Efficacy of indoor air purification in the treatment of Artemisia pollen‐allergic rhinitis: A randomised, double‐blind, clinical controlled trial

Abstract Objectives To evaluate the clinical efficacy of a high‐efficiency air purifier in patients with allergic rhinitis. Design We conducted a randomised, double‐blind, clinical controlled trial with active and inactive versions of an air purifier. Our study included patients with allergic rhinitis who were sensitive to Artemisia pollen and treatment of the indoor environment using air filtration at night. We evaluated the clinical efficacy of indoor air filtration during the Artemisia pollen scattering season in Yulin City in Shanxi Province, China. Setting The First Hospital of Yulin (Yulin City, Shanxi Province, China). Participants A total of 90 patients with allergic rhinitis who were sensitive to allergens of Artemisia pollen were randomly assigned to one of two groups in equal numbers. Main outcome measures The primary outcome measure was the difference in visual analogue scale scores from baseline. Secondary outcomes were changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores and tolerability scores for the air purifier. Results Based on the allergy symptom score, we found significant differences in rhinitis symptoms between the groups who used the active versus the inactive air purifier. Conclusions The results of our investigation demonstrated the health benefits of particle filtration.


| Background
Artemisia pollen is one of the most common causes of pollinosis in many parts of the world. [1][2][3][4][5] Pollen concentrations fluctuate daily and by region. Theoretically, avoiding exposure to allergens could lead to recovery without treatment. While seasonal migration may alleviate allergy symptoms for some patients with AR, this is an unrealistic option for most. In Japan, a nationwide map of daily pollen concentrations is published to help patients with AR avoid areas with high pollen concentrations. 6 When outdoor pollen levels are high, patients with AR are advised to stay indoors. Although particle filtration can modestly reduce the adverse outcomes of allergy and asthma in homes with pets, 7 the findings of previous related studies varied because of differences in observation times and the enrolled participants. [8][9][10][11] Exposure to Artemisia pollen may cause an attack or exacerbation of allergic rhinitis (AR) among people who are sensitive to the allergens of the pollen. The diameter of Artemisia pollen ranges from 19 to 25 μm, which means it can be filtered with an air purifier. 12 Thus, treatment with air purifiers is a viable option to limit exposure and thereby improve clinical outcomes. We sought to identify a convenient, economical and practical way to avoid or mitigate allergen exposure. Therefore, in this study, we aimed to determine the effect of an indoor air environment with low or minimal allergen density via indoor air purification at night to reduce the exposure time to allergens in the home.

| Objectives
We aimed to assess the clinical efficacy of indoor air filtration during the Artemisia pollen scattering season in Yulin City, Shanxi Province, China. Primarily, we wished to determine whether artificially reducing or eliminating indoor pollen concentrations could help minimise exposure to Artemisia pollen during the pollen scattering season and whether such treatment can have beneficial clinical effects in patients with AR.

| Ethical considerations
This clinical trial was reviewed, and ethical approval for the study protocol was granted by the Ethics Committee of the First Hospital of Yulin (number 201601). All patients were required to sign consent forms to participate in the study. Written informed consent was obtained from each participant. All personal identifying information was protected.

| Study design and participants
The study protocol and details of the physiological and biochemical assessments undertaken have been described previously. 13 This study was implemented in Yulin City from June 2016 to September 2018. We enrolled patients with AR, based on the definition outlined by ARIA, 14 and those who showed sensitivity to the allergens of Artemisia pollen in the recruitment radioallergosorbent test (RAST). They were referred to the study team by physicians of the First Hospital of Yulin. All patients lived in Yulin. In this randomised, double-blind, placebo-controlled clinical trial, we tested active and placebo versions of an air purifier. The air purifiers were equipped with monitors that could measure the number of hours of operation.
Enrolled patients were randomly assigned to one of two groups in equal numbers. All patients underwent a 4-week treatment period and a 4-week observation period. Patient evaluation was conducted at baseline (day 0) and on days 7, 14, 21 and 28 (Table 1). Specific tests conducted at each follow-up session are outlined in Table 1.
At patient enrolment, collection of specimens and data was undertaken at the Outpatient Department of the First Hospital of Yulin.
Biochemical examinations were carried out by King Med Diagnostics (Guangzhou, China). The data were analysed at the University of Toronto (Canada).

| Enrolment
We recruited, screened and enrolled or excluded patients on the basis of specific criteria. Patients were clearly informed of the study aims and procedures, as well as their right to discontinue participation in this trial at any time. After patients signed consent forms, the research staff randomly assigned recruited patients to the treatment or control group. Inclusion and exclusion criteria, as well as criteria for participant rejection or termination, are presented in Tables 2 and 3.

Keypoints
• In theory, avoiding exposure to allergens could lead to recovery without treatment. In this study, patients used an air purifier to avoid allergens as much as possible at night, but they were still exposed to allergens during the day. Though the time of allergen exposure was reduced, the allergens the patients were exposed to during the day would trigger allergic reactions.
• Artemisia pollen can be filtered with an air purifier.
• For some patients with allergic rhinitis, seasonal migration may alleviate allergy symptoms, but this is an unrealistic option for most.
• We sought to identify a convenient, economical and practical way to avoid or mitigate allergen exposure.

| Interventions in the treatment and control groups
An Atmosphere ® air purifier (Amway, China) was placed in the participants' bedrooms. The air purifiers provided to participants in the treatment group contained an Atmosphere® HEPA (model number 101076CH) two-way filter. This filter has an airflow velocity of 100-200 cubic feet/min and a filtration rate of 6000-12 000 cubic feet/ hour. This purifier produces 4-8 air changes per hour in a typical bedroom measuring 15 × 12 × 8 feet. The air purifiers provided to participants in the control group contained a placebo filter, which also had a two-way design with an airflow velocity of 100-200 cubic feet/min. Instructions were given to keep the purifier running continuously even if participants left the bedroom. Participants were required to remain in their bedroom at night for 4 weeks, that is, participants were to remain in their bedroom for >8 hours per day.

| Concomitant care and intervention
During the treatment and follow-up periods, participants were pro-

| Data collection and management
Research staff were responsible for the data collection. A third party set up the study database and programme settings and also implemented monitoring and management of the data. All data were imported in duplicate into an electronic database by two assistants. Identified input errors were corrected to ensure that there were no differences in the database. The statistical manager was responsible for data organisation, coding, range checking of data values and data conversion to ensure quality of the data.

| Data analysis
Statistical analyses were performed at the Guangzhou Institute of Respiratory Diseases using SPSS version 17.0 (SPSS Inc).
Continuous variables were expressed as mean (±SD) and categorical data as n (%). All statistical inferences were determined using two-sided tests. A significance level of 0.05 with 95% confidence intervals was used to measure the uncertainty of the estimates.
Baseline data analyses (two sets) included demographic indicators, history of AR and smoking status of the participants and their family members. Measurement data were compared using a Student t test. Pearson's chi-squared test was used to compare the groups using active and inactive air purifiers. Effects of interventions on the outcome indicators were evaluated by logistic regression models that included the VAS score, RQLQ score, allergy symptom score, Epworth Sleepiness Scale score and tolerability score for the Atmosphere ® air purifier. (4) Violated the terms of the trial (eg improper use of air purifiers, leading to effects that cannot be evaluated) (4) Not cooperated with the examination and 26 (58%) women and 19 (42%) men in the inactive air purifier group. All participants were non-smokers, but family members of five participants (11%) in the treatment group smoked;

| RE SULTS
family members of three participants (7%) in the control group were smokers. There were no significant differences between the active and inactive air purifier groups for any medical or demographic variables ( Table 4).
The allergy symptom scores showed significant differences between the active and inactive air purifier groups with respect to rhinitis symptoms, with a p value of 0.004. No significant differences were detected between the groups for measures on the RQLQ (Table 5).
The RQLQ contains 28 questions covering seven topics, and the cumulative score for the seven topics is considered the score for the general status indicators. A line chart revealed that the cumulative score for the general status indicators showed a significant decline in both groups; furthermore, the score for each item declined gradually each week. The cumulative score in the active air purifier group fell from a baseline value of 96.89 to 58.67. The cumulative score in the control group fell from a baseline value of 101.27 to 63.45 (Table 5, Figure 1).
The line chart also revealed that the following scores decreased progressively each week from baseline to the end of the intervention: nasal symptom score, allergy symptom score (VAS), Epworth Sleepiness Scale score and tolerability score for the Atmosphere ® air purifier. The nasal symptom data trend line cut high and low in both directions between the active and inactive air purifier groups. The sleepiness data trend decreased in steps between the two groups.
The trend of the tolerability score for the Atmosphere ® air purifier also decreased with no lines crossing between the groups, but the range ability during the second week in the control group was greater than that in the treatment group. The data trend in the inactive air purifier group was ascending at the end of intervention. VAS scores showed progressive weekly increases; scores were higher in the intervention group than in the controls (Table 5, Figure 1).

| Synopsis of the key findings
Artemisia is a rare annual, biennial or perennial herbaceous bush that mostly grows on slopes, in the wilderness or by the roadside. With the   We chose individuals with AR who were sensitive to Artemisia pollen as the focus of this study for three main reasons. First, Artemisia pollen can be filtered using an air purifier. 12 Second, Artemisia pollen is extremely common; pollen counts can be obtained for each province of mainland China. Artemisia is the primary outdoor allergen in

TA B L E 5 Effect of the intervention on outcome indicators
China. 17 Third, it has been proposed that an air purifier is likely to be of benefit against Artemisia pollen because this outdoor allergen is common inside the home in many regions of China. Fourth, the incidence of Artemisia pollen allergy is increasing together with urbanisation in Yulin City, a typical area undergoing desertification in China.
Using a double-blind, placebo-controlled protocol, we sought to evaluate the effects of a room air purifier in patients with sensitivity to Artemisia pollen. We found that rhinitis symptoms improved significantly after the intervention. Intervention studies conducted in the homes of patients with allergy or asthma who were supplied with filtered air to the areas where they slept have reported improvements in some assessed health outcomes. In our study, participants in the intervention group used an air purifier to deliver filtered air to their sleeping areas, such as the bedroom. Tolerability scores for the Atmosphere ® air purifier in the treatment group were lower than those in the control group. This could be because rhinitis symptoms improved, leading to improved tolerance. Our findings also showed that the air purifier had little impact on sleep at night, even when placed in the bedroom.

| Comparison with other studies and clinical applicability
Morris and co-workers conducted research into 1-week, nocturnal, indoor air purification treatment in patients who were allergic F I G U R E 1 Weekly change in outcomes after intervention. RQLQ: Rhinoconjunctivitis Quality of Life Questionnaire to ragweed. Those authors recommended that patients with seasonal AR use air purification devices during the ragweed pollen season. 9  Allergen exposure is considered to be an important risk factor for allergic respiratory disease. 18 Bronchoprovocation experiments have proven that allergens could induce bronchospasm, eosinophilic airway inflammation and prolonged increases in bronchial hyperreactivity, indicating that allergen exposure was related to asthma. 19 These findings indicate that allergic patients should reduce allergen exposure in their houses as part of the management of asthma and AR. 20 However, the findings did not clarify why the asthma symptoms did not completely resolve with the rhinitis. This study showed that the air purifier may be effective for AR, but we did not enrol participants who had asthma. The benefits of air purifiers for patients with asthma who were sensitive to Artemisia pollen and the effect of the environment on the progression of allergic disease may deserve additional research.

| Limitations of the study
In this pilot study, no other metrics (outside of the allergy symptom score) were different between the two groups. The number of patients was relatively small; therefore, further studies with a larger number of patients are needed to confirm our findings. It is also possible that more aggressive environmental control measures would produce a greater effect. Furthermore, the use of additional air purifiers in other areas of the home or workplace could further reduce allergen exposure and thereby reduce allergy symptoms. We did not include this measure because our intent in this study was to assess the effect of a relatively simple approach that can be applied by most patients, namely use of an air purifier in the bedroom.
If patients had AR symptoms, medications could provide them relief, but some patients did not show complete remission. Even though patients had light AR symptoms, they did not always take medication. Before they enrolled in the study, they would have hesitation period. They had been informed that the air purifier was a kind of replacement therapy, and they received anti-allergic agents only when they were treated with severe symptoms. For some patients with AR, seasonal migration may alleviate allergy symptoms, but this is an unrealistic option for most. When outdoor pollen levels were high, the morbidity caused by AR increased. We aimed to determine the effect of an indoor air environment with low or minimal allergen density via indoor air purification at night, in reducing the exposure time to allergens in the home. Therefore, in this study, we did not enrol patients with poorly controlled AR.

| CON CLUS ION
We investigated the clinical effect of air purification among participants with AR who were sensitive to the allergens of Artemisia pollen. The present findings demonstrated the health benefits of particle filtration. Filtration may be modestly effective in reducing adverse outcomes of AR, particularly in homes with Artemisia pollen, such as areas with desertification. Our study also suggested that filtration of air in the sleeping areas of individuals with allergies may be effective in improving health.

ACK N OWLED G EM ENTS
We thank all participants for their patience and commitment to this study. This work was supported by the Technical Research and Development Program Project in 2016. Air purifiers (active and placebo versions) were provided by Amway (China). Amway only provided free air purifiers and had no role in the study design; collection, management, analysis and interpretation of the data; writing of the report; or the decision to submit the report for publication.

CO N FLI C T S O F I NTE R E S T
The authors declare that they have no competing interests.