Background
Allergic rhinitis (AR) is a global health problem. The reported incidence of AR is 11.8–46% worldwide [
1,
2] and 11.1–19.1% [
3,
4] in China. Allergen avoidance is strongly recommended for AR patients. In Japan, a country-wide map of pollen concentrations is published daily so that AR patients can avoid high-concentration areas [
5]. Seasonal migration of AR patients is an effective but expensive option. We searched for more convenient and less expensive ways to avoid and mitigate allergen exposure.
Our research team focused on air purification because this strategy can reduce the concentrations of particles in indoor air. In addition, air purifiers can filter particles smaller than 1 μm in diameter [
6], and the diameter of mugwort (
Artemisia spp.) pollen is typically 19–25 μm [
7] .Air purifiers are recommended by clinicians for AR patients [
8], as they can reduce airborne indoor allergen levels significantly [
9]. Few studies, however, have focused on the removal of airborne allergens in home environments. Moreover, those studies have been limited by a lack of blinding, small samples, and a failure to measure allergen levels, disease activity, or a combination of these factors.
Project aim
Studies have suggested that indoor particle purification may reduce clinical symptoms or improve clinical outcomes, particularly for individuals with allergies [
10] .Little robust clinical evidence has been provided, however, for the efficacy of indoor-air purification as a treatment. We sought to investigate, by means of a double-blind, placebo-controlled protocol, the efficacy of a high-efficiency particulate air (HEPA) purifier in reducing disease activity in the homes of AR patients sensitive to the allergens produced by
Artemisia pollen.
Follow-up
Upon completion of the 4-week treatment, patients will undergo a 4-week follow-up period. Research staff will continue to follow participants by telephone, short messaging via mobile telephone, or in the clinic. During the treatment period, follow-up will be conducted weekly. A record of symptom assessment and treatment compliance/changes will be maintained. If participants discontinue/deviate from the intervention protocols, research staff will record the reasons for the change. Such participants and their data will be excluded from the study.
Intervention in the treatment group
The patients will operate an Atmosphere® air purifier (Amway China, Guangzhou, China) in their bedrooms. This air purifier contains a HEPA two-way filter (model number 101076CH) with an airflow velocity of 100/200 cubic feet/minute at a filtration rate of 6000/12,000 cubic feet/hour. This represents 4/8 air changes per hour in a typical bedroom measuring 15 × 12 × 8 ft. The air purifier will be placed in the bedroom of the patient. Instructions will be given for the units to be left running continuously. The patients must stay in their bedrooms at night for 4 weeks (> 8 h each day).
Intervention in the control group
The patients will operate an Atmosphere air purifier in their bedrooms, but this air purifier will contain a placebo filter. This filter is also of a two-way design with an airflow velocity of 100/200 cubic feet/minute. Instructions will be given for the units to be left running continuously. The patients must stay in their bedroom at night for 4 weeks (> 8 h each day).
Concomitant care and interventions
During the treatment and observation periods, participants will be prohibited from taking medications such as antihistamines, corticosteroids, decongestants, or leukotriene receptor antagonists orally or intranasally. Only patients with severe symptoms would be permitted to use anti-allergy agents. The type of medication, dose, and use will be recorded by the patient for analysis. For other complex chronic diseases, patients must continue taking their routine medications and therapies. Research staff will record the details of the diseases, medications, and therapies in the case report.
Primary outcome measure
The visual analog scale (VAS) will be used to measure symptom severity and quality of life. The primary outcome measure is a difference in the VAS.
Secondary outcome measures
The secondary outcomes will be changes in nasal symptoms, allergy symptom scores, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, Epworth Sleepiness Scale scores, and tolerability scores for the Atmosphere air purifier.
Nasal symptoms
The most important symptom is a swelling of the turbinates, which will be graded as 1 (“mild”), 2 (“moderate”), or 3 (“severe”).
Allergy symptom scores
Allergy symptom scores will be used to grade symptoms as 0 (“no symptoms”), 1 (“mild symptoms”), 2 (“moderate symptoms”), and 3 (“severe symptoms”). The symptoms graded will be congestion, sneezing, nasal itch, rhinorrhea, eye itch, ear/palate itch, eye redness, and tearing.
RQLQ
The RQLQ contains 28 questions covering seven topics (daily life activities, sleep, non-eye/nasal symptoms, practical problems, nasal symptoms, eye symptoms, and emotional status). The questions will be graded on a scale from 0 (“none”) to 6 (“very often/always”).
Epworth sleepiness score
The Epworth Sleepiness Score comprises eight questions about the patient’s sleepiness, which are scored from 0 (“none”) to 3 (“probably”).
Tolerability of the atmosphere air purifier
Tolerability measure of the Atmosphere air purifier is based on answers to five questions, which will be graded on a scale from 1 (“complete disagreement”) to 5 (“complete agreement”).
Collection and management of data
Research staff is responsible for data collection. The baseline variables will be age, sex, highest education level achieved, dwelling environment, career, diagnosis, results of allergen examination, disease course, family history, VAS score, nasal symptoms, allergy symptom score, RQLQ score, Epworth Sleepiness Scale score, and tolerability of the Atmosphere air purifier. Participants will be required to record the intake of any medication during this study period.
Monitoring and management of data will be performed by a third party, which will build the study database and program settings. All data will be double-imported into an electronic database by two operators. Identified input errors will be corrected until there are no discrepancies in the database. Data organisation, data coding, range checking for data values, and data conversion to ensure quality will be the responsibility of the statistician.
Statistical analyses
Statistical analyses will be carried out using SPSS v. 17.0 (IBM, Armonk, NY, USA) in the Clinical Evaluation Center of Southern Medical University (Guangzhou, China). Data will be described as the mean and standard deviation for normally distributed data, median and interquartile range for non-normally distributed data, and frequency and proportion for categorical data. All statistical inferences will be determined using two-sided tests. We will set a significance level of 0.05 and use 95% confidence intervals to measure the uncertainty of the estimate. Efficacy analyses will use last observation carried forward (LOCF) methodology to impute for cases not fully followed up during treatment. Pearson’s χ2 test will be used to compare the differences between the dropout rate and the dropout rate attributable to adverse events. Baseline data analyses (two sets) will include demographic indicators and general, primary, and secondary indicators before intervention. Measurement data will be compared using a paired t-test. For analyses of efficacy, for quantitative variables, comparisons between groups will be made by repeated measurement variance analysis and covariance analysis. For qualitative variables, comparisons between groups will be made using Pearson’s χ2 test, whereas central effects will be tested by a mixed-effects model. For rating variables, comparisons between groups will be made using the Kruskal-Wallis test. In terms of analyses of centre effects, the quantitative indicators will be tested by the general linear method, and the qualitative indicators will be tested by the Cochran-Mantel-Haenszel test methods. A logistic regression model will be used to evaluate and correct the rating variables.
Trial status
This clinical trial was reviewed by the Ethics Committee of the First Hospital of Yulin in 2016. The first patient was enrolled in 2016. From the middle of 2016 to the end of 2017, 45 patients completed the treatment and observation periods. This clinical trial is expected to be completed at the end of 2018.
Dissemination plan
Researcher will assign the recruited patients anonymous recruitment numbers and de-identified data-sets will be used to perform all subsequent references and analyses. All of the collected patient information of this study will be kept confidential in compliance to the China Personal Data Protection Act. All the data will kept by the full-time manager. And the data will only be available to the researchers. All study data will be kept for 10 years.
Discussion
The Atmosphere air purfier has been approved for daily use. The Atmosphere air purifier filter (101076CH) was certified to filter pollen allergens by Allergy UK. Before treatment commences, we will explain to patients in detail the research purpose, methods, and possible risks of the clinical trial, and also inform them explicitly of their right to discontinue their participation. Researchers will accept the research plan, treatment procedure, patients, research schedule, case report forms, and written informed consent forms. After the trial, if the participants are willing to continue treatment, we will provide appropriate therapies. Patients who suffer harm from participation in this clinical trial will be provided a certain amount of economic compensation or free treatment, especially if they suffer adverse events. Any moderate/serious adverse events will be reported to the Ethics Committee of the First Hospital of Yulin.
Reducing exposure to allergens can reduce the risk of conditions such as AR. We hypothesise that AR patients sensitive to the allergens produced by Artemisia pollen will not suffer symptoms in a pollen-free environment. AR patients can remove pollen from their homes using air purifiers, decreasing the risk of symptoms.
The city of Yulin is part of Guangxi Province in western China, south of the Mu Us Desert. In recent years,
Artemisia desertorum Sprengel has been sown extensively in and around Yulin, increasing the prevalence of allergic reaction [
11‐
13]. We therefore selected Yulin as the study site. Morris et al. (2006) recommended that individuals with seasonal AR use indoor air purifiers during the ragweed-pollen season [
14]. Stillerman and colleagues conducted a 12-week air-purification treatment in patients with perennial AR [
15], and found that nasal congestion, sneezing, runny nose, itchy eyes, tearing, and other symptoms improved, as did quality of life. They therefore suggested that reducing allergen exposure effectively has clinical value and benefits AR patients [
15]. Therapy based on reducing allergic sensitisation by avoiding allergen exposure at night may have clinical applications. Considering that plant pollen can be removed by air purification, we selected AR patients sensitive to the allergens of
Artemisia pollen as our research subjects. The treatment periods in the studies cited above were 1–12 weeks, and the follow-up period was short, which may have resulted in inadequate evaluation of the efficacy of air-purification treatments. The duration of follow-up in our study will be 4 weeks, to ensure an adequate evaluation of treatment efficacy. In addition, those studies were not randomised controlled trials. Hence, we will conduct a double-blind, parallel-design, air purifier and placebo controlled randomised clinical trial. We expect that our study results will provide reliable evidence for determining the effects of air-purification treatment.
Acknowledgements
Special thanks should go to the patient advisers Li Li, Li Zhang, Qiao-yan Chen, Yun-ying Li and Ji-yan Xia, who have put considerable time and effort into our study.