, traditional Chinese medicine (Tongqiao Biyan Granule, Biyuanshu Oral Liquid, Xinqin Granule), nasal allergy medications (levocabastine, azelastine hydrochloride), desensitization treatment (Dermatophagoides Farinae Drops), inhaled hormones to control asthma (Budesonide Suspension For Inhalation, Seretide, Flixonase, Symbicort Turbuhaler).
- The number of asthma attacks, emergency visits, frequency of hospitalization
- Side effects: rash, enuresis, irritability, drug-related cough, and others
On the assumption that a reduction of 25% in VAS scores would be of clinical significance, 44 patients in each group are required at the 5% significance level (two-tailed) and a power of 90% to detect this difference between the two groups . Considering a 10% possible dropout, each group needs to enrol at least 49 people.
In this experiment, we will recruit 60 people for a placebo-controlled, double-blind crossover trial. After crossover, the placebo group and the experimental group will each be increased to 60 people.
Recruitment information will be posted in the Respiratory Clinic of Shanghai Children's Medical Center and released through the WeChat public account of Respiratory Department.
Assignment of interventions: allocation
Random sequences will be generated by the random number table.
Random sequences will be successively assigned to the subjects according to the enrolment order.
Odd numbered subjects will be entered into Group 1, and the even numbered ones will be entered into Group 2.Three copies of the generated distribution sequence table will be distributed among the designer, pharmacist and statistician. Each copy should be sealed with an opaque envelope and kept with a lock.
A special person is responsible for enrolling the test subject according to the selection and exclusion criteria who is not involved in the subsequent grouping and intervention. A random sequence is generated by the statistician. The test designer decides that odd numbered subjects will be entered into Group 1, and the even numbered ones will be entered into Group 2.
Assignment of interventions: Blinding
Who will be blinded
The placebo used in the study looks and smells indistinguishably from mite bait and will be labelled either A or B. The identities of Tag A or Tag B will be known only to the pharmacists and unknown to the subjects and researchers.
Procedure for unblinding if needed
When the trial is over, the number of each subject and the treatment plan received need to be checked, and the sealed distribution sequence needs to be decrypted. When unblinding, the intervention measures recorded in the assigned serial number were checked with the drug delivery record sheet, and the result data was classified for analysis by the test group and the control group.
Data collection and management
Baseline data and questions related to the outcome indicators will be designed into questionnaires at https://www.wjx.cn/ , and will be regularly pushed to parents to fill out via WeChat. Parents who fill out questionnaires are usually a fixed one who is mainly responsible for the daily life of the child. During the follow-up period, once the questionnaire is completed and submitted, no one has the right to modify the contents of the questionnaire. In addition, there will be a fixed staff check whether the parents fill in the questionnaire and whether the questionnaire is completed. He will not know the parent grouping and intervention. After the end of the whole experiment, all data will be exported in the form of EXCEL and analyzed by SPSS 2.0 software.
SPSS 2.0 will be used to analyse the experimental data. Descriptive statistics will be used for the following data analysis: RCAT scores, ACQ-5 scores, drug usage for asthma and AR, frequency of acute asthma attacks and emergency visits, frequency of hospitalization, etc.—these categorical variables by frequency tables (i.e., number of evaluable subjects, frequency and percentage for categorical values) and VAS scores, RQLQ scores—these continuous variables (i.e., mean, SD, minimum, median and maximum). One-way analysis of variance will be adopted for normally distributed data, and the non-parametric rank sum test will be adopted for non-normally distributed data. Fisher's exact chi-square test will be used to compare classified data, and P<0.05 will be considered statistically significant.