Research on the improvement of allergic rhinitis in asthmatic children after reducing dust mite exposure: a randomized, double-blind, cross-placebo study protocol

doi:10.21203/rs.2.24698/v1

Download PDF

Study protocol

Research on the improvement of allergic rhinitis in asthmatic children after reducing dust mite exposure: a randomized, double-blind, cross-placebo study protocol

https://doi.org/10.21203/rs.2.24698/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 29 Jul, 2020

Read the published version in Trials →

You are reading this older preprint version

Read the latest preprint version →

Background: Allergic rhinitis (AR) in children has become a major respiratory inflammatory disease with a high incidence that is increasing yearly. In China, 54.93% of children with asthma have AR, which often requires synchronous treatment. House dust mites (HDMs) are common allergens that often cause attacks of AR and asthma. Reducing allergen exposure is one of the most important measures to control and treat AR and asthma attacks. Hestelia Mite Bait, containing 0.1% emamectin, is a new tool for trapping and killing dust mites that can reduce the number of dust mites on mattresses, thereby may reduce stimulation by allergens and ultimately improve asthma and rhinitis symptoms. This single-centre, randomized double-blind cross-placebo trial will explore the improvement of allergic rhinitis in asthmatic children after reducing dust mite exposure.

Methods: We will recruit 60 children (aged 3-12 years) who have been diagnosed with allergic rhinitis and asthma and are allergic to dust mites as confirmed by a serum allergen test. Participants will randomly receive the Hestelia Mite Bait intervention for 8 weeks and the placebo intervention for 8 weeks. There will be a 4-week washout period between the two interventions. The primary outcome is the v isual analogue scale (VAS) score of AR symptoms; the secondary outcomes include the Rhinitis Control Assessment Test (RCAT) score, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score , changes in the dust mite level, drug usage for asthma and AR , Asthma Control Questionnaire-5 (ACQ-5) score, frequency of acute asthma attacks and emergency visits, and frequency of hospitalization.

Discussion: This study will scientifically and objectively evaluate the improvement effect on rhinitis and asthma after reducing dust mite exposure and provide a convenient means for the prevention and treatment of children's airway allergic diseases in the future.

Trial registration : ChiCTR1900024688 (www.chictr.org.cn) registration date: July 21, 2019

Integrative & Complementary Medicine

Internal Medicine

Translational Medicine

allergic rhinitis

asthma

dust mite

Background and rationale

Allergic rhinitis (AR) is a non-infectious disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. It is a common allergic disease in children. The incidence of AR may be increased by 10–30% in adults and by 40% in children ^[1]. AR manifests as sneezing,

rhinorrhoea, sinus itch, and other symptoms, which have an adverse effect on quality of life, leading to sleep disordered breathing, as well as increased attention deficit disorder ^[2−3].

AR often coexists with organ-complicated allergic diseases, among which asthma is one of the most common condition. In a Chinese epidemiological study, the incidence of asthma in children with AR was 35.01%, and the prevalence of AR in children with asthma was 54.93% ^[4]. There are common pathophysiological elements in AR and asthma. The immunopathology of AR and asthma are quite similar in regard to their cellular influx of eosinophils, mast cells, and T-helper type 2 (Th2) cells. A similar array of mediators can also be found in the lavage of patients with AR and asthma ^[5]. Therefore, AR and tension are proposed as "the same respiratory tract, the same disease". In the presence of asthma, the treatment of allergic rhinitis is often overlooked, and poor control of AR has also been shown to be one of the causes of refractory and recurrent asthma ^[6−8]. The control of allergic rhinitis reduces the incidence and hospitalization of asthma attack ^[9].

Dust mites are a common trigger for AR ^[10]. The prevalence of house dust mites (HDMs) in AR patients in southern China is 95% ^[11]. Avoiding allergen exposure is an important measure to treat AR. Currently, reduced HDM exposure measures include keeping the room humidity below 50%, wrapping mattresses and pillows with impervious covers, regularly cleaning bedding with hot water, removing carpets and plush toys, and regularly using high-efficiency particulate air filters and acaricide. A systematic review of randomized controlled trials was conducted in which HDM control measures were evaluated in comparison with placebo or other HDM avoidance measures in patients with clinically proven AR. In this review, seven of the nine trials reported that compared with control, the interventions studied resulted in significant reductions in HDM load. However, of the interventions studied to date, acaricides appear to be the most promising ^[12]. Hestelia Mite Bait, containing 0.1% emamectin, induces dust mites into the mite trapping bag through the combined action of an oligomeric aromatic factor and dust-mite atopic agents; then, it kills the dust mites, thereby achieving the goal of reducing allergens. As a new safe and effective tool to trap and kill dust mites, whether it can improve rhinitis and asthma symptoms has not been verified.

The purpose of this study is to evaluate the improvement of rhinitis and asthma symptoms after reducing dust mite exposure with a acaricide–Hestelia Mite Bait,through a randomized double-blind cross-placebo clinical trial.

This is a randomized, double-blind, cross-placebo clinical trial to determine the improvement of rhinitis and asthma symptoms after reducing dust mite exposure. Participants will be randomly divided into 2 groups (Group 1 and Group 2), with intervention by mite bait or the placebo package, respectively; for the first 8 weeks, parents will fill out the questionnaires three times (V1-V3, V1 = the first day after enrolment; V2 = the fourth week plus or minus 3 days after enrolment; V3 = the eighth week plus or minus 3 days after enrolment). House sampling must be conducted twice (V1 and V3) during this period. Then, the children will undergo a washout period for 4 weeks, and cross over to mite bait or the placebo package for 8 weeks. Questionnaires will be completed three times (V4-V6, V4 = the twelfth week plus or minus 3 days after enrolment, V5 = the sixteenth week plus or minus 3 days after enrolment, V6 = the twentieth week plus or minus 3 days after enrolment), and house sampling (V4 and V6) will need to be completed twice again. Finally, we will conduct the questionnaire survey 4 weeks after the end of the intervention (V7, V7 = the twenty-fourth week plus or minus 3 days after enrolment). Throughout the study, the children will receive standard treatment in accordance with asthma and AR guidelines ^[13−14]. The efficacy of mite bait in AR and asthma symptoms will be assessed by a visual analogue score (VAS) for rhinitis symptoms, RACT score, RQLQ score, changes in the level of dust mites, drug usage for asthma and AR, ACQ-5, frequency of acute asthma attacks and emergency visits, and frequency of hospitalization.

Study setting

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.

Eligibility criteria

Participants:

Inclusion criteria:

Age 3 -12 years, male or female.
Children diagnosed with AR in accordance with the 2019 guidelines for diagnosis and treatment of allergic rhinitis^[13]. 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^[14].
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.

Exclusion criteria:

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.

Interventions

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.

Intervention description

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 ^[15]. 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.

Outcomes

Primary outcome：

VAS of clinical symptoms of AR
- In 1988, Linder first applied VAS to the assessment of AR symptoms, demonstrating its sensitivity and specificity ^[17]. 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.

Secondary outcomes

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. ^[18]
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 ^[19]
- 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

Sample size

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 ^[16]. 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

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

Sequence generation

Random sequences will be generated by the random number table.

Concealment mechanism

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.

Implementation

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.

Statistical methods

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.

In recent years, the prevalence of allergic diseases has been increasing. In the past 20 years, China has conducted three national epidemiological surveys on asthma in children. The results show that in 1990, the average prevalence of asthma among children aged 0-14 years was 1.08%. In 2000, this number increased to 1.97%. In 2010, when 400,000 children were surveyed, the figure was 3.01%, up approximately 50% from 2000^[20]. Zhao Jing et al. adopted the multi-stage sampling method to conduct epidemiological investigations on children with AR in Beijing, Chongqing and Guangzhou and found that the incidence rates of AR were 14.46%, 20.42% and 7.83%, respectively. At the same time，it was found that the incidence level of AR in China was gradually increasing, and the gap with developed countries was narrowed ^[21]. Consequently, allergic diseases are increasingly affecting people's health and quality of life.^[1]

Taking asthma as an example, the causes of allergic diseases are mostly related to indoor allergens, such as dust mites, moulds and animal dander, among which dust mites are the most closely involved ^[20]. A longitudinal population-based study, which included 29 centres (14 countries) mostly in western Europe, showed that AR with allergies to dust mites was associated with an increased risk of asthma independently of other allergens ^[23].

There is still no ideal treatment for diseases caused by dust mite allergy. In clinical practice, dust mite antigen extract infusion or drug inhibition can be used to reduce the immune tolerance of the body and thereby alleviate or relieve symptoms. However, patients with an allergic constitution can reduce their symptoms through treatment, but this condition is difficult to completely cure ^[24-25]. Therefore, compared with expensive and long-cycle treatment, controlling the number of dust mites in the house and reducing the exposure of patients to allergens is an inexpensive and easy method to promote.

There are several common ways of physical mite removal in clinical practice ^[26], such as anti-mite bed covers and anti-mite vacuum cleaners, but these measures cannot significantly reduce the number of live dust mites and cannot remove hidden allergens. Chemical control for different purposes can be divided into two types: acaricide and other types. Acaricide can quickly and effectively kill individual dust mites, but it cannot effectively remove dust mite carcasses, faeces and other allergens, and as a chemical agent, its safety cannot be guaranteed. Repellent only enables the avoidance of dust mites but cannot isolate allergens and is characterized by a bad odour, a thick and oily texture, no resistance to sweat or washing, and other defects. However, the mite bait used in this experiment enables the compound oligomeric aromatic factor and dust mite atopic agents to work together to induce dust mites to enter the bag and ingest only the effective agents against dust mites until they die, thus effectively achieving the purpose of blocking allergens.

The main effective components of the mite bait emamectin benzoate is a low toxicity insecticide and acaricide. It is a highly effective biological agent synthesized on the basis of avermectin and has the characteristics of super-high efficiency, low toxicity (nearly non-toxic), no residue, and no pollution. Compared with that of avermectin, the insecticidal activity of emamectin benzoate is improved by 1-3 orders of magnitude, and it has a very high activity against the larvae of lepidoptera insects, mites and many other injurious insects. Emamectin benzoate has both the gastric toxicity and action of a contact poison with a good effect at a very low dose (0.084~2 g/ha) ^[27]. After testing, the 0.1% emamectin benzoate used in the mite bait has a slight toxicity through skin, mouth and nose. It was found that the product attracted 93% of dust mites, killed 74% of dust mites within 48 hours, and killed nearly 100% of dust mites within 72 hours.

At present, Chinese people with allergic diseases account for approximately 30% of the total population (approximately 400 million), with hundreds of millions of people, especially among those who are young ^[28]. Based on the prevalence of childhood asthma in 2010, there were 6.7 million children with asthma in China alone. Therefore, the potential consumer group for this product is very large. If the efficacy and safety of this product in allergic diseases can be further confirmed through this test, it will provide a new tool for the treatment of such allergic diseases in the future.

Additionally, the random grouping, double-blind and crossover test method is adopted in this experiment, which reduces the influence of selection bias, measurement bias and other errors on the test results. Each subject will receive two schemes successively, which has its own before-and-after comparison, eliminating individual differences and obtaining the results of inter-group comparison.

However, due to the long period of this study, problems such as loss to follow-up, exit and decline in compliance may easily occur. It is difficult to ensure that each case is in the same condition as it is at the beginning of the first phase of the trial when receiving the second phase of treatment.

To improve the compliance of the experiment, during the study, we will contact the parents through WeChat, receive the questions raised by the parents in real time, and record and answer them. They will receive regular questionnaires reviewed by clinical professionals. Workers who collect dust mite specimens indoors should receive training and assessment and complete specimen collection in strict accordance with sampling procedures with the consent of parents. In terms of trial safety, we will track all the events during the study until the incident is alleviated, the situation is stable, other explanations of the incident are obtained, or the subjects lose contact. Subjects can drop out of the study at any time and continue to receive standard treatment for rhinitis and asthma in the outpatient department.

In summary, this study will scientifically and objectively evaluate the improvement effect of mite bait on rhinitis and asthma and provide a convenient means for the prevention and treatment of children's airway allergic diseases in the future.

Trial status

Protocol version and date: April 25, 2019

Start date: 28-7-2019

Planned end date: 28-6-2020

Allergic rhinitis

HDMs

House dust mites

Th2 cells

T-helper type 2 cells

VAS

Visual analogue scale

RCAT

Rhinitis Control Assessment Test

RQLQ

Rhinoconjunctivitis Quality of Life Questionnaire

ACQ-5

Asthma Control Questionnaire-5

Acknowledgements

The Hestelia Mite Bait used in this experiment was provided by Shanghai Jianlida Medical Technology co., LTD

Authors’ contributions

Ming Chen and Yufen Wu are joint first authors. Yong Yin obtained funding. Ming Chen, Yufen Wu, and Jing Zhang designed the study. Jiande Chen, Luanluan Li and Jinhong Wu collected the data. Ming Chen and Yufen Wu analysed the data. Shuhua Yuan and Ming Chen drafted the manuscript. Jing Zhang contributed to the critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript. Jing Zhang and Yong Yin are the study guarantors.

Funding

The project was funded by the Important Weak Discipline of Shanghai Health and Family Planning Commission Pediatrics (no. 2016ZB0104), the Shanghai Pudong New Area Municipal Planning Commission of Science and Research Fund (no. PW2017E-1), "Action plan of scientific and technological innovation" medical device field project of the Shanghai Science and Technology Commission (19441909000) and the Key Project of China Hospital Development Institute of Shanghai Jiaotong University (CHDI-2017-A-06). These funding bodies did not play any role in

designing the study, the collection, analysis,and interpretation of data, or writing the manuscript.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Shanghai Children’s Medical Center Affiliated with Shanghai Jiaotong University of Medicine. Prior to randomization, written informed consent will be obtained from the parents/caretakers of each participant.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests

Author affiliations

1Department of Respiratory Medicine, Shanghai Children's Medical Center affiliated with Shanghai Jiaotong University of Medicine, Shanghai, China.

Authors’ information

Ming Chen, Email: [email protected]

YuFen Wu, Email: [email protected]

Shuhua Yuan, Email: [email protected]

Jiande Chen, Email: [email protected]

Luanluan Li, Email: [email protected]

Jinhong Wu, Email: [email protected]

Corresponding author:

Jing Zhang, Department of Respiratory Medicine, Shanghai Children's Medical Center affiliated with Shanghai Jiaotong University of Medicine,

No. 1678, Dongfang Road, Pudong, Shanghai, China. 200127.

Email: [email protected] Tel: 021-38626161

Yong Yin, Department of Respiratory Medicine, Shanghai Children's Medical Center affiliated with Shanghai Jiaotong University of Medicine,

No. 1678, Dongfang Road, Pudong, Shanghai, China. 200127.

Email: [email protected] Tel: 18930830705

Meltzer EO . Allergic Rhinitis: Burden of Illness, Quality of Life, Comorbidities, and Control. Immunol Allergy Clin North Am. 2016 May;36(2):235-48.
Kong DL, Qin Z, Shen H, et al. Association of Obstructive Sleep Apnea with Asthma: A Meta-Analysis. Sci Rep. 2017 Jun 22;7(1):4088.
Wu J , Gu M , Chen S , et al. Factors related to pediatric obstructive sleep apnea–hypopnea syndrome in children with attention deficit hyperactivity disorder in different age groups. Medicine (Baltimore). 2017 Oct;96(42):e8281.
Kou W , Li X , Yao H , et al. Meta-analysis of the comorbidity rate of allergic rhinitis and asthma in Chinese children. Int J Pediatr Otorhinolaryngol. 2018 Apr;107:131-134.
Khan DA , Allergic rhinitis and asthma: Epidemiology and common pathophysiology. Allergy Asthma Proc. 2014 Sep-Oct;35(5):357-61.
De Groot EP , Nijkamp A , Duiverman EJ , et al. Allergic rhinitis is associated with poor asthma control in children with asthma. Thorax.2012 Jul;67(7):582-7.
Pedro G B , Marcelo A , Priscila T , et al. United airway disease: current perspectives. J Asthma Allergy. 2016 May 11;9:93-100.
Tay TR , Hew M . Comorbid ‘treatable traits’ in difficult asthma: Current evidence and clinical evaluation. 2018 Jul;73(7):1369-1382.
Lun HK , Min BY , Chan KC , et al. Determinants for asthma control, quality of life and use of complementary and alternative medicine in asthmatic pediatric patients in four cities. World J Pediatr. 2018 Oct;14(5):482-491.
Jung CG , Lee JH , Ban GY , et al. Prevalence and Clinical Characteristics of Local Allergic Rhinitis to House Dust Mites. Yonsei Med J.2017 Sep;58(5):1047-1050.
Tao XY , Ng CL , Chen D , et al. Clinical Characteristics and Allergen Sensitization Patterns of Patients with Local Allergic Rhinitis in Southern China. Int Arch Allergy Immunol. 2018;175(1-2):107-113.
Nurmatov U, van Schayck CP, Hurwitz B, et al. House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review. Allergy. 2012 Feb;67(2):158-65.
SeidmanMichael D.,GurgelRichard K.,LinSandra Y., et al.Clinical Practice Guideline.Otolaryngology–Head and Neck Surgery,2015,152(1_suppl):S1-S43. DOI:10.1177/0194599814561600.
SeidmanMichael D.,GurgelRichard K.,LinSandra Y., et al.Clinical Practice Guideline.Otolaryngology–Head and Neck Surgery,2015,152(1_suppl):S1-S43. DOI:10.1177/0194599814561600.
Calderón MA, Linneberg A, Kleine-Tebbe J, et al. Respiratory allergy caused by house dust mites: What do we really know?. J Allergy Clin Immunol. 2015 Jul;136(1):38-48.
Gerth Van Wijk R ，Terreehorst IT，Mulder PG , et al. Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo-controlled study. Clin Exp Allergy. 2000 Dec;30(12):1792-8.
Linder A. Symptom scores as measures of the severity of rhinitis. Clin Exp Allergy., 1988, 18(1): 29-37.
Meltzer EO, Schatz M, Nathan R, et al. Reliability, validity, and responsiveness of the Rhinitis Control Assessment Test in patients with rhinitis. J Allergy Clin Immunol. 2013 Feb;131(2):379-86.
Zhao J, Bai J, Shen KL , et al. Questionnaire-based survey of allergic diseases among children aged 0 - 14 years in the downtown of Beijing, Chongqing and Guangzhou. Zhonghua Er Ke Za Zhi. 2011 Oct;49(10):740-4.
Okubo K，Kurono Y，Ichimura K，et al. Japanese guidelinesfor allergic rhinitis 2017. Allergol Int. 2017 Apr;66(2):205-219.
Lee SL, Wong W, Lau YL. Increasing prevalence of allergic rhinitis but not asthma among children in Hong Kong from 1995 to 2001 (Phase 3 International Study of Asthma and Allergies in Childhood). Pediatr Allergy Immunol. 2004 Feb;15(1):72-8.
Sheehan WJ , Phipatanakul W . Indoor allergen exposure and asthma outcomes. Curr Opin Pediatr. 2016 Dec;28(6):772-777.
Shaaban R , Zureik M , Soussan D , et al. Rhinitis and onset of asthma: a longitudinal population-based study. 2008 Sep 20;372(9643):1049-57.
Mortuaire G , Michel J , Papon JF , et al. Specific immunotherapy in allergic rhinitis. Eur Ann Otorhinolaryngol Head Neck Dis. 2017 Sep;134(4):253-258.
Jiang Z, Xiao H, Zhang H, et al .Comparison of adverse events between cluster and conventional immunotherapy for allergic rhinitis patients with or without asthma: A systematic review and meta-analysis. Am J Otolaryngol. 2019 Aug 7. pii: S0196-0709(19)30486-7.
Nankervis H , Pynn EV , Boyle RJ . House dust mite reduction and avoidance measures for treating eczema. Cochrane Database Syst Rev. 2015 Jan 19;1:CD008426.
Luan S , Yun X , Rao W , et al. Emamectin benzoate induces ROS-mediated DNA damage and apoptosis in Trichoplusia Tn5B1-4 cells. Chem Biol Interact. 2017 Aug 1;273:90-98.
Huang K, Yang T, Xu J,et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet. 2019 Aug 3;394(10196):407-418.

SPIRIT2013.doc

Download PDF

Journal Publication

published 29 Jul, 2020

Read the published version in Trials →

Editorial decision: Major revision
23 Apr, 2020
Reviewer #3 agreed at journal
23 Apr, 2020
Review #2 received at journal
23 Apr, 2020
Reviewer #2 agreed at journal
22 Apr, 2020
Reviewer #1 agreed at journal
09 Mar, 2020
Review #1 received at journal
09 Mar, 2020
Reviewers invited by journal
02 Mar, 2020
Editor assigned by journal
29 Feb, 2020
Submission checks completed at journal
25 Feb, 2020
First submitted to journal
07 Feb, 2020

You are reading this older preprint version

Read the latest preprint version →

Research on the improvement of allergic rhinitis in asthmatic children after reducing dust mite exposure: a randomized, double-blind, cross-placebo study protocol

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Objectives

Trial Design

Methods: Participants, Interventions And Outcomes

Discussion

Abbreviations

Declarations

References

Supplementary Files

Status:

Journal Publication

Version 1